Acute Stress Disorder & Posttraumatic Stress Disorder
Promoting recovery after trauma
Australian Guidelines for the Treatment of Acute Stress Disorder & Posttraumatic Stress Disorder
Appendices List of appendices
APPENDIX 1: ADELAIDE HEALTH TECHNOLOGY ASSESSMENT (AHTA) REVIEWERS ...... 3 APPENDIX 2: TERMS OF REFERENCE ...... 4 APPENDIX 3: AHTA SYSTEMATIC REVIEW OF THE EVIDENCE ...... 19 APPENDIX 4: PUBLIC CONSULTATION ...... 579 APPENDIX 5: DSM-5 CRITERIA FOR PTSD ...... 592
Appendix 1: Adelaide Health Technology Assessment (AHTA) reviewers
Skye Newton B Psych (Hons), GDPH Senior Research Officer, Adelaide Health Technology Assessment, Discipline of Public Health, University of Adelaide, Adelaide, SA 5005
Jacqueline Parsons BA BHealthSc MPH Senior Research Officer, Adelaide Health Technology Assessment, Discipline of Public Health, University of Adelaide, Adelaide, SA 5005
Ben Ellery BHealthSc, GDPH Research Officer, Adelaide Health Technology Assessment, Discipline of Public Health, University of Adelaide, Adelaide, SA 5005
Joanne Milverton BSci, GDPH Research Officer, Adelaide Health Technology Assessment, Discipline of Public Health, University of Adelaide, Adelaide, SA 5005
Judy Morona B.Sc., PhD., GDPH Research Officer, Adelaide Health Technology Assessment, Discipline of Public Health, University of Adelaide, Adelaide, SA 5005
Stynke Docter BHlthSci (Physio), MHlthSci (Int Pub Hlth) Research Officer, Adelaide Health Technology Assessment, Discipline of Public Health, University of Adelaide, Adelaide, SA 5005
Zhaohui Liufu MPH, MMed Senior Research Officer, Adelaide Health Technology Assessment, Discipline of Public Health, University of Adelaide, Adelaide, SA 5005
Tracy Merlin BA (Hons), MPH Managing Director, Adelaide Health Technology Assessment, Senior Lecturer, Discipline of Public Health, University of Adelaide, Adelaide, SA 5005
3 Appendix 2: Terms of reference
Section 1: Project Terms of Reference
1.1 Aim
To update the Australian Guidelines for the treatment of adults with ASD and PTSD on the basis of literature published since the 2007 Guideline, and extend the scope to include an evidence review and recommendations for the treatment of children and adolescents with ASD and PTSD.
1.2 Target groups
The Guidelines are intended to influence the care of all Australians, across the full range of ages and populations, who develop or are at risk of developing forms of distress that are generally consistent with the criteria for Acute Stress Disorder (ASD) and Posttraumatic Stress Disorder (PTSD) following traumatic events.
1.3 Credibility and broad influence
The Guidelines will be developed according to the requirements of NHMRC using a process and format designed to maximise support for their implementation. For mental health clinicians their influence is intended to support the implementation of the main guideline recommendations; for primary care and general health and welfare workers their influence is intended to promote awareness of the Guidelines that pertain to specialist mental health interventions and to guide primary care interventions.
1.4 Conflict of Interest
Each individual involved in the development of the Guidelines is required to declare all known or perceived conflicts of interest (COI). It is acknowledged that COI will arise from time to time; however, the process outlined within these Terms of Reference will ensure that all conflicts are identified, disclosed, and managed in a rigorous and transparent way that promotes confidence in the legitimacy, impartialness, integrity, and fairness of the outcomes of these Guidelines.
The process for managing declared conflicts is presented in detail below.
1.5 Limitations
The Guidelines are principally limited to forms of distress consistent with the constructs of ASD and PTSD. They do not seek to address the full range of possible responses to traumatic exposure, including those known as Complex PTSD or Disorders of Extreme Stress Not Otherwise Specified (DESNOS).
The original Guidelines were limited to adults; however, the revised version will also include children and adolescents.
4 1.6 Practitioners
The Guidelines are intended to be used by a range of health professionals in a way that is commensurate with their level of expertise. Thus it is intended that individual practitioners will deliver interventions within their area of expertise, and refer the client to other appropriately qualified practitioners for interventions outside of their own expertise. There is insufficient evidence available in either the research or clinical practice literature to allow an authoritative specification of competencies required for particular interventions, and so the individual practitioner should be guided by his or her own professional code of conduct with regard to this issue.
1.7 Settings
The Guidelines are targeted to intervention, support and care provided across the full range of settings including primary health care, community care, day programs, specialist outpatient, residential and inpatient settings. It will also consider implications for interventions in rural and remote settings.
1.8 Outcomes
The Guidelines will identify key measures and processes for use in practice settings to monitor outcomes.
1.9 Research and competency development
The Guidelines will identify priority areas for future research and competency development required to address gaps in scientific evidence and inadequate practitioner knowledge and competency.
1.10Future review
The Guidelines will have a defined life of 5 years and will be subject to review by 2017.
1.11Organisational context
The Guidelines will be developed within, and supported by, the following organisational structure.
5 Figure 1: Organisational structure of the Guidelines
Terms of reference for each of the Steering Group, Working Party and Multidisciplinary Panel are outlined below.
6 Process for managing Conflict(s) of Interest The process for managing COI is presented in Figure 2 below. Each individual involved in the development of the Guidelines (including all members of the working party and multidisciplinary panel) will be required to complete a COI declaration prior to each activity or meeting. For example, working party members will be required to complete a COI prior to each working party meeting (approximately once per quarter). Declarations will then be collated by the ACPMH project manager and sent to the Steering Committee for review.
The Steering Committee is responsible for reviewing all declarations and determining if a conflict is present and relevant. If a conflict is identified and it is determined that the conflict would result in undue influence to the process of developing the Guidelines then the Steering Committee must complete the Conflict of Interest Action Taken document. This document identifies what action needs to be taken to mitigate the conflict (for example, remove that individual from a specific part of the decision making process).
Declarations of COI from Working Party members (including the ACPMH development team) will be discussed at the beginning of all Working Party meetings. Declarations from the MDP will be shared with the Chair of the MDP before each activity involving the MDP. All declarations and any action taken from those declarations will be recorded in the final Guidelines document as an appendix.
7 Figure 2: Process for managing COI
Declaration of COI completed
Reviewed by Steering Committee
Report back to Chair Conern? No of Working Party
No further action Yes required
Appropriate action to be taken, refer to “Conflict of Interest Action Taken” document
8 Section 2: Terms of Reference for the Steering Group
2.1 Steering Group Mission Statement The Steering Group will direct and oversee the work of the Working Party, consider the advice of the Multidisciplinary Panel and have ultimate responsibility for the content and format of the Guidelines.
2.2 Problem Statement Practitioners in the field of posttraumatic mental health operate across a diverse range of clients, trauma types and therapeutic paradigms. This diversity will be reflected in the composition of the Multidisciplinary Panel, creating a forum in which diverse views will be expressed and taken into consideration. Whilst representing a significant challenge, this forum importantly creates an opportunity to develop a set of Treatment Guidelines which are endorsed by that diverse range of practitioners, and subsequently used across settings and practitioners. The Steering Group will have a critical role in maintaining the focus on the broad objectives and having ultimate responsibility for any disputes which cannot be resolved at a lower level in the organisational structure of the Guideline Development team. The Steering Group will also have ultimate responsibility for decisions relating to conflict(s) of interest.
2.3 Boundaries x The Steering Group will review and offer advice on the set of questions to be put to the systematic review for the project. x The Steering Group has ultimate responsibility for the format and content of the Treatment Guidelines, and as such has the authority to make final decisions in their regard. x The Steering Group will review declarations of COI and make decisions as to the course of action to take for any declarations. x Responsibility for the day to day work required in developing the Treatment Guidelines will be delegated to the development team at ACPMH.
2.4 Specific issues to be addressed The Steering Group will approve the questions to be put to the systematic review, review the progress of MDP and WP through six monthly reports from the ACPMH Project Leader, review and direct modifications to drafts of the Guidelines towards the end of the process and sign off on the final Guidelines.
2.5 Desired Outcomes Each treatment recommendation will accurately represent the best research evidence available, or in the absence of research evidence, expert consensus opinion. Each recommendation will be written in a way that is easy to understand and implement. Overall, the recommendations will be presented in an organised and coherent manner, with appropriate linkages between recommendations and advice to practitioners on how to use the recommendations to inform treatment planning and clinical decision making.
2.6 Persons Involved The Steering Group will be co-chaired by David Forbes, ACPMH (the organisation with trauma expertise carrying responsibility for the Guideline development process) and Chair of the Working Party, and Beverley Raphael, Chair of the Multidisciplinary Panel.
9 2.7 Project Administration
2.7.1 Time frames For a period of 3 months from March 2011, the research questions will be drafted by the working party, reviewed by the MDP and endorsed by the Steering Group.
The research questions, updating the literature covered in the previous Guidelines, extending to cover children and address any gaps identified in the previous Guidelines, will be submitted to a systematic review in August 2011. The Working party will oversee the systematic review. Draft recommendations will be complete by the end of July 2012. Over the following six month period, in consultation with the Multidisciplinary Panel and key stakeholders, the content and presentation of the Guidelines will be finalised. During the period July to December 2012, we envisage that the Guidelines will pass back and forth between the Working Party and Multidisciplinary Panel, on 3 or 4 occasions, and be the subject of extensive consultation with key stakeholders. This consultation process will establish the infrastructure needed to support the forthcoming dissemination process.
The content of the Guidelines will be finalised by the end of March 2013, and forwarded to NHMRC. It is anticipated that dissemination will commence in financial year 2013/14.
2.7.2 Meetings The Steering Group will generally communicate by telephone, email and telephone link up where necessary. Face-to-face meetings will be held only if required, with travel and accommodation costs being met by ACPMH.
2.7.3 Resources Members of the Steering Group will need to undertake work in their own time and using their own resources.
2.7.4 Reporting Guidelines The Steering Group will receive six monthly reports from the ACPMH Project Leader.
2.7.5 Dispute Resolution In the event of a dispute arising between members of the Multidisciplinary Panel or Working Party, the Chair of those respective groups will seek to resolve the dispute in the first instance. If this is unsuccessful, the issue will be referred to the Steering Group for resolution. In the event of a dispute arising between the MDP and Working Party, the matter will be referred to the Steering Group.
10 Section 3: Terms of Reference for the Guidelines Developers: ACPMH
3.1 ACPMH Guidelines Developers Mission Statement ACPMH will coordinate and oversee the revision of the Guidelines. ACPMH will be responsible for the day to day work required in developing the Guidelines.
3.2 Problem Statement The current Australian Guidelines – the Australian Guidelines for the Treatment of Adults with Acute Stress Disorder (ASD) and Posttraumatic Stress Disorder – were released in May 2007 with limited life approval from the National Health and Medical Research Council (NHMRC). Consistent with ACPMH’s mission, the Guidelines sought to ensure that Australians affected by trauma receive the best possible care.
The revised Guidelines will additionally address an identified area that was not part of the scope in the original document, namely evidence-based interventions for children and adolescents and address in more detail early interventions for survivors of trauma and disasters. Due to the limited life of the NHMRC’s approval, the revision of the Guidelines needs to be completed by the end of 2012.
3.3 Boundaries x The Guidelines Development team at ACPMH will be responsible for project managing the revision of the Guidelines including budgeting, securing funding for the project, maintaining timelines, providing progress reports to funders and the Steering Committee. x ACPMH will draft the tender for the external literature review and secure the external review. x Review of the literature for the special populations and early intervention sections as well as a new section on recovery after disaster will be completed by ACPMH. x The financial responsibility of the Guidelines revision rests with ACPMH. x The ACPMH project team will be responsible for completing declarations of COI prior to each working party meeting. These declarations will be sent to the Steering Committee for review and action (if required).
3.4 Specific issues to be addressed The Guidelines Development team at ACPMH will be responsible for the overall management of the revision process. It will create and monitor the budget and timeline for the project. It will monitor and prompt the Working Party and Multidisciplinary Panel members completion of tasks within the time frame required. It will draft the Guideline document for approval by the Working Party.
3.5 Desired Outcomes As the developers, ACPMH will ensure that each recommendation is written in a way that is easy to understand and implement. ACPMH will also ensure that the guideline revision process adheres to the requirements of NHMRC guideline development standards.
3.6 Persons Involved The Guidelines Development team at ACPMH will be co-led by David Forbes and Andrea Phelps. Lisa Dell and Bronwyn Wolfgang will be the project managers. Additional support staff will be involved in the project as required.
11 3.7 Project Administration
3.7.1 Time frames For a period of 3 months from March 2011, the research questions will be drafted by the working party, reviewed by the MDP and endorsed by the Steering Group.
The research questions, updating the literature covered in the previous Guidelines, extending to cover children and address any gaps identified in the previous Guidelines, will be submitted to a systematic review in August 2011. The Working party will oversee the systematic review. Draft recommendations will be complete by the end of July 2012. Over the following six month period, in consultation with the Multidisciplinary Panel and key stakeholders, the content and presentation of the Guidelines will be finalised. During the period July to December 2012, we envisage that the Guidelines will pass back and forth between the Working Party and Multidisciplinary Panel, on 3 or 4 occasions, and be the subject of extensive consultation with key stakeholders. This consultation process will establish the infrastructure needed to support the forthcoming dissemination process.
The content of the Guidelines will be finalised by the end of March 2013, and forwarded to NHMRC. It is anticipated that dissemination will commence in financial year 2013/14.
3.7.2 Meetings ACPMH will organise all telephone link-up meetings and host all face-to-face meetings for the Working Party. All travel and accommodation costs related to meeting will be met by ACPMH.
3.7.3 Resources External funding has been secured to cover the cost of the systematic reviews, consultant fees, travel and accommodation and project coordination.
3.7.4 Reporting Guidelines ACPMH will provide six-monthly reports for the Steering Group. It will also complete all reports as required by external funders.
12 Section 4: Terms of Reference for the Working Party
4.1 Working Party Mission Statement The Working Party will formulate Guidelines for interventions for ASD and PTSD on the basis of evidence-based literature and in the absence of an evidence-base, expert consensus opinion.
4.2 Problem Statement Significant variations in clinical practice are apparent across the range of settings and practitioners providing services to traumatised individuals. If consistency and quality of clinical practice is to be improved, practitioners must have ready access to Guidelines for best practice interventions for ASD and PTSD, which are relevant and helpful in their daily clinical practice. To meet this aim, the Guidelines must address the range of presenting problems associated with ASD and PTSD including common comorbid disorders, and to guide the clinician in tailoring recommended and acceptable treatments to clients.
The working party will revise the proposed Practice Guidelines for ASD and PTSD in Adults on the basis of a systematic review of the literature published since the original Australian Guidelines for the Treatment of Adults with Acute Stress Disorder (ASD) and Posttraumatic Stress Disorder (PTSD) were published (2007). The revised edition of the Guidelines will be expanded to include recommendations for the treatment of children and adolescents with ASD and PTSD. These recommendations will be based on a systematic review of the literature.
4.3 Boundaries x The Working Party will review and offer advice on the set of questions to be put to the systematic review for the project. x The Working Party will generate questions for the systematic review, oversee its conduct, and write treatment recommendations based on the outcome. x Individual members of the Working Party will take responsibility for one or more questions. x The allocation of questions to members will be made by the Chair of the Working Party, following expressions of interest and discussion with all members. x The Working Party will consider feedback on the Guidelines from the Multidisciplinary Panel. x The Steering Group has authority to address disputes regarding content or format if they arise. x The Working Party will be responsible for completing declarations of COI prior to each working party meeting. These declarations will be sent to the Steering Committee for review and action (if required).
4.4 Specific issues to be addressed Each member of the working party will be responsible for overseeing the conduct of the systematic review in relation to one or more question. Where questions are not adequately answered by review of the literature, expert opinion will be used through existing documentation or Delphi processes. When the review is complete the Working Party member will draft the treatment recommendation/s in relation to that question/s and forward them to ACPMH, who will forward them to other members of the Working Party. Each member of the Working Party will provide feedback and the individual member will consider that
13 feedback in revising the recommendation. As best as possible, consensus should be reached amongst members of the Working Party before the recommendations are forwarded to the MDP for comment. The chair of the working party will facilitate the working party meetings. Importantly, the chair will lead the working party through the process of voting on the final recommendations.
Should disagreements arise, the Chair will seek to resolve them, before referring the matter on to the Steering Group, if necessary.
Similarly, when the recommendations are circulated to members of the MDP for comment, individual members of the Working Party will be responsible for incorporating feedback into the draft recommendations where appropriate, and highlighting differences of opinion where consensus is not reached. These differences may be resolved at the level of the Steering Group, or may be documented as irreconcilable differences on the final Guideline document. The Chair of the Working Party will be responsible for ensuring that panel members complete tasks within the time frame required and will provide a brief report to the Steering Group on a three monthly basis on the progress of the Working Party.
Should there be disagreements between the suggestions of the MDP and the WP, the WP will be responsive to the recommendations of the Steering Group. If major differences of opinion remain, consideration will be given to including a statement of dissenting views in the Guidelines.
4.5 Desired Outcomes Each treatment guideline will accurately represent the best research evidence available, or in the absence of research evidence, expert consensus opinion. Each guideline will be written in a way that is easy to understand and implement. Overall, the Guidelines will be presented in an organised and coherent manner, with appropriate linkages between items and advice to practitioners on how to use the Guidelines to inform treatment planning and clinical decision making.
4.6 Persons Involved The Working Party will be chaired by Beverly Raphael and will comprise established experts in trauma research and practice from throughout Australia, an expert in psychosocial rehabilitation and a health economist.
The Chair of the Working Party will have the authority to accept or reject nominations for membership.
4.7 Project Administration
4.7.1 Time frames For a period of 3 months from March 2011, the research questions will be drafted by the working party, reviewed by the MDP and endorsed by the Steering Group.
The research questions, updating the literature covered in the previous Guidelines, extending to cover children and address any gaps identified in the previous Guidelines, will be submitted to a systematic review in August 2011. The Working party will oversee the systematic review. Draft recommendations will be complete by the end of July 2012. Over the following six month period, in consultation with the Multidisciplinary Panel and key
14 stakeholders, the content and presentation of the Guidelines will be finalised. During the period July to December 2012, we envisage that the Guidelines will pass back and forth between the Working Party and Multidisciplinary Panel, on 3 or 4 occasions, and be the subject of extensive consultation with key stakeholders. This consultation process will establish the infrastructure needed to support the forthcoming dissemination process.
The content of the Guidelines will be finalised by the end of March 2013, and forwarded to NHMRC. It is anticipated that dissemination will commence in financial year 2013/14.
4.7.2 Meetings The Working Party will generally communicate by telephone, email and telephone link up where necessary. Face-to-face meetings may be held on 3 or 4 occasions over the 18 month period. All travel and accommodation costs related to meeting will be met by ACPMH.
4.7.3 Resources External funding has been secured to cover the cost of the systematic reviews and project coordination. ACPMH will meet the cost of a sitting fee for members of the working party for meeting attendance but members will need to undertake additional work in their own time and using their own resources.
4.7.4 Reporting Guidelines Members of the Working Party will report to the Chair Beverley Raphael, who in turn will report to the Steering Group.
4.7.5 Dispute Resolution Any difficulties or disputes which arise should be directed in the first instance to the Chair of the Working Party, who may act to resolve the difficulty or dispute, or may refer the matter on to the project Steering Group.
15 Section 5: Terms of reference for the Multidisciplinary Panel
5.1 Multidisciplinary Panel Mission Statement The Multidisciplinary Panel will review the Guidelines in the process of their development, and provide advice to the Working Party on the Guideline relevance and utility for the target audience of service providers and recipients who will use and/or benefit from the Guidelines.
5.2 Problem Statement The assessment and intervention for problems consistent with ASD and PTSD is undertaken by a diverse range of mental health and general health practitioners, across different trauma types and health care settings. The success of the Guidelines is determined by the extent to which they are adopted across those diverse contexts, and ultimately the extent to which they result in improvement in the assessment and interventions for clients/patients with ASD and PTSD. The Guidelines revision, therefore, will be written and presented in a way which is consistent with the original Guidelines and accessible to a diverse range of health care professionals and is of practical value across clinical settings. To achieve this, the advice of clinicians who work across those settings is essential. Similarly, consumer involvement is important to ensure that treatment recommendations meet the needs of consumers and that the Guidelines will assist consumers in making informed choices about their treatment.
5.3 Boundaries x The Multidisciplinary Panel will review and offer advice on the set of questions to be put to the systematic review for the project. x The Multidisciplinary Panel will review the draft Guideline recommendations and offer advice on the way information is presented in terms of relevance and utility to the groups they represent. x The Multidisciplinary Panel will not have authority or decision making power over how that advice is used. x The Multidisciplinary Panel will be responsible for completing declarations of COI prior to each activity of consultation. These declarations will be sent to the Steering Committee for review and action (if required).
5.4 Specific issues to be addressed Contact with the members of the panel is anticipated to occur in two phases. The first phase will involve members receiving by mail/email, draft terms of reference for the project and questions to be put to the systematic review. Their task will be to read the terms of reference and review questions and provide written feedback to the Chair of the MDP on the appropriateness and comprehensiveness of these documents.
The second phase, which is anticipated to occur approximately six months later, will involve members receiving by mail/email copies of the draft recommendations. Members’ task will be to read the recommendations and provide written feedback to the Chair of the MDP on the Guidelines, in terms of: x Ease of reading and understanding x Usefulness as a clinical tool x Suggestions for improvement
16 The panel may be asked for feedback on the Guidelines as they are progressively modified, on 2 or 3 occasions over a subsequent 3 – 4 month period. Feedback will be required within 2-3 weeks on each occasion. The degree to which the panel have reached consensus on the presentation of the Guidelines, will be documented.
5.5 Desired Outcomes The Guidelines will be written and presented in a way that the multidisciplinary representative members of the panel believe will be accepted and used by those professionals they represent, and that the consumer representative believes will benefit consumers in terms of accessibility and quality of treatment provided.
5.6 Persons Involved The Multidisciplinary Panel will be chaired by Professor Beverly Raphael and will comprise representatives from each of the following:
Mental health professional associations (Australian College of Mental Health Nurses, Australian College of Rural and Remote Medicine, Australian General Practice Network, Australian Psychological Society, Australian Associate of Social Workers, Australian and New Zealand College of Psychiatrists, Occupational Therapy Australia, Royal Australian College of General Practitioners, Royal Australian College of Nurses), multidisciplinary trauma specialists, multidisciplinary mental health providers and consumers.
The Chair of the panel will have the authority to accept or reject nominations for panel membership.
5.7 Project Administration
5.7.1 Time frames For a period of 3 months from March 2011, the research questions will be drafted by the working party, reviewed by the MDP and endorsed by the Steering Group.
The research questions, updating the literature covered in the previous Guidelines, extending to cover children and address any gaps identified in the previous Guidelines, will be submitted to a systematic review in August 2011. The Working party will oversee the systematic review. Draft recommendations will be complete by the end of July 2012. Over the following six month period, in consultation with the Multidisciplinary Panel and key stakeholders, the content and presentation of the Guidelines will be finalised. During the period July to December 2012, we envisage that the Guidelines will pass back and forth between the Working Party and Multidisciplinary Panel, on 3 or 4 occasions, and be the subject of extensive consultation with key stakeholders. This consultation process will establish the infrastructure needed to support the forthcoming dissemination process.
The content of the Guidelines will be finalised by the end of March 2013, and forwarded to NHMRC. It is anticipated that dissemination will commence in financial year 2013/14.
5.7.2 Meetings Communication with the MDP will primarily be convened electronically (teleconference or email).
17
5.7.3 Resources With the exception of consumer and carer representatives, members of the Multidisciplinary Panel will need to undertake the work in their own time and using their own resources. A sitting fee will be provided to consumer and carer representatives in line with Commonwealth Government recommendations. The cost of this will be met by ACPMH.
5.7.4 Reporting Guidelines Members of the panel will report via the ACPMH project team to the Chair Professor Beverly Raphael, who in turn will report to the Steering Group.
5.7.5 Dispute Resolution Any difficulties or disputes which arise should be directed in the first instance to the Chair of the Multidisciplinary Panel, who may act to resolve the difficulty or dispute, or may refer the matter on to the project Steering Group.
18 Appendix 3: AHTA systematic review of the evidence
19 EVIDENCE REPORT Australian Centre for Posttraumatic Mental Health
Update of the Australian Guidelines for the Treatment of Acute Stress Disorder and Posttraumatic Stress Disorder
ADELAIDE HEALTH TECHNOLOGY ASSESSMENT DISCIPLINE OF PUBLIC HEALTH UNIVERSITY OF ADELAIDE ADELAIDE SA 5005
May 25th 2012
20 This systematic literature review was commissioned by the Australian Centre for Posttraumatic Mental Health and undertaken by Adelaide Health Technology Assessment, University of Adelaide.
Reviewers
Skye Newton B Psych (Hons), GDPH Senior Research Officer, Adelaide Health Technology Assessment, Discipline of Public Health, University of Adelaide, Adelaide, SA 5005
Jacqueline Parsons BA BHealthSc MPH Senior Research Officer, Adelaide Health Technology Assessment, Discipline of Public Health, University of Adelaide, Adelaide, SA 5005
Ben Ellery BHealthSc, GDPH Research Officer, Adelaide Health Technology Assessment, Discipline of Public Health, University of Adelaide, Adelaide, SA 5005
Joanne Milverton BSci, GDPH Research Officer, Adelaide Health Technology Assessment, Discipline of Public Health, University of Adelaide, Adelaide, SA 5005
Judy Morona B.Sc., PhD., GDPH Research Officer, Adelaide Health Technology Assessment, Discipline of Public Health, University of Adelaide, Adelaide, SA 5005
Stynke Docter BHlthSci (Physio), MHlthSci (Int Pub Hlth) Research Officer, Adelaide Health Technology Assessment, Discipline of Public Health, University of Adelaide, Adelaide, SA 5005
Zhaohui Liufu MPH, MMed Senior Research Officer, Adelaide Health Technology Assessment, Discipline of Public Health, University of Adelaide, Adelaide, SA 5005
Tracy Merlin BA (Hons), MPH Managing Director, Adelaide Health Technology Assessment, Senior Lecturer, Discipline of Public Health, University of Adelaide, Adelaide, SA 5005
21 Table of Contents
TABLE OF CONTENTS ...... 22 Research questions ...... 25 Overview of methodology...... 26 LIMITATIONS OF THE REVIEW ...... 31 INTERVENTIONS FOR PEOPLE EXPOSED TO TRAUMA (INCLUDING THE SUBGROUP WITH ASD) ...... 32 Pre-incident preparedness training ...... 32 Early psychological interventions ...... 35 Treatment for all ...... 35 Treatment for people with ASD or acute PTSD ...... 67 Pharmacological interventions ...... 97 Single vs multiple interventions ...... 102 SCHOOL-BASED INTERVENTIONS ...... 107 In those exposed to trauma / with ASD ...... 107 In those with PTSD ...... 115 INTERVENTIONS FOR PEOPLE WITH PTSD ...... 118 Psychological interventions ...... 118 Pharmacological interventions ...... 325 Psychosocial rehabilitation...... 387 Exercise and physical therapies ...... 389 Combined Interventions ...... 399 Comorbidities ...... 429 Child specific questions ...... 430 GLOSSARY...... 437 APPENDIX A ...... GUIDELINE WORKING PARTY MEMBERS ...... 438 APPENDIX B ...... PROCESS REPORT ...... 439 Search Strategy...... 439 Study selection ...... 441 Inclusion criteria...... 443 Critical Appraisal Checklists...... 458 Grading the body of evidence ...... 464 APPENDIX C ...... MULTIDISCIPLINARY PANEL MEMBERS ...... 470 APPENDIX D ...... HTA INTERNET SITES ...... 472 APPENDIX E ...... SPECIALTY WEBSITES ...... 475
22 APPENDIX F ...... NHMRC MINIMUM REQUIREMENTS ...... 476 Minimum requirements for formulating NHMRC evidence-based guidelines...... 476 APPENDIX G ...... EVIDENCE TABLES ...... 478 APPENDIX H ...... PUBLICATION BIAS FUNNEL PLOTS ...... 480 APPENDIX I ...... EXCLUDED STUDIES ...... 499 Reasons for exclusion of studies involving psychological interventions (questions 1-4, 7-14, 20-21, and 23-24) ...... 499 Incorrect study design ...... 499 Non-systematic reviews ...... 499 Reviews including studies with non-randomised or pseudorandomised design ...... 499 Studies with non-randomised or pseudorandomised design ...... 501 Not a study ...... 505 Incorrect study population...... 506 Analogue ...... 512 Incorrect intervention ...... 512 Not treatment for PTSD ...... 512 No intervention ...... 513 Intervention for those exposed to trauma, after 1 month ...... 513 Early exercise intervention (not in those diagnosed with PTSD) ...... 513 Incorrect comparator ...... 513 No comparator ...... 514 No outcomes data ...... 515 Cannot extract data ...... 519 Patient dropout exceeding 50 per cent ...... 519 Data included in another intervention study or review ...... 520 Studies predating the year 2005 and included in the NICE review ...... 525 Not in English ...... 533 Reasons for exclusion of studies involving pharmacological interventions (Questions 5-7, 15-16, and 20-21) ...... 534 Incorrect study design ...... 534 Non-systematic reviews ...... 534 Reviews including studies with non-randomised or pseudorandomised design ...... 535 Studies with non-randomised or pseudorandomised design ...... 535 Conference abstracts ...... 536 Letters ...... 536 Commentaries ...... 537 Incorrect study population...... 537 Studies for which population did not have PTSD ...... 537 Studies for which insufficient proportion of population had PTSD ...... 538 Incorrect intervention ...... 538 Observational studies with no intervention...... 538 Incorrect outcome...... 539 No PTSD-relevant outcomes data ...... 539 Cannot extract data ...... 539
23 Data included in another intervention study or review ...... 540 Studies for which full text was unavailable/unobtainable within time constraints .... 541 Incorrect intervention (psychotherapy rather than psychosocial rehabilitation) ...... 543 Incorrect population (not PTSD) ...... 543 Studies with non-randomised or pseudorandomised design ...... 544 Duplicate information (SRs where primary studies are already included) ...... 546 REFERENCES ...... 557
24
Research questions
The main research questions that this report was commissioned to investigate were:
1. For people exposed to trauma, does pre-incident preparedness training improve outcomes compared to no intervention? 2. For people exposed to trauma, does any pre-incident preparedness training confer any advantage over other pre-incident preparedness training? 3. For people exposed to trauma, do early psychological interventions improve outcomes compared to no intervention? 4. For people exposed to trauma, does any early psychological intervention confer any advantage over other early psychological interventions? 5. For people exposed to trauma, do early pharmacological interventions improve outcomes compared to no intervention? 6. For people exposed to trauma, does any early pharmacological intervention confer any advantage over other early pharmacological interventions? 7. For people exposed to trauma, is a single early intervention more effective than multiple early interventions? 8. For children exposed to trauma, does any intervention delivered through school improve outcomes for the child over no intervention? 9. For children exposed to trauma, does any intervention delivered through school improve outcomes for the child over any other intervention delivered through school? 10. For people with PTSD, do psychological interventions improve outcomes compared to no intervention? 11. For people with PTSD, does any psychological intervention confer any advantage over other psychological interventions? 12. For people with PTSD, is individual therapy more effective than group therapy? 13. For people with PTSD, is the combination of individual therapy and group therapy more effective than either alone? 14. Are established interventions for PTSD effective when self-delivered or self-delivered with practitioner support compared to practitioner delivered intervention or no intervention? 15. For people with PTSD, do pharmacological interventions improve outcomes compared with placebo? 16. For people with PTSD, does any pharmacological intervention confer any advantage over other pharmacological interventions? 17. For people with PTSD, does psychosocial rehabilitation improve outcomes compared to no intervention? 18. For people with ASD or PTSD, do physical interventions or exercise improve outcomes compared to no intervention?
25 19. For people with ASD or PTSD, do physical interventions or exercise confer an advantage over psychological or pharmacological interventions? 20. For people with PTSD, is a single intervention more effective than multiple interventions? 21. For people with PTSD, is any intervention (pharmacotherapy, psychotherapy or psychosocial rehabilitation) more effective than any other intervention (pharmacotherapy, psychotherapy or psychosocial rehabilitation)? 22. In the context of PTSD and comorbidity, is sequencing of intervention per diagnosis more effective than simultaneous interventions for both diagnoses? 23. For children with PTSD, does the inclusion of parents/primary care givers improve outcomes compared to no parent/primary care giver inclusion? 24. For children with PTSD, does any psychological intervention that includes parents/primary care givers improve outcomes compared to any other psychological intervention that includes parents/primary care givers?
Overview of methodology
Inclusion Criteria
Criteria for including studies in the updated systematic literature review and clinical practice guidelines document are provided in Box 1 to ld specific questions
Box 190. In order to ensure that the selection of studies to answer specific research questions was not biased, these criteria were delineated prior to collating the literature. The type of patient Population, Intervention (treatment), Comparator (against which the treatment’s effectiveness is measured), and Outcomes of interest were made explicit – these are known as the PICO criteria and they relate directly to the research question that is being addressed. Additional limits to the literature search were also made clear ie restricting the search to studies of a certain research design(s) (eg likely to provide unbiased or more reliable results), to a certain search period or language.
Studies were excluded if they: x did not meet the inclusion criteria; x could not provide adequate data on the outcomes eg in graphical format, missing information, format or type of data are unable to be used; x were updated by the same research group on the same research question for the same patients, with no different information provided; or x could not be located x used an analogue for a traumatic event
Studies assessing the benefits of interventions in adults were included if: x PTSD symptoms were measured x the main target of the treatment was ASD or PTSD or preventing the development of these disorders x for questions pertaining to PTSD, at least 70 percent of the participants had PTSD, and the remaining participants had symptoms of PTSD following a traumatic event
26 x for continuous data at least 50 percent of the intent-to-treat sample were assessed at the relevant time point
The inclusion criteria for children and adolescents were the same as for adults, except the inclusion criteria that 70% of participants within a study require PTSD was not applied, as the diagnostic criteria for child and adolescent PTSD is still evolving and relatively undeveloped (National Institute for Clinical Excellence 2005). All studies must have included a measure of the child’s PTSD symptoms.
This systematic review included the studies already identified in the previous 2007 guidelines review conducted by AHTA for ACPMH, the NICE guidelines and the VA/DoD guidelines, where the research questions were the same, provided they met the inclusion criteria.
Literature sources
To be consistent with the evidence-based guidelines’ documents that have gone before this one, including the NICE and VA/DoD guidelines and the previous Australian guidelines, the following databases were searched: Medline, Embase, Cinahl, PsychINFO, the Dartmouth College Published International Literature on Traumatic Stress (PILOTS) catalogue and the Cochrane Library (See Table 200). To meet NHMRC Minimum Requirements standards, Clinical Evidence and the Internet (GoogleScholar, and websites of specialty organisations) were also searched (See Table 201 and Appendix E), and the reference lists of all included studies were pearled for potentially relevant studies. The Australian and New Zealand Clinical Trials Register was searched in January 2012, and where a relevant study was identified as being completed, the corresponding research groups were contacted to see whether they had any recently published or in press articles, in an attempt to ensure the guidelines were based on the most recent applicable evidence available.
Also to be consistent with the previous evidence-based guidelines’ documents, the searches was restricted to English language literature and to either a systematic review/meta-analysis of randomised controlled trials (level I evidence), or to randomised controlled trials (level II evidence), unless fewer than two randomised controlled trials were identified to answer a particular question, in which case, lower levels of evidence were assessed for inclusion.
Search strategies
This systematic review was designed to update the systematic review performed by AHTA which informed the 2007 Australian Guidelines for the Treatment of Adults with Acute Stress Disorder and Posttraumatic Stress Disorder. The previous systematic review undertaken by AHTA updated two prior systematic reviews performed by NICE and VA/DoD and utilised elements of the search strategies from both reviews.
A series of six separate searches were conducted to extract comparative studies relating to psychological interventions, pharmacological interventions, psychosocial rehabilitation, physical therapies and exercise, and co-morbidities, from which relevant papers were identified for each research question. Searches that related to research questions which were addressed by the 2007 “Australian Guidelines for the Treatment of Adults with Acute Stress Disorder and Posttraumatic Stress Disorder”, and where no additional levels of evidence were being sought, were performed separately for the years 1966 to 2004 (with additional search terms relating to children and adolescents) and 2005 – 10/2011 (all people).
27 The search terms used are listed in Table 202. The search terms were developed on a PubMed platform. Similar search strategies were used for the different bibliographic databases, with the same text words being used along with the relevant alternatives to MeSH headings.
Validity Assessment
All studies identified through the new searches, and those identified through the previous reviews (AHTA, NICE and VA/DoD) were critically appraised – in terms of internal and external validity - and the statistical and clinical relevance and applicability of results were determined utilising the NHMRC dimensions of evidence (NHMRC 2000a; NHMRC 2000b) and the recently developed NHMRC interim levels and grades of evidence (see Table 205). Critical appraisal of the included systematic reviews, and randomised trials was performed using the NHMRC quality checklist(NHMRC 2000a)(see Appendix B). The checklist for appraising the quality of intervention studies was determined to be aimed towards features of randomised trials. Only those trials which reported a correct, blinded randomisation method, and high rates of follow up with intention to treat analyses conducted, were considered to be low in bias, which was applicable to very few studies identified in the systematic review, resulting in the majority of studies being considered to be at moderate or high risk of bias. For cohort studies, a protocol amendment was made, and a checklist by Downs and Black was used (see Appendix B).
Publication bias was assessed using funnel plots. Comparisons within the review with three or more studies were assessed for publication bias on the primary outcomes (PTSD diagnosis and severity).
The NHMRC dimensions of evidence (Table 204) consider three main aspects that are critical to an assessment of evidence: strength of the evidence, size of the effect and relevance of the evidence. The first domain is derived directly from the literature identified as informing a particular intervention. The last two require expert clinical input as part of their determination.
Table 1 Evidence dimensions Type of evidence Definition Strength of the evidence Level The study design used, as an indicator of the degree to which bias has been eliminated by design.* Quality The methods used by investigators to minimise bias within a study design. Statistical precision The p-value or, alternatively, the precision of the estimate of the effect. It reflects the degree of certainty about the existence of a true effect. Size of effect The distance of the study estimate from the “null” value and the inclusion of only clinically important effects in the confidence interval. Relevance of evidence The usefulness of the evidence in clinical practice, particularly the appropriateness of the outcome measures used. *See Table 205
Data Extraction and Analysis
The process of study selection went through six phases and the number of literature citations retrieved and retained at each phase was documented (See Table 203).
Evidence tables were used as a guide to summarise the extraction of data from the individual studies (See Appendix G) (NHMRC 2005a). Intention-to-treat analyses (ITT) should be used
28 in preference to completer data as it limits the effect of selection bias on the results. Therefore intention-to-treat data was used in preference to completer data, when it was available. However when such data was not available, completer data were used.
Meta-analyses for specific research questions were conducted originally in the NICE guidelines document (National Institute for Clinical Excellence 2005) and updated where appropriate in the previous ACPMH guidelines. These meta-analyses were again updated, where appropriate, using the results of the new randomised controlled trials identified for this report. Meta-analyses were conducted using a fixed effects model when studies were homogenous (p>0.05) or a random effects model in the presence of between-study heterogeneity (where that heterogeneity could not be explained). Effect measures that were extracted or calculated for individual or pooled results included Relative Risk (for count data) and standardised mean differences (SMD; Hedges g) for continuous data. As per the methodology used by NICE, mean post-treatment scores (or follow-up scores) were combined with mean change-from-baseline scores, where the scores were on the same outcome measure.
It should be noted that the SMD method does not correct for differences in the direction of the scale. For meta-analyses where some scales increase with disease severity whilst others decrease, the mean values from one set of studies were multiplied by –1 to ensure that all the scales point in the same direction. Heterogeneity in the meta-analysis was assessed using the Cochran Q statistic and publication bias was tested using the Begg funnel plot. Where a meta- analysis could not be conducted, a qualitative synthesis of the data was undertaken.
Effect sizes were interpreted using methodology developed by NICE (see below) and NHMRC designations of level of evidence were used (Appendix B):
“For each outcome a clinical statement describing the evidence found was developed. To assess clinical importance where a statistically significant summary was obtained (after controlling for heterogeneity) the Group set thresholds for determining clinical importance, in addition to taking into account the trial population and nature of the outcome. Two separate thresholds for determining clinical importance were set. For comparisons of one active treatment against waiting list or non-active interventions, a higher threshold was applied than for comparisons of active treatments against one another. For comparisons of one active treatment against another treatment the following thresholds were applied: for dichotomous outcomes an RR of 0.80 or less/1.25 or more was considered clinically important and for continuous outcomes an effect size of approximately 0.5 (a ‘medium’ effect size; Cohen, 1988) or more (or less than -0.5) was considered clinically important. For comparisons of active treatment against waiting list the following thresholds were applied: for dichotomous outcomes a RR of 0.65 or less/1.53 or more was considered clinically important and for continuous outcomes an effect size of approximately 0.8 (a ‘large’ effect size; Cohen, 1988) or more (or less than -0.8) was considered clinically important. In cases where the point estimate of the effect was judged clinically important, a further consideration was made about the precision of the evidence by examining the range of estimates defined by the CI. Where the effect size was judged clinically important for the full range of plausible estimates, the result was described as evidence favouring intervention x over intervention y (i.e. statement 1, or S1). In situations where the point estimate was clinically important but the CI included clinically unimportant effects, the result was described as limited evidence favouring intervention x over intervention y (i.e. S2). Where a point estimate was judged as not clinically important and the CI did not include any clinically important effects, the result was described as unlikely to be clinically important (i.e. S3). Alternatively, if the range of estimates defined by the CI included clinically important benefits as well as no effect or harmful effects, the result was described as inconclusive
29 (i.e. S4). S1= There is evidence favouring x over y on… S2= There is limited evidence favouring x over y on… S3= There is evidence suggesting that there is unlikely to be a clinically important difference between x and y on… S4= The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between x and y on….”
All statistical calculations and testing were undertaken using the biostatistical computer package, Stata version 12.0 (Stata Corporation 2011). Calculations of effect sizes (Hedges G) for individual studies were performed using The Effect Size Generator version 4.1 (Devilly G, 2007).
Assessing the body of evidence
Once each included study was assessed according to the three dimensions of evidence, a grade for the whole body of evidence supporting each recommendation can be determined (See Appendix B).
NHMRC grades of recommendation are provided to assist users of the clinical practice guideline in making clinical judgements and to indicate the strength of the recommendation. Grade A and B recommendations are generally based on a body of evidence which can be trusted to guide clinical practice, whereas Grade C and D recommendations must be applied carefully to individual clinical and organisational circumstances and should be followed with care (NHMRC 2005a).
Grade of recommendation Description A Body of evidence can be trusted to guide practice Body of evidence can be trusted to guide practice in most B situations Body of evidence provides some support for C recommendation(s) but care should be taken in its application Body of evidence is weak and recommendation must be D applied with caution
30 Limitations of the review
This systematic review of the treatments for ASD and PTSD is limited by the following factors. The review: x Does not cover questions pertaining to an assessment of some additional multiple treatments versus other multiple treatments or versus placebo/waitlist for the populations under review; x Does not assess levels of evidence lower than randomised controlled trials (level II intervention evidence) for many questions; x Does not provide a comprehensive review of potential safety issues (ie. studies too small to detect many adverse events particularly rare adverse events) – this is of specific relevance to the section on pharmacological treatments; x Some reports were excluded if they were updates of previously published studies, and patient follow-up was less than 50 percent; x These guidelines were based on the NICE systematic review and the VA/DoD guidelines, which both have their own limitations. In updating these guidelines, some of these limitations must be acknowledged, despite the use of a near- identical methodology. o Some studies that potentially met the inclusion criteria were missed. o Effect sizes were calculated on the difference in post-treatment scores between the groups. The assumption being that randomisation negated any potential baseline differences between the groups. This assumption may be valid for large trials but is not necessarily correct for small trials. o Some of the included studies included in the reviews presented statistical testing on a large range of outcomes, without correction for multiple comparisons in their analysis. This increases the likelihood that a statistically significant difference will be identified, just through chance.
31 Interventions for people exposed to trauma (including the subgroup with ASD)
There are three early interventions sections. The first addresses interventions for people exposed to potentially traumatic events, prior to exposure occurring. This type of intervention would apply to military personnel being deployed into war or peacekeeping zones, emergency service workers, police, etc., who will almost certainly be exposed to highly stressful and potentially traumatic situations and aims to prevent or reduce the likelihood of developing symptoms of ASD or PTSD. The second section addresses interventions that are intended to prevent the development of psychiatric sequelae for all who are exposed to potentially traumatic events, regardless of the presence or absence of symptoms of psychological disorder. The third early intervention section addresses interventions aimed at treating the subgroup of people exposed to traumatic events that have developed symptoms of ASD or early PTSD.
Pre-incident preparedness training
Box 1 Study selection criteria for research questions 1 and 2
Research Question 1. For people exposed to trauma, does pre-incident preparedness training improve outcomes compared to no intervention? 2. For people exposed to trauma, does any pre-incident preparedness training confer any advantage over other pre-incident preparedness training? Selection criteria Inclusion criteria Population People exposed to trauma (including the sub-group with ASD) Intervention Pre-incident preparedness training, delivered by any method Comparator 1. No training 2. Other pre-incident preparedness training Outcome Primary outcome: symptoms of ASD or PTSD Secondary outcomes: symptoms of depression, anxiety and substance misuse/ social and occupational function / quality of life / treatment refusal/ dropout over 12 months/ side-effects/ posttraumatic growth/ physical comorbidity. Additional outcomes for children: attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials As fewer than two Level II studies were found, then pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before- and-after controlled studies, and case-control studies were also considered. Search Period 1966-10/2011 for adults, children and adolescentsa Language English a New research questions
One study was identified that fulfilled the search criteria for Questions 1 and 2. This good quality retrospective cohort study assessed the effectiveness of pre-operational stress briefing among Navy and Marine service personnel compared with no briefing (Sharpley et al 2008).
PRE-INCIDENT STRESS BRIEFING VERSUS NO BRIEFING
Sharpley et al (2008) investigated the effectiveness of giving information about stress and stress reactions to people about to be deployed during the first phase of the Iraq War compared to providing no information in preventing adverse health and occupational outcomes. The briefing covered a range of topics including: the role of the mental health team and an outline of the medical facilities in the Primary Casualty Receiving Facility; definitions
32 of stress, pressure and strain, types of stressors (physical, social, occupational and traumatic), and the effects of stress on individuals; advice on handling human remains; managing stressful thinking in a chemical or biological environment; simple advice on reducing stress; the importance of morale, levels of support available and when/where to seek them.
Lists of Royal Navy and Royal Marine personnel that attended one of 91 stress briefings given prior to deployment to the Iraq War were cross-referenced to a database of personnel with questionnaires voluntarily completed 2-3 years post-deployment. Personnel that were identified on both lists were included in the study as the intervention group. The remainder of the Royal Navy and Royal Marine personnel with completed voluntary post-deployment questionnaires comprised the control group. When examined, there were some statistically significant differences in baseline characteristics between the intervention and control groups. Attendees were younger (p < 0.05), more likely to be Marines (p < 0.001), and had more traumatic experiences (p < 0.001) than non-attendees. Sharpley et al (2008) used multiple logistic regression analyses to adjust for these potential confounders on outcome data. There was a clinically important point estimate found showing that those who attended briefing were less likely to have PTSD symptoms at 2-3 years follow-up, however, the range of estimates defined by the confidence interval included clinically unimportant effects, and effects which also supported no briefing in favour to briefing.
The authors found no apparent effect in terms of psychological health at 3 years post- operational deployment associated with having a pre-operational stress briefing prior to combat operations. Attendees appeared to have statistically significantly higher morale than non-attendees (p < 0.01), but after adjustment for potential confounders no statistically significant association was apparent. The evidence statements and relative risk (RR) for each relevant outcome and the evidence matrix (Box 2) for pre-incident stress briefing are presented below.
Table 2 Study profile for study comparing pre-incident stress briefing with a no briefing control in treating people prior to exposure to trauma Reference Risk of bias Population Setting N Outcomes measured (Sharpley et al Low Royal Naval and Royal United Kingdom 735 Symptoms of PTSD (PCL-C) 2008) Marine military personnel to Alcohol misuse (AUDIT) be deployed to the Iraq War Social function Retrospective Occupational function cohort Physical comorbidity AUDIT = Alcohol Use Disorders Identification Test; PCL-C = PTSD Checklist – Civilian version
There is limited evidence favouring a stress briefing over no briefing on reducing the likelihood of having PTSD symptoms (PCL-C) at 2-3 years follow-up (k = 1; n = 735; RR = 0.61; 95%CI 0.24, 1.55). There is evidence suggesting that there is unlikely to be a clinically important difference between stress briefing and no briefing on reducing the likelihood of having a severe alcohol use disorder at 2-3 years follow-up (k = 1; n = 735; RR = 1.13; 95%CI 0.85, 1.50). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between stress briefing and no briefing on reducing the likelihood of having fair or poor health at 2-3 years follow-up (k = 1; n = 735; RR = 0.96; 95%CI 0.63, 1.45). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between stress briefing and no briefing on reducing the
33 likelihood of having a common mental disorder (GHQ-12) at 2-3 years follow-up (k = 1; n = 735; RR = 0.86; 95%CI 0.61, 1.20). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between stress briefing and no briefing on reducing the likelihood of having multiple physical symptoms at 2-3 years follow-up (k = 1; n = 735; RR = 1.12; 95%CI 0.69, 1.80). There is limited evidence favouring a stress briefing over no briefing on the likelihood of having a high occupational morale (occupational functioning) at 2-3 years follow-up (k = 1; n = 735; RR = 1.58; 95%CI 1.22, 2.04). There is evidence suggesting that there is unlikely to be a clinically important difference between stress briefing and no briefing on reducing the likelihood of having problems at home (social functioning) at 2-3 years follow-up (k = 1; n = 735; RR = 0.99; 95%CI 0.72, 1.36). Box 2 Evidence statement matrix for pre-incident stress briefing with a no briefing control in treating people prior to exposure to trauma Component Rating Description
Evidence base C One level III-2 study with a low risk of bias
Consistency NA Only one study
Clinical impact D The point estimates favouring stress briefing over no briefing were clinically important for reducing the severity of PTSD symptoms and for improved occupational functioning at 2-3 years follow-up but the CIs included clinically unimportant effects and did not reach statistical significance for reducing severity of PTSD symptoms. The point estimates for other mental and physical health outcomes were not clinically important and did not reach statistical significance.
Generalisability A Population consisted of military personnel deployed during the first phase of Iraq War
Applicability B The study was conducted in the UK, which has comparable healthcare for patients exposed to potentially traumatic events compared to the Australian healthcare context.
Summary of evidence There was limited evidence favouring pre-incident stress briefing over no briefing for reducing the severity of PTSD symptoms and for improved occupational functioning of people prior to exposure to potentially traumatic events but the full range of plausible estimates outlined by the confidence intervals included clinically unimportant effects and were not statistically significant. (Grade C)
34 Early psychological interventions
Box 3 Study selection criteria for research question 3 and 4
Research Question 3. For people exposed to trauma, do early psychological interventions improve outcomes compared to no intervention? 4. For people exposed to trauma, does any early psychological intervention confer any advantage over other early psychological interventions? Selection criteria Inclusion criteria Population People exposed to trauma, including the subgroup of patients with ASD Intervention Early psychological intervention (eg debriefing, trauma-focused counselling, education, performed within one month of trauma) Comparator No intervention (eg assessment only) Outcome Primary outcomes: symptoms of ASD and PTSD Secondary outcomes: symptoms of depression, anxiety and substance misuse/ social and occupational function/ quality of life/ treatment refusal/ dropout over 12 months/ posttraumatic growth / physical comorbidity Additional outcomes for children: attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies are found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before- and-after controlled studies, case-control studies. Search Period 8/2005-10/2011 for adultsa; 1966-10/2011 if required 1966-10/2011 for children and adolescentsc Language English a updated search from 2007 Guideline b expanded search period if fewer than two Level II studies are found c New research questions
Treatment for all
Twenty RCTs meeting the inclusion criteria determined a priori were identified by a systematic search of the literature, focusing on early psychological interventions for all individuals exposed to potentially traumatic events. Eight of these studies (9 articles) had originally been included in the NICE guidelines (Bisson et al 1997; Brom et al 1993; Campfield & Hills 2001; Conlon et al 1999; Hobbs et al 1996; Lee et al 1996; Mayou et al 2000; Rose et al 1999; Zatzick et al 2001). One study had been previously identified and included in the updated Australian guidelines commissioned by the Australian Centre for Posttraumatic Mental Health in 2005 (Gamble et al 2005). A further ten studies were identified in the systematic search for the current update to the Australian guidelines (Beatty et al 2010; Bernard et al 2011; Cox et al 2010; Jones et al 2010; Kazak et al 2005; Marchand et al 2006; Sijbrandij et al 2006; Stallard et al 2006; Wu et al 2011; Zehnder et al 2010). These studies described six different types of interventions that were all started within the first month following traumatic exposure. The effectiveness of interventions including education, collaborative care, debriefing, trauma-focused CBT, trauma-focused counselling, providing a diary of events, and providing interactive self-help material were compared to no treatment, wait listed controls, usual care, or another psychological intervention. Comparsisons addressing question 3 are as follows: • one study tested an educational intervention against control (Rose et al 1999) • seven studies (eight publications) compared psychological debriefing to no debriefing in adults (Bisson et al 1997; Conlon et al 1999; Gamble et al 2005; Hobbs et al 1996; Lee et al 1996; Marchand et al 2006; Mayou et al 2000; Wu et al 2011)
35 • two studies compared psychological debriefing to control in children (Stallard et al 2006; Zehnder et al 2010) • one study compared trauma-focused counselling with monitoring control (Brom et al 1993) • one study compared the provision of an ICU diary to a wait listed control (Jones et al 2010) • one study compared a self-help website for children and an information booklet for parents with an assessment only control group (Cox et al 2010)
Comparisons addressing question 4 are as follows: • two studies compared a collaborative care program with usual care (Tsosie et al 2011; Zatzick et al 2001) • one study compared immediate versus delayed psychological debriefing (Campfield & Hills 2001) • one study compared emotional debriefing with educational debriefing (Sijbrandij et al 2006) • two studies compared CBT with usual care (Bernard et al 2011; Kazak et al 2005) • one study compared an interactive self-help workbook with an information booklet (Beatty et al 2010)
EDUCATION VERSUS CONTROL
One study (Rose et al 1999) included a 30 minute educational intervention in its randomised design, comparing it with debriefing plus education and with an assessment-only control group. Participants were victims of violent crimes (including sexual assaults) and the intervention was delivered to them 9–31 days after the assault. The 30 minute education session was based on a specially prepared leaflet and provided information regarding normal reactions to trauma and on finding help. The information was also adapted to relate to the individual’s experiences. Education was delivered by one of two experienced interviewers. Outcomes were reported at 6 months and 11 months post-intervention but the number of participants in each group at 11 months could not be determined. There were no statistically significant differences between groups on the likelihood of having PTSD, or in the severity of symptoms related to PTSD as observed at 6 months.
A comparison of the effectiveness of the educational intervention and debriefing plus education in preventing PTSD is included for Question 7.
Table 3 Study profile for RCT comparing education and control in treating people recently exposed to trauma Reference Risk of bias Population Setting N Outcomes measured
(Rose et al 1999) Moderate Adult victims of a violent Outpatient setting, 157 PTSD diagnosis crime within the past month United Kingdom Severity of PTSD symptoms Depression
There is limited evidence favouring education over the assessment only control on reducing the likelihood of having a PTSD diagnosis (self-reported) at 6 months follow-up (k=1; n=103; RR = 0.41, 95%CI 0.16, 1.03). There is evidence suggesting that there is unlikely to be a clinically important difference between education and the assessment only control for self-reported PTSD symptoms at 6 months follow-up (k = 1; n = 91; SMD = –0.33, 95%CI –0.75, 0.08).
36 There is evidence suggesting that there is unlikely to be a clinically important difference between education and the assessment only control on reducing the severity of depression (self-reported BDI) at 6 months follow-up (k = 1; n = 91; SMD = –0.36, 95%CI –0.77, 0.06).
Box 4 Evidence statement matrix for RCTs comparing education with assessment only in treating people recently exposed to trauma Component Rating Description
Evidence base C One level II study with a moderate risk of bias
Consistency NA Only one study
Clinical impact D Clinically important point estimate for PTSD diagnosis, but other outcomes suggest no difference between treatments
Generalisability A Population consisted of victims of violent crimes
Applicability B The study was conducted in the UK, which has comparable healthcare for patients exposed to potentially traumatic events compared to the Australian healthcare context.
Summary of evidence One study with a moderate risk of bias found limited evidence suggesting that an educational intervention reduces the likelihood of victims of violent crimes having a PTSD diagnosis at 6 months follow-up compared to an assessment only control, but other outcomes suggested no clinically important differences. (Grade C)
COLLABORATIVE CARE VERSUS CONTROL
Two studies compared a collaborative care programme with usual medical care. One study (Zatzick et al 2001) compared a collaborative care programme, delivered by a trauma support specialist for road traffic accident survivors or violent assault survivors, with usual medical care. The other study (Tsosie et al 2011), compared a culturally tailored care management intervention for physically injured American Indian/Alaska native patients, against usual medical care.
Collaborative care in both of these studies involved eliciting and monitoring patients’ post- traumatic concerns and joint provider–patient treatment planning. In the study by Zatzick et al (2001), collaborative care also involved a psychotherapy module specifically targeting posttraumatic distress and substance use and a psychoeducational component including a review of the traumatic event, followed by a discussion of related emotions, cognitions, and possible future posttraumatic symptoms, and suggested coping strategies. Most of the psychological components of the intervention (75%) were delivered in the first month while the trauma survivors were still in hospital, with the remainder occurring by phone between the 1-month and 4-month post-trauma interviews, which were predominantly conducted over the phone.
Tsosie et al (2011) stated that their study did not directly provide patients with psychotherapy, but care managers did discuss emotional reactions to the injury, PTSD or depressive symptoms, alcohol or drug use and problem solving. As appropriate, she recommended traditional activities such as weaving, drumming, or crafting. On average,
37 those in the intervention group had 15 (range 8 – 44) contacts with the care manager, corresponding to a mean of 7.9 ± 7.0 hours of contact over 6 months.
No significant differences between groups were reported on PTSD severity, or depressive symptoms. Zatzick et al (2001) reported no significant difference between groups on the number of drinks consumed in the previous month, while Tsosie et al (2011) reported that those in the usual medical care condition drank significantly less than those in the collaborative care condition at 3 months (SMD=0.83, 95%CI 0.01, 1.66), however, the authors discussed that these differences were related to higher baseline levels of drinking, younger age and a higher proportion of male gender in the collaborative care group.
Table 4 Study profile for RCT comparing collaborative care and usual care in treating people recently exposed to trauma Reference Risk of bias Population Setting N Outcomes measured (Zatzick et al 2001) Moderate Adolescent and adult motor Predominantly 34 Symptoms of PTSD vehicle crash or assault inpatient setting, Depressive symptoms survivors United States Alcohol intoxication Attrition (Tsosie et al 2011) Moderate American Indian/Native Inpatient setting, 30 Symptoms of PTSD Alaskan patients with followed by Depressive symptoms physical injuries outpatient setting, Alcohol use United States
There is evidence suggesting that there is unlikely to be a clinically important difference between collaborative care and usual care in severity of PTSD symptoms (self-rated) at 1-3 months post-trauma (k=2, n=54, SMD= -0.13, 95%CI -0.67, 0.42).
38
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between collaborative care and usual care on severity of PTSD symptoms at 4-6 months post-trauma (k=2, n=51, SMD=0.30, 95%CI -0.25, 0.86).
There is evidence suggesting that there is unlikely to be a clinically important difference between collaborative care and usual care on depressive symptoms 1-3 months post-trauma (k=2, n=54, SMD= -0.08, 95%CI -0.62, 0.45)
39
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between collaborative care and usual care on depressive symptoms 4-6 months post-trauma (k=2, n=51, SMD=0.29, 95%CI -0.27, 0.85).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between collaborative care and control in attrition at 4 - 6 months post- trauma (k = 2, n= 64, RR=0.92, 95%CI 0.35, 2.43).
Box 5 Evidence statement matrix for RCTs comparing collaborative care and usual care in treating people recently exposed to trauma Component Rating Description
Evidence base C Two level II studies with a moderate risk of bias
Consistency B The two studies were consistent in showing no clinically important or significant differences.
40 Clinical impact D There were no statistically significant or clinically important differences between collaborative care and usual care on reducing either PTSD severity or depressive symptoms at either 1-3 or 4-6 months follow- up.
Generalisability A Evidence from one study likely to be highly generalisable to target population (motor vehicle accident and violence assault survivors). Unclear whether evidence from second study generalisable (American Indians/Native Alaskans)
Applicability C Evidence probably applicable to Australian healthcare context with come caveats (study done in United States). Follow-up of trauma survivors who did not have health insurance was limited.
Summary of evidence Two small studies provided limited evidence showing that there were no clinically important differences in the effectiveness of collaborative care compared to usual care in treating people recently exposed to a potentially traumatic event. (Grade D).
DEBRIEFING VERSUS NO DEBRIEFING FOR ADULTS EXPOSED TO TRAUMA
Twelve RCTs investigating the effectiveness of psychological debriefing in preventing PTSD and related conditions were identified. The studies involved individuals who had experienced a range of potentially traumatic events including road traffic accidents (Conlon et al 1999; Hobbs et al 1996; Mayou et al 2000; Stallard et al 2006; Zehnder et al 2010), various accidents and assaults (Sijbrandij et al 2006), robberies (Campfield & Hills 2001; Marchand et al 2006), traumatic childbirth (Gamble et al 2005), miscarriages (Lee et al 1996), fires (Bisson et al 1997), and earthquakes (Wu et al 2011). The debriefing protocols were mostly based on the Critical Incident Stress Debriefing model by Mitchell (1983) that was originally designed for first responders (e.g. police, fire fighters, emergency workers) to help them overcome the emotional after-effects of potentially traumatic events encountered in their line of employment. Although the protocols varied, they all used the same basic elements from Mitchell's original process: Fact Phase (factual description of the traumatic event), Feeling Phase (thoughts about event and recall of feelings during event), Symptom Phase (description of stress symptoms experienced), Teaching Phase (information about stress and PTSD), and Re-Entry Phase (information about other services available).
The debriefing was delivered between 2 hours and 33 days after the potentially traumatic event and consisted of a single session of between 30 minutes and 2 hours in all studies except two: Marchand et al. (2006) conducted two 1-hour sessions one week apart, and Gamble et al. (2005) included a follow-up session 4-6 weeks later. All sessions were one-on- one with an experienced ‘debriefer’ except in three studies: Campfield & Hills (2001) conducted debriefings for up to five individuals, depending on the number of people involved in the traumatic event (robbery), Wu et al. (2011) conducted debriefings in groups of 8-13 military rescue workers, and a caregiver was present during the debriefings conducted with child victims of motor vehicle accidents in the study by Zehnder et al. (2010). Debriefing was delivered by a range of professionals, including nurses, midwives, researchers, psychiatrists and psychologists with varying levels of training and experience. One study reported outcomes at 2 weeks post-intervention, two studies reported outcomes at 1–1.5 months, seven studies reported post- intervention outcomes at 2–4 months, three studies reported outcomes at 6–8 months, one study reported outcomes at 13 months, and one study reported outcomes 3 years post- intervention.
41 Seven studies reported in eight papers investigated the effectiveness of debriefing after a potentially traumatic event in preventing PTSD and related conditions compared to a no debriefing control (Table 5). The study by Marchand et al (2006), which involved two 1-hour sessions one week apart was included in the meta-analysis as it provided the same amount of counselling as other studies with a single 2-hour debriefing session. The single session outcomes reported at 4-6 weeks by Gamble et al (2005) were also included, but the outcomes following a second session delivered 4-6 weeks after the first are reported in a separate section below. Meta-analysis was performed whenever data from more than one study could be combined. One study reported a clinically important and statistically significant difference favouring no debriefing over debriefing for reducing the likelihood of having a PTSD diagnosis at 13 months (p = 0.01). This study also reported a clinically important point estimate favouring no debriefing over debriefing for reducing the likelihood of changing occupations at 13 months, but the confidence intervals included clinically unimportant effects and the difference was not statistically significant (p = 0.28). Another study reported that the point estimate favouring no debriefing over debriefing was clinically important for having after-effects interfering with everyday functioning at 3 years, but the confidence intervals included clinically unimportant effects even though the difference was statistically significant (p < 0.001). The point estimates for other outcomes were not clinically important and the differences between groups were not statistically significant.
Table 5 Study profiles for RCTs comparing debriefing and no debriefing in treating adults recently exposed to trauma Reference Risk of bias Population Setting N Outcomes measured (Gamble et al 2005) Low Women who experienced Antenatal clinics, 103 PTSD diagnosis traumatic childbirth Australia Severity of PTSD symptoms Postnatal depression Depression) Anxiety (Wu et al 2011) Moderate Military rescue workers after Field study, China 1267 Severity of PTSD symptoms a severe earthquake Depression Anxiety Attrition
(Marchand et al Moderate Victims of violent armed Outpatient 75 PTSD diagnosis 2006) robberies in workplace setting, Canada Severity of PTSD symptoms Attrition
(Conlon et al 1999) Moderate Road traffic accident Outpatient trauma 40 PTSD diagnosis survivors clinic, Ireland Severity of PTSD symptoms
(Bisson et al 1997) High Burns patients Inpatient burns 133 PTSD diagnosis unit, United Severity of PTSD symptoms Kingdom Depression Anxiety Alcohol consumption increase Occupational change Attrition (Hobbs et al 1996) High Motor vehicle accident Inpatient setting, 106 Severity of PTSD symptoms survivors United Kingdom Travel anxiety Attrition
(Mayou et al 2000) 61 Severity of PTSD symptoms Depression Anxiety
42 Effect on everyday functioning Physical problems (Lee et al 1996) High Women who suffered Inpatient setting, 60 Severity of PTSD symptoms miscarriage 6 – 19 weeks United Kingdom Depression gestation Anxiety
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between debriefing and no debriefing on reducing the likelihood of having a PTSD diagnosis (clinical) at 1-1.5 months follow-up (k = 2; n = 178; RR = 1.27, 95%CI 0.74, 2.18).
The funnel plot showed no indication of publication bias (Appendix H). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between debriefing and no debriefing on reducing the likelihood of
43 having a clinician-rated PTSD diagnosis at 2-4 months follow-up (k=3; n=248; RR=1.06, 95%CI 0.50, 2.24). There is limited evidence favouring no debriefing over debriefing on reducing the likelihood of having a clinician-rated PTSD diagnosis at 13 months follow-up (k=1; n=103; RR=3.23, 95%CI 1.25, 8.89).
There is evidence suggesting that there is unlikely to be a clinically important difference between debriefing and no debriefing on reducing the severity of clinician-rated PTSD symptoms at 1-1.5 months follow-up (k = 2; n = 1330; SMD = –0.08, 95%CI –0.19, 0.03).
There is evidence suggesting that there is unlikely to be a clinically important difference between debriefing and no debriefing on reducing the severity of clinician-rated PTSD symptoms at 2-4 months follow-up (k = 2; n = 1162; SMD = –0.23, 95%CI –0.35, -0.11).
44
The funnel plot showed no indication of publication bias (Appendix H). There is evidence suggesting that there is unlikely to be a clinically important difference between debriefing and no debriefing on reducing the severity of self-reported PTSD symptoms at 2-4 months follow-up (k = 5; n = 348; SMD = 0.19, 95%CI –0.03, 0.40).
There is evidence suggesting that there is unlikely to be a clinically important difference between debriefing and no debriefing on reducing the severity of self-reported PTSD symptoms at 1-3 years follow-up (k = 2; n = 164; SMD = 0.40, 95%CI 0.09, 0.72). There is evidence suggesting that there is unlikely to be a clinically important difference between debriefing and no debriefing on reducing the likelihood of having postnatal depression (self-reported EPDS) at 4-6 weeks postpartum follow-up (k = 1; n = 103; RR = 0.96, 95%CI 0.56, 1.67). There is evidence suggesting that there is unlikely to be a clinically important difference between debriefing and no debriefing on reducing the severity of depression at 1 month follow-up (k = 1; n = 1227; SMD = -0.08, 95%CI –0.20, 0.03).
45
There is evidence suggesting that there is unlikely to be a clinically important difference between debriefing and no debriefing on reducing the severity of depression (self-reported measures) at 3-4 months follow-up (k = 3; n = 1272; SMD = -0.11, 95%CI -0.23, 0.00). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between debriefing and no debriefing on the likelihood of having self- reported travel anxiety at 4 months follow-up (k = 1; n = 106; RR = 1.08, 95%CI 0.63, 1.89). There is evidence suggesting that there is unlikely to be a clinically important difference between debriefing and no debriefing on reducing the severity of anxiety at 1 months follow- up (k = 1; n = 1227; SMD = –0.15, 95%CI –0.27, -0.04).
There is evidence suggesting that there is unlikely to be a clinically important difference between debriefing and no debriefing on reducing the severity of anxiety at 3-4 months follow-up (k = 4; n = 1363; SMD = –0.05, 95%CI –0.38, 0.28).
46
There is evidence suggesting that there is unlikely to be a clinically important difference between debriefing and no debriefing on reducing the severity of anxiety at 1-3 years follow- up (k = 4; n = 996; SMD = –0.05, 95%CI –0.17, 0.08). There is limited evidence favouring no debriefing over debriefing on reducing the likelihood of changing occupation at 13 months follow-up (k = 1; n = 103; RR = 1.82, 95%CI 0.63, 5.38). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between debriefing and no debriefing on increased alcohol consumption at 13 months follow-up (k = 1; n = 103; RR = 0.97, 95%CI 0.33, 2.87). There is limited evidence favouring no debriefing over debriefing on reducing the likelihood of interference with everyday function (on a scale of 0-3) at 3 years follow-up (k = 1; n = 61; SMD = 0.90, 95%CI 0.38, 1.43). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between debriefing and no debriefing on reducing the likelihood of having physical problems (on a scale of 0-2) at 3 years follow-up (k = 1; n = 61; SMD = 0.58, 95%CI 0.07, 1.10).
47
There is limited evidence favouring no debriefing over debriefing on reducing the attrition rate at 1-4 months follow-up (k = 4; n = 1,164; RR = 1.89, 95%CI 1.23, 2.90). Box 6 Evidence statement matrix for RCTs comparing debriefing and no debriefing in treating adults recently exposed to trauma Component Rating Description
Evidence base B Seven level II studies, one with low risk of bias, three studies with a moderate risk of bias, and three studies with a high risk of bias
Consistency A All studies were consistent in showing very little difference between treatment and control.
Clinical impact D Most outcomes showed no clinically important difference between treatment and control..
Generalisability A Populations consisted of military rescue personnel, women suffering from miscarriages or traumatic childbirths, burns victims, victims of violent robberies, and road traffic accident survivors.
Applicability A One study was conducted in Australia and is therefore directly applicable; five studies were conducted in the UK, Ireland and Canada, which has comparable healthcare for patients exposed to potentially traumatic events compared to the Australian healthcare context; and one study was conducted in China, which has a different healthcare system.
Summary of evidence Evidence from seven RCTs, one with a low risk of bias but the rest with a moderate to high risk, failed to demonstrate any clinically important differences between debriefing and no debriefing, particularly on the primary outcomes. (Grade B).
Debriefing versus control for the subgroup of people involved in motor vehicle accidents
Two studies listed in Table 5 investigated the effectiveness of debriefing for preventing PTSD and related conditions, compared to a control group, in survivors of road traffic accidents (Conlon et al 1999; Hobbs et al 1996). Both studies reported the severity of PTSD symptoms using the self-reported IES questionnaire at 2-4 months follow-up and meta- analysis found no clinically important or statistically significant difference between the two groups.
48
There is evidence suggesting that there is unlikely to be a clinically important difference between debriefing and no debriefing on reducing the severity of self-reported PTSD symptoms at 2-4 months follow-up (k = 2; n = 131; SMD = 0.14, 95%CI ‒0.20, 0.48).
Box 7 Evidence statement matrix for RCTs comparing debriefing and control in treating adults recently exposed to trauma Component Rating Description
Evidence base C Two level II studies, one with a moderate risk of bias, one with a high risk of bias.
Consistency B Studies each favoured a different treatment arm, however both very close to no difference.
Clinical impact D There were no statistically significant or clinically important benefits favouring debriefing over no debriefing on reducing the severity of PTSD symptom at 2-4 months in people recently injured in road traffic accidents.
Generalisability A Populations consisted of road traffic accident survivors.
Applicability B One study was conducted in the UK, and one in Ireland, which have comparable healthcare for patients exposed to potentially traumatic events compared to the Australian healthcare context.
Summary of evidence The evidence suggested that there were no clinical benefit for debriefing compared to no debriefing on reducing the severity of PTSD symptoms in people that had survived a motor vehicle accident at 1-4 months follow-up. (Grade C).
DEBRIEFING VERSUS CONTROL FOR CHILDREN EXPOSED TO TRAUMA
Two studies investigated the effectiveness of debriefing after traffic accidents in preventing PTSD and related conditions compared to a control group in children aged 7 to 18 years (Table 6). The study by Stallard et al (2006) compared the effectiveness of a debriefing session, delivered about 10 days after the accident, with a control group who were involved in a general non-accident focused discussion. The authors looked at the rate and symptoms of
49 PTSD and related outcomes, as well as behavioural problems after 8 months. Zehnder et al (2010) compared the effectiveness of a 30-minute debriefing session delivered about 4 weeks after the accident to standard medical care. Psychological support was also available to the children in the control group but none was provided during the duration of the study. The authors looked at the symptoms of PTSD and depression, as well as behavioural problems at 2-month and 6-month follow-ups. There were no statistically significant or clinically important benefits favouring debriefing over usual care for any of the outcomes reported.
Table 6 Study profiles for RCTs comparing debriefing and control in treating children recently exposed to trauma Reference Risk of bias Population Setting N Outcomes measured (Stallard et al 2006) Moderate Child road traffic accident Outpatient setting, 158 PTSD diagnosis survivors, aged 7-18 years UK Severity of PTSD symptoms Depression Anxiety Behavioural problems Attrition (Zehnder et al 2010) Moderate Child road traffic accident Inpatient/ 101 Severity of PTSD symptoms survivors, aged 7-16 years outpatient Depression settings, Behavioural problems Switzerland Attrition
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between debriefing and control on reducing the likelihood of having a clinician-rated PTSD diagnosis in children at 8 months follow-up (k = 1; n = 158; RR = 0.85, 95%CI 0.40, 1.79). There is evidence suggesting that there is unlikely to be a clinically important difference between debriefing and control on reducing the severity of clinician-rated PTSD symptoms in children at 2 months follow-up (k = 1; n = 99; SMD = 0.16, 95%CI –0.23, 0.56).
There is evidence suggesting that there is unlikely to be a clinically important difference between debriefing and control on reducing the severity of PTSD symptoms (clinically- administered IBS-KJ and self-reported C-IES) in children at 6-8 months follow-up (k = 2; n = 231; SMD = 0.02, 95%CI –0.24, 0.28).
50 There is evidence suggesting that there is unlikely to be a clinically important difference between debriefing and control on reducing the severity of depression in children at 2 months follow-up (k = 1; n = 99; SMD = –0.07, 95%CI –0.46, 0.33).
There is evidence suggesting that there is unlikely to be a clinically important difference between debriefing and control on reducing the severity of depression in children at 6-8 months follow-up (k = 2; n = 231; SMD = –0.13, 95%CI –0.39, 0.13). There is evidence suggesting that there is unlikely to be a clinically important difference between debriefing and control on reducing the severity of anxiety symptoms in children at 8 months follow-up (k = 1; n = 132; SMD = –0.08, 95%CI –0.42, 0.27). There is evidence suggesting that there is unlikely to be a clinically important difference between debriefing and control on reducing behavioural problems (parent-reported CBCL) in children at 2 months follow-up (k = 1; n = 99; SMD = 0.00, 95%CI –0.39, 0.39).
51 There is evidence suggesting that there is unlikely to be a clinically important difference between debriefing and control on reducing behavioural problems (parent-reported measures) in children at 6-8 months follow-up (k = 2; n = 209; SMD = –0.19, 95%CI –0.46, 0.08).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between debriefing and control on reducing the attrition rate in children at 6-8 months follow-up (k = 2; n = 259; RR = 0.93, 95%CI 0.48, 1.82). Box 8 Evidence statement matrix for RCTs comparing debriefing and control in treating children recently exposed to trauma Component Rating Description
Evidence base C Two level II studies with a moderate risk of bias
Consistency A The studies were consistent in reporting no differences
Clinical impact D There were no statistically significant or clinically important benefits favouring debriefing over usual care for any outcome or at any time point
Generalisability A Populations consisted of child road traffic accident survivors.
Applicability B The studies were conducted in Switzerland and the UK, which has comparable healthcare for patients exposed to potentially traumatic events compared to the Australian healthcare context.
Summary of evidence The evidence suggested that debriefing did not provide any clinical benefits over usual care in the prevention of PTSD, or in the reduction of PTSD symptoms, depression, anxiety or behavioural problems following recent exposure to a potentially traumatic event in children. (Grade B).
TWO DEBRIEFING SESSIONS 4-6 WEEKS APART VERSUS NO DEBRIEFING
Gamble et al (2005) also investigated the effectiveness of adding a second debriefing session 4-6 weeks following the first session at preventing mothers developing PSTD and postnatal depression after having a traumatic childbirth. The first session was delivered within 72 hours
52 of giving birth. The outcome measures for diagnosis of PSTD or postnatal depression did not differ between the two groups 4-6 weeks after the first debriefing session. The introduction of a second debriefing session at this time had a statistically significant effect in reducing the number of mothers diagnosed with postnatal depression at 3 months postpartum compared to mothers that received no debriefing. However, it had no statistically significant effect on the number of mothers diagnosed with PTSD or on their anxiety levels (despite clinically important point estimates, the confidence intervals were too broad to be statistically significant). The evidence statements, RR or SMD for each relevant outcome and the evidence matrix (Box 9) are presented below.
Table 7 Study profile for RCT comparing two debriefing sessions 4-6 weeks apart and no debriefing in treating people recently exposed to trauma Reference Risk of bias Population Setting N Outcomes measured (Gamble et al 2005) Low Women who experienced Antenatal clinics, 103 PTSD diagnosis traumatic childbirth Australia Severity of PTSD symptoms Postnatal depression Depression Anxiety
There is limited evidence favouring 2 debriefing sessions 4-6 weeks apart over no debriefing on reducing the likelihood of having a PTSD diagnosis (clinically-administered MINI-PTSD) at 3 months postpartum follow-up (k = 1; n = 103; RR = 0.35, 95%CI 0.10, 1.23). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between 2 debriefing sessions 4-6 weeks apart and no debriefing on reducing the severity of PTSD symptoms (clinically-administered MINI-PTSD) at 3 months postpartum follow-up (k = 1; n = 103; SMD = –0.41, 95%CI –0.81, –0.02). There is limited evidence favouring 2 debriefing sessions 4-6 weeks apart over no debriefing on reducing the likelihood of developing postnatal depression (self-reported EPDS score > 12) at 3 months postpartum follow-up (k = 1; n = 103; RR = 0.25, 95%CI 0.09, 0.69). There is limited evidence favouring 2 debriefing sessions 4-6 weeks apart over no debriefing on reducing the likelihood of developing depression (self-reported DASS-D score > 13) at 3 months postpartum follow-up (k = 1; n = 103; RR = 0.23, 95%CI 0.07, 0.76). There is limited evidence favouring 2 debriefing sessions 4-6 weeks apart over no debriefing on reducing the likelihood of developing anxiety (self-reported DASS-A score > 9) at 3 months postpartum follow-up (k = 1; n = 103; RR = 0.18, 95%CI 0.02, 1.45). Box 9 Evidence statement matrix for RCTs comparing debriefing and control in treating people recently exposed to trauma Component Rating Description
Evidence base B One level II study with low risk of bias
Consistency N/A Only one study
Clinical impact C The point estimates favouring 2 debriefing sessions 4-6 weeks apart over no debriefing were clinically important for reducing the likelihood of developing PTSD, postnatal depression, depression or anxiety at 3 months post-partum, but the confidence intervals included clinically unimportant effects.
Generalisability A Populations consisted of women who experienced a traumatic childbirth.
Applicability A The study was conducted in Australia and is therefore directly applicable.
53 Summary of evidence Limited evidence suggested that the addition of a second debriefing session 4-6 weeks later may improve PTSD, depression and anxiety outcomes compared to no debriefing, but only the depression outcomes reached statistical significance. (Grade B).
EMOTIONAL DEBRIFING VERSUS NO DEBRIEFING
One study compared the effectiveness of emotional debriefing, educational debriefing and no debriefing for trauma survivors (Sijbrandij et al 2006). The two debriefing protocols were based on the critical incident stress debriefing protocol by Mitchell (1983), were individually administered about 2 weeks after the trauma and lasted for up to 1 hour. Emotional debriefing excluded two of Mitchell’s stages; description of stress symptoms experienced, and the teaching stage where participants are provided with information about stress and PTSD symptoms. Educational debriefing excluded the reaction stage, where participants reconstruct the trauma. PTSD symptoms, depression and anxiety were measured 2 weeks, 6 weeks and 6 months after the debriefing sessions but no clinically important or statistically significant differences were reported. The evidence statements, RR or SMD for each outcome and the evidence matrix for emotional debriefing compared to no debriefing (Box 10) are presented below.
Table 8 Study profile for RCT comparing emotional debriefing, educational debriefing and no debriefing in treating people recently exposed to trauma Reference Risk of bias Population Setting N Outcomes measured (Sijbrandij et al Moderate Adult trauma survivors Outpatient setting, 236 Severity of PTSD symptoms 2006) (accident or assault) The Netherlands Depression Anxiety
There is evidence suggesting that there is unlikely to be a clinically important difference between emotional debriefing and no debriefing on reducing the severity of clinician-rated PTSD symptoms at 2 weeks follow-up (k = 1, n = 126, SMD = 0.18 95%CI –0.17, 0.53), 6 weeks follow-up (k = 1, n = 125, SMD = 0.33 95%CI –0.02, 0.69) or 6 months follow-up (k = 1, n = 115, SMD = 0.05 95%CI –0.31, 0.42). There is evidence suggesting that there is unlikely to be a clinically important difference between emotional debriefing and no debriefing on reducing the severity of depression at 2 weeks follow-up (k = 1, n = 126, SMD = 0.23 95%CI –0.12, 0.58), 6 weeks follow-up (k = 1, n = 129, SMD = 0.13 95%CI –0.22, 0.47), or 6 months follow-up (k = 1, n = 118, SMD = 0.13 95%CI –0.23, 0.50). There is evidence suggesting that there is unlikely to be a clinically important difference between emotional debriefing and no debriefing on reducing the severity of anxiety at 2 weeks follow-up (k = 1, n = 127, SMD = 0.22 95%CI –0.13, 0.57), 6 weeks follow-up (k = 1, n = 129, SMD = 0.18 95%CI –0.16, 0.53), or 6 months follow-up (k = 1, n = 119, SMD = 0.08 95%CI –0.28, 0.44).
Box 10 Evidence statement matrix for RCTs comparing emotional debriefing and no debriefing in treating people recently exposed to trauma Component Rating Description
Evidence base C One level II study with moderate risk of bias
54 Consistency N/A Only one study
Clinical impact D There was no evidence suggesting that there were any statistically significant or clinically important differences between emotional debriefing and no debriefing on any outcome or at any time point
Generalisability A Population consisted of adult trauma survivors
Applicability B The study was conducted in the Netherlands, which has comparable healthcare for patients exposed to potentially traumatic events compared to the Australian healthcare context.
Summary of evidence There is limited evidence suggesting that there is no clinically important difference between emotional debriefing and no debriefing in preventing PTSD and reducing PTSD-related symptoms, depression or anxiety in people who have been exposed to a potentially traumatic event. (Grade C).
EDUCATIONAL DEBRIEFING VERSUS NO DEBRIEFING
One study compared the effectiveness of educational debriefing and no debriefing for trauma survivors (Sijbrandij et al 2006). Educational debriefing was similar to emotional debriefing (previously discussed), but excluded the reaction stage, where participants reconstruct the trauma. PTSD symptoms, depression and anxiety were measured 2 weeks, 6 weeks and 6 months after the debriefing sessions but no clinically important or statistically significant differences were reported. The evidence statements, RR or SMD for each outcome and the evidence matrix for educational debriefing compared to no debriefing (see Box 11) are presented below.
Table 9 Study profile for RCT comparing emotional debriefing, educational debriefing and no debriefing in treating people recently exposed to trauma Reference Risk of bias Population Setting N Outcomes measured (Sijbrandij et al Moderate Adult trauma survivors Outpatient setting, 236 Severity of PTSD symptoms 2006) (accident or assault) The Netherlands Depression Anxiety
There is evidence suggesting that there is unlikely to be a clinically important difference between educational debriefing and no debriefing on reducing the severity of clinician-rated PTSD symptoms at 2 weeks follow-up (k = 1, n = 126, SMD = 0.03 95%CI –0.32, 0.38), 6 weeks follow-up (k = 1, n = 125, SMD = 0.13 95%CI –0.22, 0.48) or 6 months follow-up (k = 1, n = 114, SMD = –0.03 95%CI –0.40, 0.34). There is evidence suggesting that there is unlikely to be a clinically important difference between educational debriefing and no debriefing on reducing the severity of depression at 2 weeks follow-up (k = 1, n = 126, SMD = 0.04 95%CI –0.31, 0.39), 6 weeks follow-up (k = 1, n = 127, SMD = –0.09 95%CI –0.44, 0.26) or 6 months follow-up (k = 1, n = 117, SMD = 0.00 95%CI –0.36, 0.36). There is evidence suggesting that there is unlikely to be a clinically important difference between educational debriefing and no debriefing on reducing the severity of anxiety at 2 weeks follow-up (k = 1, n = 128, SMD = 0.04 95%CI –0.31, 0.39), 6 weeks follow-up (k = 1, n = 127, SMD = 0.08 95%CI –0.27, 0.43), or 6 months follow-up (k = 1, n = 118, SMD = – 0.05 95%CI –0.41, 0.32).
55 Box 11 Evidence statement matrix for RCTs comparing educational debriefing and no debriefing in treating people recently exposed to trauma Component Rating Description
Evidence base C One level II study with moderate risk of bias
Consistency N/A Only one study
Clinical impact D There was no evidence suggesting that there were any statistically significant or clinically important differences between educational debriefing and no debriefing at 2 weeks, 6 weeks or 6 months follow-up.
Generalisability A Population consisted of adult trauma survivors
Applicability B The study was conducted in the Netherlands, which has comparable healthcare for patients exposed to potentially traumatic events compared to the Australian healthcare context.
Summary of evidence There is limited evidence suggesting that there is no clinically important difference between educational debriefing and no debriefing in preventing PTSD and reducing PTSD-related symptoms, depression or anxiety in patients that have been exposed to a potentially traumatic event. (Grade C).
TRAUMA-FOCUSED COUNSELLING VERSUS MONITORING CONTROL
One study compared the effectiveness of a three– to six–session counselling program and a monitored control condition in reducing the likelihood of road traffic accident survivors suffering from long–term psychological effects (Brom et al 1993). Counselling began 1 month after the traumatic accident and continued over a 2-month period. Counselling included practical help, education, support, reality testing, confrontation with the traumatic experience, and referral to a specialised psychotherapist if PTSD is detected. Details of the monitoring conducted for the control group, other than assessment at 1 and 6 months post– trauma were not reported. Outcomes were measured at 3-months post-intervention (equal to 6 months following the accident) but no clinically important or statistically significant differences between groups were reported. The evidence statements, RR or SMD for each outcome and the evidence matrix (Box 12) are presented below.
Table 10 Study profile for RCT comparing trauma-focused counselling and control in treating people recently exposed to trauma Reference Risk of bias Population Setting N Outcomes measured (Brom et al 1993) High Patients that had survived a Outpatient setting, 156 Severity of PTSD symptoms motor vehicle accident The Netherlands Attrition
There is evidence suggesting there is unlikely to be a clinically important difference between trauma-focused counselling and control on reducing the severity of self-reported PTSD symptoms at 3 months follow-up (k = 1; n = 120; SMD = 0.17, 95%CI –0.19, 0.53). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between trauma-focused counselling and control in attrition at 3 months follow-up (k = 1; n = 156; RR = 0.67, 95%CI 0.35, 1.28).
56 Box 12 Evidence statement matrix for RCT comparing trauma-focused counselling and control in treating people recently exposed to trauma Component Rating Description
Evidence base D One level II study with a high risk of bias
Consistency N/A Only one study
Clinical impact D There were no clinically important differences between trauma-focused counselling and control
Generalisability A Population consisted of road traffic accident survivors.
Applicability B The study was conducted in the Netherlands; therefore the evidence is applicable to Australian healthcare context with few caveats.
Summary of evidence Limited evidence suggested that trauma-focused counselling offered no clinical benefits compared to control at reducing severity of PTSD symptoms at 6 months. (Grade C)
PROVISION OF AN ICU DIARY VERSUS WAIT LISTED CONTROL
One average quality study with a moderate risk of bias and good sample size investigated the effectiveness of receiving an ICU diary one month after discharge from the ICU compared to waitlist (Jones et al 2010). The wait listed control group receiving the ICU diary after completion of the 3–month follow-up. The diary provided a detailed written record with photographs of their stay in the ICU and was introduced to the patient by a research nurse or doctor who ensured that they understood its contents but did not give any advice on what to do with it. The number of patients with a PTSD diagnosis was reported at 2 months post– intervention (equivalent to 3 months post–discharge).
Table 11 Study profile for RCT comparing provision of an ICU diary and control in treating people recently exposed to trauma Reference Risk of bias Population Setting N Outcomes measured (Jones et al 2010) Moderate Patients had been in the ICU Outpatient setting, 352 Diagnosis of PTSD and ventilated USA Attrition
There is limited evidence favouring providing an ICU diary over waitlist on reducing the likelihood of having a PTSD diagnosis (clinically-administered PDS) at 3 months follow-up (k = 1; n = 352; RR = 0.38, 95%CI 0.17, 0.81). There is evidence suggesting there is unlikely to be a clinically important difference between providing an ICU diary and waitlist on attrition rate at 3 months follow-up (k = 1; n = 352; RR = 0.99, 95%CI 0.47, 2.06). Box 13 Evidence statement matrix for RCT comparing provision of an ICU diary and control in treating people recently exposed to trauma Component Rating Description
Evidence base C One level II study with a moderate risk of bias
Consistency N/A Only one study
57 Clinical impact C One clinically important point estimate favouring the provision of an ICU diary over waitlist for PTSD diagnosis
Generalisability B Population consisted of patients that had been in the ICU and ventilated (45% considered it to be a traumatic experience)
Applicability C Evidence is probably applicable to Australian healthcare context with some caveats (from the USA)
Summary of evidence Limited evidence suggested that providing an ICU diary was clinically beneficial in preventing a diagnosis of PTSD 3 months after discharge from the ICU. (Grade C)
SELF-HELP WEBSITE FOR CHILDREN AND INFORMATION BOOKLET FOR PARENTS VERSUS ASSESSMENT ONLY CONTROL
Cox et al. (2010) investigated the effectiveness of an interactive website for children recovering from an unintentional injury and an information booklet for their parents compared to an assessment only control group. The website had separate sections for children (aged 7–10 years) and adolescents (aged 11–16 years) and had icons covering issues such as feelings, problem solving, reaching out, and growing and learning. Each section contained information aiming to normalize and promote recovery, examples to encourage learning and implementation and practical tools based on cognitive behavioural and resiliency strategies such as relaxation, coping statements, identifying personal strengths, and reflection on the event (learning and growing from the challenge). The parent’s four-page booklet emphasized their role in their child’s recovery and contained information regarding common child reactions and how they can assist their child’s emotional recovery. It also covered their own potential distress with coping strategies. The intervention was provided between 2 and 4 weeks post-injury and outcomes were assessed 4-6 weeks and 6 months post-injury. There were no clinically important or statistically significant differences between the provision of a self-help website for children with unintentional injuries and an information booklet for parents to an assessment only control for either parents or children.
Table 12 Study profile for RCT comparing a self-help website for children plus an information booklet for parents and an assessment only control in treating people recently exposed to trauma Reference Risk of bias Population Setting N Outcomes measured (Cox et al 2010) High Children recovering from an Outpatient setting, 85 In parents: unintentional injury and a Australia Severity of PTSD symptoms parent Attrition In children: Severity of PTSD symptoms Depression Anxiety
Outcome measures in adults: There is evidence suggesting there is unlikely to be a clinically important difference between a self-help website for children and information booklet for parents and an assessment only control on reducing the severity of self-reported PTSD symptoms at 4-6 weeks follow-up (k = 1; n = 56; SMD = 0.12, 95%CI –0.40, 0.65) or at 6 months follow-up (k = 1; n = 56; SMD = 0.05, 95%CI –0.47, 0.58). There is evidence suggesting there is unlikely to be a clinically important difference between a self-help website for children and information booklet for parents and an assessment only
58 control on attrition rate at 4-6 weeks follow-up (k = 1; n = 85; RR = 1.45, 95%CI 0.72, 3.00).
Box 14 Evidence statement matrix for RCT comparing a self-help website for children plus an information booklet for parents and an assessment only control in treating adults recently exposed to trauma Component Rating Description
Evidence base D One level II study with a high risk of bias
Consistency N/A Only one study
Clinical impact D No clinically important differences between treatments in adults
Generalisability B Population consisted of a parent of a child recovering from an unintentional injury
Applicability A The study was conducted in Australia and is therefore directly applicable to the Australian healthcare context.
Summary of evidence The evidence suggested that providing a self-help website for children and an information booklet for parents provided no clinical benefits for parents in reducing the severity of PTSD symptoms at 6 months when compared to waitlist. (Grade C)
Outcome measures in children: There is evidence suggesting there is unlikely to be a clinically important difference between a self-help website for children and information booklet for parents and an assessment only control on reducing the severity of clinician-rated PTSD symptoms at 4-6 weeks follow-up (k = 1; n = 56; SMD = 0.11, 95%CI –0.42, 0.63), or at 6 months follow-up (k = 1; n = 56; SMD = –0.13, 95%CI –0.65, 0.40). There is evidence suggesting there is unlikely to be a clinically important difference between a self-help website for children and information booklet for parents and an assessment only control on reducing the severity of depression at 4-6 weeks follow-up (k = 1; n = 56; SMD = 0.09, 95%CI –0.43, 0.62), or at 6 months follow-up (k = 1; n = 56; SMD = –0.14, 95%CI – 0.67, 0.38). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between a self-help website for children and information booklet for parents and an assessment only control on reducing the severity of anxiety at 4-6 weeks follow-up (k = 1; n = 56; SMD = 0.32, 95%CI –0.21, 0.85). There is evidence suggesting there is unlikely to be a clinically important difference between a self-help website for children and information booklet for parents and an assessment only control on reducing the severity of anxiety at 6 months follow-up (k = 1; n = 56; SMD = – 0.21, 95%CI –0.73, 0.32).
Box 15 Evidence statement matrix for RCT comparing a self-help website for children plus an information booklet for parents and an assessment only control in treating children recently exposed to trauma Component Rating Description
Evidence base D One level II study with a high risk of bias
59 Consistency N/A Only one study
Clinical impact D No clinically important differences.
Generalisability A Population consisted of children recovering from an unintentional injury
Applicability A The study was conducted in Australia and is therefore directly applicable to the Australian healthcare context.
Summary of evidence The evidence suggested that providing a self-help website for children and an information booklet for parents was not clinically beneficial for children in reducing the severity of PTSD symptoms, depression and anxiety at 4-6 weeks or 6 months when compared to an assessment only control group. (Grade C)
IMMEDIATE VERSUS DELAYED DEBRIEFING
One study investigated the effectiveness of immediate debriefing (within 10 hours of robbery) with delayed debriefing (11 – 168 hours after robbery) for victims of robbery (Campfield & Hills 2001). Debriefing lasted 1–2 hours and was conducted individually or in small groups. The authors measured the severity of PTSD symptoms 2 weeks after the debriefing and reported a clinically important and statistically significant difference favouring immediate debriefing. The evidence statements, SMD evidence matrix (Box 2) are presented below.
Table 13 Study profile for RCT comparing immediate debriefing and delayed debriefing in treating people recently exposed to trauma Reference Risk of bias Population Setting N Outcomes measured (Campfield & Hills Moderate Adults exposed to a robbery National Trauma 77 Severity of PTSD symptoms 2001) at their place of employment Clinic, Sydney, Australia
PDS = Posttraumatic Stress Diagnostic Scale.
There is evidence favouring immediate debriefing over delayed debriefing on reducing the severity of PTSD at 2 weeks post-trauma (k = 1, n = 77, SMD = –2.56 95%CI –3.16, –1.95). Box 16 Evidence statement matrix for RCTs comparing immediate debriefing and delayed debriefing in treating people recently exposed to trauma Component Rating Description
Evidence base C One level II study with moderate risk of bias
Consistency N/A Only one study
Clinical impact C The point estimate and the entire range of the confidence interval showed a clinically important benefit favouring immediate debriefing over delayed debriefing on reducing PTSD symptoms at 2 weeks post- trauma.
Generalisability A Australian sample of adults exposed to robbery in their place of employment
Applicability A The study was conducted in Australia and is therefore directly applicable to the Australian healthcare
60 context.
Summary of evidence There is evidence from one small study with a moderate risk of bias suggesting that immediate debriefing may improve PTSD symptoms compared to delayed debriefing two weeks after exposure to a potentially traumatic event. However, the lack of longer term follow-up data and the absence of a no debriefing control prevented the assessment of its true clinical effectiveness. (Grade C)
EMOTIONAL DEBRIFING VERSUS EDUCATIONAL DEBRIEFING
One study compared the effectiveness of emotional debriefing, educational (Sijbrandij et al 2006). The two debriefing protocols were based on the critical incident stress debriefing protocol by Mitchell (1983), were individually administered about 2 weeks after the trauma and lasted for up to 1 hour. Emotional debriefing excluded two of Mitchell’s stages; description of stress symptoms experienced, and the teaching stage where participants are provided with information about stress and PTSD symptoms. Educational debriefing excluded the reaction stage, where participants reconstruct the trauma. PTSD symptoms, depression and anxiety were measured 2 weeks, 6 weeks and 6 months after the debriefing sessions but no clinically important or statistically significant differences were reported. The evidence statements, RR or SMD for each outcome and the evidence matrix for emotional debriefing compared to educational debriefing (Box 17) are presented below.
Table 14 Study profile for RCT comparing emotional debriefing and educational debriefing in treating people recently exposed to trauma Reference Risk of bias Population Setting N Outcomes measured (Sijbrandij et al Moderate Adult trauma survivors Outpatient setting, 236 Severity of PTSD symptoms 2006) (accident or assault) The Netherlands Depression Anxiety PDS = Posttraumatic Stress Diagnostic Scale.
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between emotional debriefing and educational debriefing on reducing the severity of clinician-rated PTSD symptoms at 2 weeks follow-up (k = 1, n = 126, SMD = 0.16 95%CI –0.19, 0.51) or 6 weeks follow-up (k = 1, n = 120, SMD = 0.19 95%CI – 0.16, 0.55). There is evidence suggesting that there is unlikely to be a clinically important difference between emotional debriefing and educational debriefing on reducing the severity of clinician-rated PTSD symptoms at 6 months follow-up (k = 1, n = 110, SMD = 0.08 95%CI ‒ 0.29, 0.46). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between emotional debriefing and educational debriefing on reducing the severity of depression at 2 weeks follow-up (k = 1, n = 124, SMD = 0.20 95%CI –0.15, 0.55) or at 6 weeks follow-up (k = 1, n = 124, SMD = 0.22 95%CI –0.13, 0.57). There is evidence suggesting that there is unlikely to be a clinically important difference between emotional debriefing and educational debriefing on reducing the severity of depression at 6 months follow-up (k = 1, n = 115, SMD = 0.13 95%CI ‒0.23, 0.50). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between emotional debriefing and educational debriefing on
61 reducing the severity of anxiety at 2 weeks follow-up (k = 1, n = 125, SMD = 0.18 95%CI – 0.17, 0.53). There is evidence suggesting that there is unlikely to be a clinically important difference between emotional debriefing and educational debriefing on reducing the severity of anxiety at 6 weeks follow-up (k = 1, n = 124, SMD = 0.10 95%CI –0.25, 0.45) or 6 months follow-up (k = 1, n = 115, SMD = 0.13 95%CI –0.23, 0.50). Box 17 Evidence statement matrix for RCTs comparing emotional debriefing and educational debriefing in treating people recently exposed to trauma Component Rating Description
Evidence base C One level II study with moderate risk of bias
Consistency N/A Only one study
Clinical impact D There were no statistically significant or clinically important differences between emotional debriefing and educational debriefing in PTSD-related outcomes at 2 weeks, 6 weeks or 6 months follow-up.
Generalisability A Population consisted of adult trauma survivors
Applicability B The study was conducted in the Netherlands, which has comparable healthcare for patients exposed to potentially traumatic events compared to the Australian healthcare context.
Summary of evidence There is limited evidence suggesting that there are no clinically significant differences between emotional debriefing and educational debriefing in preventing PTSD and reducing PTSD-related symptoms, depression or anxiety in patients that have been exposed to a potentially traumatic event. (Grade C).
“512” DEBRIEFING VERSUS STANDARD CRITICAL INCIDENT DEBRIEFING
Wu et al. (2011) compared the effectiveness of two different debriefing programs in reducing PTSD related symptoms in military rescue workers involved in rescue and body recovery after a major earthquake in China. The 2-hour “512” psychological intervention was based on the critical incident stress debriefing protocol developed by Mitchell (1983) and differed in the addition of a cohesion training section, which is aimed at increasing the relationship and support between personnel in a military unit. This was compared to a 1-hour critical incident stress debriefing; the debriefings were conducted 20-33 days after the traumatic incident. A third randomised group that received no debriefing was also included in this study to enable the comparison of the effectiveness of “512” debriefing and no debriefing. The outcomes were measured at 1, 2 and 4 months post-intervention. Most outcomes favouring “512” debriefing over debriefing or no debriefing were statistically significant, but the differences were mostly not large enough to be clinically important. Clinically important differences favouring “512” debriefing over debriefing were observed for reducing the severity of PTSD symptoms at 2 months and for reducing depression at 4 months. The evidence statements, RR or SMD for each outcome and the evidence matrix for “512” debriefing over debriefing (Box 18) are presented below.
Table 15 Study profile for RCT comparing “512” debriefing and debriefing or no debriefing in treating people recently exposed to trauma Reference Risk of bias Population Setting N Outcomes measured
62 (Wu et al 2011) Moderate Military rescue workers after Field study, China 1,267 Severity of PTSD symptoms a severe earthquake Depression Anxiety Attrition HADS = Hospital Anxiety and Depression Scale; SI-PTSD = Structured Interview for PTSD.
There is evidence suggesting that there is unlikely to be a clinically important difference between “512” debriefing and debriefing on reducing the severity of clinician-rated PTSD symptoms at 1 month follow-up (k = 1; n = 802; SMD = –0.08, 95%CI –0.22, 0.06). There is limited evidence favouring “512” debriefing over debriefing on reducing the severity of clinician-rated PTSD symptoms at 2 months follow-up (k = 1; n = 772; SMD = – 0.50, 95%CI –0.64, –0.35). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between “512” debriefing and debriefing on reducing the severity of clinician-rated PTSD symptoms at 4 months follow-up (k = 1; n = 739; SMD = ‒0.42, 95%CI –0.57, –0.27). There is evidence suggesting that there is unlikely to be a clinically important difference between “512” debriefing and debriefing on reducing the severity of depression at 1 month follow-up (k = 1; n = 802; SMD = –0.30, 95%CI –0.44, –0.16). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between “512” debriefing and debriefing on reducing the severity of depression at 2 months follow-up (k = 1; n = 772; SMD = –0.47, 95%CI –0.61, –0.32). There is evidence favouring “512” debriefing over debriefing on reducing the severity of depression at 4 months follow-up (k = 1; n = 739; SMD = –0.76, 95%CI –0.91, –0.61). There is evidence suggesting that there is unlikely to be a clinically important difference between “512” debriefing and debriefing on reducing the severity of anxiety at 1 month follow-up (k = 1; n = 802; SMD = –0.19, 95%CI –0.33, –0.06) or at 2 months follow-up (k = 1; n = 772; SMD = –0.32, 95%CI –0.46, –0.17). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between “512” debriefing and debriefing on reducing the severity of anxiety at 4 months follow-up (k = 1; n = 739; SMD = –0.48, 95%CI ‒0.63, –0.33). There is limited evidence favouring debriefing over “512” debriefing on the attrition rate at 1 month follow-up (k = 1; n = 802; RR = 1.59, 95%CI 0.83, 3.03).
Box 18 Evidence statement matrix for RCTs comparing “512” debriefing and debriefing in treating people recently exposed to trauma Component Rating Description
Evidence base C One level II study with moderate risk of bias
Consistency N/A Only one study
Clinical impact D Most evidence suggests there is no clinically important difference between the two types of debriefing
Generalisability B Population consisted of Chinese military rescuers working to rescue survivors and recover bodies of victims of a major earthquake.
Applicability D The study was conducted in China, which is not applicable to Australian healthcare context
63 Summary of evidence One large trial with a moderate risk of bias found very few clinically important differences between “512” debriefing and debriefing for people recently exposed to trauma. (Grade C).
CBT VERSUS USUAL CARE
Two studies investigated the effectiveness of brief CBT programs compared to usual care in preventing long–term psychological effects in parents of children who were either admitted to the ICU after birth or newly diagnosed with cancer (Bernard et al 2011; Kazak et al 2005). Kazak et al. (2005) compared the effectiveness of a three-session surviving cancer competently intervention program and usual psychological care in parents or caregivers of newly diagnosed paediatric oncology patients. The surviving cancer intervention was an adaptation of an integrated cognitive behavioural and family therapy intervention developed Kazak et al. (1999), and was intended for two caregivers of a child newly diagnosed with cancer. The three 45-minute sessions were to be completed within 1 month of the child’s diagnosis but in reality it took considerably longer (2–3 months). For usual psychological care, each family was assigned a social worker who provided resources and supplemental information about the diagnosis and treatment, and offered support. Outcomes were reported at 2-months post-intervention. Although the authors reported that the IES-R total scores for both primary and partner caregivers in the CBT arm showed declines in the severity of PTSD symptoms, whereas those in the usual care arm showed an increase at 2 months follow-up, the actual IES-R scores were not provided. One study investigated the effectiveness of a three– session CBT-based intervention compared to usual care in reducing symptoms of depression and trauma in mothers of infants admitted to the ICU within 72 hours of birth and expected to survive (Bernard et al 2011). The CBT intervention was designed to be preventative rather than for treating existing disorders and was delivered over a 2-week period while the child was in the ICU. Mothers in the usual care group received typical care for ICU parents including contact with nurses, physicians, social workers, and chaplaincy (if requested). Outcomes for PTSD and depression were measured one month after the child’s discharge from the ICU. Clinically important differences favouring CBT over usual care were reported for reducing the severity of PTSD symptoms and depression in mothers of infants admitted to the ICU at 1 month, in reducing anxiety in primary caregivers of children newly diagnosed with cancer at 2 months, but not in the partners of the primary caregivers.
Table 16 Study profiles for RCTs comparing CBT and usual care in treating people recently exposed to trauma Reference Risk of bias Population Setting N Outcomes measured (Kazak et al 2005) Moderate Caregivers of a child newly Outpatient setting, 38 Severity of PTSD symptoms diagnosed with cancer USA Anxiety Attrition (Bernard et al 2011) High Mothers of children admitted ICU, USA 56 Severity of PTSD symptoms to the ICU within 72 hours of Depression birth Attrition
There is evidence favouring CBT over usual care on reducing self-reported PTSD symptoms for mothers of infants admitted to the ICU after birth at 1 month follow-up (k = 1; n = 50; SMD = –1.70, 95%CI –2.34, –1.05).
64 There is evidence favouring CBT over usual care on reducing depression for mothers of infants admitted to the ICU after birth at 1 month follow-up (k = 1; n = 50; SMD = –2.70, 95%CI –3.46, –1.93). There is limited evidence favouring CBT over usual care on reducing anxiety for primary caregivers at 2 months follow-up (k = 1; n = 17; SMD = –0.83, 95%CI –1.84, 0.17). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between CBT and usual care on reducing anxiety (self-reported STAI) for partners at 2 months follow-up (k = 1; n = 16; SMD = –0.65, 95%CI –1.69, 0.39).
There is evidence favouring usual care over CBT on attrition rate at 1-2 months follow-up (k = 2; n = 94; RR = 11.30, 95%CI 1.53, 83.55).
Box 19 Evidence statement matrix for RCTs comparing CBT and usual care in treating people recently exposed to trauma Component Rating Description
Evidence base C One level II study with a moderate risk of bias and one level II study with a high risk of bias
Consistency A Both studies are consistent in favouring CBT over usual care.
Clinical impact B There were clinically important effects favouring CBT over usual care for PTSD and depression
Generalisability A Evidence likely to be directly generalisable to target population-
Applicability C Evidence is probably applicable to Australian healthcare context with some caveats (from the USA)
Summary of evidence Two studies provided limited evidence suggesting that CBT provided a clinical benefit to mothers and/or primary caregivers of either children newly diagnosed with cancer or infants admitted to ICU within 72 hours of birth, in reducing PTSD symptoms, depression and anxiety when compared to usual care at 1-2 months follow-up. (Grade B)
65 SELF-HELP WORKBOOK VERSUS INFORMATION BOOKLET
One study investigated the effectiveness of an interactive self-help workbook for women diagnosed with stage 0-II breast cancer within the last month compared to an information booklet (Beatty et al 2010). The workbook contained educational information, suggestions and worksheets on common medical and psychosocial issues including topics on: relaxation and meditation CD, coping with side effects such as insomnia fatigue and pain, emotional adjustment including cognitive restructuring for self-blame and stress management activities, body image and identity including mirror-desensitisation and exposure, social support, and survivorship including cognitive restructuring for fear of recurrence and goal setting. The control group received an information booklet that contained identical information to the workbook, but were provided with no suggestions, worksheets or relaxation CD. PTSD outcomes and quality of life were assessed 3 and 6 months after receiving the workbook. The authors reported a clinically important difference favouring the provision of a self-help workbook over an information booklet on reducing the severity of PTSD symptoms at 3 and 6 months and improving quality of life at 6 months. Conversely, there was a clinically important difference favouring the provision of an information booklet over a self-help workbook on reducing depression at 3 and 6 months and anxiety at 6 months. The authors did not suggest any reasons for this divergence. The evidence statements, RR or SMD for each relevant outcome and the evidence matrix (Box 20) are presented below.
Table 17 Study profile for RCT comparing a self-help workbook and an information booklet in treating people recently exposed to trauma Reference Risk of bias Population Setting N Outcomes measured (Beatty et al 2010) Moderate Women diagnosed with Stage Outpatient setting, 49 Severity of PTSD symptoms 0 to II breast cancer in the Australia Depression previous month Anxiety Global QOL
There is evidence favouring the provision of a self-help workbook over an information booklet on reducing the severity of self-reported PTSD symptoms at 3 months follow-up (k = 1; n = 49; SMD = –4.20, 95%CI –5.20, –3.19) and at 6 months follow-up (k = 1; n = 49; SMD = –1.20, 95%CI –2.68, –1.31). There is limited evidence favouring an information booklet over the provision of a self-help workbook on reducing depression at 3 months follow-up (k = 1; n = 49; SMD = 0.83, 95%CI 0.25, 1.41). There is evidence favouring an information booklet over the provision of a self-help workbook on reducing depression at 6 months follow-up (k = 1; n = 49; SMD = 1.50, 95%CI 0.86, 2.14). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between the provision of a self-help workbook and an information booklet on reducing anxiety at 3 months follow-up (k = 1; n = 49; SMD = 0.34, 95%CI – 0.34, 0.90). There is evidence favouring an information booklet over the provision of a self-help workbook on reducing anxiety at 6 months follow-up (k = 1; n = 49; SMD = 1.10, 95%CI 0.50, 1.70). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between the provision of a self-help workbook and an information
66 booklet on an improved global quality of life at 3 months follow-up (k = 1; n = 49; SMD = ‒ 0.47, 95%CI –1.04, 0.10). There is evidence favouring the provision of a self-help workbook over an information booklet on an improved global quality of life at 6 months follow-up (k = 1; n = 49; SMD = ‒ 1.00, 95%CI –1.60, –0.40).
Box 20 Evidence statement matrix for RCT comparing a self-help workbook and an information booklet in treating people recently exposed to trauma Component Rating Description
Evidence base C One level II study with a moderate risk of bias
Consistency N/A Only one study
Clinical impact B Clinically important benefits of self-help workbook for many outcomes
Generalisability A Population consisted of women diagnosed with Stage 0 to II breast cancer in the previous month
Applicability A The study was conducted in Australia and is therefore directly applicable to the Australian healthcare context.
Summary of evidence Evidence from a small trial with moderate risk of bias suggested that providing a self-help workbook was clinically beneficial in reducing the severity of PTSD symptoms at 3 and 6 months and improving quality of life at 6 months when compared to providing an information booklet. Conversely, there was limited evidence suggesting that providing an information booklet was clinically beneficial in reducing the severity of depression at 3 and 6 months and anxiety at 6 months follow-up when compared to providing a self-help workbook. (Grade C)
Treatment for people with ASD or acute PTSD
Ten RCTs (eleven articles) meeting the inclusion criteria determined a priori were identified by a systematic search of the literature. These RCTs reported on early psychological interventions for individuals who were exposed to traumatic events within the past month and developed ASD or acute PTSD. Four of these studies had originally been included in the NICE guidelines (Bryant et al 1998; Bryant et al 2005; Bryant et al 2003b; Bryant et al 1999). A further five studies were identified in the systematic search for the current update to the Australian guidelines (Bryant et al 2008a; Catani et al 2009; Foa et al 2006; Jarero et al 2011; Scholes et al 2007). An additional article, providing long-term follow-up data for the study previously published by Bryant et al. (2005) was also identified (Bryant et al 2006). These studies described four different types of interventions that were all started within the first month after a traumatic event. The effectiveness of interventions including trauma- focused CBT (or using the cognitive restructuring, and prolonged exposure (PE) components), narrative exposure therapy, eye movement desensitization and reprocessing (EMDR), and providing a self-help booklet, were compared to no treatment, wait listed controls, usual care, or another psychological intervention. These nine RCTs were as follows: • five studies (six publications) compared CBT with supportive counselling (Bryant et al 1998; Bryant et al 2005; Bryant et al 2006; Bryant et al 2003b; Bryant et al 1999; Foa et al 2006)
67 • one study compared CBT with an assessment condition (Foa et al 2006) • one study compared CBT with PE (Bryant et al 1999) • two studies compared the cognitive and PE components of CBT with waitlist (Bryant et al 2008a) (Shalev et al 2011) • one study compared PE with supportive counselling (Bryant et al 1999) • one study compared narrative exposure therapy with relaxation-meditation therapy in children (Catani et al 2009) • one study compared an assessment condition with supportive counselling (Foa et al 2006) • one study compared eye movement desensitization and reprocessing with a wait listed control (Jarero et al 2011) • one study compared a self-help booklet with no information (Scholes et al 2007)
COGNITIVE RESTRUCTURING OR PROLONGED EXPOSURE VERSUS WAITLIST Two studies compared components of CBT (cognitive restructuring and prolonged exposure) against each other, and against a waitlist group. Bryant et al. (2008a) conducted an RCT in Australia in patients who had been exposed to recent trauma (a nonsexual assault or motor vehicle accident in the previous month) and had a primary diagnosis of ASD, while Shalev et al (2011) conducted an RCT in Israel in patients with unspecified trauma causing them to go to an emergency department (with the majority having a motor vehicle accident, followed by experiencing terrorism), resulting in acute PTSD. PE treatment included psychoeducation, breathing control training, imaginal and in vivo exposure, plus instruction on relapse prevention strategies. Cognitive restructuring therapy involved psychoeducation, monitoring and modifying of thoughts and affective states such as guilt about one’s behaviour, plus instruction on relapse prevention strategies. The wait listed group in Bryant et al (2008a) were reassessed after 6 weeks and then offered active treatment. Bryant et al. (2008a) reported adverse effects in five patients; three patients became overly distressed during PE therapy with two discontinuing treatment, and two patients became overly distressed during cognitive restructuring therapy and proceeded to drop out. Bryant et al (2008a) reported clinically important and statistically significant differences favouring PE over cognitive restructuring were reported in reducing the likelihood of having a PTSD diagnosis, depression and anxiety post-treatment and at 6 months and a reduction of PTSD symptoms at 6 months. These results were contradictory to those reported by Shalev et al (2011) which showed no difference on the outcomes of PTSD diagnosis (21.6% after prolonged exposure, and 20.0% after cognitive therapy*), or on severity of PTSD (SMD=0.08, 95%CI -0.35, 0.52). The reasons for these differences are unclear.
Bryant et al (2008a) reported no clinically important or statistically significant differences for cognitive restructuring compared to waitlist for any outcome, whereas Shalev et al (2011) reported a clinically important point estimate for the outcome of PTSD diagnosis. Both studies reported that the differences between PE and waitlist were clinically important and statistically significant in reducing the likelihood of having a PTSD diagnosis and the severity of PTSD symptoms post-treatment. The differences between groups in reducing depression or anxiety post-treatment were also statistically significant but the effect sizes were too small to be clinically important.
* Due to inconsistencies within the data presented, data from Shalev et al (2011) could not be incorporated into the evidence statement on the likelihood of having a PTSD diagnosis.
68 Table 18 Study profile for RCT comparing cognitive restructuring, PE and wait listed control in treating people who were recently exposed to trauma and were diagnosed with acute PTSD or ASD Reference Risk of bias Population Setting N Outcomes measured (Shalev et al 2011) Moderate Unspecified trauma (MVA, Outpatient setting, 158 Diagnosis of PTSD terrorism, work incident or Israel Severity of PTSD symptoms other)
(Bryant et al 2008a) Moderate Patients that had PTSD unit, NSW 90 Diagnosis Of PTSD experienced a nonsexual Australia Severity of PTSD symptoms assault or motor vehicle Depression crash in the previous month and were diagnosed with Anxiety ASD Adverse effects
COGNITIVE RESTRUCTURING VERSUS WAITLIST
There is limited evidence favouring cognitive restructuring over waitlist on the likelihood of having a diagnosis of PTSD at post-treatment (k = 2; n = 165; RR = 0.56, 95%CI 0.20, 1.55).
69
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between cognitive restructuring and waitlist on reducing the severity of clinician-rated PTSD symptoms at post-treatment (k = 2; n = 165; SMD = -0.66, 95%CI - 0.99, -0.32). There is evidence suggesting there is unlikely to be a clinically important difference between cognitive restructuring and waitlist on reducing the severity of depression at post-treatment (k = 1; n = 60; SMD = 0.27, 95%CI ‒0.24, 0.78). There is evidence suggesting there is unlikely to be a clinically important difference between cognitive restructuring and waitlist reducing the severity of anxiety at post-treatment (k = 1; n = 60; SMD = 0.22, 95%CI ‒0.29, 0.73). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between cognitive restructuring and waitlist on reducing the attrition rate post-treatment (k = 1; n = 60; RR = 0.78, 95%CI 0.33, 1.78).
Box 21 Evidence statement matrix for RCT comparing cognitive restructuring and waitlist in treating people who were recently exposed to trauma and were diagnosed with acute PTSD or ASD Component Rating Description
Evidence base C Two level II studies with a moderate risk of bias
Consistency C Some inconsistency between studies regarding whether cognitive therapy is beneficial over waitlist or not.
Clinical impact D One study found no clinically important differences; with evidence suggesting no difference on some outcomes. However, second study found limited evidence (significant point difference) favouring cognitive restructuring on the outcome of PTSD diagnosis, and a trend towards favouring cognitive restructuring over waitlist on severity of PTSD diagnosis.
Generalisability A Population of Australian study consisted of adults involved in either an MVA or nonsexual assaults within the past 2 weeks and diagnosed with ASD. Other study included patients with trauma from predominantly motor vehicle accidents, which would be generalisable.
Applicability A One study was conducted in Australia and is therefore directly applicable to the Australian healthcare
70 context. Other study performed in Israel – unclear how applicable.
Summary of evidence There was inconsistent evidence regarding whether cognitive restructuring is beneficial compared to waitlist or not, in patients exposed to recent trauma and diagnosed with ASD or acute PTSD. There was no significant difference in the attrition rate between groups. (Grade C)
PROLONGED EXPOSURE VERSUS WAITLIST
There is evidence favouring PE over waitlist on reducing the likelihood of having a diagnosis of PTSD at post-treatment (k = 2; n = 188; RR = 0.40, 95%CI 0.27, 0.60).
There is limited evidence favouring PE over waitlist on reducing the severity of clinician- rated PTSD symptoms at post-treatment (k = 2; n = 188; SMD = -0.86, 95%CI -1.17, -0.56).
71 The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between PE and waitlist on reducing the severity of depression at post- treatment (k = 1; n = 60; SMD = 0.75, 95%CI 0.23, 1.27). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between PE and waitlist on reducing the severity of anxiety at post- treatment (k = 1; n = 60; SMD = 0.42, 95%CI 0.09, 0.93). There is limited evidence favouring PE over waitlist on reducing the attrition rate post- treatment (k = 1; n = 60; RR = 0.56, 95%CI 0.21, 1.40).
Box 22 Evidence statement matrix for RCT comparing PE and waitlist in treating people who were recently exposed to trauma and were diagnosed with acute PTSD or ASD Component Rating Description
Evidence base C Two level II studies with a moderate risk of bias
Consistency B Both studies consistent in favouring PE over waitlist for measures of PTSD
Clinical impact B Evidence to suggest PE is better than waitlist on PTSD outcomes, with full range of plausible estimates clinically important for PTSD diagnosis. Effect sizes for depression and anxiety too small to be considered clinically important.
Generalisability A Population of Australian study consisted of adults involved in either an MVA or nonsexual assaults within the past 2 weeks and diagnosed with ASD. Other study included patients with trauma from predominantly motor vehicle accidents, which would be generalisable.
Applicability A One study was conducted in Australia and is therefore directly applicable to the Australian healthcare context. Other study performed in Israel – unclear how applicable.
Summary of evidence There was evidence favouring prolonged exposure over waitlist in reducing the likelihood of having a PTSD diagnosis and the severity of PTSD symptoms post-treatment, although no clinically important benefit was found on measures of anxiety or depression. The attrition rate was lower in the prolonged exposure group than the wait listed control, but this did not reach statistical significance. (Grade C)
EMDR VERSUS WAITLIST
Jarero et al. (2011) investigated the effectiveness of eye movement desensitization reprocessing (EMDR) compared to a waitlist/delayed treatment condition in employees of a private company living in the area affected by a 7.2 magnitude earthquake. The employees underwent a crisis management briefing intervention and undertook the IES questionnaire. The employees who scored more than 44 were than randomised to an immediate single session EMDR treatment or waitlist/delayed treatment. The EMDR group received treatment 16 days after the earthquake and those who were waitlisted received treatment four days later. Thus, only post-treatment scores are available for comparison between EMDR and waitlist. IES scores for participants in the EMDR treatment and delayed EMDR treatment groups were reported for post-treatment and 12 weeks follow-up.
The authors reported a clinically important and statistically significant difference favouring EMDR over waitlist in reducing the severity of PTSD symptoms. When the wait listed
72 control group received delayed EMDR treatment, no significant differences between the two treatment groups were reported. The evidence statements, RR or SMD for each relevant outcome and the evidence matrix comparing immediate EMDR treatment and waitlist (Box 23) and immediate and delayed EMDR treatment (Box 33) are presented below.
Table 19 Study profile for RCT comparing immediate EMDR treatment and waitlist for people with acute PTSD or ASD Reference Risk of bias Population Setting N Outcomes measured (Jarero et al 2011) Moderate Employees of a private Field setting, 18 Severity of PTSD symptoms company living in the area Mexico affected by a major earthquake who had IES scores > 44 2 weeks after the event.
There is evidence favouring EMDR over waitlist on reducing the severity of PTSD symptoms (self-reported) post-treatment (k = 1; n = 18; SMD = ‒3.50, 95%CI ‒4.97, ‒2.03).
Box 23 Evidence statement matrix for RCT comparing EMDR and waitlist in treating people with acute PTSD or ASD Component Rating Description
Evidence base C One level II study with a moderate risk of bias
Consistency N/A Only one study
Clinical impact B The point estimate and the entire range of effect measures in the confidence interval favouring EMDR over waitlist were clinically important in reducing the severity of PTSD symptoms, and this difference was statistically significant.
Generalisability B Population consisted of employees of a private company living in the area affected by a major earthquake who had an IES score > 44, 2 weeks after the event.
Applicability D The study was conducted in Mexico and is therefore unlikely to be directly applicable to the Australian healthcare context.
Summary of evidence Limited evidence from a very small study with a moderate level of bias suggested that EMDR was highly beneficial in immediately reducing the severity of PTSD symptoms in employees with high IES scores 2 weeks after a major earthquake, when compared wait listed controls. However, no long-term data was available to determine the robustness of this improvement, and given the size of the trial and risk of bias, the results should be interpreted with caution. (Grade C)
SELF-HELP BOOKLET VERSUS NO INFORMATION
One study investigated the effectiveness of providing a self-help booklet compared to not providing any information in treating patients with injuries sustained as a result of a road traffic accident, an occupational injury or an assault, and diagnosed with ASD (Scholes et al 2007). The self-help booklet provided comprehensive information about the psychological sequelae of trauma and structured proactive advice based on cognitive behavioural strategies and was sent to the patients within one month of their injury. The control group were
73 assessed only, and received no information about trauma or coping mechanisms. PTSD- related outcomes were reported for post-treatment and at 6 months follow-up. However, the loss to follow-up was greater than 50% at 6 months and those results are therefore not reported. There were no clinically important or statistically significant differences between providing a self-help booklet and providing no information reported at post-treatment. The evidence statements, RR or SMD for each relevant outcome and the evidence matrix (Box 24) are presented below.
Table 20 Study profile for RCT comparing providing a self help booklet and no information in treating people with acute PTSD or ASD Reference Risk of bias Population Setting N Outcomes measured (Scholes et al 2007) High Patients with injuries Outpatient setting, 227 Severity of PTSD symptoms sustained as a result of a UK Depression road traffic accident, an Anxiety occupational injury or an assault, and diagnosed with Quality of life ASD Attrition
There is evidence suggesting there is unlikely to be a clinically important difference between providing a self-help booklet and no information on reducing the severity of self-reported PTSD symptoms at post-treatment (k = 1; n = 120; SMD = ‒0.02 95%CI ‒0.38, 0.34). There is evidence suggesting there is unlikely to be a clinically important difference between providing a self-help booklet and no information on reducing the severity of depression at post-treatment (k = 1; n = 120; SMD = 0.00 95%CI ‒0.36, 0.36). There is evidence suggesting there is unlikely to be a clinically important difference between providing a self-help booklet and no information on reducing the severity of anxiety at post- treatment (k = 1; n = 120; SMD = 0.05 95%CI ‒0.31, 0.41). There is evidence suggesting there is unlikely to be a clinically important difference between providing a self-help booklet and no information on reducing the quality of life (physical health) at post-treatment (k = 1; n = 120; SMD = 0.24 95%CI ‒0.12, 0.60). There is evidence suggesting there is unlikely to be a clinically important difference between providing a self-help booklet and no information on reducing the quality of life (social relationships) at post-treatment (k = 1; n = 120; SMD = 0.06 95%CI ‒0.30, 0.42). There is evidence suggesting there is unlikely to be a clinically important difference between providing a self-help booklet and no information on reducing the attrition rate at post- treatment (k = 1; n = 227; RR = 1.13 95%CI 0.86, 1.50). There is evidence suggesting there is unlikely to be a clinically important difference between providing a self-help booklet and no information on reducing the attrition rate at 6 months follow-up (k = 1; n = 227; RR = 1.05 95%CI 0.84, 1.32). Box 24 Evidence statement matrix for RCT comparing providing a self help booklet and no information in treating people with acute PTSD or ASD Component Rating Description
Evidence base D One level II study with a high risk of bias
Consistency N/A Only one study
74 Clinical impact D There were no clinically important or statistically significant difference between providing a self-help booklet and providing no information on reducing the severity of PTSD, depression, anxiety, quality of life or attrition rate.
Generalisability A Population consisted of patients with injuries sustained as a result of a road traffic accident, an occupational injury or an assault, and diagnosed with ASD
Applicability B The study was conducted in the UK, which has comparable healthcare for patients exposed to potentially traumatic events compared to the Australian healthcare context.
Summary of evidence Limited evidence suggested that there is unlikely to be a clinical benefit for treatment with a self-help booklet compared to no information in reducing the severity of PTSD symptoms, depression, anxiety, and attrition rate, and improving the quality of life post-treatment. The attrition rate was too high to determine the effectiveness of treatment at 6 months. (Grade D)
TRAUMA-FOCUSED CBT VERSUS SUPPORTIVE COUNSELLING Three RCTs (5 publications) investigated the effectiveness of CBT compared to supportive psychotherapy (or supportive counselling) in people who had experienced motor vehicle accidents, industrial accidents or nonsexual assaults within the previous month and met the DSM-IV criteria for ASD (Table 21). The fourth RCT included females who had experienced a sexual or non-sexual assault in the past month and met the DSM-IV criteria (except duration) for PTSD (Table 21). CBT involved prolonged exposure, cognitive restructuring, and anxiety management. The patients randomised to CBT treatment received either five 90- minute or four 2-hour weekly sessions (a total time of 7.5‒8 hours of therapy), starting within the first month for either all (Bryant et al 1998; Bryant et al 2003b; Bryant et al 1999)or most patients (Bryant et al 2005; Bryant et al 2006; Foa et al 2006). Patients in the control group received supportive counselling for an equivalent time period; which included nondirective counselling and general problem solving. PTSD-related outcomes were reported post- treatment, at 3‒6 months follow-up and at 1‒4 years follow-up. Clinically important differences favouring the trauma-focused CBT over supportive counselling were reported on reducing the likelihood of having a PTSD diagnosis post- treatment and at 3-6 months. Additionally, clinically important differences were seen for reducing the likelihood of having a PTSD diagnosis at 1-4 years, the severity of PTSD symptoms post-treatment, and anxiety at 3-6 months if supportive counselling is considered an active treatment, but these were unimportant if supportive counselling is considered to be an inactive control. There were also statistically significant differences favouring trauma- focused CBT over supportive counselling in reducing the severity of PTSD symptoms at 3-6 months and anxiety post-treatment but the effect size was too small to be clinically important. The funnel plot indicates that there could potentially be some publication bias as all studies are skewed to the left and one falls well outside the 95% confidence limits (Appendix H). However, this may be a reflection of the moderate heterogeneity (57.2%) between studies, although this does not reach statistical significance (p = 0.072).
75 Table 21 Study profiles for RCTs comparing trauma focused CBT and supportive counselling in treating people who were recently exposed to trauma and were diagnosed with acute PTSD or ASD Reference Risk of bias Population Setting N Outcomes measured (Bryant et al 2003b) Moderate Patients involved in an MVA, PTSD unit, NSW 80 Diagnosis of PTSD 4-year follow-up of industrial accident or Australia Severity of PTSD symptoms nonsexual assaults within the Bryant et al (1998) Attrition and Bryant et al past 2 weeks and diagnosed (1999) with ASD
(Bryant et al 2005) Moderate Patients involved in either an PTSD unit, NSW 57 Diagnosis of PTSD MVA or nonsexual assaults Australia Severity of PTSD symptoms within the past month and Depression diagnosed with ASD Anxiety End-state functioning Attrition (Bryant et al 2006) Diagnosis of PTSD Severity of PTSD symptoms Depression Attrition (Bryant et al 1998) Moderate Patients involved in either an PTSD unit, NSW 24 Diagnosis of PTSD MVA or industrial accidents Australia Severity of PTSD symptoms within the past 2 weeks and Depression diagnosed with ASD Anxiety (Foa et al 2006) High Females that survived sexual Center for the 60 Diagnosis of PTSD and nonsexual assaults within Treatment and Severity of PTSD symptoms the last month and met all the Study of Anxiety, Depression criteria for PTSD except USA duration Anxiety End-state functioning Attrition (Bryant et al 1999) High Patients involved in either an PTSD unit, NSW 38 Diagnosis Of PTSD MVA or nonsexual assaults Australia Severity of PTSD symptoms within the past 2 weeks and Depression diagnosed with ASD Anxiety Attrition
CBT vs supportive counselling PTSD diagnosis post-treatment
76 There is limited evidence favouring trauma-focused CBT over supportive counselling on reducing the likelihood of having a clinician-rated PTSD diagnosis post-treatment (k = 4; n = 164; RR = 0.55, 95%CI 0.37, 0.81).
CBT vs supportive counselling PTSD diagnosis 3-6m
The funnel plot indicates that there could potentially be some publication bias as all studies are skewed towards the left and two studies fall outside the 95% confidence limits (Appendix H). However, this may be a reflection of the moderate heterogeneity (39.3%) between studies, although this does not reach statistical significance (p = 0.176). There is limited evidence favouring trauma-focused CBT over supportive counselling on reducing the likelihood of having a clinician-rated PTSD diagnosis at 3-6 months follow-up (k = 4; n = 161; RR = 0.57, 95%CI 0.39, 0.84).
CBT vs supportive counselling PTSD diagnosis 1-4y
The funnel plot shows that all studies are skewed to the left and one falls just outside the 95% confidence limits, indicating that there is potential for publication bias.
77 There is limited evidence favouring trauma-focused CBT over supportive counselling on reducing the likelihood of having a clinician-rated PTSD diagnosis at 1-4 years follow-up (k = 3; n = 197; RR = 0.73, 95%CI 0.52, 1.04). CBT vs supportive counselling PTSD severity (clinician) post-treatment
There is limited evidence favouring trauma-focused CBT over supportive counselling on reducing the severity of clinician-rated PTSD symptoms post-treatment (k = 2; n = 91; SMD = –0.65, 95%CI –1.08, –0.23).
CBT vs supportive counselling PTSD severity (clinician) 3-6m
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between trauma-focused CBT and supportive counselling on reducing the severity of clinician-rated PTSD symptoms at 3-6 months follow-up (k = 2; n = 88; SMD = –0.42, 95%CI –0.85, 0.00).
78 CBT vs supportive counselling PTSD severity (clinician) 1-3y
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between trauma-focused CBT and supportive counselling on reducing the severity of clinician-rated PTSD symptoms at 1-3 years follow-up (k = 2; n = 81; SMD = –0.24, 95%CI –0.68, 0.20).
CBT vs supportive counselling PTSD severity (self) post-treatment
The funnel plot indicates that there could potentially be some publication bias as one study falls just outside the 95% confidence limits (Appendix H). However, this may be a reflection of the moderate heterogeneity (57.4%) in the forest plot above, although this does not reach statistical significance (p = 0.096). There is limited evidence favouring trauma-focused CBT over supportive counselling on reducing the severity of self-reported PTSD symptoms post-treatment (k = 3; n = 125; SMD = –0.60, 95%CI –0.97, –0.24).
79 CBT vs supportive counselling PTSD severity (self) 3-6m
The funnel plot indicates that there is no publication bias (Appendix H). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between trauma-focused CBT and supportive counselling on reducing the severity of self-reported PTSD symptoms at 3-6 months follow-up (k = 3; n = 119; SMD = –0.44, 95%CI –0.81, –0.07). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between trauma-focused CBT and supportive counselling on reducing the severity of self-reported PTSD symptoms at 1 year follow-up (k = 1; n = 46; SMD = 0.18, 95%CI –0.76, 0.40).
CBT vs supportive counselling depression post-treatment
The funnel plot indicates that there is no publication bias (Appendix H). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between trauma-focused CBT and supportive counselling on reducing depression post-treatment (k = 3; n = 125; SMD = –0.28, 95%CI –0.64, 0.07).
80 CBT vs supportive counselling depression 3-6m
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between trauma-focused CBT and supportive counselling on reducing depression (self-reported measures) at 3-6 months follow-up (k = 3; n = 119; SMD = –0.27, 95%CI –0.63, 0.10). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between trauma-focused CBT and supportive counselling on reducing depression (self-reported measures) at 1 year follow-up (k = 1; n = 46; SMD = –0.08, 95%CI –0.66, 0.50). CBT vs supportive counselling anxiety post-treatment
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between trauma-focused CBT and supportive counselling on reducing anxiety post-treatment (k = 3; n = 124; SMD = ‒0.43, 95%CI –0.79, ‒0.07).
81 CBT vs supportive counselling anxiety 3-6m
There is limited evidence favouring trauma-focused CBT over supportive counselling on reducing anxiety at 3-6 months follow-up (k = 3; n = 119; SMD = –0.52, 95%CI –0.89, – 0.15). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between trauma-focused CBT and supportive counselling on reducing anxiety at 1 year follow-up (k = 1; n = 45; SMD = –0.42, 95%CI –1.01, 0.17).
CBT vs supportive counselling attrition post-treatment
There is limited evidence favouring supportive counselling over trauma-focused CBT on reducing the attrition rate post-treatment (k = 4; n = 179; RR = 2.02, 95%CI 1.05, 3.87).
82 CBT vs supportive counselling attrition 3-6m
There is limited evidence favouring supportive counselling over trauma-focused CBT on reducing the attrition rate at 3-6 months follow-up (k = 4; n = 179; RR = 1.33, 95%CI 0.81, 2.18). CBT vs supportive counselling attrition 1-4y
There is limited evidence favouring supportive counselling over trauma-focused CBT on reducing the attrition rate at 1-4 years follow-up (k = 3; n = 197; RR = 1.21, 95%CI 0.83, 1.74). Box 25 Evidence statement matrix for RCTs comparing trauma-focused CBT and supportive counselling in treating people who were recently exposed to trauma and were diagnosed with acute PTSD or ASD Component Rating Description
Evidence base C Three level II studies with a moderate risk of bias and two level II studies with a high risk of bias
Consistency A All studies were consistent for all outcomes
Clinical impact C There was limited evidence favouring TF-CBT on PTSD diagnosis at all time points, and severity of PTSD (both clinician-rated and self-rated) immediately post-treatment, although not at follow-ups. Most other outcomes were inconclusive suggestive of no difference.
83 Generalisability A Population consisted of adults recovering from motor vehicle accidents, industrial accidents, sexual or non-sexual assaults
Applicability A Three studies were conducted in Australia and is therefore directly applicable to the Australian healthcare context and one study was conducted in the USA and is probably applicable to Australian healthcare context with some caveats.
Summary of evidence There is limited evidence showing a clinical benefit favouring trauma-focused CBT over supportive counselling for reducing the likelihood of having a PTSD diagnosis at any time point, the severity of PTSD symptoms post-treatment, and anxiety at 3-6 months. Most outcomes showed no differences between the treatments (Grade C)
TRAUMA-FOCUSED CBT VERSUS PSYCHOEDUCATION Foa et al. (2006) investigated the effectiveness of CBT and a psychoeducation program in preventing PTSD-related outcomes in adult females who had experienced a sexual or non- sexual assault in the past month and met the DSM-IV criteria (except duration) for PTSD. The trauma-focused CBT intervention consisted of four 2-hour weekly sessions that included education, breathing/ relaxation training, imaginal and in vivo exposure, and cognitive restructuring. The psychoeducation program was referred to as an assessment condition and consisted of four weekly sessions of two hours, involved no detailed discussion of the traumatic event and was delivered by PTSD clinicians. It focused on a thorough assessment of each of the PTSD symptoms in the interview version of the PTSD Symptom Scale, and the effect of the assault on functioning (work, home, social, leisure, and intimate relationship domains) using the Social Adjustment Scale. PTSD-related outcomes were reported post- treatment, at 3 months and at 1 year follow-up. There were no clinically important or statistically significant differences between trauma-focused CBT and psychoeducation reported.
Table 22 Study profile for RCT comparing trauma focused CBT and psychoeducation in treating people who were recently exposed to trauma and were diagnosed with acute PTSD or ASD Reference Risk of bias Population Setting N Outcomes measured (Foa et al 2006) High Females that survived sexual Center for the 61 Diagnosis of PTSD and nonsexual assaults Treatment and Severity of PTSD symptoms within the last month and met Study of Anxiety, Attrition all the criteria for PTSD USA except duration
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between trauma-focused CBT and psychoeducation on reducing the likelihood of having a clinician-rated PTSD diagnosis at post-treatment (k = 1; n = 42; RR = 0.83, 95%CI 0.46, 1.51), at 3 months follow-up (k = 1; n = 40; RR = 0.72, 95%CI 0.40, 1.43) or at 1 year follow-up (k = 1; n = 61; RR = 1.08, 95%CI 0.51, 2.27). There is evidence suggesting there is unlikely to be a clinically important difference between trauma-focused CBT and psychoeducation on having a clinically significant change in self- reported PTSD symptoms post-treatment (k = 1; n = 41; RR = 0.95, 95%CI 0.82, 1.16), at 3 months follow-up (k = 1; n = 38; RR = 1.06, 95%CI 0.91, 1.16), or at 1 year follow-up (k = 1; n = 42; RR = 1.07, 95%CI 0.88, 1.25).
84 Box 26 Evidence statement matrix for RCT comparing trauma focused CBT and psychoeducation in treating people who were recently exposed to trauma and were diagnosed with acute PTSD or ASD Component Rating Description
Evidence base D One level II study with a high risk of bias
Consistency N/A Only one study
Clinical impact D No clinically important differences
Generalisability A Population consisted of women recovering from sexual and nonsexual assaults within the last month who met all the criteria for PTSD except duration
Applicability C The study was conducted in USA and is probably applicable to Australian healthcare context with some caveats.
Summary of evidence The limited evidence suggested that there was no clinical benefit when patients with ASD were treated using trauma-focused CBT over a psychoeducational intervention for either PTSD diagnosis or change in symptoms. (Grade C)
TRAUMA-FOCUSED CBT VERSUS PROLONGED EXPOSURE One study compared the effectiveness of trauma-focused CBT and prolonged exposure (PE), a component of CBT, in patients who survived motor vehicle accidents or nonsexual assaults in the last two weeks and were diagnosed with ASD (Bryant et al 1999). The authors predicted that in treating ASD, CBT would result in fewer PTSD symptoms than PE. Both interventions included prolonged exposure and cognitive restructuring, but only the CBT group received anxiety management (exercises to manage anxiety-producing situations and graded in vivo exposure to avoided situations). PE was supplemented with supportive counselling to ensure that sessions were of equal time and that there was equal prolonged exposure training in both groups. PTSD-related outcomes were reported post-treatment and at 6 months follow-up. Clinically important differences favouring CBT over PE for reducing the likelihood of having a diagnosis of PTSD post-treatment and at 6 months, and increasing the likelihood of having a clinically-significant improvement in anxiety post-treatment were reported but they did not reach statistical significance. Conversely, there was a clinically important difference favouring PE over CBT in increasing the likelihood of having a clinically-significant improvement in anxiety at 6 months but this also did not reach statistical significance. The evidence statements, RR or SMD for each relevant outcome and the evidence matrix (Box 27) are presented below.
Table 23 Study profile for RCT comparing trauma focused CBT and PE in treating people who were recently exposed to trauma and were diagnosed with acute PTSD or ASD Reference Risk of bias Population Setting N Outcomes measured (Bryant et al 1999) High Patients involved in either an PTSD unit, NSW 37 Diagnosis Of PTSD MVA or nonsexual assaults Australia Severity of PTSD symptoms within the past 2 weeks and Depression diagnosed with ASD Anxiety
85 There is limited evidence favouring trauma-focused CBT over PE on reducing the likelihood of having a diagnosis of PTSD at post-treatment (k = 1; n = 37; RR = 1.42, 95%CI 0.31, 6.81) and at 6 months follow-up (k = 1; n = 37; RR = 1.42, 95%CI 0.31, 6.81). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between trauma-focused CBT and PE on increasing the likelihood of having a clinically-significant improvement in the severity of self-reported PTSD symptoms (Impact of Events scales, intrusion and avoidance) at post-treatment (k = 1; n = 37; RRIES-I = 1.14, 95%CI 0.68, 1.90; RRIES-A = 0.95, 95%CI 0.53, 1.70) and at 6 months follow-up (k = 1; n = 37; RRIES-I = 1.18, 95%CI 0.62, 2.30; RRIES-A = 0.84, 95%CI 0.42, 1.69). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between trauma-focused CBT and PE on increasing the likelihood of having a clinically-significant improvement in depression at post-treatment (k = 1; n = 37; RR = 0.95, 95%CI 0.24, 3.82). There is limited evidence favouring PE over trauma-focused CBT on increasing the likelihood of having a clinically-significant improvement in depression at 6 months follow-up (k = 1; n = 37; RR = 0.63, 95%CI 0.13, 2.94). There is limited evidence favouring trauma-focused CBT over PE on increasing the likelihood of having a clinically-significant improvement in anxiety post-treatment (k = 1; n = 37; RR = 1.26, 95%CI 0.56, 2.94). There is limited evidence favouring PE over trauma-focused CBT on increasing the likelihood of having a clinically-significant improvement in anxiety at 6 months follow-up (k = 1; n = 37; RR = 0.79, 95%CI 0.29, 2.09). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between trauma-focused CBT and PE on the attrition rate post- treatment (k = 1; n = 37; RR = 0.95, 95%CI 0.29, 3.12) or at 6 months follow-up (k = 1; n = 37; RR = 1.14, 95%CI 0.43, 3.07). Box 27 Evidence statement matrix for RCT comparing trauma focused CBT and PE in treating people who were recently exposed to trauma and were diagnosed with acute PTSD or ASD Component Rating Description
Evidence base D One level II study with a high risk of bias
Consistency N/A Only one study
Clinical impact C Some outcomes had clinically important point estimates favouring PE whilst some favoured CBT, others inconclusive
Generalisability A Population consisted of adults involved in either an MVA or nonsexual assaults within the past 2 weeks and diagnosed with ASD
Applicability A The study was conducted in Australia and is therefore directly applicable to the Australian healthcare context
Summary of evidence There was limited evidence favouring CBT over prolonged exposure in reducing the likelihood of having a PTSD diagnosis post-treatment and at 6 months, and in reducing anxiety post-treatment. Conversely, there was limited evidence favouring prolonged exposure over CBT for increasing the likelihood of having a clinically-significant improvement in
86 depression and anxiety scores at 6 months. However, these differences did not reach statistical significance. (Grade C)
COGNITIVE RESTRUCTURING VERSUS PROLONGED EXPOSURE Two studies compared components of CBT (cognitive restructuring and prolonged exposure) against each other. Bryant et al. (2008a) conducted an RCT in Australia in patients who had been exposed to recent trauma (a nonsexual assault or motor vehicle accident in the previous month) and had a primary diagnosis of ASD, while Shalev et al (2011) conducted an RCT in Israel in patients with unspecified trauma causing them to go to an emergency department (with the majority having a motor vehicle accident, followed by experiencing terrorism), resulting in acute PTSD. PE treatment included psychoeducation, breathing control training, imaginal and in vivo exposure, plus instruction on relapse prevention strategies. Cognitive restructuring therapy involved psychoeducation, monitoring and modifying of thoughts and affective states such as guilt about one’s behaviour, plus instruction on relapse prevention strategies. Bryant et al. (2008a) reported adverse effects in five patients; three patients became overly distressed during PE therapy with two discontinuing treatment, and two patients became overly distressed during cognitive restructuring therapy and proceeded to drop out. Bryant et al (2008a) reported clinically important and statistically significant differences favouring PE over cognitive restructuring were reported in reducing the likelihood of having a PTSD diagnosis, depression and anxiety post-treatment and at 6 months and a reduction of PTSD symptoms at 6 months. These results were contradictory to those reported by Shalev et al (2011) which showed no difference on the outcomes of PTSD diagnosis (21.6% after prolonged exposure, and 20.0% after cognitive therapy†), or on severity of PTSD (SMD=0.08, 95%CI -0.35, 0.52). The reasons for these differences are unclear.
Table 24 Study profile for RCT comparing cognitive restructuring, PE and wait listed control in treating people who were recently exposed to trauma and were diagnosed with acute PTSD or ASD Reference Risk of bias Population Setting N Outcomes measured (Shalev et al 2011) Moderate Unspecified trauma (MVA, Outpatient setting, 158 Diagnosis of PTSD terrorism, work incident or Israel Severity of PTSD symptoms other)
(Bryant et al 2008a) Moderate Patients that had PTSD unit, NSW 90 Diagnosis Of PTSD experienced a nonsexual Australia Severity of PTSD symptoms assault or motor vehicle Depression crash in the previous month and were diagnosed with Anxiety ASD Adverse effects
There is limited evidence favouring PE over cognitive restructuring on reducing the likelihood of having a diagnosis of PTSD at post-treatment (k = 1; n = 60; RR = 1.90, 95%CI 1.10, 3.29) and at 6 months follow-up (k = 1; n = 60; RR = 1.73, 95%CI 1.03, 2.90).
† Due to inconsistencies within the data presented, data from Shalev et al (2011) could not be incorporated into the evidence statement on the likelihood of having a PTSD diagnosis.
87
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between cognitive restructuring and prolonged exposure on the severity of PTSD post-treatment (k = 2, n = 144, SMD=0.22, 95%CI -0.11, 0.55). There is limited evidence favouring PE over cognitive restructuring on reducing the severity of clinician-rated PTSD symptoms at 6 months follow-up (k = 1; n = 60; SMD = 0.60, 95%CI 0.08, 1.11). There is limited evidence favouring PE over cognitive restructuring on reducing the severity of depression at post-treatment (k = 1; n = 60; SMD = 0.54, 95%CI 0.01, 1.05) and at 6 months follow-up (k = 1; n = 60; SMD = 0.60, 95%CI 0.09, 1.12). There is limited evidence favouring PE over cognitive restructuring on reducing the severity of anxiety at post-treatment (k = 1; n = 60; SMD = 0.67, 95%CI 0.15, 1.19) and at 6 months follow-up (k = 1; n = 60; SMD = 0.63, 95%CI 0.11, 1.15). There is limited evidence favouring cognitive restructuring over PE on reducing the number of adverse events during treatment (k = 1; n = 60; RR = 1.50, 95%CI 0.31, 7.32). There is evidence favouring PE over cognitive restructuring on reducing the attrition rate post-treatment (k = 1; n = 60; RR = 0.71, 95%CI 0.26, 1.93).
Box 28 Evidence statement matrix for RCT comparing cognitive restructuring and PE in treating people who were recently exposed to trauma and were diagnosed with acute PTSD or ASD Component Rating Description
Evidence base C Two level II studies with a moderate risk of bias
Consistency C Bryant et al (2008a) showed larger benefits from PE than cognitive restructuring, whereas Shalev et al (2011) found no clinically important difference between the two. The reason for the difference is unclear.
Clinical impact C Most outcomes from one study had clinically important point estimates favouring PE over cognitive restructuring. No clinically important difference on outcome measure of PTSD diagnosis or severity (clinician-rated) from second study.
Generalisability A Population of Australian study consisted of adults involved in either an MVA or nonsexual assaults within the past 2 weeks and diagnosed with ASD. Other study included patients with trauma from predominantly
88 motor vehicle accidents, which would be generalisable.
Applicability A One study was conducted in Australia and is therefore directly applicable to the Australian healthcare context. Other study performed in Israel – unclear how applicable.
Summary of evidence There was contradictory evidence regarding whether prolonged exposure was clinically beneficial compared to cognitive restructuring or not. There were fewer adverse events with cognitive restructuring than with prolonged exposure but the attrition rate was higher, although these differences did not reach statistical significance. (Grade C)
PROLONGED EXPOSURE VERSUS DELAYED PROLONGED EXPOSURE In a further comparison, Shalev et al (2011) compared prolonged exposure starting within a month of trauma, against delayed prolonged exposure, administered approximately 5 months after the trauma. Patients were recruited using emergency department records from a hospital in Israel, and had acute PTSD at study intake, resulting predominantly from motor vehicle accidents.
Table 25 Study profile for RCT comparing PE and delayed PE in treating people who were recently exposed to trauma and were diagnosed with acute PTSD Reference Risk of bias Population Setting N Outcomes measured (Shalev et al 2011) Moderate Unspecified trauma (MVA, Outpatient setting, 104 Diagnosis of PTSD terrorism, work incident or Israel Severity of PTSD symptoms other)
The evidence is inconclusive, and so it is not possible to determine whether there is a clinically important difference between PE versus delayed PE on the likelihood of having a PTSD diagnosis post-treatment (k=1, n=104, RR=0.97, 95%CI 0.46, 2.05)
There is evidence suggesting that there is unlikely to be a clinically important difference between PE and delayed PE on the severity of PTSD symptoms post-treatment (k=1, n=105, SMD=-0.12, 95%CI -0.50, -0.27). Box 29 Evidence statement matrix for RCT comparing PE and waitlist in treating people who were recently exposed to trauma and were diagnosed with acute PTSD or ASD Component Rating Description
Evidence base C One level II study with a moderate risk of bias
Consistency NA Only one study
Clinical impact D No clinically important differences found between early prolonged exposure (starting within one month of trauma) versus delayed prolonged exposure (starting 5 months post-trauma)
Generalisability B Majority of patients had acute PTSD due to motor vehicle accidents, which would be generalisable to Australia. Unclear how generalisable trauma due to terrorism would be.
Applicability C Healthcare system in Israel likely different to Australian healthcare system, but evidence possibly still applicable.
89 Summary of evidence There was evidence suggesting that prolonged exposure administered early (starting within one month of trauma) was equally effective as prolonged exposure administered after a delay (starting five months after a trauma) in patients with acute PTSD. (Grade C)
PROLONGED EXPOSURE VERSUS SUPPORTIVE COUNSELLING One study compared the effectiveness of PE and supportive counselling in patients who had survived motor vehicle accidents or nonsexual assaults in the last two weeks and were diagnosed with ASD (Bryant et al 1999). PTSD-related outcomes were reported post- treatment and at 6 months follow-up. The differences favouring PE over supportive counselling were clinically important and statistically significant in reducing the likelihood of having a PTSD diagnosis post-treatment and at 6 months, and increasing the likelihood of having a clinically-significant improvement in PTSD symptoms and anxiety post-treatment. The point estimates favouring PE over supportive counselling were also clinically important in increasing the likelihood of having a clinically-significant improvement in PTSD symptoms and anxiety at 6 months, but this did not reach statistical significance. The evidence statements, RR or SMD for each relevant outcome and the evidence matrix (Box 30) are presented below.
Table 26 Study profile for RCT comparing PE and supportive counselling in treating people who were recently exposed to trauma and were diagnosed with acute PTSD or ASD Reference Risk of bias Population Setting N Outcomes measured (Bryant et al 1999) High Patients involved in either an PTSD unit, NSW 38 Diagnosis Of PTSD MVA or nonsexual assaults Australia Severity of PTSD symptoms within the past 2 weeks and Depression diagnosed with ASD Anxiety Attrition
There is limited evidence favouring PE over supportive counselling on reducing the likelihood of having a diagnosis of PTSD at post-treatment (k = 1; n = 38; RR = 0.33, 95%CI 0.11, 0.94) and at 6 months follow-up (k = 1; n = 38; RR = 0.33, 95%CI 0.11, 0.94). There is limited evidence favouring PE over supportive counselling on increasing the likelihood of having a clinically-significant improvement in self-reported PTSD symptoms (Impact of Events Scale, Intrusions and Avoidance scales) at post-treatment (k = 1; n = 38; RRIES-I = 2.00, 95%CI 1.00, 4.08; RRIES-A = 2.50, 95%CI 1.03, 6.58). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between PE and supportive counselling on increasing the likelihood of having a clinically-significant improvement in PTSD symptoms (self-reported IES-Intrusion) at 6 months follow-up (k = 1; n = 38; RR = 1.11, 95%CI 0.59, 2.08). There is limited evidence favouring PE over supportive counselling on increasing the likelihood of having a clinically-significant improvement in PTSD symptoms (self-reported IES-Avoidance) at 6 months follow-up (k = 1; n = 38; RR = 2.67, 95%CI 0.92, 8.51). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between PE and supportive counselling on increasing the likelihood of having a clinically-significant improvement in depression at post-treatment (k = 1; n = 38; RR = 1.00, 95%CI 0.25, 5.07) or at 6 months follow-up (k = 1; n = 38; RR = 1.00, 95%CI 0.18, 5.43).
90 There is limited evidence favouring PE over supportive counselling on increasing the likelihood of having a clinically-significant improvement in anxiety at post-treatment (k = 1; n = 38; RR = 4.00, 95%CI 1.15, 15.81) and at 6 months follow-up (k = 1; n = 38; RR = 2.50, 95%CI 0.63, 10.68). There is limited evidence favouring supportive counselling over PE on reducing the attrition rate post-treatment (k = 1; n = 38; RR = 1.33, 95%CI 0.37, 4.95) and at 6 months follow-up (k = 1; n = 37; RR = 1.50, 95%CI 0.53, 4.45). Box 30 Evidence statement matrix for RCT comparing PE and supportive counselling in treating people who were recently exposed to trauma and were diagnosed with acute PTSD or ASD Component Rating Description
Evidence base D One level II study with a high risk of bias
Consistency N/A Only one study
Clinical impact C Limited evidence for clinically important benefits of PE over supportive counselling, with some inconclusive outcomes
Generalisability A Population consisted of adults involved in either an MVA or nonsexual assaults within the past 2 weeks and diagnosed with ASD
Applicability A The study was conducted in Australia and is therefore directly applicable to the Australian healthcare context
Summary of evidence There was limited evidence favouring prolonged exposure over supportive counselling in reducing the likelihood of having a PTSD diagnosis, in increasing the likelihood of having a clinically-significant improvement in PTSD symptoms and anxiety post-treatment and at 6 months. (Grade C)
NARRATIVE EXPOSURE THERAPY VERSUS RELAXATION-MEDITATION IN CHILDREN WITH PRELIMINARY PTSD
One study investigated the effectiveness of using short-term narrative exposure therapy compared to a meditation-relaxation therapy immediately after a mass disaster (tsunami) in a population of child refugees already affected by prior conflicts and crisis (Catani et al 2009). The children included in this study all met the diagnostic criteria for preliminary PTSD according to the UCLA PTSD Index for DSM-IV (UPID) used in interview form. Both treatments consisted of six sessions applied by local counsellors lasting for 60-90 minutes over a two-week period starting approximately three weeks after the tsunami. During narrative exposure therapy, the child and therapist construct a detailed chronological account of the child’s own biography. Particular attention is given to traumatic experiences related to the tsunami, as well as earlier events linked to violence and war situations and is corrected and filled with more details with each reading to help transform the reports into a coherent narrative to be given to the child. The child is also encouraged to talk about current and past emotional, physiological, cognitive, and behavioural reactions. Meditation-relaxation therapy started with psychoeducation and an assessment of the child's current problems. Sessions also consisted of breathing exercises, and different meditation and relaxation techniques and exercises. PTSD outcomes and physical problems were assessed 1 and 6 months after receiving the therapy.
91 Although there were clinically important differences favouring narrative exposure therapy over meditation-relaxation therapy in reducing the likelihood of having a PTSD diagnosis at 1 month and 6 months, it did not reach statistical significance. Conversely, there was a clinically important difference favouring meditation-relaxation therapy over narrative exposure therapy in reducing physical problems but this was also not statistically significant. The evidence statements, RR or SMD for each relevant outcome and the evidence matrix (Box 31) are presented below.
Table 27 Study profiles for RCT comparing narrative exposure therapy and relaxation-meditation therapy in treating children exposed to recent trauma and who developed preliminary PTSD Reference Risk of bias Population Setting N Outcomes measured (Catani et al 2009) Moderate Children aged 8–14 years, field setting in a 31 Diagnosis of PTSD that had been living in a refugee camp in Severity of PTSD symptoms refugee camp in northern Sri Sri Lanka Functioning problems Lanka, which was completely destroyed by the 2004 Physical problems tsunami
There is limited evidence favouring narrative exposure therapy over meditation-relaxation therapy on reducing the likelihood of having a diagnosis of PTSD at 1 month follow-up (k = 1; n = 31; RR = 0.75, 95%CI 0.25, 2.21), and at 6 months follow-up (k = 1; n = 31; RR = 0.56, 95%CI 0.16, 1.83). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between narrative exposure therapy and meditation-relaxation therapy on reducing the severity of clinician-rated PTSD symptoms at 1 month follow-up (k = 1; n = 31; SMD = –0.01, 95%CI –0.72, 0.69), and at 6 months follow-up (k = 1; n = 31; SMD = 0.25, 95%CI –0.46, 0.96). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between narrative exposure therapy and meditation-relaxation therapy on reducing psychosocial functioning problems at 1 month follow-up (k = 1; n = 31; SMD = – 0.33, 95%CI –1.04, 0.38), or at 6 months follow-up (k = 1; n = 31; SMD = –0.29, 95%CI – 1.00, 0.42). There is limited evidence favouring meditation-relaxation therapy over narrative exposure therapy on reducing physical problem at 1 month follow-up (k = 1; n = 31; SMD = 0.68, 95%CI –0.05, 1.40). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between narrative exposure therapy and meditation-relaxation therapy on reducing physical problems at 6 months follow-up (k = 1; n = 31; SMD = 0.16, 95%CI – 0.55, 0.86). Box 31 Evidence statement matrix for RCT comparing narrative exposure therapy and relaxation-meditation therapy in treating children exposed to recent trauma and who developed preliminary PTSD Component Rating Description
Evidence base C One level II study with a moderate risk of bias
Consistency N/A Only one study
92 Clinical impact D The point estimates favouring narrative exposure therapy over meditation-relaxation therapy were clinically important in reducing the likelihood of having a PTSD diagnosis at 1 month and 6 months, but the confidence intervals included clinically unimportant effects. The point estimate favouring meditation- relaxation therapy over narrative exposure therapy was clinically important in reducing physical problems but the confidence intervals included clinically unimportant effects.
Generalisability D Population consisted of child refugees already affected by prior conflicts and crisis that survived a tsunami. Difficult to determine how generalisable to the target population.
Applicability D The study was conducted in Sri Lanka and is therefore unlikely to be directly applicable to the Australian healthcare context.
Summary of evidence Limited evidence from one small study suggested that narrative exposure therapy was beneficial in reducing the number of children diagnosed with PTSD at 1 and 6 months post- intervention when compared to meditation-relaxation therapy. Conversely, there was limited evidence that meditation-relaxation therapy reduced the severity of physical problems at 1 month follow-up when compared to narrative exposure therapy. However, the full range of plausible estimates outlined by the confidence intervals included clinically unimportant effects and effects in the opposite direction. (Grade D)
PSYCHOEDUCATION VERSUS SUPPORTIVE COUNSELLING Foa et al. (2006) investigated the effectiveness of a psychoeducation program compared to supportive counselling in preventing PTSD-related outcomes in adult females who had experienced a sexual or non-sexual assault in the past month and met the DSM-IV criteria (except duration) for PTSD. The psychoeducation program was referred to as an assessment condition and consisted of four weekly sessions of two hours, involved no detailed discussion of the traumatic event and was delivered by PTSD clinicians. It focused on a thorough assessment of each of the PTSD symptoms in the interview version of the PTSD Symptom Scale, and the effect of the assault on functioning (work, home, social, leisure, and intimate relationship domains) using the Social Adjustment Scale. Supportive counselling consisted of four 2-hour weekly sessions of active listening only, with no discussion of assault-related symptoms. PTSD-related outcomes were reported post-treatment, at 3 months and at 1 year follow-up. The differences favouring psychoeducation over supportive counselling in reducing the likelihood of having a PTSD diagnosis at 1 year and having a clinically-significant change in PTSD symptoms post-treatment were clinically important, but there were no statistically significant clinical benefits for psychoeducation compared to supportive counselling for any outcome measured. The evidence statements, RR or SMD for each relevant outcome and the evidence matrix (Box 32) are presented below.
Table 28 Study profile for RCT comparing psychoeducation and supportive counselling in treating people who were recently exposed to trauma and were diagnosed with acute PTSD or ASD Reference Risk of bias Population Setting N Outcomes measured (Foa et al 2006) High Females that survived sexual Center for the 59 Diagnosis of PTSD and nonsexual assaults Treatment and Severity of PTSD symptoms within the last month and met Study of Anxiety, Attrition all the criteria for PTSD USA except duration
93 The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between psychoeducation and supportive counselling on reducing the likelihood of having a PTSD diagnosis at post-treatment (k = 1; n = 43; RR = 1.05, 95%CI 0.60, 1.80), or at 3 months follow-up (k = 1; n = 40; RR = 1.23, 95%CI 0.64, 2.31). There is limited evidence favouring psychoeducation over supportive counselling on reducing the likelihood of having a PTSD diagnosis at 1 year follow-up (k = 1; n = 59; RR = 0.73 95%CI 0.36, 1.44). There is limited evidence favouring psychoeducation over supportive counselling on having a clinically significant change in self-reported PTSD symptoms at post-treatment (k = 1; n = 43; RR = 1.29 95%CI 0.95, 1.53). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between psychoeducation and supportive counselling on reducing the likelihood of having a PTSD diagnosis at 3 months follow-up (k = 1; n = 38; RR = 1.13 95%CI 0.87, 1.35). There is evidence suggesting there is unlikely to be a clinically important difference between psychoeducation and supportive counselling on having a clinically significant change in self- reported PTSD symptoms at 1 year follow-up (k = 1; n = 44; RR = 0.97, 95%CI 0.80, 1.18).
Box 32 Evidence statement matrix for RCT comparing psychoeducation and supportive counselling in treating people who were recently exposed to trauma and were diagnosed with acute PTSD or ASD Component Rating Description
Evidence base D One level II study with a high risk of bias
Consistency N/A Only one study
Clinical impact D Limited evidence favouring psychoeducation over supportive counselling on reducing the likelihood of having PTSD at 1 year follow-up, and self-rated PTSD symptoms post-treatment, but other time-points and outcomes were inconclusive.
Generalisability A Population consisted of women recovering from sexual and nonsexual assaults within the last month who met all the criteria for PTSD except duration
Applicability C The study was conducted in USA and is probably applicable to Australian healthcare context with some caveats.
Summary of evidence There was limited evidence suggesting that psychoeducation was beneficial in reducing the likelihood of having a PTSD diagnosis at 1 year, or a clinically-significant change in PTSD symptoms post-treatment, when compared to supportive counselling. (Grade C)
EMDR VERSUS DELAYED EMDR TREATMENT
Jarero et al. (2011) investigated the effectiveness of eye movement desensitization reprocessing (EMDR) compared to a delayed treatment condition in employees of a private company living in the area affected by a 7.2 magnitude earthquake. The employees underwent a crisis management briefing intervention and undertook the IES questionnaire. The employees who scored more than 44 were than randomised to an immediate single session EMDR treatment or delayed treatment. The EMDR group received treatment 16 days
94 after the earthquake and those who were waitlisted received treatment four days later. IES scores for participants in the EMDR treatment and delayed EMDR treatment groups were reported for post-treatment and 12 weeks follow-up.
When the wait listed control group received delayed EMDR treatment, no significant differences between the two treatment groups were reported. The evidence statements, RR or SMD for each relevant outcome and the evidence matrix comparing immediate and delayed EMDR treatment (Box 33) are presented below.
Table 29 Study profile for RCT comparing immediate EMDR treatment and delayed EMDR treatment for people with acute PTSD or ASD Reference Risk of bias Population Setting N Outcomes measured (Jarero et al 2011) Moderate Employees of a private Field setting, 18 Severity of PTSD symptoms company living in the area Mexico affected by a major earthquake who had IES scores > 44 2 weeks after the event.
IES = Impact of Events Scale; STAI = State-Trait Anxiety Inventory.
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between immediate and delayed EMDR on reducing the severity of self- reported PTSD symptoms at post-treatment (k = 1; n = 18; SMD = ‒0.09, 95%CI –1.01, 0.84), or at 12 weeks follow-up (k = 1; n = 18; SMD = ‒0.02, 95%CI –0.94, 0.90). Box 33 Evidence statement matrix for RCT comparing immediate and delayed EMDR in treating people with acute PTSD or ASD Component Rating Description
Evidence base C One level II study with a moderate risk of bias
Consistency N/A Only one study
Clinical impact D No clinically important differences
Generalisability B Population consisted of employees of a private company living in the area affected by a major earthquake who had an IES score > 44, 2 weeks after the event.
Applicability D The study was conducted in Mexico and is therefore unlikely to be directly applicable to the Australian healthcare context.
Summary of evidence Limited evidence from a small study with a moderate risk of bias suggested that immediate and delayed EMDR were equally effective in reducing the severity of PTSD symptoms post- treatment and at 12 weeks. (Grade D)
CAREGIVER-CHILD PSYCHOSOCIAL AND STRESS MANAGEMENT INTERVENTION VERSUS CHILD SUPPORTIVE COUNSELLING AND PSYCHOEDUCATION One study would have met the inclusion criteria for question 24 had the population been in children with PTSD. This study included children aged between 7 and 17 who had experienced a potentially traumatic event (such a motor vehicle accident, sexual or physical assault, witnessing violence, etc), and endorsed at least one new symptom of PTSD within
95 one month of the event (Berkowitz et al 2011). They compared a Child and Family Traumatic Stress Intervention (CFTSI) against a child-only intervention which provided supportive counselling and psychoeducation. The CFTSI aims to increase communication between the affected child and their caregiver, in order to increase caregivers’ support of the child. It also teaches specific behavioural skills to assist in coping with symptoms. Both the intervention and control condition occurred over 4 sessions. Berkowitz et al (2011) provided data in the format of least square means and standard error, so standard evidence statements could not be constructed. On the basis of logistic regression, the authors reported that children in the CFTSI condition had a significantly less chance of having PTSD at 3 month follow-up than those in the child-only intervention, with 65% reduced odds. Post-treatment, the Post Traumatic Stress (PTS) subscale on the Trauma Symptom Checklist for Children (TSCC) was lower in the CFTSI condition (least square mean=42.97, SE=1.37) than the comparison group (least square mean=46.12, SE=1.33). This difference was statistically significant. {Berkowitz, 2011, 20868370} Table 30 Study profile for RCT comparing caregiver-child psychosocial and stress management intervention versus supportive counselling and psychoeducation Reference Risk of bias Population Setting N Outcomes measured (Berkowitz et al Moderate Children and youth aged 7 – Outpatient 106 Diagnosis of PTSD 2011) 17, exposed to potentially setting, United Severity of PTSD symptoms traumatic event, with at least States one symptom of PTSD within 30 days of trauma
Box 34 Evidence statement matrix for RCT comparing caregiver-child psychosocial and stress management intervention versus supportive counselling and psychoeducation Component Rating Description
Evidence base C One level II study with a moderate risk of bias
Consistency N/A Only one study
Clinical impact D The limited data available suggest a clinical impact on the likelihood of diagnosis of PTSD and severity of PTSD symptoms.
Generalisability B Good generalisability – children/youth exposed to a mix of traumas
Applicability C The study was conducted in the United States, so likely to be applicable to the Australian healthcare system with some caveats.
Summary of evidence One moderate quality study provided evidence suggesting that an intervention aimed at increasing caregiver support is more beneficial than child-only psychoeducation and supportive counselling, but further data is required in order to determine if the difference is clinically important. (Grade C).
96 Pharmacological interventions
Box 35 Study selection criteria for research question 5 and 6
Research Question 5. For people exposed to trauma, do early pharmacological interventions improve outcomes compared to no intervention? 6 For people exposed to trauma, does any early pharmacological intervention confer any advantage over other early pharmacological interventions? Selection criteria Inclusion criteria Population People exposed to trauma, including the subgroup of patients with ASD Intervention Early pharmacological intervention, (eg imipramine, propranolol, benzodiazepines, other sympatholytics, other antidepressants, anticonvulsants, antipsychotics, chloral hydrate, given within one month of trauma) Comparator No intervention (eg assessment only) Outcome Primary outcomes: symptoms of ASD or PTSD Secondary outcomes: symptoms of depression, anxiety and substance misuse/ social and occupational function/ quality of life/ treatment refusal/ dropout over 12 months/ side effects/ posttraumatic growth/ physical comorbidity. Additional outcomes for children: attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies are found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies. Search Period 8/2005-10/2011 for adultsa ; possibly 1966-10/2011 if requiredb 1966-10/2011 for children and adolescentsc Language English aUpdated search from 2007 Guidelines bExpanded search period if fewer than two Level II studies are found c New research questions
Early intervention drug treatments for PTSD There are few trials of early intervention drug treatments and only two studies met the inclusion criteria for question 5. The results of the review of these studies are summarised below. There were no studies comparing the effectiveness of one early pharmacological intervention against another (Question 6). Both included studies were in adult population. ESCITALOPRAM VERSUS PLACEBO One small double-blind study with a low risk of bias compared the use of escitalopram (a selective serotonin reuptake inhibitor; SSRI) against placebo, in a group of patients with acute PTSD, recruited by contacting consecutive patients from an Israeli emergency department (Shalev et al 2011). All patients were administered one table daily for one week (either 10mg escitalopram or placebo), followed by two tablets daily for 11 weeks. Patients were also given weekly sessions with a psychiatrist for the first 4 weeks, followed by sessions with the psychiatrist every second week, for weeks 6 to 12. The content of these sessions with the psychiatrist was not stated by Shalev et al (2011). Adverse events were not mentioned in the article by Shalev et al (2011) so it is unknown how the rate of adverse events compared between the SSRI and placebo. No significant differences were found between escitalopram or placebo on the likelihood of having PTSD or the severity of PTSD post-treatment.
Table 31 Study profile for RCT comparing escitalopram and placebo in treating people who were recently exposed to trauma and were diagnosed with acute PTSD Reference Risk of bias Population Setting N Outcomes measured
97 (Shalev et al 2011) Low Unspecified trauma (MVA, Outpatient setting, 39 Diagnosis of PTSD terrorism, work incident or Israel Severity of PTSD symptoms other)
The evidence is inconclusive, and so it is not possible to determine whether there is a clinically important difference between escitalopram and placebo on the likelihood of having a PTSD diagnosis post-treatment (k=1, n=39, RR=0.85, 95%CI 0.51, 1.44).
There is evidence suggesting there is no clinically important difference between escitalopram and placebo on the severity of PTSD symptoms (clinician-rated) post-treatment (k=1, n=39, SMD=0.06, 95%CI -0.57, 0.69).
Box 36 Evidence statement matrix for RCT comparing escitalopram and placebo in treating people who were recently exposed to trauma and were diagnosed with acute PTSD or ASD Component Rating Description
Evidence base B One level II study with a low risk of bias
Consistency NA Only one study
Clinical impact D No significant differences found between escitalopram and placebo.
Generalisability B Majority of patients had acute PTSD due to motor vehicle accidents, which would be generalisable to Australia. Unclear how generalisable trauma due to terrorism would be.
Applicability C Healthcare system in Israel likely different to Australian healthcare system, but evidence possibly still applicable.
Summary of evidence One small study with a low risk of bias found no clinically important differences between escitalopram (SSRI) and placebo in patients recently exposed to trauma, with acute PTSD. (Grade C).
PROPRANOLOL VERSUS PLACEBO One study (Pitman et al 2002) compared propranolol and placebo. Propranolol is a beta- adrenoceptor blocker and crosses the blood–brain barrier. This trial was based on a priori hypotheses about the role of the amygdala in the development of PTSD. Participants were administered propranolol (40 mg four times a day) or placebo, beginning within 6 hours of the traumatic event. This study was considered to be at a high risk of bias as only 11/18 (61%) of those randomised to propranolol returned for the 1 month assessment, and results were based only on treatment completers.
Table 32 Study profiles for RCTs comparing propranolol and placebo for people with acute PTSD Reference Risk of bias Population Setting N Outcomes measured (Pitman et al 2002) High Unspecified trauma Emergency 41 PTSD diagnosis (70-72% motor vehicle Department, United PTSD severity accidents) States
98 The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between propranolol and placebo on reducing the likelihood of having a PTSD diagnosis at 1 month (k=1; n=41; RR=1.14, 95% CI 0.55, 2.35) or at 3 months’ follow-up (k=1; n=41; RR=1.28, 95% CI 0.69 to 2.38). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between propranolol and placebo on reducing the severity PTSD symptoms at 1 month (k=1; n=41; SMD=-0.39, 95%CI -1.1, 0.35).
Box 37 Evidence statement matrix for RCT comparing propanolol and placebo for people exposed to trauma Component Rating Description Evidence base D One level II study with a high risk of bias
Consistency NA Only one study
Clinical impact D No statistically significant or clinically important differences detected between placebo and propanolol.
Generalisability B Results likely to be generalisable to the Australian trauma population.
Applicability C Evidence probably applicable to the Australian healthcare context with some caveats (from the United States)
Summary of evidence One small study with a high risk of bias assessed propanolol versus placebo for people exposed to trauma and found no clinically important differences between the two. (Grade D)
HYDROCORTISONE VERSUS PLACEBO One study (Schelling et al 2001) explored the effect of hydrocortisone (a corticosteroid) and placebo on the reactions to the intense physical and psychological stress during septic shock in the intensive care environment. Studies of hydrocortisone are of particular interest given the evidence of disturbance in the HPA axis in PTSD.
Table 33 Study profiles for RCTs comparing hydrocortisone and placebo for people with acute PTSD Reference Risk of bias Population Setting N Outcomes measured (Schelling et al High Septic shock Intensive care unit, 20 PTSD diagnosis 2001) Germany
There is limited evidence suggesting a difference favouring hydrocortisone over placebo on reducing the likelihood of having a PTSD diagnosis at approximately 31 months after treatment (k=1; n=20; RR=0.17, 95% CI 0.03 to 1.17). II
Box 38 Evidence statement matrix for RCT comparing hydrocortisone and placebo for people exposed to trauma Component Rating Description Evidence base D One small level II study with a high risk of bias due to high loss to follow-up from original sample
Consistency NA Only one study
Clinical impact C Relatively large difference in the risk of having PTSD between groups (1/9 in hydrocortisone group and 7/11 in control group), but study too small to make any strong conclusions. Generalisability B Results likely to be generalisable to the Australian trauma population.
99 Applicability B Evidence applicable to the Australian healthcare context with some caveats (from Germany)
Summary of evidence One small study found limited evidence favouring the administration of hydrocortisone over placebo at reducing the likelihood of having a PTSD diagnosis at follow-up, when administered to people exposed to trauma. (Grade D)
SERTRALINE VERSUS PLACEBO IN CHILDREN AND ADOLESCENTS One small double-blind study with a high risk of bias, due to lack of ITT analysis and a high loss to follow-up, compared the effectiveness of sertraline and placebo at preventing the onset of PTSD symptoms in children and adolescents (mean age 12.4±3.7 years) who had acute burn injuries, or who were undergoing reconstructive burn surgery (Stoddard et al 2011). The external generalisability of this study is limited, as there were 70 cases (73% of those approached) who met the inclusion criteria, where either the parent or child/adolescent were not comfortable with participating.
Patients were started on a dose of 25 mg/day, on a flexible fixed schedule, and increased as high as 150 mg/day. Treatment occurred over 24 weeks, with tapering to reduce the dose by 25 mg/day every 3 days after the initial 12 weeks of treatment. No standard deviations were provided in the article by Stoddard et al (2011), so effect sizes were not able to be calculated. By the end of the 24 weeks of treatment, PTSD symptom severity, as rated on parents on the Diagnostic Interview Schedule for Children and Adolescents (DICA) was reduced from a mean of 10.2 to 6.2 in the sertraline group, and from 7.0 to 6.8 in the control group (difference in change: p<0.05). Mean child rated symptom severity (on the DICA) showed less difference between sertraline and placebo, reducing from 8.8 to 4.3 in the sertraline group, and from 10.0 to 6.8 in the placebo group. The only outcome measure that was reported to be statistically significant was the reduction in depression, which was 7.5 points on the Child Depression Inventory (CDI) in the sertraline group, and a reduction of 2.4 in the placebo group (p<0.001). It is unknown whether these differences are clinically important.
Adverse events were noted in one boy who had tremors, and who experienced suicidal ideation when stressed with his mother. 2011, SN101}
Table 34 Study profiles for RCT comparing sertraline and placebo for children and adolescents exposed to trauma Reference Risk of bias Population Setting N Outcomes measured (Stoddard et al High Children and Inpatient and 26 Severity of PTSD symptoms (parent and 2011) adolescents with acute outpatient setting, child rated) burns of undergoing United States Depressive symptoms reconstructive burn surgery
Box 39 Evidence statement matrix for RCT comparing hydrocortisone and placebo for children/adolescents exposed to trauma Component Rating Description Evidence base D One small level II study with a high risk of bias due to high loss to follow-up and only completer-data provided Consistency NA Only one study
100 Clinical impact D Little difference between sertraline and placebo on child rated PTSD severity. Larger difference in change found on parent-rated PTSD severity, but final scores very similar. A statistically significant difference in reduction in depressive symptoms Generalisability B Population were children and adolescents with acute burns or undergoing reconstructive burn surgery. Likely to be generalisable to the broader target population. Applicability C Healthcare setting in United States likely to be applicable with some caveats.
Summary of evidence One small study in children and adolescents exposed to trauma found statistically significant differences in the reduction of depressive symptoms and parent-rated PTSD symptoms between sertraline and placebo. However, there was no statistically significant difference on child-rated PTSD symptom severity, and it is unknown whether any of these differences were clinically important. (Grade D)
101 Single vs multiple interventions
Box 40 Study selection criteria for research question 7
Research Question 7. For people exposed to trauma, is a single early intervention more effective than multiple early interventions? Selection criteria Inclusion criteria Population People exposed to trauma, including the subgroup of patients with ASD Intervention Single early psychological or pharmacological intervention Comparator Early combined psychological or combined pharmacological interventions (within one month of the traumatic event) or combined psychological and pharmacological interventions (within one month of the traumatic event) Outcome Primary outcomes: symptoms of ASD or PTSD Secondary outcomes: symptoms of depression, anxiety and substance misuse/ social and occupational function/ quality of life/ treatment refusal/ dropout over 12 months/ side-effects/ posttraumatic growth/ physical comorbidity. Additional outcomes for children: attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies are found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies. Search Period 8/2005-10/2011 for adultsa , 1966-10/2011 if requiredb 1966-10/2011 for children and adolescentsc Language English aUpdated search from 2007 Guidelines. b expanded search period if less than two Level II studies are found c New research questions
Three RCTs meeting the inclusion criteria were identified by a systematic search of the literature. One study compared the effectiveness of an educational intervention with debriefing plus education in preventing PTSD-related outcomes in all people who had been assaulted in the previous month (Rose et al 1999). Two studies (3 articles) investigated the effectiveness of combining trauma-focused CBT with either acupoint stimulation or hypnosis compared to CBT alone (Bryant et al 2005; Bryant et al 2006; Zhang et al 2011).
EDUCATION VERSUS DEBRIEFING PLUS EDUCATION
One study compared the effectiveness of using a 30 min educational intervention on its own or in combination with debriefing in individuals who were assaulted 9–31 days prior to receiving the intervention (Rose et al 1999). Education consisted of a 30 min session related to the individual’s experiences and information on when and where to find help, and included a specially written leaflet. Education was delivered by a therapist whose qualifications were not described. Debriefing was loosely based on the Critical Incident Stress Debriefing model by Mitchell (1983) and aimed at encouraging participants to verbalize a full narrative account of the trauma, including facts, cognitions and feelings. Outcomes were reported at 6 months post-intervention. There were no statistically significant differences between education and debriefing plus education. However, the point estimate favouring education over debriefing plus education in reducing the likelihood of having a PTSD diagnosis at 6 months was clinically important.
Table 35 Study profile for RCT comparing education and debriefing plus education in treating people recently exposed to trauma Reference Risk of bias Population Setting N Outcomes measured
102 (Rose et al 1999) High Adult victims of a violent Outpatient setting, 157 PTSD diagnosis crime within the past month United Kingdom Severity of PTSD symptoms Depression
There is limited evidence favouring education over debriefing plus education on reducing the likelihood of having a PTSD diagnosis at 6 months follow-up (k = 1; n = 106; RR = 0.47, 95%CI 0.18, 1.21). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between education and debriefing plus education on reducing the severity of self-reported PTSD symptoms at 6 months follow-up (k = 1; n = 92; SMD = –0.15, 95%CI –0.56, 0.26). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between education and debriefing plus education on reducing the severity of depression at 6 months follow-up (k = 1; n = 92; SMD = –0.20, 95%CI ‒0.61, 0.21). Box 41 Evidence statement matrix for RCT comparing education and debriefing plus education in treating people recently exposed to trauma Component Rating Description
Evidence base D One level II study with a high risk of bias
Consistency N/A Only one study
Clinical impact D One clinically important point estimate favouring education but other outcomes inconclusive.
Generalisability A Population consisted of victims of violent crimes
Applicability B The study was conducted in the UK, which has comparable healthcare for patients exposed to potentially traumatic events compared to the Australian healthcare context.
Summary of evidence There was limited evidence favouring the educational intervention alone over combining education with debriefing on reducing the likelihood of having a PTSD diagnosis at 6 months follow-up, but no difference in the effectiveness of education alone and debriefing plus education on reducing the severity of PTSD symptoms or depression in people exposed to potentially traumatic violent crimes. (Grade C)
CBT VERSUS CBT PLUS ACUPOINT STIMULATION
One study investigated the effectiveness of adding acupoint stimulation to CBT in reducing the emotional reactions to recalling horrifying scenes, in people who either were buried under rubble or suffered the loss of loved ones in the aftermath of a severe earthquake in China(Zhang et al 2011). Both randomised groups received CBT for 30 minutes every second day for one week, starting 8-12 days after the earthquake had struck. During these sessions patients were encouraged to describe the earthquake scene and their experiences of being buried or rescuing their relatives, the most unforgettable and most horrifying scenes they experienced and their feelings. Following the prolonged exposure, cognitive restructuring was used to help patients deal with these experiences. One of the two groups also received acupoint stimulation at Laogong (PC 8; located on left palm) using a 50 Hz stimulator for 30
103 minutes every other day for 1 week. There was some discomfort associated with acupoint stimulation for some patients, but they were able to tolerate the slight numbness in their left palm. A clinically important and statistically significant difference favouring CBT plus acupoint stimulation over CBT was reported on reducing the severity of PTSD symptoms post-treatment, but no longer-term follow-up was undertaken. It is unknown whether a similar effect would be found in an Australian population. The evidence statement, SMD and evidence matrix (Box 42) are presented below.
Table 36 Study profile for RCT comparing trauma focused CBT either alone or in combination with acupoint stimulation in treating people who were recently exposed to trauma and were diagnosed with acute PTSD or ASD Reference Risk of bias Population Setting N Outcomes measured (Zhang et al 2011) Moderate Patients who either were buried Field study, 91 Severity of PTSD symptoms or lost loved ones during a China strong earthquake and diagnosed with preliminary PTSD
IES-R = Impact of Events Scale-revised
There is evidence favouring CBT plus acupoint stimulation over CBT alone on reducing the severity of self-reported PTSD symptoms at post-treatment (k = 1; n = 90; SMD = 1.21, 95%CI 0.71, 1.71).
Box 42 Evidence statement matrix for RCT comparing trauma focused CBT either alone or in combination with acupoint stimulation in treating people who were recently exposed to trauma and were diagnosed with acute PTSD or ASD Component Rating Description Evidence base C One level II study with a moderate risk of bias
Consistency N/A Only one study
Clinical impact B Clinically important benefit for addition of acupoint stimulation to CBT for self-reported PTSD symptoms
Generalisability C Population consisted of people who either were buried or lost loved ones during a strong earthquake
Applicability D The study was conducted in a field setting in China, which has different healthcare for patients exposed to potentially traumatic events compared to the Australian healthcare context.
Summary of evidence The evidence favoured the addition of acupoint stimulation to CBT on reducing the severity of PTSD symptoms post-treatment, but as no long-term follow-up was conducted, the durability of this treatment beyond one week cannot be determined. (Grade C)
CBT VERSUS CBT PLUS HYPNOSIS
One study published in two articles investigated the effectiveness of the addition of hypnosis to CBT for the treatment of ASD in people who were involved in either motor vehicle accidents or nonsexual assaults within the past month (Bryant et al 2005; Bryant et al 2006). Patients were randomised to receive five once weekly 90-minute sessions of CBT with or without hypnosis. CBT involved psychoeducation, imaginal exposure and cognitive restructuring. The CBT protocol was modified for patients receiving hypnosis such that prior to each imaginal exposure exercise, they listened to a 15-minute audiotape that described a
104 hypnotic induction. This included suggestions for focused attention and muscle relaxation so that patients could engage fully in the CBT exposure exercises. There were no clinically important or statistically significant differences comparing CBT alone and CBT plus hypnosis on reducing the likelihood of having a PTSD diagnosis, severity of PTSD symptoms, depression or anxiety reported. The evidence statements, RR or SMD for each relevant outcome and the evidence matrix (Box 43) are presented below.
Table 37 Study profiles for RCT comparing CBT either alone or in combination with hypnosis in treating people who were recently exposed to trauma and were diagnosed with acute PTSD or ASD Reference Risk of bias Population Setting N Outcomes measured (Bryant et al 2005) Moderate Patients involved in either a PTSD unit, NSW 63 Diagnosis of PTSD MVA or nonsexual assaults Australia Severity of PTSD symptoms within the past month and Depression diagnosed with ASD Anxiety Attrition (Bryant et al 2006) Diagnosis of PTSD Severity of PTSD symptoms Depression Attrition
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between CBT alone and CBT plus hypnosis on reducing the likelihood of having a PTSD diagnosis at post-treatment (k = 1; n = 63; RR = 1.21, 95%CI 0.61, 2.48), at 6 months follow-up (k = 1; n = 63; RR = 1.06, 95%CI 0.59, 1.92), or at 3 years follow-up (k = 1; n = 63; RR = 0.84, 95%CI 0.48, 1.49). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between CBT alone and CBT plus hypnosis on reducing the severity of self-reported PTSD symptoms (Impact of Events Scale; Intrusions and Avoidance subscales) at post-treatment (k = 1; n = 63; SMDIES-I = 0.46, 95%CI ‒0.04, 0.96; SMDIES-A = ‒0.31, 95%CI ‒0.80, 0.19), or at 6 months follow-up (k = 1; n = 63; SMDIES-I = 0.31, 95%CI ‒0.19, 0.81; SMDIES-A = ‒0.16, 95%CI ‒0.65, 0.34). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between CBT alone and CBT plus hypnosis on reducing the severity of clinician-rated PTSD symptoms at 3 years follow-up (k = 1; n = 37; SMD = 0.03, 95%CI ‒ 0.67, 0.62). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between CBT alone and CBT plus hypnosis on reducing the severity of depression at post-treatment (k = 1; n = 63; SMD = 0.19, 95%CI ‒0.31, 0.68), at 6 months follow-up (k = 1; n = 63; SMD = 0.10, 95%CI ‒0.40, 0.59), or at 3 years follow-up (k = 1; n = 37; SMD = 0.14, 95%CI ‒0.51, 0.78). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between CBT alone and CBT plus hypnosis on reducing the severity of anxiety at post-treatment (k = 1; n = 63; SMD = ‒0.04, 95%CI ‒0.54, 0.45), or at 6 months follow-up (k = 1; n = 63; SMD = ‒0.11, 95%CI ‒0.60, 0.39). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between CBT alone and CBT plus hypnosis on the attrition rate post- treatment (k = 1; n = 63; RR = 1.17, 95%CI 0.51, 2.75) or at 3 years follow-up (k = 1; n = 63; RR = 1.06, 95%CI 0.59, 1.92).
105
Box 43 Evidence statement matrix for RCT comparing CBT either alone or in combination with hypnosis in treating people who were recently exposed to trauma and were diagnosed with acute PTSD or ASD Component Rating Description Evidence base C One level II study with a moderate risk of bias Consistency N/A Only one study Clinical impact D The point estimates comparing CBT alone and CBT plus hypnosis on reducing the likelihood of having a PTSD diagnosis, severity of PTSD symptoms, depression or anxiety were not clinically important and the differences were not statistically significant. Generalisability A Population consisted of people involved in either a MVA or nonsexual assaults within the past month and diagnosed with ASD Applicability A The study was conducted in Australia and is therefore directly applicable to the Australian healthcare context.
Summary of evidence The limited evidence showed no clinical benefit for the addition of hypnosis to CBT compared to CBT alone when treating ASD in people who had experienced a motor vehicle accident of a nonsexual assault. There were no clinically or statistically significant differences between groups in the likelihood of having a PTSD diagnosis, the reduction of the severity of PTSD symptoms, depression or anxiety post-treatment, at 6 months or at 3 years. (Grade C)
106 School-based interventions
In those exposed to trauma / with ASD
Box 44 Study selection criteria for research questions 8 and 9
Research Question 8. For children exposed to trauma, does any intervention delivered through school, improve outcomes for the child over no intervention? 9. For children exposed to trauma, does any intervention delivered through school, improve outcomes for the child compared to any other intervention delivered through school? Selection criteria Inclusion criteria Population Children exposed to trauma. Intervention Any intervention delivered through school. Comparator 1. No intervention. 2. Other intervention delivered through school. Outcome Primary outcome: resolution of symptoms of PTSD Secondary outcomes: resolution of symptoms of depression, anxiety and substance misuse/ social and occupational function / quality of life / treatment refusal/ dropout over 12 months/ posttraumatic growth/ oppositional defiant disorder / attention deficit hyperactivity disorder/ social anxiety disorder/ physical comorbidity. Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies are found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies. Search Period 1966-10/2011a Language English
a New research questions
Five RCTs meeting the a priori inclusion criteria for Question 8 were identified by a systematic search of the literature. No RCTs met inclusion criteria for Question 9 (see Box 44).
Of the five RCTs meeting inclusion criteria for Question 8, four studies with a moderate risk of bias compared cognitive behavioural therapy (CBT) with a waitlisted control group. Of these four RCTs, two were conducted in the United States among middle school-age children exposed to violence (Jaycox et al 2009; Stein et al 2003), one evaluated Nepalese school children affected by armed conflict (Jordans et al 2010), and one was a cluster trial of Indonesian children exposed to political violence (Tol et al 2008). For the two studies conducted in the United States, the interventions were defined explicitly as CBT; the main text of both these studies suggests similarity between the respective interventions, and that the CBT was trauma-focused. The studies conducted in Nepal and Indonesia were defined as (psychosocial) interventions that integrated CBT with cooperative play and creative- expressive exercises (drama, dance and/or music). Consequently, the US studies (see “Trauma-focused CBT versus waitlist”) have been presented separately from the non-US studies (see “CBT plus cooperative play versus waitlist”).
One RCT compared group supportive counselling with a waitlist control group. This study assessed war-exposed students with trauma related symptoms from across 18 primary and secondary schools in Israel (Shechtman & Mor 2010).
107 TRAUMA-FOCUSED CBT VERSUS WAITLIST
Jaycox et al (2009) investigated the effectiveness of the SSET Program (Support for Students Exposed to Trauma), a CBT-based program including imaginal exposure to trauma. The therapy comprised 10 sessions designed to reduce the symptoms of PTSD and depression, and to improve functioning in trauma-exposed youth. The sessions were delivered within a classroom group setting among sixth through eighth grade students attending two Los Angeles middle schools (mean age ± SD = 11.5±0.7 years). Students were eligible for study inclusion if they had experienced ‘severe violence in the prior year’ as indicated by response on the Life Experiences (LES) scale. Severe violence was defined as being the victim or witness of violence involving a gun or knife, or scoring three or greater on the LES scale. Core elements of the intervention included learning about common reactions to stress/trauma, relaxation training, cognitive coping, techniques to process/internally cope with traumatic memories and anxiety and social problem-solving.
The authors concluded that the results indicated that their CBT-based program contributed to small reductions in symptom severity among students. Comparison of the post-test continuous data provided no point estimates of effect size that indicated clinically important differences between the treatment groups according to cut-offs determined a priori for this review. However, the confidence intervals associated with the effect size analyses on PTSD and depression symptoms outcomes could not completely exclude clinically important effects, meaning that the evidence for clinically important differences between the treatment groups is therefore inconclusive on these outcomes. For behavioural problems (parent and teacher report) the confidence intervals included no clinically important values, and as such, there is evidence to suggest that there is unlikely to be a clinically important difference between CBT and waitlist on these outcomes (Jaycox et al 2009).
Another RCT (Stein et al 2003) also investigated the effectiveness of a CBT-based intervention among middle school students in Los Angeles (CBITS; Cognitive Behavioural Intervention for Trauma in Schools). The intervention comprised 10 CBT sessions, which included imaginal trauma exposure, delivered to groups of five to eight sixth grade students, and was designed to address symptoms of PTSD, anxiety and depression related to violence exposure. Main eligibility criteria and components of the CBT were similar to those noted above in regard to Jaycox et al (2009), and full details of these are provided in the relevant study table.
Stein and colleagues reported on a number of outcomes, but only PTSD and depressive symptoms (self report) and psychosocial dysfunction outcomes (parent report) were determined to be relevant for the purposes of this review. The authors reported that compared to waitlisted students, students in the intervention group experienced significantly fewer self and parent reported symptoms of trauma exposure. While the mean symptom score values provided support this conclusion, the confidence intervals were not included in the tabulated or main text of the paper, but were presented graphically on a scale with poor precision. Data used for meta-analyses are therefore based on a “best guess”.
Table 38 Study profiles for RCTs comparing trauma-focused CBT and waitlist Reference Risk of bias Population Setting N Outcomes measured (Jaycox et al 2009) Moderate Middle school 2 middle schools, 78 Self-reported symptoms of PTSD students exposed to United States students Depressive symptoms severe violence Parent and teacher-reported behavioural (Modified Life problems Experiences Scale
108 score >3 or victim/witness of gun/knife violence) (Stein et al 2003) Moderate Middle school 2 middle schools, 126 Self-reported symptoms of PTSD students exposed to United States students Depressive symptoms severe violence Parent-reported psychosocial dysfunction (Modified Life Experiences Scale score >3 or victim/witness of gun/knife violence)
There is limited evidence favouring CBT over waitlist on the severity of self report PTSD symptoms at post-treatment (k=2, n=202, SMD=-2.73, 95%CI -7.19, 1.74).
109 There is limited evidence favouring CBT over waitlist on the severity of depressive symptoms at post-treatment (k=2, n=202, SMD=-1.55, 95%CI -3.87, 0.77).
There is limited evidence favouring CBT over waitlist on parent-reported behavior problems post-treatment (k=2, n=202, SMD=-1.40, 95%CI -3.59, 0.78).
There is evidence suggesting that there is unlikely to be a clinically important difference between CBT and waitlist on reducing teacher-reported behavior problems at post-treatment (k=1, n=78, SMD=-0.13, 95%CI -0.32, 0.58).
Box 45 Evidence statement matrix for RCTs comparing trauma-focused CBT and waitlist Component Rating Description Evidence base C Two level II studies with a moderate risk of bias
Consistency D The studies were inconsistent in their size of effect, although consistent in direction of effect. The reason for the difference in size of effect is unknown. Clinical impact C One study found large clinically important effect sizes for PTSD symptoms severity, depressive symptoms and behaviour, while the other study found clinically unimportant effects on these same outcomes. Generalisability C Evidence not directly generalisable to the target population but could be sensibly applied
Applicability C Evidence probably applicable to Australian healthcare context with some caveats
Summary of evidence The evidence available to assess the effectiveness of trauma-focused CBT compared to waitlist among violence exposed children was of moderate quality and inconsistent. One study suggested clinically important differences on severity of PTSD symptoms, depressive symptoms and behaviour, while the other study found clinically unimportant effects on these same outcomes. (Grade C).
110 CBT PLUS COOPERATIVE PLAY VERSUS WAITLIST
The cluster RCT by Jordans et al (2010) assessed the effectiveness of a classroom-based group intervention among Nepalese school children exposed to armed conflict. The mean age of the children was 12.7 ± 1.04. While most (91%) reported being Hindu, the study authors acknowledged that the intervention and comparator groups differed significantly on gender, education, caste/ethnicity, religion and place of residence. The authors reported that the Child Psychosocial Distress Screener (CPDS) was used to screen for participation of children in the study, however no cut-off score by which eligibility could be met was specified. In addition to the objectives of reducing psychosocial problems and mal-adaptation, the intervention is also intended to facilitate resilience and empowerment through enhancement of coping, pro- social behaviour and hope. However, this review reports on the relevant outcomes, which included PTSD and depression symptoms, anxiety/emotional disorders, functional impairment, physical aggression and psychological difficulties.
Jordans et al (2010) reported statistically significant differences between changes on mean scores when the intervention and control groups were compared on several outcome measures and moderate effect sizes (Cohen’s d statistic) were found for function impairment, psychological difficulties and depression. Small effect sizes were reported for anxiety and PTSD outcomes. Despite these results, comparison of the relevant post-test continuous data provided no point estimates of effect size that indicated clinically important differences between the treatment groups according to cut-offs (Hedges’ g statistic) determined a priori for this review. The confidence intervals associated with the effect size analyses on all included outcomes completely excluded clinically important effects, and the evidence therefore suggests any clinically important differences between the treatment groups are unlikely.
Another cluster RCT (Tol et al 2008) was conducted among Indonesian school children exposed to political violence and compared the effectiveness of a classroom-based group intervention. Mean ages were 10.08 ± 1.39 and 9.78 ± 1.21 for the intervention and waitlist groups, respectively. The students were eligible if they attended a school within a district with known communal violence and if they had a score of 17 or greater on the CPSS. The intervention integrated CBT techniques with cooperative play and creative-expressive exercises (drama, dance, and music).
The study reported a reduction in symptoms of child reported PTSD, but concluded that there was no clinically meaningful reduction in symptoms of child reported depression and anxiety, nor a reduction in child or parent reported functional impairment. Based on Cohen’s d values calculated by the authors, none of the results indicated the likelihood of clinically important benefits for the CBT intervention according to criteria defined in the NICE guidelines (Tol et al 2008).
Table 39 Study profiles for RCTs comparing CBT plus cooperative play and waitlist Reference Risk of bias Population Setting N Outcomes measured (Jordans et al 2010) Moderate School-age children 8 schools, Nepal 325 Severity of PTSD symptoms affected by armed children Depression conflict Anxiety Function impairment Physical aggression Non-clinical psychological difficulties
111 (Tol et al 2008) Moderate School children 14 schools, Indonesia 403 Child-reported symptoms of PTSD and exposed to community children depression violence and with Child-reported anxiety related disorders score >17 on the Impairment and functioning CPSS
There is evidence suggesting that there is unlikely to be a clinically important difference between CBT plus cooperative play and waitlist on reducing the severity of child-reported PTSD symptoms at post-treatment (k=1, n=325, SMD=-0.18, 95%CI -0.40, -0.04).
There is evidence suggesting that there is unlikely to be a clinically important difference between CBT plus cooperative play and waitlist on reducing the severity of child-reported PTSD symptoms at post-treatment (k=1, n=403, SMD [Cohens’ d] =0.55, 95%CI 0.35, 0.75).
There is evidence suggesting that there is unlikely to be a clinically important difference between CBT plus cooperative play and waitlist on reducing the severity of depression symptoms at post-treatment (k=1, n=325, SMD=-0.37, 95%CI -0.59, -0.15).
There is evidence suggesting that there is unlikely to be a clinically important difference between CBT plus cooperative play and waitlist on reducing the severity of depression symptoms at post-treatment (k=1, n=403, SMD [Cohen’s d]=0.31, 95%CI 0.12, 0.51).
There is evidence suggesting that there is unlikely to be a clinically important difference between CBT plus cooperative play and waitlist on reducing the severity of anxiety related emotional disorders at post-treatment (k=1, n=325, SMD=0.09, 95%CI -0.12, 0.31).
There is evidence suggesting that there is unlikely to be a clinically important difference between CBT plus cooperative play and waitlist on reducing the severity of child-reported functional impairment at post-treatment (k=1, n=325, SMD=-0.35, 95%CI -0.57, -0.13).
There is evidence suggesting that there is unlikely to be a clinically important difference between CBT plus cooperative play and waitlist on reducing the severity of child-reported functional impairment at post-treatment (k=1, n=403, SMD [Cohen’s d]=0.42, 95%CI 0.22, 0.61).
There is evidence suggesting that there is unlikely to be a clinically important difference between CBT plus cooperative play and waitlist on reducing the severity of parent-reported functional impairment at post-treatment (k=1, n=403, SMD [Cohen’s d]=0.06, 95%CI -0.13, 0.25).
There is evidence suggesting that there is unlikely to be a clinically important difference between CBT plus cooperative play and waitlist on reducing physical aggression at post- treatment (k=1, n=325, SMD=0.39, 95%CI 0.17, 0.61).
There is evidence suggesting that there is unlikely to be a clinically important difference between CBT plus cooperative play and waitlist on reducing the severity of psychological difficulties at post-treatment (k=1, n=325, SMD=-0.19, 95%CI -0.41, -0.02).
112 Box 46 Evidence statement matrix for RCTs comparing CBT plus cooperative play and waitlist Component Rating Description Evidence base C Two level II studies with moderate risk of bias
Consistency A High
Clinical impact D No differences between CBT plus cooperative play and waitlist
Generalisability D Evidence not directly generalisable to the target population and hard to judge whether it is sensible to apply
Applicability D Evidence not applicable to Australian healthcare context
Summary of evidence The evidence available to assess the effectiveness of CBT plus cooperative compared to waitlist among conflict exposed children in developing countries was of moderate quality. For all included outcomes (self reported symptoms of PTSD and depression, self reported anxiety related emotional disorders and functional impairment, self reported physical aggression and psychological difficulties, and parent reported functional impairment) the evidence suggests that it is that a clinically important effect for the intervention is unlikely (Grade C).
GROUP SUPPORTIVE COUNSELLING VERSUS CONTROL Shechtman and Mor (2010) assessed the effectiveness of supportive counselling in small groups within a classroom setting, for Israeli children after the Lebanon war in 2006. The children were aged between 9 and 14, in grades 5 to 9, and were included in this cluster RCT if they met the cut-off score of at least 12 (mild trauma) on the Child Post-Traumatic Stress Reaction Index. The group intervention focused on expression and exploration of feelings in a supportive environment, to help children deal with their grief and mourning, exploring the subjective and objective nature of trauma, and reconstructing their personal narratives to integrate the trauma into their current lives.
The authors concluded that the results indicated that the supportive counselling was effective in reducing both PTSD symptoms and anxiety, however, a comparison of the post-test continuous data did not find any clinically important differences detected, using the cut-offs determined a priori for this systematic review. A comparison of those who met the clinical PTSD category of severe or very severe trauma symptoms vs no symptoms or mild symptoms or moderate symptoms, the point estimated of the risk of having severe-very severe symptoms post-treatment was found to be clinically superior to no treatment, although the result was not statistically given that the full range of plausible estimates crossed zero.
Table 40 Study profiles for RCT comparing group supportive counselling and control for children with symptoms of trauma Reference Risk of bias Population Setting N Outcomes measured (Shechtman & Mor High Children exposed to 18 schools, northern 164 PTSD diagnosis 2010) war-related or Israel Severity of PTSD symptoms divorse/loss-related Anxiety trauma
113 There is evidence favouring group supportive counselling over assessment only on PTSD diagnosis (severe or very severe symptoms) at post-treatment (k=1, n=107, RR=0.56, 95%CI 0.3, 1.05).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between group supportive counselling and assessment only on reducing the severity of self report PTSD symptoms at post-treatment (k=1, n=164, SMD=- 0.68, 95%CI: -1.09, 0.26).
There is evidence suggesting that there is unlikely to be a clinically important difference between group supportive counselling and assessment only on reducing the severity of anxiety at post-treatment (k=1, n=164, SMD=-0.20, 95%CI -0.56, 0.16).
Box 47 Evidence statement matrix for RCT comparing group supportive counselling and control for children with symptoms of trauma Component Rating Description Evidence base D One level II study with a high risk of bias due to school and counsellor differences, and no ITT analyses
Consistency NA Only one study
Clinical impact D Limited evidence to support the use of support groups on the dichotomous outcome of having severe- very severe trauma symptoms. No other clinically important differences detected Generalisability C Population studied differs from the target population of the guidelines, but it is clinically sensible to apply this evidence to the target population. School students exposed to war – may have relevance to refugee populations within Australia. Applicability C Evidence probably applicable to Australian school system, but with some caveats.
Summary of evidence Limited evidence suggested there may be a slight benefit in group supportive counselling compared to no intervention in children with trauma symptoms, given a clinically important difference in the number of children determined to have severe or very severe levels of PTSD symptoms. However, the benefit of group supportive counselling compared to assessment only was not determined to be clinically important on the continuous measure of severity of PTSD symptoms. (Grade D).
114 In those with PTSD
Box 48 Study selection criteria for research questions 10 and 11 (school setting)
Research Question 10. For people with PTSD do psychological interventions improve outcomes compared to no intervention? 11. For people with PTSD, does any psychological intervention confer any advantage over other psychological interventions? Selection criteria Inclusion criteria Population People with PTSD Intervention Psychological intervention (eg trauma-focused CBT, stress management therapy, EMDR, narrative exposure therapy, supportive counselling, interapy, thought field therapy) within a school setting Comparator 1. No intervention (eg assessment only) 2. Other psychological intervention Outcome Primary outcome: resolution of symptoms of PTSD Secondary outcomes: symptoms of depression, anxiety and substance misuse/ social and occupational function/ quality of life/ treatment refusal/ dropout over 12 months/ side-effects/ posttraumatic growth/ physical comorbidity Additional outcomes for children: attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies are found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies Search Period 8/2005-10/2011 for adultsa; 1966-10/2011 if requiredb 1966–10/2011 for children and adolescentsc Language English a Updated search from 2007 Guidelines b expanded search period if fewer than two Level II studies are found c New research questions CBT = cognitive behavioural therapy; EMDR = eye movement desensitisation and reprocessing
Two studies met the inclusion criteria for questions 10 and 11 as shown in Box 51, assessing the impact of class-room based treatments for adolescents with PTSD (Gordon et al 2008; Layne et al 2008). Two further studies included treatments on the school premesis (Chemtob et al 2002a; Salloum & Overstreet 2008) but have been included in other sections of this review (question 10 and question 12), as it was considered that they were not classroom- based.
STRESS MANAGEMENT VERSUS WAITLIST IN ADOLESCENTS One study assessed the benefit of a mind-body skills program within schools in Kosovo in 1999-2000. Students were screened for eligibility, and those who met PTSD criteria were randomised to either a mind-body skills group or the waitlist group. The intervention was held in small groups twice a week over 6 weeks, and included guided imagery, relaxation techniques, meditation, autogenic training and biofeedback. Self-expression through spoken and written word, drawings and movement was also encouraged, but discussions of specific traumas were not required. Self-care techniques were taught to decrease stress, increase cognitive and imaginative functioning, to try to give them skills to they could use in daily life deal with traumatic events. The mind-body skills groups occurred during school hours and were run by teachers who had received intensive but brief training. The authors explained that initially psychologists and psychiatrists were approached to perform the assessments and lead the focus groups, but the students mistrusted strangers, and feared the stigma attached to mental illness, leading them to be reluctant to speak openly with mental health professionals.
The mind-body skills group resulted in clinically important reductions in PTSD severity, which were maintained at 3 months follow-up. Follow-up data were provided for the
115 intervention group, but not for the waitlist group, who subsequently received the intervention.
Table 41 Study profiles for RCT comparing group stress management and waitlist for adolescents with PTSD Reference Risk of bias Population Setting N Outcomes measured (Gordon et al 2008) Moderate Adolescents with war- School setting, 82 Severity of PTSD related trauma, 5 Kosovo years after war had ended
There is limited evidence favouring group stress management over waitlist on reducing the severity of clinician-rated PTSD symptoms at post-treatment (k=1, n=82, SMD=-1.12, 95%CI -1.59, -0.64).
Box 49 Evidence statement matrix for RCT comparing group stress management and waitlist for adolescents with PTSD Component Rating Description Evidence base C One level II study with a moderate risk of bias. Teachers both conducted the intervention and also performed post-intervention questionnaires. Consistency N/A Only one study
Clinical impact B A substantial benefit was found on the ability of a group stress management intervention to reduce clinician-rated PTSD severity compared to waitlist. However, the full range of plausible estimates includes a benefit too small to be considered clinically important compared to waitlist. Generalisability C Population studied differs from the target population of the guidelines, but it is clinically sensible to apply this evidence to the target population. School students exposed to war – may have relevance to refugee populations within Australia. Applicability C Evidence probably applicable to Australian school system, but with some caveats.
Summary of evidence Limited evidence suggests that a group stress management program held for school children with PTSD reduces PTSD symptom severity compared to waitlist. (Grade C).
TRAUMA-FOCUSED CBT VERSUS PSYCHOEDUCATION AND STRESS MANAGEMENT IN ADOLESCENTS
One study assessed the effectiveness of a classroom-based, manualised trauma and grief component therapy for adolescents (TGCT) (Layne et al 2008). The comparison treatment was two out of four components of the TGCT, and included psychoeducation regarding common stress reactions, coping skills for management trauma and loss reminders, relaxation training, and skills training relating to regulation of emotions, social skills, and problem- solving skills. The complete TGCT intervention included additional unique components focused on the trauma experiences, distressing cognitions and preoccupations, and components promoting beneficial grieving and psychoeducation about processing grief, retrieving or constructing a nontraumatic memory/image of the deceased and reminiscing. Students were invited to participate in the study if they 1) had experienced significant trauma exposure prior to, during, and/or after the war, 2) were experiencing significant distress, especially severe symptoms of PTSD, depression, or traumatic grief, and 3) had significant functional impairment , including family or peer relationships and school performance.
116
This study was considered to be at a high risk of bias due to the lack of any blinding, measurement bias was not adequately controlled for (the intervention group received additional interviews), and the results presented included only those who completed treatment (excluding the 20% who were lost-to-follow-up).
Table 42 Study profiles for RCT comparing group trauma-focused CBT and psychoeducation and stress management skills in adolescents with PTSD Reference Risk of bias Population Setting N Outcomes measured (Layne et al 2008) High Adolescents exposed 10 secondary schools 159 Severity of PTSD to war in Bosnia Depressive symptoms
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between trauma-focused CBT and psychoeducation and stress management skills on reducing the severity of PTSD symptoms at post-treatment (k=1, n=127, SMD= -0.22, 95%CI -0.57, 0.13).
There is evidence suggesting that there is unlikely to be a clinically important difference between trauma-focused CBT and psychoeducation and stress management on reducing symptoms of anxiety at post-treatment (k=1, n=127, SMD=-0.1, 95%CI -0.45, 0.26).
Box 50 Evidence statement matrix for RCT comparing group trauma-focused CBT and psychoeducation and stress management skills in adolescents with PTSD Component Rating Description Evidence base D One level II study with a high risk of bias.
Consistency NA Only one study
Clinical impact D No additional benefit was found in grief and trauma specific components when added to the psychoeducation and stress management components of the trauma and grief component therapy for Adolescents (TGCT). Generalisability C Population studied differs from the target population of the guidelines, but it is clinically sensible to apply this evidence to the target population. School students exposed to war in Bosnia– may have relevance to refugee populations within Australia. Applicability C Evidence probably applicable to Australian school system, but with some caveats.
Summary of evidence Limited evidence suggests no clinically important benefit in specific trauma and grief components, over the psychoeducation and stress management components of the Trauma and Grief Component Therapy for Adolescents. (Grade D).
117 Interventions for people with PTSD
Psychological interventions
Box 51 Study selection criteria for research questions 10 and 11
Research Question 10. For people with PTSD do psychological interventions improve outcomes compared to no intervention? 11. For people with PTSD, does any psychological intervention confer any advantage over other psychological interventions? Selection criteria Inclusion criteria Population People with PTSD Intervention Psychological intervention (eg trauma-focused CBT, stress management therapy, EMDR, narrative exposure therapy, supportive counselling, interapy, thought field therapy) Comparator 1. No intervention (eg assessment only) 2. Other psychological intervention Outcome Primary outcome: resolution of symptoms of PTSD Secondary outcomes: symptoms of depression, anxiety and substance misuse/ social and occupational function/ quality of life/ treatment refusal/ dropout over 12 months/ side-effects/ posttraumatic growth/ physical comorbidity Additional outcomes for children: attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies are found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies Search Period 8/2005-10/2011 for adultsa; 1966-10/2011 if requiredb 1966–10/2011 for children and adolescentsc Language English a Updated search from 2007 Guidelines b expanded search period if fewer than two Level II studies are found c New research questions CBT = cognitive behavioural therapy; EMDR = eye movement desensitisation and reprocessing
In the previous NICE review and Australian update, waitlist conditions and treatment as usual were combined. However, treatment as usual frequently included interventions expected to be active, so have been separated from waitlist in this review. Where the authors defined the control condition as “treatment as usual”, these studies were put into sections using this heading, even if the majority of participants received another specific treatment. Treatment as usual and supportive counselling have been considered active interventions (ie comparisons against these treatments have been considered under question 11).
The following comparisons are discussed for question 10: x Twenty-nine studies compared trauma-focused CBT against a waitlist/control condition in adults (Basoglu et al 2007; Basoglu et al 2005; Bisson et al 2004; Blanchard et al 2003; Brom et al 1989; Cloitre et al 2002; Davidson et al 2005b; Duffy et al 2007; Ehlers et al 2005; Ehlers et al 2003; Fecteau & Nicki 1999; Foa et al 1999; Foa et al 1991; Gersons et al 2000; Keane et al 1989; Kubany et al 2003; Kubany et al 2004; Lindauer et al 2005; McDonagh et al 2005; Monson et al 2006; Pacella et al 2011; Power et al 2002; Resick et al 2002; Resick et al In press; Rothbaum et al 2005; Schnyder et al 2011; Sijbrandij et al 2007; Vaughan et al 1994; Wagner et al 2007) x Two studies compared trauma-focused CBT against a waitlist/control condition in children (Smith et al 2007; Ahrens & Rexford 2002),
118 x One study compare a trauma affect regulation therapy against a waitlist condition in adults (Ford et al 2011), x Six studies compared EMDR against waitlist in adults (Jensen 1994; Power et al 2002; Rothbaum 1997; Rothbaum et al 2005; Hogberg et al 2007). x Three studies compared EMDR against waitlist in children/adolescents (Ahmad et al 2007; Chemtob et al 2002a; Kemp et al 2010). x One study compared stress management therapy against a waitlist condition in adolescents (Gordon et al 2008) x Two studies compared problem-solving therapy against a waitlist condition in adults x (McDonagh et al 2005; Ford et al 2011) x One study compared interpersonal psychotherapy against a waitlist condition in adults (Krupnick et al 2008) x One study compared psychodynamic therapy against a waitlist condition in adults (Brom et al 1989) x One study compared hypnotherapy against a waitlist condition in adults (Brom et al 1989) x Two studies compared supportive counselling against a waitlist condition in adults (Blanchard et al 2003; Foa et al 1991) x Two studies compared group CBT against a waitlist condition in adults (Zlotnick et al 1997; Beck et al 2009) x One study compared group and individual CBT against a waitlist condition in adults(Chard 2005) x One study compared group imagery rehearsal therapy against a waitlist condition in adults (Krakow et al 2001) x Four studies compared stress management therapy against a waitlist condition in adults (Vaughan et al 1994; Foa et al 1999; Foa et al 1991; Carlson et al 1998) x Two studies compared narrative exposure therapy against a waitlist condition in adults (Ertl et al 2011; Ruf et al 2010) x Two studies compared a spiritually-based intervention against waitlist (Bormann et al 2008; Lesmana et al 2009)
The following comparisons are discussed for question 11: x Sixteen studies compared trauma-focused CBT against treatment as usual in adults (Asukai et al 2010; Bryant et al 2011; Cooper & Clum 1989; Feske 2008; Forbes et al 2012; Hinton et al 2005; Hinton et al 2009; Johnson et al 2011; Johnson & Lubin 2006; McLay et al 2011; Mueser et al 2008; Nacasch et al 2011; Neuner et al 2010; Peniston & Kulkosky 1991; Vera et al 2011; Zlotnick et al 2009) x Four studies (six citations) compared trauma-focused CBT against treatment as usual in children; ((Celano et al 1996; Cohen et al 2011; Deblinger et al 1996), followed up in(Deblinger et al 1999), and (Lieberman et al 2005) followed up in (Lieberman et al 2006) x Three studies (four citations) compared EMDR against treatment as usual in adults (Marcus et al 1997; Marcus et al 2004; Johnson & Lubin 2006; Carlson et al 1998) x One study compared EMDR against standard care in children (Farkas et al 2010) x One study compared narrative exposure therapy against treatment as usual in adults (Neuner et al 2010) x One study compared ‘the counting method’ against treatment as usual in adults (Johnson et al 2011)
119 x Nine studies compared trauma-focused CBT against stress management therapies in adults (Marks et al 1998; Foa et al 1999; Taylor et al 2003; Vaughan et al 1994; McDonagh et al 2005; Foa et al 1991);(Echeburua et al 1997; Hinton et al 2011; Echeburua et al 1996) x One study compared trauma-focused CBT against a psychoeducation and stress management condition in adolescents (Layne et al 2008). x Six studies (seven citations) compared trauma-focused CBT against supportive counselling in adults, including one study where both conditions were delivered over the internet (Schnurr et al 2007; Bryant et al 2003a)(Schnurr et al 2007)(Schnurr et al 2007) (Foa et al 1991; Blanchard et al 2003)followed up in(Blanchard et al 2004; Cottraux et al 2008; Litz et al 2007) x One study (two citations) compared trauma-focused CBT against supportive therapy (child centred therapy) in children (Cohen et al 2004b; Deblinger et al 2006) x One study compared trauma-focused CBT against psychoeducation (Women’s Health Education) in adults (Hien et al 2009) x One study compared trauma-focused CBT against hypnotherapy in adults (Brom et al 1989) x One study compared trauma-focused CBT against psychodynamic therapy in adults (Brom et al 1989) x One study compared trauma-focused CBT against psychodynamic therapy in adolescents (Gilboa-Schectman et al 2010) x One study compared trauma-focused CBT against the counting method in adults (Johnson et al 2011) x One study compared trauma-focused CBT administered to different people to treat children with PTSD (Deblinger et al 1996; Deblinger et al 1999) x One study compared narrative exposure therapy against supportive counselling in adults (Neuner et al 2004b) x One study compared narrative exposure therapy against supportive counselling in adolescents/young adults (Ertl et al 2011) x Two studies compared narrative exposure therapy against brief psychoeducation in adults (Neuner et al 2004b; Bichescu et al 2007) x One study compared narrative exposure therapy against stress inoculation training (Hensel-Dittmann et al 2011) x One study compared narrative exposure therapy with cognitive processing therapy including NET (Resick et al 2008) x One study compared narrative exposure therapy with cognitive processing therapy without NET (Resick et al 2008) x One study compared written emotional disclosure with a control writing condition in adults (Sloan et al 2011) x One study compared supportive counselling against brief psychoeducation in adults (Neuner et al 2004b) x One study compared CBT (non-trauma-focused) against present centred therapy (Ford et al 2011) x Three studies (four citations) compared CBT with an exposure component against CBT without an exposure component in adults (Tarrier et al 1999a; Tarrier et al 1999b; Marks et al 1998; Resick et al 2008) x Two studies compared CBT with an exposure component against CBT without an exposure component in children (Deblinger et al 2011; Nixon et al 2011)
120 x Two studies compared trauma-focused CBT against “other” therapies in adults: skills training plus exposure; skills training plus supportive counselling, and supportive counselling plus exposure (Cloitre et al 2010) and imaginal exposure (IE), in vivo exposure (IVE), imaginal plus in vivo exposure (I/IVE), and imaginal and in vivo exposure with cognitive therapy (I/IVE/CR) (Bryant et al 2008b) x Six studies compared EMDR against trauma-focused CBT in adults (Taylor et al 2003; Vaughan et al 1994; Johnson & Lubin 2006; Power et al 2002; Rothbaum et al 2005; Ironson et al 2002) x Two studies compared trauma-focused CBT against EMDR in children (Jaberghaderi et al 2004; De Roos et al 2011) x Three studies compared EMDR against stress management therapies in adults (Vaughan et al 1994; Carlson et al 1998; Taylor et al 2003) x One study compared EMDR against supportive counselling in adolescents/adults (Scheck et al 1998) x One study compared EMDR against “the counting method” in adults (Johnson & Lubin 2006) x One study compared EMDR against Emotional Freedom Techniques in adults (Karatzias et al 2011) x One study compared stress management against supportive counselling (Foa et al 1991) x One study compared group CBT (trauma-focused) against group CBT (non-trauma- focused) in adults (Schnurr et al 2003) x One study compared group CBT (videoconference) against group CBT (same-room) (Frueh et al 2007) x One study compared group non-trauma focused CBT against group psychoeducation (Dunn et al 2007) x One study compared group imagery rehearsal therapy against group sleep and nightmare management (Cook et al 2010) x One study compared parent and child group CBT with parent-only group CBT for children (Runyon et al 2010)
Three studies assessing interapy versus waitlist fitted the criteria for question 10, but are discussed under question 14 “Are established interventions for PTSD effective when self- delivered or self-delivered with practitioner support compared to practitioner delivered intervention or no intervention” One study met the inclusion criteria for question 10, but has been considered in the separate section of ‘School-based interventions’.
TRAUMA-FOCUSED CBT VERSUS WAITLIST There were 29 studies which met the inclusion criteria determined a priori, which addressed the comparison between trauma-focused CBT and waitlist/minimal contact control groups in an adult population. The types of treatment which were included under the term trauma- focused CBT include: x prolonged exposure (Foa et al 1999; Foa et al 1991; Pacella et al 2011; Foa et al 2005), x image habituation training (Vaughan et al 1994), x imaginal flooding (implosive flooding) therapy (Keane et al 1989), x cognitive reprocessing therapy (Resick et al 2002), x cognitive processing therapy (Monson et al 2006),
121 x cognitive-behavioural treatment (Blanchard et al 2003; Fecteau & Nicki 1999; Bisson et al 2004) x brief cognitive-behavioural therapy -(Sijbrandij et al 2007), x cognitive therapy for PTSD (Ehlers et al 2005; Ehlers et al 2003); x cognitive restructuring (Marks et al 1998), x cognitive trauma therapy (Kubany et al 2003; Kubany et al 2004), x brief eclectic psychotherapy (Gersons et al 2000; Schnyder et al 2011; Lindauer et al 2005) x skills training in affective and interpersonal regulation followed by exposure (Cloitre et al 2002) and x single session modified behavioural treatment (Basoglu et al 2005; Basoglu et al 2007). Sessions ranged from one session (Basoglu et al 2005; Basoglu et al 2007) through to 16 (Cloitre et al 2004; Keane et al 1989), but were most commonly 12 sessions long.
Given the volume of literature on trauma-focused CBT versus waitlist, it is considered noteworthy that every study included was consistent in favouring CBT over waitlist on the primary outcome measures of PTSD diagnosis and symptom severity, as well as the secondary outcomes of depressive symptoms, and social and occupational functioning. On the outcome measure of anxiety, all but one study favoured trauma-focused CBT. Evidence statements with RR and SMD for each outcome are provided underneath Table 43. However, as can be seen in the study profiles table (Table 43), the vast majority of studies were considered to be at either a moderate or high risk of bias. One common reason for this was that many studies provided post-treatment summary data based only on those who completed treatment, which would systematically exclude data from participants who drop-out of treatment, biasing results in favour of the intervention. Therefore, there is strong evidence regarding the beneficial effect of trauma-focused CBT in those who completed treatment, and more limited evidence regarding all those randomly allocated to receive trauma-focused CBT. Attrition was slightly higher on average in the trauma-focused CBT group than the waitlist group, suggesting that some patients may not tolerate treatment. However, this difference was not large enough to be considered clinically important.
Table 43 Study profiles for RCTs comparing trauma-focused CBT and waitlist/control for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Lindauer et al Low Unspecified trauma type Outpatient setting, 24 PTSD diagnosis 2005) the Netherlands Depressive symptoms Anxiety (Bisson et al 2004) Moderate Physical trauma (motor Outpatient setting, 152 PTSD diagnosis vehicle accident, assault, United Kingdom Severity of PTSD other) Depressive symptoms Anxiety Attrition (Resick et al 2002) Moderate Raped or physically Outpatient setting, 109 PTSD diagnosis assaulted women United States Severity of PTSD Depressive symptoms
(Monson et al 2006) Moderate Veterans (mostly male) Outpatient setting, 60 PTSD diagnosis with military-related trauma United States Severity of PTSD Depressive symptoms Anxiety Social functioning Attrition
122 (Basoglu et al 2005) Moderate Earthquake victims Outpatient setting, 59 Severity of PTSD Turkey Depressive symptoms Functioning (Duffy et al 2007) Moderate Trauma related to Outpatient setting, 58 Severity of PTSD Northern Ireland “troubles” Northern Ireland Depressive symptoms (terrorism and civil conflict) Work and social functioning
(Pacella et al 2011) Moderate People living with HIV Outpatient setting, 58 Severity of PTSD United States Depressive symptoms Substance use Attrition
(Ehlers et al 2003) Moderate Motor vehicle accident Outpatient setting, 57 PTSD diagnosis survivors United Kingdom Severity of PTSD Depressive symptoms Anxiety Social, work and family functioning
(Brom et al 1989) Moderate Experienced a violent Outpatient setting, 54 PTSD diagnosis crime, traffic accident, or the Netherlands Severity of PTSD lost a loved one due to Anxiety murder/suicide, traffic Attrition accident, or illness
(Blanchard et al Moderate Motor vehicle accident Outpatient, United 51 PTSD diagnosis 2003) survivors, adults States Severity of PTSD Depressive symptoms Anxiety Attrition (Gersons et al 2000) Moderate Police officers Outpatient setting, 42 PTSD diagnosis the Netherlands Severity of PTSD Depressive symptoms Anxiety Attrition
(Foa et al 1999) Moderate Female victims of sexual Outpatient setting, 40 PTSD diagnosis and nonsexual assault United States Severity of PTSD Depressive symptoms Anxiety Attrition (Basoglu et al 2007) Moderate Earthquake victims (buried Outpatient setting, 31 Severity of PTSD under rubble, physical Turkey Depressive symptoms injury, death of relative or Work and Social functioning friend)
(Schnyder et al Moderate Mixed trauma types: Outpatient setting, 30 Severity of PTSD 2011) serious accidents, violent Switzerland Depressive symptoms sexual or nonsexual Anxiety assaults, non-combat- Posttraumatic growth related war exposure, natural disaster, childhood trauma and other (Ehlers et al 2005) Moderate Accident, assault, or Outpatient setting, 28 PTSD diagnosis having witnessed a death United Kingdom Severity of PTSD Depressive symptoms Anxiety Functioning Attrition
123 (Fecteau & Nicki Moderate Motor vehicle accident Outpatient setting, 20/23 PTSD diagnosis 1999) Canada Severity of PTSD Depressive symptoms Anxiety Attrition (Vaughan et al Moderate Victims of violent crime, Outpatient PTSD 20 PTSD diagnosis 1994) rape, child abuse or motor clinic, Australia Severity of PTSD accident Depressive symptoms
(Wagner et al 2007) Moderate Physical injuries (such as Outpatient setting, 8 Severity of PTSD from motor vehicle United States Physical comorbidity accident, motor bike accident, fall from ladder)
(Sijbrandij et al High Mixed traumas: assault, Outpatient setting, 117 PTSD diagnosis 2007) witnessing assault, sexual the Netherlands Severity of PTSD assault, accidental injury, Depressive symptoms sudden death of loved Anxiety one, other Attrition (Foa et al 2005) High Female victims of sexual Outpatient setting, 100 Severity of PTSD assault, nonsexual assault, United States Depressive symptoms or childhood sexual abuse Social functioning
(Kubany et al 2004) High Women who had been Outpatient setting, 86/107 Severity of PTSD physically and/or United States Depressive symptoms emotionally abused by an intimate or a romantic partner (Rothbaum et al High Adult rape victims Outpatient setting, 60 PTSD diagnosis 2005) United States Depressive symptoms Anxiety Functioning
(McDonagh et al High Women with PTSD Outpatient setting, 52 Severity of PTSD 2005) secondary to Child Sexual United States Depressive symptoms Abuse Anxiety (Cloitre et al 2002) High Women who had Outpatient setting, 46 PTSD diagnosis experienced childhood United States Severity of PTSD sexual abuse, physical Depressive symptoms abuse or both Anxiety (Kubany et al 2003) High Women who had been Outpatient setting, 32 PTSD diagnosis physically and/or United States Severity of PTSD emotionally Depressive symptoms (Power et al 2002) High Unspecified trauma (road Outpatient setting, 25/66 PTSD diagnosis accidents, occupational Scotland Depressive symptoms accidents, sexual or non- Anxiety sexual assault, witnessing Attrition traumatic death, real/implied physical threat) (Dunne et al In High Motor vehicle accident- Outpatient setting, 26 PTSD diagnosis press) related whiplash Australia Severity of PTSD Depressive symptoms Anxiety Physical functioning Attrition
124 (Keane et al 1989) High Vietnam combat veterans Outpatient setting, 24 PTSD diagnosis United States Severity of PTSD Attrition
(Foa et al 1991) High Women who had Outpatient setting, 24 PTSD diagnosis experienced sexual United States Severity of PTSD assault, aggravated Depressive symptoms assault, or assault with a Anxiety weapon, aged over 16 Attrition
There is evidence there may be publication bias, as those small studies with the greatest standard error were consistently those with the largest relative risks in favour of CBT (see funnel plot in Appendix H).
There is evidence favouring trauma-focused CBT over waitlist/control on the likelihood of having a PTSD diagnosis post-treatment (k= 21, n=1256, RR=0.52, 95%CI 0.43, 0.62).
There is no sign of publication bias when assessing the rate PTSD diagnosis at follow-up (funnel plot in Appendix H).
125 There is limited evidence favouring trauma-focused CBT over waitlist/control on the likelihood of having a PTSD diagnosis at 3 – 9 months follow-up (k=3, n=310, RR=0.56 (0.41, 0.76)
126
There is no evidence of publication bias when assessing the outcome of PTSD severity (clinician-rated) (see funnel plot in Appendix H).
There is limited evidence favouring trauma-focused CBT over waitlist/control on reducing the severity of clinician-rated PTSD symptoms at post-treatment (k=22, n=1324, SMD=-0.87, 95%CI -1.10, -0.64).
127
There is evidence suggesting there is unlikely to be a clinically important difference between trauma-focused CBT and waitlist/control on the severity of clinician-rated PTSD symptoms at 3 – 9 months follow-up (k=4, n=327, SMD=-0.42, 95%CI -0.62, -0.20).
There is evidence favouring trauma-focused CBT over waitlist/control on reducing the severity of self-rated PTSD symptoms at post-treatment (k=11, n=558, SMD=-1.14, 95%CI - 1.32, -0.95).
128
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between trauma-focused CBT and waitlist/control on reducing depressive symptoms at post-treatment (k=24, n=1306, SMD=-0.78, 95%CI -1.00, -0.57).
129
There is evidence suggesting that there is unlikely to be a clinically important difference between trauma-focused CBT and waitlist/control on reducing depressive symptoms at 3 – 9 months (k=3, n=215, SMD=-0.36,95%CI -0.63, -0.09).
There is limited evidence favouring trauma-focused CBT over waitlist/control on reducing anxiety at post-treatment (k=16, n=704, SMD=-0.87, 95%CI -1.22, -0.52).
There is evidence suggesting that there is unlikely to be a clinically important difference between trauma-focused CBT and waitlist on reducing anxiety at 4 months’ follow-up (k=1, n=104, SMD= -0.30, 95%CI -0.69, 0.09).
130
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between trauma-focused CBT and waitlist/control on social and occupational functioning at post-treatment (k=10, n=534, SMD=-0.67, 95%CI -0.93, - 0.40).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between trauma-focused CBT a control condition on physical functioning at post-treatment (k=2, n=34, SMD=0.72, 95%CI 0.02, 1.43).
There is evidence suggesting that there is unlikely to be a clinically important difference between trauma-focused CBT and waitlist on the frequency of substance use at 3 months’ follow-up (k=1, n=58, SMD=0.06, 95%CI -0.46, 0.59).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between trauma-focused CBT and a minimal attention control on post-traumatic growth at post-treatment (k=1, n=30, SMD=0.15, 95%CI -0.57, 0.87).
131
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between trauma-focused CBT and waitlist/control on attrition at post-treatment (k=18, n=1,181, RR=1.39, 95%CI 1.07, 1.79).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between trauma-focused CBT and waitlist/control on attrition at 3 – 9 months follow-up (k=3, n=353, RR=1.33, 95%CI 0.50, 3.51).
Box 52 Evidence statement matrix for RCTs comparing trauma-focused CBT and waitlist for adults with PTSD Component Rating Description Evidence base A Twenty-nine RCTs (level II evidence), 1 with low risk of bias, 17 with moderate risk of bias, and 11 with a high risk of bias. Those studies deemed to be at risk of bias were commonly considered so due to greater than 15% loss to follow-up, and some studies providing analyses based on completer data only. Consistency B All studies consistent in the direction of effect for the primary outcome measures, with some variation in size of effect likely due to differences in treatment length, treatment style, and differences in populations.
132 Clinical impact C There is strong evidence that trauma-focused CBT is better waitlist or a no treatment control at reducing the likelihood of having a PTSD diagnosis and reducing the severity of PTSD symptoms as determined on self-report measures. There were also clinically important point estimates favouring trauma-focused CBT over waitlist/control for reducing PTSD severity on clinician-rated measures and a trend for depressive symptoms post-treatment, although the full range of plausible estimates included effects below the cut-off of what is considered clinically important. Generalisability A A broad range of studies, covering a wide range of traumas, including an Australian sample. The evidence is therefore applicable to the target population.
Applicability A Evidence from a wide range of healthcare systems, including Australia, which would be directly applicable.
Summary of evidence There is strong evidence that trauma-focused CBT is beneficial when compared to a waitlist or no treatment control condition post-treatment on key patient-relevant outcomes such as the likelihood of having a PTSD diagnosis, and PTSD symptom severity (self-rated). On outcomes of PTSD symptom severity (clinician-rated), depressive symptoms and anxiety, the full range of plausible estimates also included clinically unimportant effects. No advantage of CBT was found from the limited studies reporting follow-up at 3-9 months post-treatment. (Grade A)
Trauma-focused CBT vs waitlist/control ITT analysis
A total of 15 studies provided intention-to-treat data on the comparison between trauma- focused CBT and a waitlist or no treatment control condition. Of these 15 studies, 11articles specified that they took specific measures to ensure treatment integrity, such using a manual and checklist for each session (Dunne et al In press; Gersons et al 2000), using a special rating system to analyse treatment integrity (Lindauer et al 2005), taping sessions so they could be watched/reviewed to ensure therapy protocol (Bisson et al 2004; Ehlers et al 2005; McDonagh et al 2005; Schnyder et al 2011; Monson et al 2005; Resick et al 2002), and holding supervisory sessions to ensure adherence to protocol (Brom et al 1989; Pacella et al 2001; Gersons et al 2000). Four articles did not specify any measures taken to monitor or ensure treatment fidelity (Duffy et al 2007; Keane et al 1989; Vaughan et al 1994; Wagner et al 2007).
Although all studies favoured CBT over waitlist/control in their direction of effect, there were only two outcome measures which were considered clinically important: the likelihood of having a diagnosis of PTSD post-treatment, and the severity of PTSD symptoms, as rated by patients (but not by clinicians). No other outcome measures (such as depressive symptoms, anxiety, functioning, or quality of life) were deemed clinically important using the cut-offs determined a priori. Effect sizes were slightly smaller than for the analyses above which included both intention-to-treat studies and those with data restricted to those who completed questionnaires post-treatment (completer-data only). There is therefore evidence that on average, those who start CBT are likely to be better off clinically post-treatment than those who are in a waitlist or control group, although these findings are not as strong as for those who not only start treatment, but for those who finish treatment as well.
Table 44 Study profiles for RCTs comparing trauma-focused CBT and waitlist/control for adults with PTSD: ITT Reference Risk of bias Population Setting N Outcomes measured
133 (Lindauer et al Low Unspecified trauma type Outpatient setting, 24 PTSD diagnosis 2005) the Netherlands Depressive symptoms Anxiety (Bisson et al 2004) Moderate Physical trauma (motor Outpatient setting, 152 PTSD diagnosis vehicle accident, assault, United Kingdom Severity of PTSD other) Depressive symptoms Anxiety Attrition (Resick et al 2002) Moderate Raped or physically Outpatient setting, 109 PTSD diagnosis assaulted women United States Severity of PTSD Depressive symptoms
(Monson et al 2006) Moderate Veterans (mostly male) Outpatient setting, 60 PTSD diagnosis with military-related trauma United States Severity of PTSD Depressive symptoms Anxiety Social functioning Attrition (Duffy et al 2007) Moderate Trauma related to Outpatient setting, 58 Severity of PTSD Northern Ireland “troubles” Northern Ireland Depressive symptoms (terrorism and civil conflict) Work and social functioning
(Pacella et al 2011) Moderate People living with HIV Outpatient setting, 58 Severity of PTSD United States Depressive symptoms Substance use Attrition
(Brom et al 1989) Moderate Experienced a violent Outpatient setting, 54 PTSD diagnosis crime, traffic accident, or the Netherlands Severity of PTSD lost a loved one due to Anxiety murder/suicide, traffic Attrition accident, or illness
(Gersons et al 2000) Moderate Police officers Outpatient setting, 42 PTSD diagnosis the Netherlands Severity of PTSD Depressive symptoms Anxiety Attrition
(Schnyder et al Moderate Mixed trauma types: Outpatient setting, 30 Severity of PTSD 2011) serious accidents, violent Switzerland Depressive symptoms sexual or nonsexual Anxiety assaults, non-combat- Posttraumatic growth related war exposure, natural disaster, childhood trauma and other (Ehlers et al 2005) Moderate Accident, assault, or Outpatient setting, 28 PTSD diagnosis having witnessed a death United Kingdom Severity of PTSD Depressive symptoms Anxiety Functioning Attrition (Vaughan et al Moderate Victims of violent crime, Outpatient PTSD 20 PTSD diagnosis 1994) rape, child abuse or motor clinic, Australia Severity of PTSD accident Depressive symptoms
(Wagner et al 2007) Moderate Physical injuries (such as Outpatient setting, 8 Severity of PTSD from motor vehicle United States Physical comorbidity accident, motor bike accident, fall from ladder)
134 (McDonagh et al High Women with PTSD Outpatient setting, 52 Severity of PTSD 2005) secondary to Child Sexual United States Depressive symptoms Abuse Anxiety (Dunne et al In High Motor vehicle accident- Outpatient setting, 26 PTSD diagnosis press) related whiplash Australia Severity of PTSD Depressive symptoms Anxiety Physical functioning Attrition
(Keane et al 1989) High Vietnam combat veterans Outpatient setting, 24 PTSD diagnosis United States Severity of PTSD Attrition
There is evidence favouring CBT over waitlist/control on the likelihood of having a PTSD diagnosis post-treatment (k=10, n=609, RR=0.51, 95%CI 0.44, 0.59). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between CBT and waitlist/control on the likelihood of having a PTSD diagnosis at 9 months’ follow-up (k=1, n=152, RR=0.69, 95%CI 0.47, 1.04).
135
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between CBT and waitlist/control on the severity of PTSD symptoms (clinician-rated) post-treatment (k=10, n=613, SMD=-0.59, 95%CI -0.87, -0.30).
There is evidence suggesting that there is unlikely to be a clinically important difference between CBT and waitlist/control on PTSD severity (clinician-rated) at 3 – 9 months follow- up (k=2, n=174, SMD=-0.37, 95%CI -0.67, -0.07).
136
There is evidence favouring CBT over waitlist/control on the severity of PTSD symptoms (self-rated) post-treatment (k=6, n=341, SMD=-1.06, 95%CI -1.06, -0.82). There is evidence suggesting that there is unlikely to be a clinically important difference between CBT and waitlist/control on the change in PTSD severity (self-rated) between baseline and 9 months follow-up (k=1, n=116, SMD=-0.43, 95%CI -0.80, -0.07).
There is evidence suggesting that there is unlikely to be a clinically important difference between CBT and waitlist/control on depressive symptoms post-treatment (k=11, n=576, SMD=-0.59, 95%CI -0.76, -0.41). There is evidence suggesting that there is unlikely to be a clinically important difference between CBT and waitlist/control on depressive symptoms at 3 months follow-up (k=1, n=58, SMD=-0.24, 95%CI -0.76, 0.29) There is evidence suggesting that there is unlikely to be a clinically important difference between CBT and waitlist/control on the reduction in depressive symptoms between baseline and 9 months follow-up (k=1, n=116, SMD=-0.09, 95%CI -0.46, 0.27).
137
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between CBT and waitlist/control on anxiety post-treatment (k=8, n=272, SMD=-0.64, 95%CI -0.88, -0.39). There is evidence suggesting that there is unlikely to be a clinically important difference between CBT and waitlist/control on the reduction of anxiety between baseline and 9 months’ follow-up (k=1, n=116, SMD=-0.09,95%CI -0.46, 0.27)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between CBT and waitlist/control on social and occupational functioning post-treatment (k=3, n=136, SMD=-0.72, 95%CI -1.39, -0.05). There is evidence suggesting that there is unlikely to be a clinically important difference between CBT and waitlist/control on the improvement in quality of life between baseline and post-treatment (k=1, n=52, SMD=-0.14, 95%CI -0.69, 0.40).
138
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between CBT and waitlist/control on physical functioning post-treatment (k=2, n=34, SMD=0.72, 95%CI 0.02, 1.43). There is evidence suggesting there is unlikely to be a clinically important difference between CBT and waitlist/control on frequency of substance use post-treatment (k=1, n=58, SMD=0.06, 95%CI -0.46, 0.59). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between trauma-focused CBT and control on post-traumatic growth at post-treatment (k=1, n=30, SMD=0.15, 95%CI -0.57, 0.87).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between CBT and waitlist/control on attrition post-treatment (k=10, n=643, RR=1.48, 95%CI 0.99, 2.21).
139 TRAUMA-FOCUSED CBT VERSUS WAITLIST IN FEMALE VICTIMS OF SEXUAL/NONSEXUAL ASSAULT OR CHILD ABUSE Studies which compared trauma-focused CBT and waitlist/control in a population including women who had suffered child sexual abuse, sexual assault or nonsexual assault were combined in subgroup analyses.
Table 45 Study profiles for RCTs comparing trauma-focused CBT and waitlist/control for adults with PTSD (sub- group: sexual/nonsexual abuse) Reference Risk of bias Population Setting N Outcomes measured (Resick et al 2002) Moderate Raped or physically Outpatient setting, 109 PTSD diagnosis assaulted women United States Severity of PTSD Depressive symptoms
(Foa et al 2005) High Female victims of sexual Outpatient setting, 100 Severity of PTSD assault, nonsexual assault, United States Depressive symptoms or childhood sexual abuse Social functioning
(Foa et al 1999) High Female victims of sexual Outpatient setting, 40 PTSD diagnosis and nonsexual assault United States Severity of PTSD Depressive symptoms Anxiety Attrition (Kubany et al 2004) High Women who had been Outpatient setting, 86/107 Severity of PTSD physically and/or United States Depressive symptoms emotionally abused by an intimate or a romantic partner (Rothbaum et al High Adult rape victims Outpatient setting, 60 PTSD diagnosis 2005) United States Depressive symptoms Anxiety Functioning (McDonagh et al High Women with PTSD Outpatient setting, 52 Severity of PTSD 2005) secondary to Child Sexual United States Depressive symptoms Abuse Anxiety (Cloitre et al 2002) High Women who had Outpatient setting, 46 PTSD diagnosis experienced childhood United States Severity of PTSD sexual abuse, physical Depressive symptoms abuse or both Anxiety (Kubany et al 2003) High Women who had been Outpatient setting, 32 PTSD diagnosis physically and/or United States Severity of PTSD emotionally Depressive symptoms (Foa et al 1991) High Women who had Outpatient setting, 24 PTSD diagnosis experienced sexual United States Severity of PTSD assault, aggravated Depressive symptoms assault, or assault with a Anxiety weapon, aged over 16 Attrition
140
There is evidence favouring trauma-focused CBT over waitlist/control on the likelihood of having a PTSD diagnosis at post-treatment in female survivors of sexual assault, nonsexual assault, or childhood abuse (k=6, n=398, RR=0.40, 95%CI 0.26, 0.62).
There is limited evidence favouring trauma-focused CBT over waitlist/control on reducing the severity of clinician-rated PTSD symptoms at post-treatment in female survivors of sexual assault, nonsexual assault, or childhood abuse (k=8, n=606, SMD=-1.18, 95%CI -1.57, - 0.78).
141
There is limited evidence favouring trauma-focused CBT over waitlist/control on reducing the severity of self-rated PTSD symptoms at post-treatment in female survivors of sexual assault, nonsexual assault, or childhood abuse (k=2, n=217, SMD=-1.04, 95%CI -1.35, - 0.73).
There is limited evidence favouring trauma-focused CBT over waitlist/control on reducing depressive symptoms at post-treatment in female survivors of sexual assault, nonsexual assault, or childhood abuse (k=9, n=636, SMD=-1.07, 95%CI -1.55, -0.59).
142
There is limited evidence favouring trauma-focused CBT over waitlist/control on reducing anxiety at post-treatment in female survivors of sexual assault, nonsexual assault, or childhood abuse (k=5, n=217, SMD=-1.12, 95%CI -1.71, -0.53).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between trauma-focused CBT and waitlist/control on attrition in female survivors of sexual assault, nonsexual assault, or childhood abuse (k=5, n=415, RR=1.19, 95%CI 0.82, 1.74).
Box 53 Evidence statement matrix for RCTs comparing trauma-focused CBT and waitlist for adults with PTSD Component Rating Description Evidence base C Nine level II studies, one with a moderate risk of bias, and eight with a high risk of bias.
Consistency B All studies consistent in the direction of effect, with some variation in size of effect likely due to differences in treatment length, treatment style, and differences in populations. Clinical impact C There is evidence that trauma-focused CBT is clearly beneficial over control/waitlist on clinician-rated outcomes of PTSD diagnosis. The point estimates for all other outcome measures (PTSD symptom severity, depression, and anxiety) were also clinically important in favour of trauma-focused CBT,
143 although the full range of plausible estimates outlined by the confidence intervals included clinically unimportant effects.
Generalisability A Evidence from survivors of sexual or non-sexual assault, or childhood physical or sexual abuse. Directly applicable to sub-population of the target population for guidelines.
Applicability C All studies from the United States. Evidence probably applicable to the Australian healthcare context with some caveats.
Summary of evidence Trauma-focused CBT is clearly beneficial in the short term compared to a waitlist/control condition in women who have PTSD due to sexual assault, nonsexual assault, or childhood abuse. No conclusions may be made about the long term benefits of treatment, given the lack of data. (Grade C).
TRAUMA-FOCUSED CBT VERSUS WAITLIST IN MILITARY VETERANS
Two studies were identified which assessed the effectiveness of trauma-focused CBT against a waitlist condition in military veterans. Keane et al (1989) used implosive (flooding) therapy, whereas Monson et al (2006) used cognitive processing therapy. Data from the two studies were not able to be combined, as Monson et al (2006) presented mean change data rather than post-treatment data, and Keane et al (1989) provided a large proportion of their data in graphical formats. Their results are therefore narratively discussed below.
Only one of the studies reported on the likelihood of having a PTSD diagnosis (Monson et al 2006), and reported limited evidence favouring CBT over waitlist (RR=0.62, 95%CI 0.46, 0.84). On the outcome measure of PTSD symptom severity, Monson et al (2006) reported stronger evidence favouring CBT over waitlist than Keane et al (1989) did, with an effect size of 1.12 (95%CI -1.67, 0.58), as compared to -0.23, 95%CI -0.93, 0.45. However, both studies included clinically unimportant effects in their full range of estimates.
Keane et al (1989) reported that on the Beck Depression Inventory (BDI), there was a group x time interaction in favour of flooding implosive therapy (F(1,22) = 4.57, p < .05). Monson et al (2006) found limited evidence favouring CBT over waitlist on the BDI (SMD= -1.16, 95%CI -1.70, -0.61). Likewise on the state-component of the Spielberger State and Trait Anxiety measure, Keane et al (1989) reported a significant group x time interaction (F(1,22) = 4.35, p < .05), although trait characteristics were not impacted. Monson et al (2006) reported a clinically important effect size favouring CBT over waitlist, although the confidence intervals included clinically unimportant effects (SMD=-0.99, 95%CI -1.53, - 0.46). Keane et al (1989) reported no impact on social marital, psychological, financial, social, and vocational dimensions of functioning.
Overall, there is limited evidence favouring trauma-focused CBT over a waitlist in combat veterans with PTSD in the short term, but further research would be required before strong conclusions could be drawn.
144 Table 46 Study profiles for RCTs comparing trauma-focused CBT and waitlist for adults with PTSD (sub-group: veterans) Reference Risk of bias Population Setting N Outcomes measured (Monson et al 2006) Moderate Veterans (mostly male) Outpatient setting, 60 PTSD diagnosis with military-related trauma United States Severity of PTSD Depressive symptoms Anxiety Social functioning Attrition (Keane et al 1989) High Vietnam combat veterans Outpatient setting, 24 PTSD diagnosis United States Severity of PTSD Attrition
Box 54 Evidence statement matrix for RCTs comparing trauma-focused CBT and waitlist for adults with PTSD Component Rating Description Evidence base C One level II study with a moderate risk of bias, and one level II study with a high risk of bias.
Consistency C Both studies consistent in the direction of effect. Difficult to determine how they compared on size of effect for most outcomes. Clinical impact C Limited evidence favoured trauma-focused CBT over waitlist on outcomes of PTSD diagnosis, PTSD symptoms severity, depressive symptoms and anxiety. The full range of estimates included clinically unimportant effects. Generalisability A Evidence from combat veterans
Applicability C Both studies from the United States. Evidence probably applicable to the Australian healthcare context with some caveats.
Summary of evidence Limited evidence suggests that trauma-focused CBT is likely to be more effective at reducing the likelihood of having a PTSD diagnosis, reducing symptoms of PTSD, depressive symptoms and anxiety than a waitlist condition in military veterans. However, the full range of estimates included clinically unimportant effects, and no long term data were provided. (Grade D)
TRAUMA-FOCUSED CBT VERSUS WAITLIST IN PEOPLE AFTER MOTOR VEHICLE ACCIDENTS Six studies assessed the benefit of trauma-focused CBT against a waitlist condition in samples who had experienced motor vehicle accidents. There was strong evidence that CBT was superior to waitlist/control on the outcome measure of PTSD severity as rated by clinicians and self-rated by patients, and clinically important point estimates favouring CBT on the likelihood of having a PTSD diagnosis post-treatment, depressive symptoms and anxiety post-treatment, although the full range of estimates included clinically unimportant effects. Attrition was higher on average in the trauma-focused CBT conditions than the control conditions, suggesting that some patients may not tolerate treatment.
Table 47 Study profiles for RCTs comparing trauma-focused CBT and waitlist/control for adults with PTSD (sub- group: vehicle accidents) Reference Risk of bias Population Setting N Outcomes measured (Ehlers et al 2003) Moderate Motor vehicle accident Outpatient setting, 57 PTSD diagnosis survivors United Kingdom Severity of PTSD Depressive symptoms Anxiety Social, work and family functioning
145 (Fecteau & Nicki Moderate Motor vehicle accident Outpatient setting, 20/23 PTSD diagnosis 1999) Canada Severity of PTSD Depressive symptoms Anxiety Attrition (Blanchard et al High Motor vehicle accident Outpatient, United 51 PTSD diagnosis 2003) survivors, adults States Severity of PTSD Depressive symptoms Anxiety Attrition (Beck et al 2009) High Trauma from motor vehicle Outpatient setting, 33 PTSD diagnosis accident (real or perceived United States Severity of PTSD death or serious injury) Depressive symptoms Anxiety (Dunne et al In High Motor vehicle accident- Outpatient setting, 26 PTSD diagnosis press) related whiplash Australia Severity of PTSD Depressive symptoms Anxiety Physical functioning Attrition
(Wagner et al 2007) High Physical injuries (such as Outpatient setting, 8 Severity of PTSD from motor vehicle United States Physical comorbidity accident, motor bike accident, fall from ladder)
There is limited evidence favouring trauma-focused CBT over waitlist/control on the likelihood of having a PTSD diagnosis at post-treatment in survivors of motor vehicle accidents (k=4, n=168, RR=0.47, 95%CI 0.35, 0.63).
146 There is evidence favouring trauma-focused CBT over waitlist/control on reducing the severity of clinician-rated PTSD symptoms at post-treatment in survivors of motor vehicle accidents (k=5, n=187, SMD=-1.22, 95%CI -1.54, -0.90).
There is evidence favouring trauma-focused CBT over waitlist/control on reducing the severity of self-rated PTSD symptoms at post-treatment in survivors of motor vehicle accidents (k=6, n=193, SMD=-1.25, 95%CI -1.57, -0.94).
147
There is limited evidence favouring trauma-focused CBT over waitlist/control on reducing depressive symptoms at post-treatment in survivors of motor vehicle accidents (k=5, n=185, SMD=-0.90, 95%CI -1.21, -0.60).
There is limited evidence favouring trauma-focused CBT over waitlist/control on reducing anxiety at post-treatment in survivors of motor vehicle accidents (k=5, n=185, SMD=-1.10, 95%CI -1.42, -0.79).
148
There is limited evidence favouring waitlist/control on attrition in survivors of motor vehicle accidents (k=4, n=129, RR=2.53, 95%CI 1.04, 6.16).
Box 55 Evidence statement matrix for RCTs comparing trauma-focused CBT and waitlist for adults with PTSD Component Rating Description Evidence base C Two level II studies with a moderate risk of bias, four level II studies with a high risk of bias.
Consistency B All studies consistent in the direction of effect, with some variation in size of effect likely due to differences in treatment length, and treatment style. Clinical impact C Strong evidence favouring treatment-focused CBT over waitlist/control on reducing PTSD symptoms severity, and clinically important point estimates for all other symptom outcome measures, although the full range of plausible estimates included clinically unimportant differences. Attrition was higher in the CBT group. Generalisability A Evidence from survivors of motor vehicle accidents.
Applicability B One study from the United Kingdom with a healthcare system similar to Australia’s. Other studies from Canada and the United States. Evidence probably applicable to the Australian healthcare context with some caveats.
Summary of evidence Limited evidence suggests a benefit in trauma-focused CBT over waitlist in people with PTSD due to motor vehicle accidents on the likelihood of having a PTSD diagnosis, depressive symptoms and anxiety. There is stronger evidence favouring CBT over waitlist on the outcome of severity of PTSD symptoms, as rated by both clinicians and patients. Patients were more likely to remain the study if they were in the waitlist/control condition, suggesting some patients do not tolerate trauma-focused CBT. (Grade C)
TRAUMA-FOCUSED CBT VERSUS WAITLIST FOR CHILDREN
Two RCTs (Ahrens et al 2002; Smith et al) met inclusion criteria and reported outcomes for a comparison of trauma focused CBT and waitlist in child populations. Ahrens and colleagues randomised 38 males incarcerated in a facility for adolescent offenders to cognitive processing therapy (n=19) or a waitlist control group (n=19). For the purposes of this comparison, cognitive processing therapy is considered to fit within the range of therapies
149 that may be denoted as CBT, and from this point onwards the intervention is referred to as CBT. The intervention consisted of eight sessions of 60 minutes duration and focused on antecedents, beliefs and consequences surrounding patient’s trauma, sharing written or taped narratives of their trauma, including thoughts and feelings, and the challenging of dysfunctional beliefs. The trial by Smith et al compared outcomes for a child/adolescent PTSD population with mixed trauma exposure randomised to either trauma-focused CBT group (n=12) or a waitlist control (n=12). The study intervention involved 10 weekly sessions of individual CBT that incorporated psychoeducation, activity scheduling/reclaiming life activities, imaginal reliving, cognitive restructuring, revisiting the site of the trauma, stimulus discrimination, direct work with nightmares, image transformation techniques, behavioural experiments, and work with parents. Of the five outcomes relevant to informing the proposed guidelines, two could be combined in meta-analyses, namely severity of self-reported PTSD and depression symptoms (results are shown in forest plots below). Smith and colleagues alone reported on the likelihood of having a PTSD diagnosis at post-treatment, clinician rated PTSD symptom severity and anxiety, and therefore evidence statements have been provided separately for these three outcomes.
Table 48 Study profiles for RCTs comparing trauma focused CBT and waitlist for children/adolescents with PTSD Reference Risk of bias Population Setting N Outcomes measured (Smith et al 2007) Low 8-18 year olds with Outpatient setting, 24 PTSD diagnosis mixed traumas (motor United Kingdom Severity of PTSD symptoms vehicle accidents, Depressive symptoms assaults, witnessed Anxiety violence) Attrition
(Ahrens & Rexford High 15-18 year old Correctional facility, 38 Severity of PTSD symptoms 2002) adolescent males with United States Depressive symptoms mixed traumas
There is limited evidence favouring trauma-focused CBT over waitlist on the likelihood of having a PTSD diagnosis post-treatment (k = 1, n = 24, RR = 0.14, 95%CI 0.02, 0.99).
There is evidence favouring trauma-focused CBT over waitlist on reducing the severity of clinician-rated PTSD symptoms at post-treatment (k = 1, n = 24, SMD = -1.55, n = 24; 95% CI -2.26, -0.84).
150
There is evidence favouring trauma-focused CBT over waitlist on reducing the severity of self- reported PTSD symptoms at post-treatment (k = 2; n = 62; SMD = -1.77, 95%CI -2.38, -1.37).
There is limited evidence suggesting that there is unlikely to be a clinically important difference between trauma-focused CBT and waitlist on reducing the severity of depression symptoms at post-treatment (k = 1; n = 62; SMD = -1.11, 95% CI -1.65, -0.56).
There is limited evidence suggesting that there is unlikely to be a clinically important difference between trauma-focused CBT and waitlist on reducing the severity of depression symptoms at post-treatment (k = 1; n = 24; SMD = -1.06, 95% CI -1.91, -0.20).
151 Box 56: Evidence statement matrix for RCT comparing trauma-focused CBT with waitlist for children/adolescents with PTSD Component Rating Description Evidence base C One level II study with low risk of bias and one level II study with high risk of bias
Consistency A Both studies consistent
Clinical impact C Moderate
Generalisability B One study conducted in the US and one in the UK, but both study populations had trauma types common to the intended Australian guideline population
Applicability C Evidence probably applicable to the Australian healthcare context with some caveats
Summary of evidence The two studies available for which measures of effect size could be calculated consistently showed that trauma-focused CBT is favourable over waitlist in child/adolescent populations. Though some clinically unimportant effects were observed in the range of estimates for three of the five outcomes measured, estimates for primary outcomes (i.e. PTSD severity/diagnostic status) included only clinically important effects. Level of generalisability is high and results are likely to be applicable to the Australian healthcare system with some exceptions, given one study was conducted in the United States (Grade C).
AFFECT REGULATION THERAPY VERSUS WAITLIST One study compared trauma affect regulation: guide for education and therapy (TARGET) against a waitlist control condition in a population of mothers or primary care-givers to children 5 years old or younger, who were from low income and ethno-minority groups (Ford et al 2011). This study was considered to have a moderate risk of bias as there was a failure to ensure that interviewers were blind to treatment condition, and there was a relatively high rate of loss to follow-up (30% in TARGET group post-treatment and 22% in the waitlist group).
Table 49 Study profiles for RCTs comparing trauma-focused CBT and waitlist/control for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Ford et al 2011) Moderate Mothers of young children Outpatient setting, 93 Diagnosis of PTSD from low income ethno- United States Severity of PTSD racial minority Depressive symptoms backgrounds with mixed Anxiety traumas
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between affect regulation therapy and waitlist on the likelihood of having a PTSD diagnosis post-treatment (k=1, n=93, RR=0.79, 95%CI 0.68, 0.92).
There is limited evidence favouring affect regulation therapy over waitlist on the severity of clinician-rated PTSD symptoms post-treatment (k=1, n=93, SMD=-0.96, 95%CI -1.39, - 0.53).
There is limited evidence favouring affect regulation therapy over waitlist on the severity of self-rated PTSD symptoms post-treatment (k=1, n=93, SMD =-1.14, 95%CI -1.58, -0.70).
152 The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between affect regulation therapy and waitlist on the likelihood of having a PTSD diagnosis post-treatment (k=1, n=93,SMD=-0.79, 95%CI -1.21, -0.37).
There is limited evidence favouring affect regulation therapy over waitlist on anxiety post- treatment (k=1, n=93, SMD -0.92(-1.35, -0.49).
Box 57: Evidence statement matrix for RCT comparing affect regulation therapy with waitlist for adults with PTSD Component Rating Description Evidence base C One level II study with a moderate risk of bias
Consistency NA Only one study
Clinical impact C Moderate – A trend favouring TARGET over waitlist on all outcome measures, with clinically important point estimates for PTSD symptom severity (clinician- and self-rated) and anxiety.
Generalisability C Evidence generalisable to a sample of the target population, and can be sensibly applied to broader population (mothers from low-income and ethnic minority groups).
Applicability C Evidence probably applicable to the Australian healthcare context with some caveats
Summary of evidence One study provided limited evidence favouring affect regulation therapy over waitlist, with clinically important point estimates on severity of PTSD (clinician- and self-rated) and anxiety. (Grade C)
EMDR VERSUS WAITLIST IN ADULTS
A total of six randomised controlled trials were identified which compared EMDR with waitlist in varying adult PTSD populations (Jensen 1994; Power et al 2002; Rothbaum 1997; Rothbaum et al 2005; Hogberg et al 2007).
Table 50: Study profiles for RCTs comparing EMDR and waitlist/usual care for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Vaughan et al Moderate Victims of violent crime, rape, child Outpatient PTSD 29 PTSD diagnosis 1994) abuse or motor accident clinic, Australia Depressive symptoms Attrition (Hogberg et al 2007) Moderate Employees of the public Outpatient setting, 24 PTSD diagnosis transportation system who had Sweden Severity of PTSD experienced a person-under-train Depressive symptoms accident or had been assaulted at Anxiety work Social and occupational functioning Quality of life (Rothbaum et al High Adult rape victims Outpatient setting, 48 PTSD diagnosis 2005) United States Depressive symptoms Anxiety (Power et al 2002) High Unspecified trauma (road Outpatient setting, 68 PTSD diagnosis accidents, occupational accidents, Scotland Severity of PTSD sexual or non-sexual assault, Depressive symptoms witnessing traumatic death, Anxiety real/implied physical threat) Attrition
153 (Jensen 1994) High Vietnam veterans Outpatient setting, 25 PTSD diagnosis United States Severity of PTSD Anxiety Attrition (Rothbaum 1997) High Female rape victims Outpatient setting, 18 PTSD diagnosis United States Severity of PTSD Depressive symptoms Anxiety Attrition
Of the six trials, Vaughan et al (1994) and Hogberg et al (2007) were of moderate quality, with outcome assessors blinded to the treatment allocation (clinicians and children/caregivers could not be blinded, given the nature of interventions in the two groups (EMDR and waitlist)) and the two intervention groups were comparable for patient demographic and disease characteristics at baseline. In the Vaughan et al trial, efficacy data were analysed on an ITT basis and all participants were followed up until 3 months after treatment. Results from the Hogberg et al trial were reported in all completers, which accounted for 88% (21/24) of all randomised participants.
In the other four low-quality trials, assessor blinding was either not performed or not reported in the published papers. Results were analysed according to per protocol principle for all of the four trials, with dropout rates of <15% in trials Jensen et al 1994 and Rothbaum et al 1997, 19% in trial Rothbaum et al 2005 and 31% in trial Power et al 2002. At baseline, the two intervention groups were not comparable for PTSD symptoms (re-experiencing) and depressive symptoms in the Rothbaum et al 1997 trial (EMDR vs waitlist: PTSD Symptom Scale (PSS)-Re-experience score: 6.1±2.5 vs 8.4±1.1; BDI score: 21.4±9.6 vs 34.8±13.8). No significant differences were reported between the two treatment arms in terms of baseline patient demographic and disease characteristics in the other three trials.
Patients were followed up for 3 to 15 months after treatment in four trials (Vaughan et al 1994, Power et al 2002, Rothbaum et al 2005 and Rothbaum et al 1997). However, comparison between EDMR and waitlist at follow-up could not be performed because participants in the waitlist groups had received active treatment by the end of follow-up periods in all of these five trials.
154 Figure 1 EMDR versus waitlist in adults: PTSD diagnosis, post-treatment
Favours EMDR Favours waitlist
The funnel plot indicates that there could potentially be some publication bias as all studies except one are skewed to the left and three studies fall outside the 95% confidence limits (Appendix H). However, this may be a reflection of the moderate heterogeneity across studies (I2=89.7%, p=0.000).
There is limited evidence favouring EMDR over waitlist on reducing the likelihood of having a PTSD diagnosis at post-treatment in adults (k=6; n=208; RR=0.48; 95% CI 0.26, 0.86).
Figure 2 EMDR versus waitlist in adults: PTSD symptom severity (clinician-rated), post-treatment
Favours EMDR Favours waitlist
The funnel plot shows no indication of publication bias (Appendix H).
155
There is evidence favouring EMDR over waitlist on reducing the severity of clinician-rated PTSD symptoms at post-treatment in adults (k=4; n=122; SMD=-1.54; 95% CI -1.96, -1.12).
Figure 3 EMDR versus waitlist in adults: PTSD symptom severity (self-report), post-treatment
Favours EMDR Favours waitlist
The funnel plot indicates that there could potentially be some publication bias as three studies fall well outside the 95% confidence limits (Appendix H). However, this may be a reflection of the high heterogeneity across studies (I2=88.0%, p=0.000). There is limited evidence favouring EMDR over waitlist on reducing the severity of self- report PTSD symptoms at post-treatment in adults (k=4; n=115; SMD=-1.20; 95% CI -2.49, 0.08).
156 Figure 4 EMDR versus waitlist in adults: depression, post-treatment
Favours EMDR Favours waitlist
There is evidence favouring EMDR over waitlist on reducing depression symptoms at post- treatment in adults (k=5; n=159; SMD=-1.39; 95% CI -1.74, -1.03).
157 Figure 5 EMDR versus waitlist in adults: anxiety, post-treatment
Favours EMDR Favours waitlist
There is evidence favouring EMDR over waitlist on reducing anxiety symptoms at post- treatment in adults (k=5; n=155; SMD=-1.18; 95% CI -1.52, -0.83).
Figure 6 EMDR versus waitlist in adults: attrition, post-treatment
Favours EMDR Favours waitlist
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between EMDR and waitlist on attrition at post-treatment in adults (k=4; n=146; RR=1.29; 95% CI 0.63, 2.64).
158 There is limited evidence favouring EMDR over waitlist on improving social, occupational, and psychological functioning at post-treatment in adults (k=1; n=21; SMD=1.13; 95% CI 0.20, 2.06).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between EMDR and waitlist on improving quality of life at post-treatment in adults (k=1, n=21; SMD=0.29; 95% CI -0.58, 1.16).
Box 58 Evidence statement matrix for RCTs comparing EMDR and waitlist for adults with PTSD Component Rating Description Evidence base C Two level II studies with a moderate risk of bias and four level II studies with a high risk of bias.
Consistency B Most studies consistent and inconsistency may be explained.
Clinical impact B There is clear evidence favouring EMDR over waitlist in terms of improving PTSD symptoms (clinician- rated), depression and anxiety. There were clinically important point estimates favouring EMDR over waitlist on reducing severity of PTSD symptoms (self-report), PTSD diagnosis and improving functioning, although the full ranges of estimates defined by the confidence interval included effect sizes too small to be clinically important. Generalisability A Evidence likely to be directly generalisable to the target population (a mix of trauma types; one study in Australian setting and the other five in developed countries (the United States, Scotland and Sweden).
Applicability B Evidence applicable to the Australian healthcare context with few caveats
Summary of evidence Six low- to moderate-quality trials were identified which compared EMDR with waitlist in adult PTSD patients. There is evidence favouring EMDR over waitlist on improving PTSD symptoms (clinician-rated), depression and anxiety. Limited evidence suggests that EMDR is more effective than waitlist at reducing the severity of PTSD symptoms (self-rated), decreasing the likelihood of have a PTSD diagnosis and improving social, occupational and psychological functioning. (Grade C).
Analysis of EMDR versus Waitlist studies according to ITT status
Only one of the six studies in this comparison used an ITT analysis (Vaughan et al 1994); the other studies based their analyses on completers only or some variation of completers. Seperate analyses of ITT studies were therefore not performed.
EMDR VERSUS WAITLIST IN CHILDREN
Three small randomised controlled trials were identified which compared EMDR with waitlist in children aged between 6 years and 16 years who grew up in a socially exposed condition (having a family member with criminality, substance abuse, chronic illness, handicap, or having the caregiver physically or mentally unavailable for the child) (Ahmad et al 2007); did not respond to pre-trial psychosocial treatment for PTSD following hurricane Iniki (Chemtob et al 2002a); or experienced a motor vehicle accident (Kemp et al 2010).
Table 51 Study profiles for RCTs comparing EMDR and waitlist for children with PTSD Reference Risk of bias Population Setting N Outcomes measured (Ahmad et al Moderate Children aged 6 – 16 years who Psychiatric outpatient 33 PTSD had experienced at least one clinic, Sweden
159 2007) traumatic experience and grown up in at least one socially exposed condition (Chemtob et al Moderate Children aged 6 – 12 years who Elementary schools, 32 PTSD 2002a) had exposed to hurricane Iniki and Hawaii, USA Depression were non-responders from previous Anxiety intervention (Kemp et al 2010) High Children aged 6 – 12 years who Community mental 27 PTSD had experience a motor vehicle health clinic, Australia Depression accident Anxiety Quality of life General functioning Child behaviour
The dropout rates were no more than 11% after 3 to 8 sessions of EMDR treatment in the three trials. Participants in the Chemtob et al (2002) and Kemp et al (2010) trials were followed up for 6 to 12 months after treatment; however, in the Kemp et al study, follow-up results of the two treatment groups were not reported separately and, therefore, cannot be compared. Among the three trials, the Ahmad et al (2007) study had the highest quality, given the similarity of the two treatment groups in terms of baseline patient demographic and disease characteristics, the ITT analysis of the efficacy data and the blinding of assessors (due to the nature of interventions in the two groups (EMDR and waitlist), clinicians and children/caregivers could not be blinded to the treatment allocation). In the Chemtob et al (2002) trial, although the assessors were also blinded to the treatment allocation, the trial was limited as the results were analysed on a per protocol basis and the comparison of the two study groups at baseline could not be performed due to a lack of patient data. Results from the low-quality trial by Kemp et al (2012) were subject to bias and confounding given that patient characteristics with respect to PTSD symptoms (avoidance) (IES-Avoidance score: 7.5±10.1 vs 16.4±11.5) and quality of life (GHQ-12 score: 1.25±1.91 vs 3.93±3.95) were not comparable at baseline between the EMDR group and the waitlist group, and that outcome assessors might not be blinded.
Figure 7 EMDR versus waitlist in children: PTSD symptom severity (clinician-rated), post-treatment
Favours EMDR Favours waitlist
160 There is evidence suggesting that there is unlikely to be a clinically important difference between EMDR and waitlist on reducing the severity of clinician-rated PTSD symptoms at post-treatment in children aged between 6 years and 16 years (k=2; n=65; SMD=-0.27; 95% CI -0.76, 0.22).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between EMDR and waitlist on reducing the severity of self- report PTSD symptoms at post-treatment in children aged between 6 years and 12 years (k=1; n=24; SMD= -0.74; 95% CI -1.57, 0.08).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between EMDR and waitlist on reducing the severity of self- report PTSD symptoms at 6-month follow-up in children aged between 6 years and 12 years (k=1; n=32; SMD= -0.53; 95% CI -1.24, 0.17).
Figure 8 EMDR versus waitlist in children: depression, post-treatment
Favours EMDR Favours waitlist
There is evidence suggesting that there is unlikely to be a clinically important difference between EMDR and waitlist on reducing depression symptoms at post-treatment in children aged between 6 years and 12 years (k=2; n=56; SMD=-0.09; 95% CI -0.62, 0.43).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between EMDR and waitlist on reducing depression symptoms at 6-month follow-up in children aged between 6 years and 12 years (k=1; n=32; SMD=-0.20; 95% CI -0.89, 0.50).
161 Figure 9 EMDR versus waitlist in children: anxiety, post-treatment
Favours EMDR Favours waitlist
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between EMDR and waitlist on reducing anxiety symptoms at post-treatment in children aged between 6 years and 12 years (k=2; n=56; SMD=-0.10; 95% CI -0.84, 0.65).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between EMDR and waitlist on reducing anxiety symptoms at 6-month follow-up in children aged between 6 years and 12 years (k=1; n=32; SMD=-0.39; 95% CI -1.09, 0.31).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between EMDR and waitlist on improving quality of life at post-treatment in children aged between 6 years and 12 years (k=1; n=24; SMD=-0.53; 95% CI -1.35, 0.28).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between EMDR and waitlist on improving general functioning at post-treatment in children aged between 6 years and 12 years (k=1; n=24; SMD=0.13; 95% CI -0.68, 0.93).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between EMDR and waitlist on reducing behavioural problems at post-treatment in children aged between 6 years and 12 years (k=1; n=24; SMD=-0.44; 95% CI -1.25, 0.37).
Box 59 Evidence statement matrix for RCTs comparing EMDR with waitlist in children with PTSD Component Rating Description Evidence base C Two small level II studies with a moderate risk of bias and one small level II study with a high risk of bias
162 Consistency A Studies consistent in finding no conclusive differences between the treatments
Clinical impact D All treatments were found to be equally effective on all outcome measures.
Generalisability A Evidence likely to be directly generalisable to the target population (a mix of trauma types; one study in Australian setting, and the other two in developed countries (the United States and Sweden)) Applicability B Evidence applicable to the Australian healthcare context with few caveats
Summary of evidence
Evidence failed to show an advantage for EMDR over waitlist in terms of improving PTSD symptoms, depression symptoms, anxiety, quality of life, general functioning and behaviour in children. (Grade C).
STRESS MANAGEMENT VERSUS WAITLIST Four studies assessed the effectiveness of a stress management program compared to waitlist and are listed in Table 52. Two studies used stress inoculation training (SIT) to treat PTSD in women who had experienced sexual or non-sexual assault (Foa et al 1999; Foa et al 1991). During the nine biweekly individual 90- to 120-minute sessions SIT sessions, the women were taught coping skills to manage assault-related anxiety and post-assault problems including deep muscle relaxation, cue-controlled and differential relaxation, thought stopping, cognitive restructuring, guided self-dialogue, covert modelling, and role-playing. No instructions for exposure were included. The final two studies used relaxation techniques to manage stress. Vaughan et al (1994) treated PTSD in outpatients who had been victims of violent crime, rape, child abuse or motor accidents with applied muscle relaxation (AMR) administered in 3-5 individual sessions of 50-minutes over a 2-3 week period. Subjects were taught to recognize early signals of anxiety so that they could use relaxation to manage the situation. Carlson et al (1998) used a computerized electrophysiological monitoring and feedback system to provide biofeedback-assisted relaxation (BAR) treatment to war veterans previously diagnosed with PTSD. Instructions were given that outlined the function of the feedback stimulus and suggestions for generalized relaxation during 12 individual treatment session lasting 40 minutes. Multiple-site biofeedback consisted of a pure tone on the headphones driven by an equally weighted average of EMG potentials on four sites. Participants were also given a recorded cassette containing modified progressive relaxation instructions, and written instructions for daily home use. The stress management interventions were carried out by experienced therapists including social workers, counsellors, clinical psychologists and psychiatrists. Outcomes for PTSD, depression, anxiety, quality of life, and attrition were reported post-treatment. Longer follow- ups were not possible as the wait listed groups were offered treatment at this point. Clinically important differences favouring the stress management over waitlist were reported on reducing the likelihood of having a PTSD diagnosis. Additionally, clinically important differences were seen for reducing the likelihood of having a PTSD diagnosis, the severity of PTSD symptoms, and anxiety. There were also statistically significant differences favouring stress management over waitlist in reducing the severity of PTSD symptoms and anxiety post-treatment but the effect size was too small to be clinically important. The evidence
163 statements, RR or SMD for each relevant outcome and the evidence matrix (Box 60) are presented below. Table 52 Study profiles for RCTs comparing stress management and waitlist for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Vaughan et al Moderate Victims of violent crime, rape, Outpatient PTSD clinic, 29 PTSD diagnosis 1994) child abuse or motor accident Australia Depressive symptoms Attrition (Foa et al 1999) High Female victims of sexual and Outpatient setting, 26 PTSD diagnosis nonsexual assault United States Severity of PTSD Depressive symptoms Anxiety Social adjustment Attrition (Foa et al 1991) High Women who had Outpatient setting, 27 PTSD diagnosis experienced rape or United States Severity of PTSD attempted rape Depressive symptoms Anxiety Attrition (Carlson et al 1998) High Male war veterans Outpatient setting, 25 PTSD diagnosis United States Severity of PTSD Depressive symptoms Anxiety Attrition
The funnel plot showed no indication of publication bias (Appendix H). There is limited evidence favouring stress management therapy over waitlist on the likelihood of having a PTSD diagnosis at post-treatment (k = 4, n = 121; RR = 0.63; 95%CI, 0.51, 0.76).
164
The funnel plot showed no indication of publication bias (Appendix H). There is limited evidence favouring stress management therapy over waitlist on reducing the severity of clinician-rated PTSD symptoms at post-treatment (k = 3, n = 86; SMD = -1.14; 95%CI, -1.62, -0.67). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between stress management therapy and waitlist on reducing the severity of clinician-rated PTSD symptoms at post-treatment (k = 1, n = 24; SMD = 0.33; 95%CI, -0.47, 1.14).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between stress management therapy and waitlist on reducing depression symptoms at post-treatment (k = 4, n = 109; SMD = -0.73; 95%CI, -1.12, -0.33).
165
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between stress management therapy and waitlist on reducing anxiety symptoms at post-treatment (k = 3, n = 82; SMD = -0.77; 95%CI, -1.23, -0.31). There is limited evidence favouring stress management therapy over waitlist on improving social adjustment at post-treatment (k = 1, n = 34; SMD = -0.98; 95%CI -1.70, -0.27).
There is limited evidence favouring waitlist over stress management therapy on attrition rate post-treatment (k = 4, n = 121; RR = 2.19; 95%CI 0.71, 6.73).
166 Box 60 Evidence statement matrix for RCTs comparing stress management and waitlist for adults with PTSD Component Rating Description Evidence base C One level II studies with a moderate risk of bias and three level II studies with a high risk of bias Consistency A Studies are consistent Clinical impact C The point estimates favouring stress management over waitlist were clinically important for reducing the likelihood of having PTSD, the severity of PTSD symptoms and for improved social adjustment post- treatment, and although the differences between the two groups were statistically significant, the CIs included clinically unimportant effects. The point estimates for depression and anxiety favoured stress management over waitlist but were too small to be clinically important even though the differences were statistically significant. Generalisability A Population consisted of women who had been abused (sexually or non-sexually), male and female survivors of mixed trauma and war veterans Applicability A One study was conducted in Australia and evidence is directly applicable. Three studies were conducted in the USA, which has similar healthcare for patients exposed to potentially traumatic events compared to the Australian healthcare context.
Summary of evidence There was a trend towards favouring stress management over waitlist on all outcome measures except for attrition, which favoured waitlist over stress management. Clinically important point estimates were found for the likelihood of having PTSD, clinician-rated PTSD severity, and social adjustment, but not for depressive symptoms and anxiety. All outcomes included clinically unimportant effects within their confidence intervals. (Grade C)
STRESS MANAGEMENT VS WAITLIST IN THE SUBGROUP OF WOMEN WHO HAD PTSD SECONDARY TO PHYSICAL OR SEXUAL ASSAULT
Two studies, both by Foa, were included in the subgroup analysis of women who had experienced sexual or non-sexual assault. In the Foa 1991 study, women who had been raped were randomised to one of four arms: prolonged exposure, stress inoculation training (SIT), supportive counselling and waitlist (only SIT vs waitlist considered here). In the Foa 1999 study, women who had experienced sexual or physical assault were randomised to prolonged exposure (PE), SIT, combined PE and SIT or waitlist (only SIT vs waitlist considered here). Both of these studies were of poor to average quality with a high risk of bias, with both lacking information on randomisation and only reporting completer analysis. However the studies were very consistent in their findings of greater effectiveness of SIT over waitlist on PTSD severity and diagnosis, depression and anxiety.
167 Table 53 Study profiles for RCTs comparing stress management and waitlist for the subgroup of abused women with PTSD Reference Risk of bias Population Setting N Outcomes measured (Foa et al 1999) High Female victims of sexual and Outpatient setting, 26 PTSD diagnosis nonsexual assault United States Severity of PTSD Depressive symptoms Anxiety Social adjustment Attrition (Foa et al 1991) High Women who had Outpatient setting, 27 PTSD diagnosis experienced rape or United States Severity of PTSD attempted rape Depressive symptoms Anxiety Attrition
There is limited evidence favouring stress management over waitlist for abused women on the likelihood of having a PTSD diagnosis at posttreatment (k=2, n=68; RR 0.60 95% CI 0.46, 0.78)
168
There is evidence favouring stress management over waitlist for abused women for reducing the severity of clinician-rated PTSD symptoms (k=2, n=58; SMD -1.53 95% CI -2.13, -0.93)
There is limited evidence favouring stress management over waitlist in abused women for reducing depression (k=2, n=57; SMD -0.87 95% CI -1.42, -0.31)
There is limited evidence favouring stress management over waitlist in abused women for reducing anxiety (k=2, n=57; SMD -0.99 95% CI -1.55, -0.43)
169
There is limited evidence favouring waitlist over stress management for study attrition (k=2, n=68; RR 2.91 95% CI 0.69, 12.27)
Box 61 Evidence statement matrix for RCTs comparing stress management and waitlist for the subgroup of abused women with PTSD Component Rating Description Evidence base D Two small studies with a high risk of bias Consistency A Studies are consistent Clinical impact C The point estimates favouring stress management over waitlist were clinically important for reducing the likelihood of having PTSD, the severity of PTSD symptoms, depression and anxiety; but for all but clinician-rated PTSD, the CIs included clinically unimportant effects. Generalisability A Population consisted of women who had been abused (sexually or non-sexually) who are a target population of the guidelines Applicability C The studies were conducted in the USA; probably applicable to the Australian healthcare context with some caveats.
Summary of evidence Two small, poor quality studies found a trend towards favouring stress management over waitlist on all outcome measures except for attrition, which favoured waitlist over stress management. On clinician-rated PTSD severity, the effect (including all within the 95% CI) was clinically important favouring stress management. Clinically important point estimates were found for the likelihood of having PTSD, depressive symptoms and anxiety, however these outcomes included clinically unimportant effects within their confidence intervals. (Grade C)
PROBLEM-SOLVING THERAPY VERSUS WAITLIST Two studies investigated the use of present-centred therapy (PCT) as a treatment for PTSD in people exposed to trauma. McDonagh et al (2005) initially developed a 14-session PCT program for individuals that they used to treat PTSD in women with histories of childhood sexual abuse. Ford et al (2011) adapted this program into a 12-session version that was used to treat PTSD in mothers/primary caregivers of young children who had past exposure to victimization or incarceration. The main elements of PCT are psychoeducation about the diagnosis of PTSD and the common after-effects of trauma, training in social problem
170 solving to enhance coping with PTSD symptoms, and journal writing. PCT does not include the breathing retraining, prolonged exposure, in vivo exposure, or cognitive restructuring elements of CBT.
Table 54 Study profiles for RCTs comparing problem-solving therapy and waitlist for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Ford et al 2011) Moderate Mothers of young children Outpatient setting, 93 Diagnosis of PTSD from low income ethno-racial United States Severity of PTSD minority backgrounds with Depressive symptoms mixed traumas Anxiety (McDonagh et al High Women with PTSD Outpatient setting, 45 Severity of PTSD 2005) secondary to Child Sexual United States Depressive symptoms Abuse Anxiety Quality of life Attrition
There is evidence suggesting that there is unlikely to be a clinically important difference between problem-solving therapy and waitlist on the likelihood of having a PTSD diagnosis post-treatment (k=1, n=98, RR=0.85, 95%CI 0.76, 0.96).
There is limited evidence favouring problem-solving therapy over waitlist for PTSD severity (clinician-rated) post-treatment (k=2, n=143, SMD=-0.97, 95%CI -1.32, -0.62).
There is limited evidence favouring problem-solving therapy over waitlist for PTSD severity (self-rated) post-treatment (k=1, n=98, SMD=-0.87, 95%CI -1.23, -0.46).
171
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between problem-solving therapy and waitlist on depressive symptoms post-treatment (k=2, n=143, SMD=-0.79, 95%CI -1.13, -0.45).
There is evidence suggesting that there is unlikely to be a clinically important difference between problem-solving therapy and waitlist on anxiety post-treatment (k=2, n=143, SMD=-0.41, 95%CI -0.75, -0.08). There is evidence suggesting that there is unlikely to be a clinically important difference between problem-solving therapy and waitlist on improving quality of life at post-treatment (k = 1, n = 45; SMD = 0.13; 95%CI -0.46, 0.71). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between problem-solving therapy and waitlist on attrition post-treatment (k=1, n=45, RR=0.70, 95%CI 0.13, 3.78).
172 Box 62 Evidence statement matrix for RCTs comparing stress management and waitlist for adults with PTSD Component Rating Description Evidence base C One level II study with a moderate risk of bias and one level II study with a high risk of bias Consistency A Studies are consistent in the direction of effect Clinical impact C The point estimates favouring problem-solving therapy over waitlist were clinically important for reducing the likelihood of having PTSD, the severity of PTSD symptoms and for improved social adjustment post- treatment, and although the differences between the two groups were statistically significant, the CIs included clinically unimportant effects. The point estimates for depression and anxiety favoured stress management over waitlist but were too small to be clinically important even though the differences were statistically significant. Generalisability A Population consisted of women who had been sexually abused as a child, or mothers of young children from low income ethno-racial minority backgrounds with mixed traumas Applicability C Both studies were conducted in the USA, which has similar healthcare for patients exposed to potentially traumatic events compared to the Australian healthcare context, with a few caveats.
Summary of evidence There was a trend towards favouring problem-solving therapy over waitlist on all outcome measures except for attrition and quality of life, which favoured waitlist over stress management. Clinically important point estimates were found for PTSD severity (both clinician- and self-rated), but not for any other outcomes. (Grade C)
INTERPERSONAL PSYCHOTHERAPY VERSUS WAITLIST One study reported on the effectiveness of interpersonal psychotherapy compared to a wait listed control in treating PTSD with or without major depressive disorder (MDD) in low- income minority women with current relationship problems (Krupnick et al 2008). Interpersonal psychotherapy involved sixteen 2-hour groups sessions of 3-5 members with a female doctoral-level clinical psychologist. The sessions were aimed at developing group cohesion, education about PTSD and related interpersonal difficulties, addressing relationship disputes and social deficits, mourning the loss of prior relationships, identification of reactivation triggers, and anticipation of future problems. The wait listed control group had face-to-face assessment interviews and were offered treatment after completion of 4-month follow-up assessment.
This study had a high attrition rate; of the 32 women who were randomised to the treatment group, only 24 (75%) actually began treatment and only 17 (53%) attended more than half of the sessions. The post-treatment assessment could only be obtained for 20 women (63%) in the treatment group and 7 of the 16 women (44%) who were randomised to the wait listed control group. Due to the greater than 50% loss in the control arm, the post-treatment data has been excluded from this review. However, at 4 month follow-up, assessments were obtained from 26 women (81%) in the treatment group and 10 women (63%) in the control group. Thus, the outcomes from the 4 month follow-up assessments have been included in this review.
The authors reported the number of patients diagnosed with PTSD and MDD at 4 months and the mean change from baseline for PTSD symptoms, depressive symptoms and for social functioning (2 of the 5 subscales of the 47-item version of the inventory of interpersonal problems questionnaire). The differences in mean change from baseline were greater for interpersonal psychotherapy compared to the wait listed control group although they did not reach statistical significance.
173 Table 55 Study profile for RCT comparing interpersonal psychotherapy with a wait listed control in treating people with chronic PTSD Reference Risk of bias Population Setting N Outcomes measured (Krupnick et al 2008) High Low income minority women Outpatient setting, 48 Diagnosis of PTSD with PTSD USA Severity of PTSD symptoms Diagnosis of MDD Depression Interpersonal functioning: Need for social approval Lack of sociability Attrition CAPS = Clinician Administered PTSD Scale; HRSD = Hamilton Rating Scale for Depression; IIP = Inventory of Interpersonal Problems; MDD = Major Depressive Disorder.
There is limited evidence favouring interpersonal psychotherapy over wait listed control on reducing the likelihood of having a PTSD diagnosis (clinically-administered CAPS-1) at 4 months follow-up (k = 1; n = 48; RR = 0.55; 95%CI 0.35, 0.97). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between interpersonal psychotherapy and wait listed control on reducing the severity of clinician-rated PTSD symptoms at 4 months follow-up (k = 1; n = 36; SMD = ‒0.38; 95%CI ‒0.99, 0.22). There is limited evidence favouring interpersonal psychotherapy over wait listed control on reducing the likelihood of having a diagnosis of clinician-rated MDD at 4 months follow-up (k = 1; n = 36; RR = 0.55; 95%CI 0.36, 1.11). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between interpersonal psychotherapy and wait listed control on reducing depression at 4 months follow-up (k = 1; n = 36; SMD = ‒0.39; 95%CI ‒0.99, 0.22). There is limited evidence favouring interpersonal psychotherapy over wait listed control on reducing the need for social approval at 4 months follow-up (k = 1; n = 36; SMD = ‒0.61; 95%CI ‒1.22, 0.00). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between interpersonal psychotherapy and wait listed control on reducing lack of sociability at 4 months follow-up (k = 1; n = 36; SMD = ‒0.05; 95%CI ‒ 0.65, 0.55). There is limited evidence favouring interpersonal psychotherapy over wait listed control on reducing the attrition rate at 4 months follow-up (k = 1; n = 36; RR = 0.50; 95%CI 0.20, 1.30).
174 Box 63 Evidence statement matrix for interpersonal psychotherapy with a wait listed control in treating people prior to exposure to trauma Component Rating Description Evidence base C One level II study with a high risk of bias Consistency NA Only one study Clinical impact C The point estimates favouring interpersonal psychotherapy over waitlist were clinically important for the likelihood of having a diagnosis of PTSD or MDD, and reducing the need for social approval at 4 months follow-up. However, the CIs included clinically unimportant effects and the difference was not statistically significant for the diagnosis of MDD. Generalisability A Population consisted of low income minority women with PTSD Applicability C The study was conducted in the USA, which has similar healthcare for patients with PTSD compared to the Australian healthcare context, with some caveats.
Summary of evidence There was limited evidence favouring interpersonal psychotherapy over waitlist for the likelihood of having a diagnosis of PTSD or MDD, and for reducing the need for social approval. However, the CIs included clinically unimportant effects on all outcomes, and the difference between interpersonal psychotherapy and waitlist was not statistically significant for MDD diagnosis. (Grade C)
PSYCHODYNAMIC THERAPY VERSUS WAITLIST One study with a high risk of bias compared the effectiveness of psychodynamic therapy versus waitlist in a group with people with PTSD due to a mix of different trauma types (Brom et al.1989).
Table 56 Study profiles for RCTs comparing psychodynamic therapy and waitlist/usual care for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Brom et al 1989) High Experienced a violent crime, Outpatient setting, the 52 Severity of PTSD traffic accident, or lost a Netherlands Anxiety loved one due to murder/suicide, traffic accident, or illness
There is limited evidence favouring psychodynamic therapy over waitlist on reducing the severity of self-report PTSD symptoms at post-treatment (k=1, n=52, SMD=-0.86, 95%CI - 1.14, -0.28)
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between psychodynamic therapy and waitlist on reducing anxiety symptoms at post-treatment (k=1, n=52, SMD=-0.61, 95%CI-1.16, -0.05).
Box 64 Evidence statement matrix for RCTs comparing psychodynamic therapy and waitlist for adults with PTSD Component Rating Description Evidence base D One level II study a high risk of bias
Consistency N/A Only one study
Clinical impact D A clinically important point estimate found favouring psychodynamic therapy over waitlist on PTSD severity post-treatment, however, the full range of estimates included clinically irrelevant effects. Psychodynamic therapy was found to also reduce anxiety more than waitlist, but this difference was not considered large enough to be clinically important.
175 Generalisability A Mix of trauma types, generalisable to the Australian population
Applicability C Limited applicability – not a treatment often used currently for PTSD. Healthcare setting was in the Netherlands, likely to be applicable with some caveats. Summary of evidence Limited evidence favoured psychodynamic therapy over waitlist at reducing PTSD severity post-treatment, but the full range of plausible estimates also included clinically irrelevant effects. (Grade D)
HYPNOTHERAPY VERSUS WAITLIST Brom et al (1989) compared a hypnotherapy condition against a waitlist condition for treating PTSD. There was a trend towards favouring hypnotherapy, but this was not considered clinically important.
Table 57 Study profiles for RCTs comparing hypnotherapy and waitlist for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Brom et al 1989) High Experienced a violent crime, Outpatient setting, the 52 Severity of PTSD traffic accident, or lost a Netherlands Anxiety loved one due to murder/suicide, traffic accident, or illness
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between hypnotherapy and waitlist on reducing the severity of self- report PTSD symptoms at post-treatment (k=1, n=52, SMD=-0.65, 95%CI -1.21, -0.09).
There is evidence suggesting that there is unlikely to be a clinically significant difference between hypnotherapy and waitlist on reducing anxiety symptoms at post-treatment (k=1, n=52, SMD=-0.15, 95%CI -0.69, 0.39).
Box 65 Evidence statement matrix for RCTs comparing hypnotherapy and waitlist for adults with PTSD Component Rating Description Evidence base D One level II study a high risk of bias
Consistency N/A Only one study
Clinical impact D A trend favouring hypnotherapy over waitlist, but not large enough to be considered clinically important.
Generalisability A Mix of trauma types, generalisable to the Australian population
Applicability C Limited applicability – not a treatment often used currently for PTSD. Healthcare setting was in the Netherlands, likely to be applicable with some caveats.
Summary of evidence Limited evidence found no clinically important differences between hypnotherapy and waitlist post-treatment. (Grade D)
176 SUPPORTIVE COUNSELLING VERSUS WAITLIST Supportive counselling includes psychoeducation about stress reactions and normalisation of PTSD symptoms. Two studies compared supportive counselling against a waitlist condition (Blanchard et al 2003; Foa et al 1991).
Table 58 Study profiles for RCTs comparing supportive psychotherapy and waitlist for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Blanchard et al High Motor vehicle accident Outpatient, United 51 PTSD diagnosis 2003) survivors, adults States Severity of PTSD Depressive symptoms Anxiety Attrition (Foa et al 1991) High Women who had Outpatient setting, 27 PTSD diagnosis experienced sexual assault, United States Severity of PTSD aggravated assault, or Depressive symptoms assault with a weapon, aged Anxiety over 16 Attrition
There is evidence suggesting that there is unlikely to be a clinically important difference between supportive counselling and waitlist on the likelihood of having a PTSD diagnosis post-treatment (k=2, n=78, RR=0.88, 95%CI 0.69, 1.14).
177
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between supportive counselling and waitlist on reducing the severity of clinician-rated PTSD symptoms at post-treatment (k=2, n=72, SMD=-0.43, 95%CI -0.90, 0.04).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between supportive counselling and waitlist on reducing the severity of self-report PTSD symptoms at post-treatment (k=1, n=51, SMD=-0.50, 95%CI - 1.06, 0.06).
There is evidence suggesting that there is unlikely to be a clinically important difference between supportive counselling and waitlist on reducing depressive symptoms at post- treatment (k=2, n=72, SMD=-0.25, -0.71, 0.22).
178
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between supportive counselling and waitlist on reducing anxiety symptoms at post-treatment (k=2, n=72, SMD=-0.56, 95%CI -1.04, -0.09).
There is limited evidence favouring waitlist over supportive counselling on attrition post- treatment (k=2, n=85, RR=4.21, 95%CI 1.00, 17.72).
Box 66 Evidence statement matrix for RCTs comparing supportive counselling and waitlist for adults/adolescents with PTSD Component Rating Description Evidence base D Two level II studies with a high risk of bias
Consistency B Both studies consistent in showing little difference between the two conditions
Clinical impact D No clinically significant differences found on any outcome measures, except for attrition, which favoured waitlist over supportive counselling.
Generalisability A Trauma due to motor vehicle accidents, sexual assault, aggravated assault, or assault with a weapon.
179 Applicability C Evidence from the United States. Likely applicable to the Australian healthcare setting with some caveats.
Summary of evidence No clinically important benefit was found from supportive counselling over a waitlist condition in adults/adolescents with PTSD. (Grade D)
GROUP CBT VERSUS WAITLIST/CONTROL Two studies were identified which compared the effectiveness of group CBT (described as CBT, or affect management) against either a waitlist condition, or a minimal attention control condition. One further RCT was identified previously by NICE (Classen 2001) but had to be excluded, as the full reference was not in their reference list, and could not be identified elsewhere.
One of the studies was in females who had survived child sexual abuse (Zlotnick et al 1997), while the remaining study included both genders, and included people who had suffered trauma from a motor vehicle accident.
Both studies were considered to have a high risk of bias as they restricted their analyses to data from patients who completed treatment, rather than an intention-to-treat analysis, and had loss to follow-up. The results may therefore be considered to be good quality in the sub- population who completed treatment, but is poorer quality if being generalised to include all who start treatment.
On all outcome measures there was a trend favouring group CBT over waitlist/minimal attention control conditions, with clinically important point differences found on the outcomes of PTSD diagnosis and severity of PTSD symptoms as rated by the patients. However, due to the small size of the studies, the variability surrounding the point estimates also included clinically unimportant effects.
Table 59 Study profiles for RCTs comparing group CBT and waitlist for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Zlotnick et al 1997) High Female survivors of child Outpatient setting, 33 PTSD diagnosis sexual abuse United States Severity of PTSD Attrition
(Beck et al 2009) High Motor vehicle accident Outpatient setting, 33 PTSD diagnosis survivors United States Severity of PTSD Depressive symptoms Anxiety Attrition
180
There is limited evidence favouring group CBT over waitlist/control on the likelihood of having a PTSD diagnosis post-treatment. (k=2, n=81, RR=0.40, 95%CI 0.23, 0.69).
There is limited evidence favouring group CBT over waitlist/control on the severity of clinician-rated PTSD symptoms at post-treatment (k=1, n=33, SMD=-0.84, 95%CI -1.56, - 0.13).
There is limited evidence favouring group CBT over waitlist/control on reducing the severity of self-rated PTSD symptoms at post-treatment (k=2, n=66, SMD=-0.91, 95%CI -1.42, - 0.40). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between group CBT and waitlist/control on reducing depressive symptoms at post-treatment (k=1, n=33, SMD=-0.63, 95%CI -1.33, 0.07). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between group CBT and waitlist/control on reducing anxiety symptoms at post-treatment (k=1, n=33, SMD-0.53, 95%CI -1.22, 0.16).
181
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between group CBT and waitlist/control on attrition post- treatment (k=2, n=92, RR=1.52, 95%CI 0.70, 3.33).
Box 67 Evidence statement matrix for RCTs comparing group CBT and waitlist/control for adults with PTSD Component Rating Description Evidence base D Two level II studies with a high risk of bias due to drop-outs, and analyses based on completer-data only Consistency B All studies and outcome measures consistent in direction of effect, with a small amount of variation in size of effect Clinical impact C There were three patient-relevant outcomes (PTSD diagnosis and PTSD symptom severity, both clinician- and self-rated) which showed clinically important improvements in the group CBT condition as compared to the no-treatment conditions. However, the full range of estimates included clinically unimportant effects, and the effect sizes found on outcomes of depressive symptoms and anxiety were all deemed too small to be considered clinically important.
Generalisability B Populations studies in the evidence are similar to target population for guideline, being a mix of child sexual abuse, and car accidents, in people from the United States
Applicability C Evidence probably applicable to the Australian healthcare context, with some caveats due to differences between United States and Australian healthcare systems.
Summary of evidence Completer data favours the use of group CBT over a waitlist/minimal attention control condition for treatment of PTSD, reducing the likelihood of having a PTSD, and the severity of PTSD symptoms on clinician-rated and self-rated measures. However, the impact on the levels of depressive symptoms or anxiety was not large enough to be considered clinically important. (Grade C).
GROUP AND INDIVIDUAL TRAUMA-FOCUSED CBT VERSUS WAITLIST One study combined 10 weeks of individual trauma-focused CBT (1-9 weeks plus week 17) with 17 weeks of group trauma-focused CBT, in a population of female survivors of childhood sexual abuse (Chard 2005). The treatment received was cognitive processing
182 therapy for sexual abuse survivors (CPT-SA) and aimed to give clients the benefits of both individual therapy. The study was considered to have a high risk of bias due to the drop-out rate (22%) and although intention-to-treat analyses were performed, only data on treatment completers were presented. For those who completed treatment, clear benefits were found on all measures of effectiveness. Chard (2005) reported that the benefits were still statistically significant when intention-to-treat analyses were performed, using the last observation carried forward approach, but insufficient data were provided in order to determine how clinically important the benefits were for the whole group, when conservatively including those who dropped out.
Table 60 Study profiles for RCTs comparing combined group and individual trauma focused CBT and waitlist for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Chard 2005) High Female survivors of Outpatient setting, 55/71 PTSD diagnosis child sexual abuse United States Severity of PTSD symptoms Depressive symptoms
There is evidence favouring individual and group trauma-focused CBT over waitlist on the likelihood of having a PTSD diagnosis post-treatment (k=1, n=55, RR=3.58, 95%CI 1.88, 6.83).
There is evidence favouring individual and group trauma-focused CBT over waitlist on reducing the severity of clinician-rated PTSD symptoms at post-treatment (k=1, n=55, SMD=-2.32, 95%CI -3.01, -1.64).
There is evidence favouring individual and group trauma-focused CBT over waitlist on reducing the severity of self-report PTSD symptoms at post-treatment (k=1, n=55, SMD= -2.42, 95%CI -3.12, -1.73).
There is evidence favouring individual and group trauma-focused CBT over waitlist on reducing depressive symptoms at post-treatment (k=1, n=55, SMD=-2.00, 95%CI -2.64, -1.35).
Box 68 Evidence statement matrix for RCTs comparing individual plus group CBT and waitlist for adults with PTSD Component Rating Description Evidence base D One level II study with a high risk of bias due to drop-out and analyses based on completer-data only.
Consistency NA Only one study
Clinical impact A Large effect sizes, indicating clearly beneficial effects of group and individual trauma-focused CBT compared to a minimal attention waitlist, in women who had experienced childhood sexual abuse. Benefits were seen on the likelihood of still having PTSD post-treatment, PTSD symptoms severity (both clinician and self-rated) and depressive symptoms. No clear differences were found on attrition although there was a higher rate of drop-out in the waitlist group. Generalisability B Evidence likely to be directly generalisable to survivors of childhood sexual abuse. May be generalisable with some caveats to survivors of other trauma types.
Applicability C Evidence probably applicable to Australian healthcare context (study perform in United States).
Summary of evidence
183 One study reported that group and individual CBT combined is clearly superior to a waitlist condition, for survivors of childhood sexual abuse on measures of PTSD and depressive symptoms. (Grade C)
GROUP IMAGERY REHEARSAL THERAPY VERUS WAITLIST One study compared group imagery rehearsal therapy (IRT) for chronic nightmares and a waitlist group in women who had experienced rape or sexual assault (Krakow et al 2001). This study was considered to have a high risk of bias due to using completer-data only and having a 32% loss to follow-up. Imagery rehearsal therapy involved describing a nightmare, rewriting the nightmare any way the patient wishes, and then rehearsing the new nightmare. Initially this was done by writing the old and new dreams down, but then after that, patients were encouraged to do this mentally, spending 5 – 20 minutes per day rehearsing pleasant imagery (Krakow et al 2001). Women who were allocated IRT received three sessions of treatment (a total of 7 hours) in groups of four to eight women. Clinician-rated PTSD symptom severity was reduced by a statistically significantly greater amount in the treatment group compared to the waitlist group, but this difference was not considered large enough to be considered clinically important.
Table 61 Study profiles for RCTs comparing group imagery rehearsal therapy and waitlist for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Krakow et al 2001) High Women who had Outpatient setting, 114/168 Severity of PTSD experienced rape or other United States Attrition sexual assault
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between group imagery rehearsal therapy and waitlist on the severity of clinician-rated PTSD post-treatment (k=1, n= 97, SMD=-0.72, 95%CI -1.13, - 0.31) The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between group imagery rehearsal therapy and waitlist on attrition (k=1, n=168, RR=1.00, 95%CI 0.59, 1.69).
Box 69 Evidence statement matrix for RCTs comparing group imagery rehearsal therapy and waitlist for adults with PTSD Component Rating Description Evidence base D One level II study with a high risk of bias due to high loss to follow-up and only completer data presented Consistency NA Only one study
Clinical impact D A trend favouring imagery rehearsal therapy for reducing the severity of clinician-rated PTSD severity, which was not large enough to be deemed clinically important.
Generalisability B Population studied in the evidence are similar to target population for guideline, being women who have experienced rape or other sexual assault, from the United States
Applicability C Evidence probably applicable to the Australian healthcare context, with some caveats due to differences between United States and Australian healthcare systems.
Summary of evidence One study with a high risk of bias found a trend favouring imagery rehearsal therapy on reducing the severity of clinician-rated PTSD symptoms, but the difference was not large
184 enough to be considered clinically important. (Grade D)
NARRATIVE EXPOSURE THERAPY (TRAUMA-FOCUSED) VERSUS WAITLIST Two moderate quality RCTs (Ertl et al 2011; Ruf et al 2010) were available for a comparison of narrative exposure therapy (NET) and waitlist (WL). The trial by Ertl and colleagues, recruited former child soliders (mean age = 18 years) while the study by Ruf et al included refugee children with a mean age of approximately 11.5 years (range 7-16 years). Therefore, it was not considered appropriate to combine the results of these studies in a meta-analysis, and thus measures of treatment effect size have been calculated separately for these two studies.
The RCT by Ertl and colleagues reported on three, six and 12-month outcomes for PTSD and depression symptom severity, as determined by the Clinician Administered PTSD Scale (CAPS) and Mini International Neuropsychiatric Interview (MINI), respectively, and on functional impairment (CAPS). Measures of effect size for severity of PTSD and functional impairment suggested that there is no difference between NET and WL at six-month follow- up, while the results at the three and 12 month time points provided only inconclusive evidence. For depression outcomes, the evidence suggested that there is unlikely to be a difference between NET and WL at any time point following treatment.
Ruf et al reported on the severity of PTSD symptoms as per the UCLA PTSD Index for DSM-IV. No secondary outcomes were reported. They followed up patients allocated to NET for 12 months, however, the latest available follow-up data for WL patients was at 6 months. Consequently, measures of treatment effect could only be calculated for this time point. Our results indicate there is limited evidence favouring NET over WL.
Table 62: Study profiles for RCTs comparing narrative exposure therapy and waitlist for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Ertl et al 2011) Moderate Former Ugandan child Participants homes, 85 Severity of PTSD and soldiers Uganda depression symptoms Severity of functional impairment
(Ruf et al 2010) Moderate Refugee children living in Outpatient clinic for 26 PTSD symptom severity Germany refugees, Germany
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between narrative exposure therapy and waitlist on reducing the severity of clinician-rated PTSD symptoms at 3 months follow-up (k = 1; n = 54; SMD = - 0.30 95% CI, -0.84 to 0.23).
There is evidence suggesting that there is unlikely to be a clinically important difference between narrative exposure therapy and waitlist on reducing the severity of clinician-rated PTSD symptoms at 6 months follow-up (k = 1; n = 54; SMD = -0.24 95% CI, -0.78, 0.29).
There is limited evidence favouring narrative exposure therapy over waitlist on reducing the severity of self-reported PTSD symptoms at 6 months follow-up (k = 1; n = 25; SMD = -1.00 95% CI, -1.83, -0.16).
185
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between narrative exposure therapy and waitlist on reducing the severity of clinician-rated PTSD symptoms at 12 months follow-up (k = 1; n = 53; SMD = - 0.44 95% CI, -0.98 to 0.11).
There is evidence suggesting that there is unlikely to be a clinically important difference between narrative exposure therapy and waitlist on reducing the severity of depression symptoms at 3 months follow-up (k = 1; n = 54; SMD = 0.10 95% CI, -0.44, 0.63), at 6 months follow-up (k = 1; n = 54; SMD = -0.04 95% CI, -0.58, 0.49), and at 12 months follow-up (k = 1; n = 53; SMD = 0.02 95% CI, -0.52, 0.56).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between narrative exposure therapy and waitlist on reducing clinician- rated functional impairment at 3 months follow-up (k = 1; n = 54; SMD = -0.63 95% CI, - 1.18, 0.87).
There is evidence suggesting that there is unlikely to be a clinically important difference between narrative exposure therapy and waitlist on reducing clinician-rated functional impairment at 6 months follow-up (k = 1; n = 54; SMD = 0.03 95% CI, -0.50, 0.56).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between narrative exposure therapy and waitlist on reducing clinician- rated functional impairment at 3 months follow-up (k = 1; n = 53; SMD = -0.59 95% CI, - 1.14, -0.03).
Box 70: Evidence statement matrix for RCT comparing trauma focused narrative exposure therapy and waitlist for adults with PTSD Component Rating Description Evidence base C Two level II studies with a moderate risk of bias
Consistency A Both studies consistently favour NET with few exceptions
Clinical impact C Moderate
Generalisability C Evidence not directly generalisable to the target population but could be sensibly applied
Applicability C Evidence probably applicable to the Australian healthcare context, with the exception that one study was in a low income country
Summary of evidence The two studies available for this comparison favoured NET on primary outcomes, however none of the differences were clinically important, possibly due to the small samples of patients recruited in both studies. Waitlist was favoured in few instances (three out of ten secondary outcomes), however, these effect sizes were very small in comparison to the effect sizes favouring NET, despite none of these differences being clinically important (Grade C).
SPIRITUAL INTERVENTION VERSUS WAITLIST/NO TREATMENT One RCT (Bormann et al 2008) compared a spiritual intervention with a waitlist/no treatment condition. The trial investigated the efficacy of an intervention focusing on repetition of a
186 patient-chosen mantram as compared to waitlist among US combat veterans. Although the trial was small, it was well designed with adequate randomisation, blinding of outcomes assessors and no participants lost to follow up, and thus was judged to have a low risk of bias.
Table 63: Study profiles for RCTs comparing spiritual intervention with waitlist/no treatment for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Bormann et al Low Combat veterans Veterans Affairs 29 Severity of PTSD symptoms, 2008) healthcare system quality of life setting, United States
There evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between a spiritual intervention and waitlist on reducing the severity of clinician-rated PTSD symptoms (k=1, n=29; SMD -0.32 95% CI -1.06, 0.41)
There evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between a spiritual intervention and waitlist on reducing the severity of self-rated PTSD symptoms (k=1, n=29; SMD -0.70 95% CI -1.45, 0.05)
There evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between a spiritual intervention and waitlist on improving quality of life (k=1, n=29; SMD 0.68 95% CI -0.07, 1.43)
Box 71: Evidence statement matrix for RCT comparing spiritual intervention with waitlist/no treatment for adults with PTSD Component Rating Description Evidence base B One level II study with low risk of bias
Consistency NA Only one study
Clinical impact D Slight/restricted: no clinically important differences found
Generalisability A Evidence directly generalisable to the target population
Applicability C Evidence probably applicable to Australian healthcare context with some caveats
Summary of evidence One small study with a low risk of bias was unable to demonstrate any advantage of spiritual intervention over no treatment. Although the study was well designed, it was limited by small numbers. (Grade C).
SPIRITUAL INTERVENTION VERSUS WAITLIST/NO TREATMENT IN CHILDREN One study by Lesmana (Lesmana et al 2009), randomised Balinese children with terrorism exposure to spiritual hypnosis assisted therapy or to a no treatment control group. This was a reasonable size study involving 226 children, although the study was only resourced to treat 48 of these children. The study was judged to have a high risk of bias due to a lack of detail about randomisation and blinding; however no subjects were lost to follow up over the two
187 year follow-up period. Lesmana and colleagues presented PTSD symptoms by subscale measures, and thus an overall effect size measure could not be calculated. It should also be noted that these subscores were measured on a specifically devised, culturally appropriate PTSD questionnaire based on DSM-IV criteria, as no other questionnaire appropriate to the study population was in existence at the time of the study. Evidence statements are presented based on the sub scores for re-experiencing, hyperarousal and avoidance symptoms.
Table 64: Study profiles for RCTs comparing a spiritual intervention with no treatment for PTSD in children (Lesmana et al High Balinese children exposed to Unspecified outpatient 226 Severity of PTSD symptoms 2009) terror attacks setting, Bali
There is limited evidence favouring spiritual intervention over no treatment on reducing the severity of PTSD symptoms (re-experiencing) at 2 years follow-up (k=1; n=226; SMD -0.93 95% CI, -1.26, -0.60).
There is limited evidence favouring spiritual intervention over no treatment on reducing the severity of PTSD symptoms (hyperarousal) at 2 years follow-up (k=1; n=226; SMD -1.01 95% CI, -1.35, -0.69).
There is limited evidence favouring spiritual intervention over no treatment on reducing the severity of PTSD symptoms (avoidance) at 2 years follow-up (k=1; n=226; SMD -0.88 95% CI, -1.21, -0.54).
Box 72: Evidence statement matrix for RCT comparing spiritual intervention with no treatment for children with PTSD Component Rating Description Evidence base D One level II study with high risk of bias
Consistency NA Only one study
Clinical impact C Slight; evidence favoured spiritual intervention but confidence intervals around the point estimates of clinical significance also included non-significant effects.
Generalisability D Difficult to judge whether sensible to apply to the target population; Balinese Hindu children, likely to be very different to the majority of Australian children
Applicability D Evidence probably not applicable to Australian healthcare context
Summary of evidence The results from one study of poor quality provide limited evidence favouring a spiritiual intervention over no treatment for children who were experiencing PTSD. The study was undertaken with Balinese Hindu children, and thus it is difficult to generalize to the Australian guidelines target population. (Grade D.)
WRITTEN EMOTIONAL DISCLOSURE VERSUS CONTROL WRITING CONDITION
Written emotional disclosure (WED) is similar to narrative exposure therapy (NET), but differs from NET, in that no revisiting or revision of the written account occurs and no help towards connecting fragmented traumatic experiences is provided. Only one study was
188 available for this comparison.
The single RCT ((Sloan et al 2011)) compared WED and a control writing condition (CW) for undergraduates of a large, urban university in the United States who had been diagnosed with PTSD. A total of 47 students were randomised to WED (n=24) or CW (n=23), and 21 students in each arm were available for the final analysis at the final follow-up conducted at one month post-treatment. Outcomes included PTSD and depression symptom severity. The study authors found no significant differences based on a comparison of mean values and this was corroborated in our independent effect size calculation which included a clinically unimportant estimate bounded by a range of clinically significant and insignificant values.
Table 65: Study profiles for RCTs comparing written emotion disclosure and control writing condition for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Sloan et al 2011) High Undergraduate students with University setting, United 47 PTSD and depression symptom history of trauma States severity
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between written emotional disclosure and control writing condition on reducing the severity of clinician-rated PTSD symptoms at 1-month follow-up (k = 1; n = 42; SMD = 0.13; 95% CI, -0.48 to 0.73).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between written emotional disclosure and control writing condition on reducing the severity of depression symptoms at 1-month follow-up (k = 1; n = 42; SMD = 0.18; 95% CI, -0.42 to 0.79).
Evidence statement matrix for RCT comparing trauma written emotional disclosure and control writing condition for adults with PTSD Component Rating Description Evidence base D One level II study with high risk of bias
Consistency NA One study only
Clinical impact D Slight/restricted; no clinically important findings
Generalisability B Evidence directly generalisable to the target population with some caveats
Applicability C Evidence probably applicable to Australian healthcare context with some caveats
Summary of evidence The evidence from one small RCT with a high level of bias is inconclusive, and it is not possible to determine whether there are clinically important differences between written emotional disclosure and control writing condition in terms of reducing PTSD and depression symptom severity. (Grade D).
189 Intervention versus intervention
TRAUMA-FOCUSED CBT VERSUS TREATMENT AS USUAL IN ADULTS
A total of 17 level II studies were identified which investigated the treatment effect of CBT relative to treatment as usual in a variety of PTSD populations. It is noted that the interventions in the CBT arms and those in the treatment as usual arms varied across studies:
x Eleven studies comparing trauma-focused CBT (involving some form of exposure and cognitive restructuring) with usual non-trauma-focused psychotherapy and pharmacotherapy. The following exposure programs were included: prolonged exposure (Asukai et al 2010; Feske 2008; Johnson & Lubin 2006; Nacasch et al 2011; Neuner et al 2010; Vera et al 2011), imaginal flooding (Cooper & Clum 1989), imaginal exposure plus biofeedback-assisted desensitisation treatment (Peniston & Kulkosky 1991) and exposure therapy not specified (Bryant et al 2011; Hinton et al 2005; Hinton et al 2009). Patients in CBT groups continued pharmacological interventions while they were receiving CBT; x Two studies comparing trauma-focused CBT with other psychotherapy with or without elements of exposure (Forbes et al 2012; McLay et al 2011); x One study compared trauma-focused CBT against unspecified ‘Usual care’ (O'Donnell et al In press); and x Three studies comparing non-trauma-focused CBT with other non-trauma-focused psychotherapy (Johnson et al 2011; Mueser et al 2008; Zlotnick et al 2009).
Further analyses are also provided, limiting the comparison of CBT vs treatment as usual to those studies which provided intention-to-treat data, and analysing the subgroups of patients with PTSD related to service in the military (Cooper & Clum 1989; Forbes et al 2012; McLay et al 2011; Peniston & Kulkosky 1991), and female survivors of physical or sexual abuse (Feske 2008; Johnson et al 2011; Zlotnick et al 2009).
Table 66 Study profiles for RCTs comparing CBT and treatment as usual for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Bryant et al 2011) Low Patients with PTSD and with direct Outpatient, Thailand 28 Severity of PTSD exposure to terrorist attack Depressive symptoms (Forbes et al Moderate Veterans with military-related PTSD Outpatient, Australia 59 Severity of PTSD 2012) Depressive symptoms Anxiety Substance misuse Attrition (O'Donnell et al In Moderate Patients who had injuries requiring Outpatient, Australia 42 PTSD diagnosis press) hospitalisation, predominantly Severity of PTSD motor vehicle accidents and Depression diagnosis assaults Depressive symptoms Anxiety diagnosis Anxiety symptoms Attrition (Neuner et al Moderate Asylum-seekers with PTSD who Outpatient clinic for 32 Severity of PTSD 2010) had a history of victimisation by refugees, Germany Depressive symptoms organised violence Attrition (Nacasch et al Moderate Patients suffering from chronic Psychiatric outpatient 30 Severity of PTSD
190 2011) PTSD following combat- or terror- clinic, Israel Depressive symptoms rated trauma Anxiety Attrition (Asukai et al Moderate Patients with PTSD due to mixed Psychiatric clinics, 24 Severity of PTSD 2010) traumatic events (eg sexual Japan Depressive symptoms assault, accident and physical Attrition assault) (McLay et al Moderate Active Duty military personnel with Navy medical facilities, 20 Severity of PTSD 2011) combat-related PTSD USA Attrition (Vera et al 2011) Moderate Adults with PTSD (type of trauma: Outpatient, Puerto 14 Severity of PTSD unknown) Rico Attrition (Mueser et al High Patients with severe mental illness Local community 108 Severity of PTSD 2008) and with PTSD primarily from mental health centre, PTSD diagnosis childhood sexual/physical abuse, USA Depression sudden unexpected death of a Anxiety loved one and adult sexual/physical Attrition assault (Johnson et al High Female victims of intimate partner Battered women’s 70 Severity of PTSD 2011) violence shelters, USA Depressive symptoms Attrition (Zlotnick et al High Female inmates with substance use Women’s prison, USA 49 Severity of PTSD 2009) disorder and with PTSD primarily PTSD diagnosis from sexual abuse and physical Substance misuse abuse Attrition (Hinton et al 2005) High Patients with treatment-resistant Outpatient clinic for 40 PTSD diagnosis PTSD who had experienced neck- Cambodian refugees, Severity of PTSD focused and orthostasis-triggered USA Anxiety panic attacks (Johnson & Lubin High Women with sexual or physical Outpatient, USA 38 Severity of PTSD 2006) abuse or who had had a motor vehicle accident (Peniston & High Vietnam theatre veterans Outpatient, USA 29 PTSD diagnosis Kulkosky 1991) Severity of PTSD (Feske 2008) High Women (predominately low income Clinic located in an 27 Severity of PTSD and African American) with chronic economically Depressive symptoms PTSD in response to sexual or disadvantaged area, Anxiety physical assault USA Attrition (Hinton et al 2009) High Survivors of Cambodian genocide Outpatient clinic for 24 Severity of PTSD with pharmacologically-resistant Cambodian refugees, PTSD USA (Cooper & Clum High Vietnam veterans Outpatient, USA 14 Depressive symptoms 1989) Anxiety
The high-quality study by Bryant et al (2011) was a well designed and executed trial with outcome assessors blinded to the treatment allocation. The results were analysed according to ITT principle, with no dropouts. Patients in the two intervention groups were matched with respect to patient demographic characteristics and disease severity at baseline.
Of the seven trials with moderate risk of bias, ITT analyses were performed in three studies (Asukai et al 2010, Forbes et al 2012 and Neuner et al 2010); whereas the results from the other five trials were analysed on a per protocol basis. Dropout rates were between 5.0% and 25.5% across trials, with rates of ≥15% in three studies (16.7% in Asukai et al 2010; 20.3% in Forbes et al 2012; 25.5% in Johnson et al 2006). Assessors were blinded in all seven trials except the two by McLay et al (2011) and Neuner et al (2010). Forbes et al (2012) reported more severe baseline PTSD symptoms in patients assigned to the CBT group than those in the treatment as usual group (CAPS (mean±SD): 75.53 ± 16.35 vs 65.75 ± 18.53, p<0.05). In
191 other six studies, no significant differences were observed between the two intervention arms in terms of patient demographic and disease characteristics at randomisation.
None of the nine trials with high risk of bias reported ITT results. Only one trial (Zlotnick et al 2009) had a loss to follow-up rate of <15% (10.2%). However, this study was limited by the open-label study design and the incomparable patient age between the two treatment arms (mean±SD: 36.5±7.6 in the CBT group vs 32.2±6.6 in the treatment as usual group). In the other seven trials, baseline variables were evenly distributed between two intervention groups. Assessor blinding was maintained in four studies (Johnson et al 2006, Hinton et al 2005, Hinton et al 2009 and Mueser et al 2008), but not reported in the other three (Cooper et al 1989, Feske et al 2008 and Peniston et al 1991).
Among the 16 included trials, the longest follow-up period was reported by Peniston et al (1991), who contacted the participants at monthly intervals for 30 months after completion of treatment. Asukai et al (2010) and Nacasch et al (2011) followed subjects for up to 12 months. However, follow-up results could not be compared between the CBT arm and the treatment as usual arm in the study by Asukai et al, as patients in the control group started trauma-focused CBT (prolonged exposure) after a 10-week waiting period. Follow-up assessment after post-test was not planned in four studies (Hinton et al 2005, Hinton et al 2009, McLay et al 2011 and Vera et al 2011). In the remaining nine studies, follow-up periods ranged between 2 months and 6 months.
Figure 10 CBT versus treatment as usual in adults: PTSD diagnosis, post-treatment
Favours CBT Favours treatment as usual
The funnel plot indicates that there could potentially be some publication bias as one study falls well outside the 95% confidence limits (Appendix H). However, this may be a reflection of the high heterogeneity across studies (I2=76.9%, p=0.005).
There is limited evidence favouring CBT over treatment as usual on reducing the likelihood of having a PTSD diagnosis at post-treatment in adults (k=4; n=171; RR=0.56; 95% CI 0.31, 1.01).
192 Figure 11 CBT versus treatment as usual in adults: PTSD diagnosis, 3-month follow-up
Favours CBT Favours treatment as usual
There is limited evidence favouringCBT over treatment as usual on reducing the likelihood of having a PTSD diagnosis at 3-month follow-up in adults (k=3; n=151; RR=0.68; 95% CI 0.32, 1.45).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between CBT and treatment as usual on reducing the likelihood of having a PTSD diagnosis at 6-month follow-up in adults (k=1; n=53; RR=0.86; 95% CI 0.65, 1.13).
Figure 12 CBT versus treatment as usual in adults: PTSD symptom severity (clinician-rated), post- treatment
Favours CBT Favours treatment as usual
193
The funnel plot indicates that there could potentially be some publication bias as three studies fall outside the 95% confidence limits (Appendix H). However, this may be a reflection of the moderate to high heterogeneity across studies (I2=65.4%, p=0.001).
There is evidence favouring CBT over treatment as usual on reducing the severity of clinician-rated PTSD symptoms at post-treatment in adults (k=13; n=442; SMD=-0.96; 95% CI -1.32, -0.61).
Figure 13 CBT versus treatment as usual in adults: PTSD symptom severity (clinician-rated), 2-month to 3- month follow-up
Favours CBT Favours treatment as usual
The funnel plot shows no indication of publication bias (Appendix H).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between CBT and treatment as usual on reducing the severity of clinician-rated PTSD symptoms at 2-month to 3-month follow-up in adults (k=7; n=325; SMD=-0.43; 95% CI -0.65, -0.20).
Favours CBT Favours treatment as usual
194 Figure 14 CBT versus treatment as usual in adults: PTSD symptom severity (clinician-rated), 6-month follow-up
The funnel plot shows no indication of publication bias (Appendix H).
There is limited evidence favouring CBT over treatment as usual on reducing the severity of clinician-rated PTSD symptoms at 6-month follow-up in adults (k=3; n=151; SMD=-0.54; 95% CI -0.87, -0.21).
There is evidence favouring CBT over treatment as usual on reducing the severity of clinician-rated PTSD symptoms (at 12-month follow-up in adults (k=1; n=26; SMD=-1.96; 95% CI -2.99, -0.93).
Figure 15 CBT versus treatment as usual in adults: PTSD symptom severity (self-report), post-treatment
Favours CBT Favours treatment as usual
The funnel plot indicates that there could potentially be some publication bias as one of four
195 studies fall well outside the 95% confidence limits (Appendix H). However, this may be a reflection of the high heterogeneity across studies (I2=88.5%, p=0.000).
There is limited evidence favouring CBT over treatment as usual on reducing the severity of self-report PTSD symptoms at post-treatment in adults (k=4; n=129; SMD=-1.51; 95% CI -2.80, -0.21).
There is evidence favouring CBT over treatment as usual on increasing the likelihood of not having PTSD symptoms at 30-month follow-up in adults (k=1; n=29: RR=5.00; 95% CI 1.82, 13.76).
Figure 16 CBT versus treatment as usual in adults: depression, post-treatment
Favours CBT Favours treatment as usual
There is limited evidence favouring CBT over treatment as usual on reducing depression symptoms at post-treatment in adults (k=8; n=298; SMD=-0.68; 95% CI -0.92, -0.44).
196 Figure 17 CBT versus treatment as usual in adults: depression, 2-month to 3-month follow-up
Favours CBT Favours treatment as usual
There is limited evidence favouring CBT over treatment as usual on reducing depression symptoms at 2-month to 3-month follow-up in adults (k=7; n=290; SMD=-0.69; 95% CI -1.08, -0.30).
Figure 18 CBT versus treatment as usual in adults: depression, 6-month follow-up
Favours CBT Favours treatment as usual Favours CBT Favours treatment as usual
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between CBT and treatment as usual on reducing depression symptoms at 6-month follow-up in adults (k=3; n=151; SMD=-0.47; 95% CI -0.80, -0.14).
There is limited evidence favouring CBT over treatment as usual on the likelihood of having had a major depressive episode by 3-months follow-up in adults (k=1; n=42; RR=0.40, 95%CI 0.15, 1.11).
197 Figure 19 CBT versus treatment as usual in adults: anxiety, post-treatment
Favours CBT Favours treatment as usual
There is limited evidence favouring CBT over treatment as usual on reducing anxiety symptoms at post-treatment in adults (k=6; n=218; SMD=-1.11; 95% CI -1.98, -0.24).
Figure 20 CBT versus treatment as usual in adults: anxiety, 2-month to 3-month follow-up
Favours CBT Favours treatment as usual
There is limited evidence favouring CBT over treatment as usual on reducing anxiety symptoms at 2-month to 3-month follow-up in adults (k=5; n=196; SMD=-0.58; 95% CI -0.57, -0.29).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between CBT and treatment as usual on reducing anxiety symptoms at 6-month follow-up in adults (k=1; n=53; SMD=-0.33; 95% CI -0.89, -0.23).
198 There is limited evidence favouring CBT over treatment as usual on the likelihood of having an anxiety disorder at 3 months-follow-up in adults (k=1; n=42; RR=0.61, 95%CI 0.2, 1.84).
Figure 21 CBT versus treatment as usual in adults: attrition, post-treatment
Favours CBT Favours treatment as usual
There is limited evidence favouring treatment as usual over CBT on attrition at post- treatment in adults (k=10; n=433; RR=1.36; 95% CI 0.86, 2.15).
Figure 22 CBT versus treatment as usual in adults: alcohol misuse, post-treatment
Favours CBT Favours treatment as usual
There is evidence suggesting that there is unlikely to be a clinically important difference between CBT and treatment as usual at post-treatment in adults (k=2; n=102; SMD=-0.07; 95% CI -0.46, 0.32).
199 Figure 23 CBT versus treatment as usual in adults: alcohol misuse, 3-month follow-up
Favours CBT Favours treatment as usual
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between CBT and treatment as usual on alcohol misuse at 3- month follow-up in adults (k=2; n=102; SMD=-0.44; 95% CI -0.83, -0.05).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between CBT and treatment as usual on drug misuse at post- treatment in adults (k=1; n=44; SMD=0.17; 95% CI -0.42, 0.76).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between CBT and treatment as usual on drug misuse at 3- month follow-up in adults (k=1; n=44; SMD=-0.16; 95% CI -0.75, 0.44).
Box 73 Evidence statement matrix for RCTs comparing CBT with treatment as usual in adults with PTSD Component Rating Description Evidence base B One level II study with a low risk of bias, seven level II studies with a moderate risk of bias and nine level II studies with a high risk of bias.
Consistency B Most studies consistent and inconsistency may be explained.
Clinical impact C There is evidence favouring CBT over treatment as usual in terms of improving PTSD symptoms (clinician-rated) at post-treatment. There were clinically important point estimates favouring CBT over treatment as usual on reducing the severity of PTSD symptoms (self-report), depression and anxiety, although the full ranges of estimates defined by the confidence interval included effect sizes too small to be clinically important. Generalisability A Evidence generalisable to the target population (a mix of trauma types; two studies in Australian setting, 14 studies in developed countries and one in developing country (Thailand).
Applicability A Applicable to Australian healthcare context (two studies within Australian healthcare setting)
Summary of evidence There were one good-quality trial and 16 trials with moderate to high risk of bias comparing CBT with treatment as usual in adults. The results are consistent in favouring CBT over
200 treatment as usual on improving PTSD symptoms, decreasing the likelihood of having a PTSD diagnosis, and reducing depression and anxiety symptoms; the clinical importance of these differences, however, varies across outcomes and across different follow-up periods (Grade B).
Trauma-focused CBT vs treatment as usual ITT analysis
Only four studies compared CBT against treatment as usual and provided intention-to-treat (ITT) data (some additional studies provided their own analyses which were stated to be based on ITT data, but provided summary data for only those patients who completed assessments). ITT data suggest that there is a trend towards favouring trauma-focused CBT over treatment as usual, but that the only outcome measure where this effect is large enough to be considered clinically important, is self-rated PTSD severity. There is no evidence of a long-term benefit. Three of the four studies used specific measures to ensure treatment fidelity. Neuner et al (2010) used both supervisory session and direct observation of randomly selected sessions to ensure proper application of narrative exposure therapy. Forbes et al (2012) and Asukai et al (2010) audiotaped or videotaped sessions and assessed treatment fidelity within either a random sample of cases and sessions or all sessions to ensure treatment fidelity. Bryant et al 2011 noted that they lacked independent fidelity checks and did not have any supervisory sessions during the trial.
Table 67 Study profiles for RCTs comparing CBT and treatment as usual for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Bryant et al 2011) Low Patients with PTSD and with direct Outpatient, Thailand 28 Severity of PTSD exposure to terrorist attack Depressive symptoms (Forbes et al Moderate Veterans with military-related PTSD Outpatient, Australia 59 Severity of PTSD 2012) Depressive symptoms Anxiety Substance misuse Attrition (Neuner et al Moderate Asylum-seekers with PTSD who Outpatient clinic for 32 Severity of PTSD 2010) had a history of victimisation by refugees, German Depressive symptoms organised violence Attrition (Asukai et al Moderate Patients with PTSD due to mixed Psychiatric clinics, 24 Severity of PTSD 2010) traumatic events (eg sexual Japan Depressive symptoms assault, accident and physical Attrition assault)
201
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between CBT and treatment as usual on severity of PTSD symptoms (clinician-rated) post-treatment (k=3, n=111, SMD=-0.72, 95%CI -1.11, -0.33).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between CBT and treatment as usual on severity of PTSD symptoms (clinician-rated) at 3 months’ follow-up (k=3, n=119, SMD=-0.55, 95%CI -0.92, - 0.18).
202
There is limited evidence favouring CBT over treatment as usual on the severity of PTSD symptoms (self-rated) post-treatment (k=2, n=82, SMD=-0.83, 95%CI -1.29, -0.37).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between CBT and treatment as usual on severity of PTSD symptoms (self-rated) at 3 months’ follow-up (k=1, n=58, SMD=-0.53, 95%CI -1.06, -0.01).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between CBT and treatment as usual on depressive symptoms post-treatment (k=3, n=110, SMD=-0.63,95%CI -1.02, -0.25).
203
There is evidence suggesting that there is unlikely to be a clinically important difference between CBT and treatment and usual on depressive symptoms at 3 – 6 months’ follow-up (k=3, n=-0.41, 95%CI -0.78, -0.05).
There is evidence suggesting that there is unlikely to be a clinically important difference between CBT and treatment and usual on anxiety post-treatment (k=1, n=58, SMD=-0.29, 95%CI -0.80, 0.23) and at 3 months’ follow-up (k=1, n=58, SMD=-0.26, 95%CI -0.78, 0.26).
There is evidence suggesting that there is unlikely to be a clinically important difference between CBT and treatment and usual on physical functioning post-treatment (k=1, n=58, SMD=-0.19, 95%CI -0.71, 0.32) and at 3 months’ follow-up (k=1, n=58, SMD=-0.11, 95%CI -0.63, 0.40).
There is evidence suggesting that there is unlikely to be a clinically important difference between CBT and treatment and usual on social functioning post-treatment (k=1, n=58, SMD= 0.05, 95%CI -0.47, 0.56) and at 3 months’ follow-up (k=1, n=58, SMD=0.34, 95%CI -0.18, 0.86).
204 The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between CBT and treatment and usual on attrition post- treatment (k=3, n=115, RR=1.50, 95%CI 0.65, 3.47).
TRAUMA-FOCUSED CBT VS TREATMENT AS USUAL: MILITARY/VETERANS SUBGROUP
Four studies compared CBT against treatment as usual in military personnel/veterens with PTSD (Table 68).
Table 68 Study profiles for RCTs comparing CBT and treatment as usual for adults with PTSD: military/veterans Reference Risk of bias Population Setting N Outcomes measured (Forbes et al Moderate Veterans with military-related PTSD Outpatient, Australia 59 Severity of PTSD 2012) Depressive symptoms Anxiety Substance misuse Attrition (McLay et al Moderate Active Duty military personnel with Navy medical facilities, 20 Severity of PTSD 2011) combat-related PTSD USA Attrition (Peniston & High Vietnam theatre veterans Outpatient, USA 29 PTSD diagnosis Kulkosky 1991) Severity of PTSD (Cooper & Clum High Vietnam veterans Outpatient, USA 14 Depressive symptoms 1989) Anxiety
There is limited evidence favouring CBT over treatment as usual in military personnel/veterans for the likelihood of having a PTSD diagnosis post-treatment (k=2, n=76, RR=0.43, 95%CI 0.12, 1.54).
205
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between CBT and treatment as usual in military personnel/veterans on severity of PTSD symptoms (clinician-rated) post-treatment (k=2, n=78, SMD=-0.45, 95%CI -0.90, -0.00) and at 3 months’ follow-up (k=1, n=58, SMD=-0.30, 95%CI -0.81, 0.22).
There is limited evidence favouring CBT over treatment as usual in military personnel/veterans on the severity of PTSD symptoms (self-rated) post-treatment (k=2, n=87, SMD=-2.17, 95%CI -5.43, 1.08).
The evidence is inconclusive and so it is not possible to determine whether there is a clinicially important difference between CBT and treatment as usual in military personnel/veterans on the severity of PTSD symptoms (self-rated) at 3 months’ follow-up (k=1, n=58, SMD=-0.53, 95%CI -1.06, -0.01).
The evidence is inconclusive and so it is not possible to determine whether there is a clinicially important difference between CBT and treatment as usual in military personnel/veterans on depressive symptoms post-treatment (k=1, n=58, SMD=-0.41, 95%CI
206 -0.93, 0.11) or at 3 months’ follow-up (k=1, n=58, SMD=-0.37, 95%CI -0.89, 0.15).
There is evidence suggesting that there is unlikely to be a clinically important difference between CBT and treatment and usual in military personnel/veterans on anxiety post- treatment (k=2, n=72, SMD=-0.33, 95%CI -0.80, 0.13).
There is evidence suggesting that there is unlikely to be a clinically important difference between CBT and treatment and usual in military personnel/veterans on anxiety at 3 months’ follow-up (k=2, n=68, SMD=-0.24, 95%CI -0.72, 0.24).
There is evidence suggesting that there is unlikely to be a clinically important difference between CBT and treatment and usual in military personnel/veterans on physical functioning post-treatment (k=1, n=58, SMD=-0.19, 95%CI -0.71, 0.32) and at 3 months’ follow-up (k=1, n=58, SMD=-0.11, 95%CI -0.63, 0.40).
There is evidence suggesting that there is unlikely to be a clinically important difference between CBT and treatment as usual in military personnel/veterans on social functioning
207 post-treatment (k=1, n=58, SMD= 0.05, 95%CI -0.47, 0.56) and at 3 months’ follow-up (k=1, n=58, SMD=0.34, 95%CI -0.18, 0.86).
The evidence is inconclusive and so it is not possible to determine whether there is a clinicially important difference between CBT and treatment as usual in military personnel/veterans on attrition post-treatment (k=2, n=79, RR=0.84, 95%CI 0.33, 2.18).
Box 74 Evidence statement matrix for RCTs comparing CBT with treatment as usual in adults with PTSD: military/veterans Component Rating Description Evidence base C Two level II studies with a moderate risk of bias, two level II studies with a high risk of bias
Consistency C Consistency in direction of effect, but variation in size of effect, likely due to small samples
Clinical impact D Clinically important point differences favouring CBT on likelihood of having a PTSD diagnosis post- treatment and severity of self-rated symptoms, the full range of plausible estimates also includes effects favouring treatment as usual (differences not statistically significant due to large amount of uncertainty). All other outcomes not clinically important.
Generalisability A The largest study in Austrailan veterans, highly generalisable to target population.
Applicability A The largest study in Australian healthcare system. Three other studies from the United States.
Summary of evidence Limited evidence suggests that in military/veteran populations with PTSD there may be a benefit in CBT over treatment as usual at reducing the likelihood of having a PTSD diagnosis post-treatment, and reducing self-report symptom severity, but there is too much uncertainty around the effects to make any strong conclusions. (Grade C).
TRAUMA-FOCUSED CBT VS TREATMENT AS USUAL: PHYSICAL/SEXUAL ABUSE SUBGROUP
Three studies comparing CBT and treatment as usual predominantly included female samples who had experienced intimate partner violence, sexual abuse or physical abuse (see Table 69). Although there was a trend favouring CBT over treatment as usual, the only difference
208 that was found to be clinically important was anxiety at 2 months, which was reported by only one study (Feske 2008).
Table 69 Study profiles for RCTs comparing CBT and treatment as usual for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Johnson et al High Female victims of intimate partner Battered women’s 70 Severity of PTSD 2011) violence shelters, USA Depressive symptoms Attrition (Zlotnick et al High Female inmates with substance use Women’s prison, USA 49 Severity of PTSD 2009) disorder and with PTSD primarily PTSD diagnosis from sexual abuse and physical Substance misuse abuse Attrition (Feske 2008) High Women (predominately low income Clinic located in an 27 Severity of PTSD and African American) with chronic economically Depressive symptoms PTSD in response to sexual or disadvantaged area, Anxiety physical assault USA Attrition
The evidence is inconclusive and so it is not possible to determine whether there is a clinicially important difference between CBT and in female survivors of sexual or physical abuse on the likelihood of having a PTSD diagnosis post-treatment (k=1, n=44, RR=0.91, 95%CI 0.45, 1.86) or at 3 months’ follow-up (k=1, n=44, RR=1.14, 95%CI 0.56, 2.34).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between CBT and treatment as usual in female survivors of sexual or physical abuse on severity of PTSD symptoms (clinician-rated) post-treatment (k=3, n=133, SMD=-0.53, 95%CI -0.88, -0.18).
209
There is evidence suggesting that there is unlikely to be a clinically important difference between CBT and treatment and usual in female survivors of sexual or physical abuse on severity of PTSD symptoms (clinician-rated) at 2 – 3 months’ follow-up (k=3, n=131, SMD=- 0.39, -0.74, -0.04).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between CBT and treatment as usual in female survivors of sexual or physical abuse on severity of PTSD symptoms (clinician-rated) at 6 months’ follow- up (k=1, n=66, SMD=-0.35, 95%CI -0.83, 0.14).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between CBT and treatment as usual in female survivors of sexual or physical abuse on depressive symptoms post-treatment (k=2, n=89, SMD=-0.76, 95%CI -1.19, -0.33).
210 The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between CBT and treatment as usual in female survivors of sexual or physical abuse on depressive symptoms at 2-3 months’ follow-up (k=2, n=87, SMD=-0.51, 95%CI -0.94, -0.08) or at 6 months’ follow-up (k=1, n=66, SMD=-0.44, 95%CI -0.93, 0.04).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between CBT and treatment as usual in female survivors of sexual or physical abuse on anxiety post-treatment (k=1, n=21, SMD=-0.77, 95%CI -1.67, 0.12).
There is limited evidence favouring CBT over treatment as usual in female survivors of sexual or physical abuse on anxiety at 2 months’ follow-up (k=1, n=21, SMD=-0.98, 95%CI- 1.90, -0.07.
There is limited evidence favouring TAU over CBT in female survivors of sexual or physical abuse on attrition post-treatment (k=3, n=146, RR=2.17, 95%CI 0.71, 6.61).
211
Box 75 Evidence statement matrix for RCTs comparing CBT with treatment as usual in adults with PTSD: sexual/nonsexual abuse Component Rating Description Evidence base D Three level II studies with a high risk of bias
Consistency C Consistency in direction of effect, but variation in size of effect, likely due to small samples
Clinical impact D Although there was a trend favouring CBT over TAU on most outcome measures, the differences between the two treatments were not large enough to be considered clinically important on all but one outcome measure/time point (CBT was beneficial compared to TAU on anxiety at 2 months in one study).
Generalisability B Likely to be generalisable. Victims of sexual and physical abuse and intimate partner violence.
Applicability C All three studies from the United States: located in battered women’s shelter, prison and clinic in low SES area of United States.
Summary of evidence Limited evidence showed a trend favouring CBT over TAU in female survivors of sexual/nonsexual assault or intimate partner violence, but the differences between treatments were not large enough to be considered clinically important. (Grade D). TRAUMA-FOCUSED CBT VS TREATMENT AS USUAL FOR CHILDREN There were four studies that compared trauma-focused CBT with treatment as usual in children ((Celano et al 1996; Cohen et al 2011; Deblinger et al 1996), followed up in Deblinger, et al (1999), and Lieberman et al (2005), followed up in Lieberman et al (2006). Short term outcomes after mother and child CBT are considered in this section, and outcomes relating specifically to the two studies in a girls who experienced sexual abuse (assessing mother and child CBT, mother only CBT and child only CBT) are shown in the next section. Two of these studies treated children who had been exposed to domestic violence (Cohen 2011, Lieberman 2005). Children and their mothers were randomised to receive trauma- focused CBT or usual care, which was child-centred therapy (without a trauma focus) in the Cohen 2011 study, and case management with referral to mental health services in the community (for the mother) in the Leiberman 2005 study. Both of these TF-CBT treatments included the mother in the treatment, together with the child in the Leiberman 2005 study, and both separately and together in the Cohen 2011 study. Both of these studies were relatively small. The Lieberman 2005 study lacked detail about the methodology however had only a small dropout rate (13.3%) at post-treatment. The Cohen 2011 study was well designed but had very high dropout rates, and it was difficult to tell if this was because of the study treatments or because of the population (women experiencing intimate partner violence who used the services of the Women’s Centre and Shelter which gave short-term help). These two studies that considered children who had been exposed to domestic violence were considered for meta-analyses, but one of these studies reported only change scores and so it was not possible to combine them.
The other two studies treated girls who had been sexually abused (Celano 1996, Deblinger 1996). Both of these studies were small and of poor quality, mostly due to a lack of detail in the reports about methodology. The Celano study compared a structured cognitive treatment for girls and their non-offending mothers with the care they would usually receive, which was unstructured, supportive individual psychotherapy. There was little detail about the
212 methodology of the study, and 35% of the sample dropped out of treatment. The Deblinger study compared TF-CBT given to the child only, the parent only, and the child and parent combined, with treatment as usual, which was standard community care. The child and parent arm of the Deblinger study were considered for meta-analysis with the Celano study, however there was only one outcome in common. Thus nearly all the comparisons are considered separately.
The only study which provided intention-to-treat data was the study by Cohen et al (2011). Seperate analyses restricted to ITT data were therefore not performed.
Table 70 Study profiles for RCTs comparing TF-CBT with treatment as usual for children with PTSD Reference Risk of bias Population Setting N Outcomes measured (Cohen et al 2011) Moderate 7-14 year old children whose Community Women’s 124 Severity of PTSD symptoms mothers were direct victims IPV Centre and Shelter, Depressive symptoms of intimate partner abuse Pittsburgh USA Anxiety Child behaviour
(Lieberman et al Moderate 3-5 year old children were University/hospital clinic, 75 PTSD diagnosis 2005) also reported exposed to marital violence San Francisco USA PTSD symptoms in (Lieberman et al Child behaviour 2006)
(Celano et al 1996) High 8-13 year old girls who had University clinic, Atlanta, 49 Severity PTSD symptoms experienced sexual abuse, USA Psychosocial functioning and their mothers (Deblinger et al High 7-13 year old girls who had Community outpatient 100 Severity of PTSD symptoms 1996) also reported experienced sexual abuse, setting, United States Depression in (Deblinger et al and their non-offending Anxiety 1999) parent Child behaviour
Mother/parent and child CBT vs TAU:
There is evidence favouring TF-CBT over TAU on PTSD diagnosis at post-treatment (k=1, n=65: RR 0.16 95% CI 0.04, 0.68)
213
There is no evidence of publication bias (see funnel plot in Appendix H).
There is limited evidence favouring TF-CBT over TAU for the severity of clinician-rated PTSD symptoms at post-treatment (k=3, n=141; SMD -0.59 95% CI -0.93, -0.25)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between TF-CBT and TAU for reducing the severity of clinician-rated PTSD symptoms between baseline and post-treatment (k=1, n=124: SMD - 0.48 95% CI -0.84,- 0.13)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between TF-CBT and TAU for reducing the severity of self- rated PTSD symptoms between baseline and post-treatment (k=1, n=124: SMD -0.47 95% CI -0.83,- 0.11)
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between mother and child CBT and TAU for reducing the severity of parent-rated PTSD symptoms (k=1, n=30: SMD -0.19 95% CI -0.90, 0.53)
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between mother and child CBT and TAU for reducing the severity of child-rated PTSD symptoms (k=1, n=32: SMD -0.21 95% CI -0.90, 0.49)
There is limited evidence favouring mother and child CBT over TAU for depressive symptoms post-treatment (k=1, n=44: SMD -0.73 95% CI -1.33, -0.12).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between TF-CBT and TAU on the reduction of depression symptoms between baseline and post-treatment (k=1, n=124: SMD -0.27 95% CI -0.63, 0.08).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between mother and child CBT and TAU for anxiety post-treatment
214 (k=1, n=44: SMD -0.13 95% CI -0.72, 0.46), or on the reduction of anxiety between baseline and post-treatment (k=1, n=124: SMD -0.47 95% CI -0.83, -0.12).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between TF-CBT and TAU on child behaviour at post- treatment (k=2, n=110, SMD=-0.32, 95%CI -0.70, 0.05) or at 6 months follow up (k=1, n=50: SMD -0.37 95% CI -0.93, 0.19).
There is evidence suggesting there is unlikely to be a clinically important difference between TF-CBT and TAU on child behaviour change between baseline and post-treatment (k=1, n=124; SMD 0.07 95% CI -0.29, 0.42).
There is limited evidence favouring TF-CBT over TAU for study attrition (k=2, n=199; RR 0.77 95% CI 0.51, 1.16)
The studies that treated girls who had experienced sexual abuse and their mothers, and compared them to treatment as usual, found some clinically important point estimates on PTSD related outcomes and other outcomes for longer term outcomes.
215
At 3 months follow up:
There is limited evidence favouring mother and child CBT over TAU for reducing the severity of clinician-rated PTSD symptoms (k=1, n=33: SMD -0.59 95% CI -1.30, 0.11)
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between mother and child CBT and TAU for reducing depression (k=1, n=34: SMD -0.33 95% CI -1.01, 0.35)
At 6 months follow up:
There is limited evidence favouring mother and child CBT over TAU for reducing the severity of clinician-rated PTSD symptoms (k=1, n=33: SMD -0.65 95% CI -1.36, 0.05)
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between mother and child CBT and TAU for reducing depression (k=1, n=34: SMD -0.08 95% CI -0.76, 0.59)
At 1 year follow up:
There is limited evidence favouring mother and child CBT over TAU for reducing the severity of clinician-rated PTSD symptoms (k=1, n=33: SMD -0.68 95% CI -1.39, 0.03)
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between mother and child CBT and TAU for reducing depression (k=1, n=34: SMD -0.16 95% CI -0.84, 0.52)
At 2 years follow up:
There is limited evidence favouring mother and child CBT over TAU for reducing the severity of clinician-rated PTSD symptoms (k=1, n=33: SMD -0.64 95% CI -1.35, 0.06)
There is limited evidence favouring mother and child CBT over TAU for reducing depression (k=1, n=33: SMD -0.50 95% CI -1.18, 0.19)
Box 76 Evidence statement matrix for RCTs comparing trauma-focused CBT and treatment as usual children with PTSD Component Rating Description Evidence base C Two studies with a moderate risk of bias and two with a high risk.
Consistency A Studies consistent in favouring TF-CBT over TAU
Clinical impact C Some clinically important point estimates; others inconclusive.
Generalisability B Children exposed to domestic violence and child abuse, similar to the guidelines population
Applicability C Applicable to Australian healthcare context with some caveats
216 Summary of evidence
Four studies of poor to average quality compared trauma-focused CBT with treatment as usual in children who had been exposed to domestic violence or had been sexually abused. Some of the TF-CBT arms included both parent and child, whilst others were child only or mother only. The study results generally favoured TF-CBT over TAU, with some of the results having a clinically important point estimate. (Grade C)
TRAUMA-FOCUSED CBT (FOR CHILD AND/OR MOTHER) VS TREATMENT AS USUAL FOR CHILDREN SURVIVORS OF SEXUAL ABUSE
Two studies compared trauma-focused CBT with treatment as usual in girls who had been sexually abused (Celano 1996, Deblinger 1996). Both of these studies were small and of poor quality, mostly due to a lack of detail in the reports about methodology. The Celano study compared a structured cognitive treatment for girls and their non-offending mothers with the care they would usually receive, which was unstructured, supportive individual psychotherapy. There was little detail about the methodology of the study, and 35% of the sample dropped out of treatment. The Deblinger study compared TF-CBT given to the child only, the parent only, and the child and parent combined, with treatment as usual, which was standard community care. The child and parent arm of the Deblinger study were considered for meta-analysis with the Celano study, however there was only one outcome in common. Thus nearly all the comparisons are considered separately. The studies that treated girls who had experienced sexual abuse and their mothers, and compared them to treatment as usual, found some clinically important point estimates on PTSD related outcomes and other outcomes.
Table 71 Study profiles for RCTs comparing TF-CBT with treatment as usual for children with PTSD Reference Risk of bias Population Setting N Outcomes measured (Celano et al 1996) High 8-13 year old girls who had University clinic, Atlanta, 49 PTSD symptoms; experienced sexual abuse, USA Psychosocial functioning and their mothers (Deblinger et al High 7-13 year old girls who had Community outpatient 100 PTSD symptoms 1996) also reported experienced sexual abuse, setting, United States Depression in (Deblinger et al and their non-offending Anxiety 1999) parent Child behaviour
Mother and child CBT vs TAU:
217
There is limited evidence favouring mother and child CBT over TAU for reducing the severity of clinician-rated PTSD symptoms post-treatment (k=2, n=76: SMD -0.57 95% CI -1.03, - 0.11), at 3 months’ follow-up (k=1, n=33: SMD -0.59 95% CI -1.30, 0.11), 6 months’ follow- up (k=1, n=33: SMD -0.65 95% CI -1.36, 0.05), 1 year follow-up (k=1, n=33: SMD -0.68 95% CI -1.39, 0.03) and 2 years’ follow-up (k=1, n=33: SMD -0.64 95% CI -1.35, 0.06).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between mother and child CBT and TAU for reducing the severity of parent-rated PTSD symptoms (k=1, n=30: SMD -0.19 95% CI -0.90, 0.53)
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between mother and child CBT and TAU for reducing the severity of child-rated PTSD symptoms (k=1, n=32: SMD -0.21 95% CI -0.90, 0.49)
There is limited evidence favouring mother and child CBT over TAU for reducing depression post-treatment (k=1, n=44: SMD -0.73 95% CI -1.33, -0.12) and at 2 years’ follow-up (k=1, n=33: SMD -0.50 95% CI -1.18, 0.19).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between mother and child CBT and TAU for reducing depression at 3 months’ follow-up (k=1, n=34: SMD -0.33 95% CI -1.01, 0.35), 6 months’ follow-up (k=1, n=34: SMD -0.08 95% CI -0.76, 0.59), and 1 year follow-up (k=1, n=34: SMD -0.16 95% CI -0.84, 0.52).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between mother and child CBT and TAU for reducing anxiety post- treatment (k=1, n=44: SMD -0.13 95% CI -0.72, 0.46)
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between mother and child CBT and TAU for reducing internalising child behaviour problems post-treatment (k=1, n=43: SMD -0.36 95% CI -0.96, 0.24)
218 There is limited evidence favouring mother and child CBT over TAU for reducing externalising child behaviour problems post-treatment (k=1, n=43: SMD -0.53 95% CI -1.14, 0.08)
The other arms of the Deblinger trial compared child-only CBT to treatment as usual, and mother-only CBT to treatment as usual.
Child CBT versus TAU:
There is limited evidence favouring child CBT over TAU for reducing the severity of clinician-rated PTSD symptoms post-treatment (k=1, n=46: SMD -0.90 95% CI -1.50, -0.29), 3 months’ follow-up (k=1, n=35: SMD -0.63 95% CI -1.32, 0.06), and 6 months’ follow-up (k=1, n=35: SMD -0.88 95% CI -1.59 ,-0.17).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between child CBT and TAU for reducing the severity of clinician-rated PTSD symptoms at 1 year follow-up (k=1, n=35: SMD -0.47 95% CI -1.16, 0.21) or at 2 years follow-up (k=1, n=35: SMD -0.45 95% CI -1.13, 0.23).
There is limited evidence favouring child CBT over TAU for reducing depression post- treatment (k=1, n=46; SMD -0.67 95% CI -1.26, -0.07), at 3 months’ follow-up (k=1, n=36: SMD -0.65 95% CI -1.32, 0.03) and at 6 months’ follow-up (k=1, n=36: SMD -0.61 95% CI - 1.28, 0.07) 1 year follow-up (k=1, n=36: SMD -0.59 95% CI -1.27, 0.08) and 2 years follow- up (k=1, n=36: SMD -0.50 95% CI -1.17, 0.18)
There is limited evidence favouring child CBT over TAU for reducing anxiety post-treatment (k=1, n=46; SMD -0.71 95% CI -1.31, -0.12)
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between child CBT and TAU for reducing internalising child behaviour problems post-treatment (k=1, n=45: SMD -0.15 95% CI -0.74, 0.44)
Mother CBT versus TAU:
There is limited evidence favouring mother CBT over TAU for reducing the severity of clinician-rated PTSD symptoms post-treatment (k=1, n=44: SMD -0.54 95% CI -1.14, 0.07) and at 2 years’ follow-up (k=1, n=34: SMD -0.77 95% CI -1.48, -0.07).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between mother CBT and TAU for reducing the severity of clinician- rated PTSD symptoms at 3 months’ follow-up (k=1, n=34: SMD -0.45 95% CI -1.15, 0.24), 6 months’ follow-up (k=1, n=34: SMD -0.43 95% CI -1.12, 0.26), 1 year follow-up (k=1, n=34: SMD -0.33 95% CI -1.02, 0.36)
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between mother CBT and TAU for reducing depression post-treatment (k=1, n=44: SMD -0.46 95% CI -1.06, 0.14) at 3 months’ follow-up (k=1, n=35: SMD -0.30 95% CI -0.97, 0.37), at 6 months’ follow-up (k=1, n=35: SMD -0.19 95% CI -0.86, 0.48), 1 year follow-up (k=1, n=35: SMD -0.34 95% CI -1.01, 0.34).
219
There is limited evidence favouring mother CBT over TAU for reducing depression at 2 years follow-up (k=1, n=35: SMD -0.68 95% CI -1.37, 0.01).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between mother CBT and TAU for reducing anxiety post-treatment (k=1, n=44: SMD -0.01 95% CI -0.60, 0.58)
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between mother CBT and TAU for reducing internalising child behaviour problems post-treatment (k=1, n=43: SMD -0.40 95% CI -1.00, 0.20)
Box 77 Evidence statement matrix for RCTs comparing trauma-focused CBT and treatment as usual children with PTSD: sexual abuse Component Rating Description Evidence base D Two studies with a high risk of bias
Consistency A Studies consistent in favouring TF-CBT (mother and child, mother or child) over TAU
Clinical impact C Some clinically important point estimates; others inconclusive.
Generalisability B Children exposed to child abuse, similar to the guidelines population
Applicability C Applicable to Australian healthcare context with some caveats
Summary of evidence
Two studies with a high risk of bias compared trauma-focused CBT for either the mother, child or combined compared to treatment as usual, to help children who had been sexually abused. The study results generally favoured TF-CBT over TAU, with some of the results having a clinically important point estimate. (Grade C)
EMDR VERSUS TREATMENT AS USUAL IN ADULTS
There were three studies identified that compared EMDR against treatment as usual ((Marcus et al 1997), followed up in (Marcus et al 2004), (Carlson et al 1998) and (Johnson & Lubin 2006)). The Marcus studies, although relatively well designed in terms of randomisation and blinding, did not report the number of subjects allocated to each arm of the trial. This prevents the calculation of effect sizes for the treatments and thus evidence statements cannot be generated. The authors reported statistically significantly greater improvement for the EMDR group in self-reported PTSD symptoms, as measured by the Impact of Events Scale and the Modified PTSD scale at post-treatment, 3 month and 6 month follow up, and statistically significantly greater improvement on depression and anxiety at 6 months follow up.
The other studies that considered EMDR versus treatment as usual were Johnson 2006 (Johnson & Lubin 2006)and Carlson 1998 (Carlson et al 1998). The Johnson 2006 was a four arm trial which also compared prolonged exposure and ‘the counting method’; these comparisons are considered elsewhere. This study was small and of average quality with a
220 moderate risk of bias, with only completer analysis presented and a dropout rate of 25%. The Carlson study was small and did not mention important methodological aspects of the trial such as randomisation and blinding, and thus it was rated as having a high level of bias.
Table 72 Study profiles for RCTs comparing EMDR and treatment as usual for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Johnson & Lubin Moderate Female victims of University clinic, United 20 Severity of PTSD symptoms 2006) psychological trauma States (Marcus et al 1997) High Unspecified traumas: assault Outpatient setting, 67 PTSD diagnosis updated in (Marcus and battery, sexual abuse, United States Severity of PTSD symptoms et al 2004) incest, rape, life-threatening Depressive symptoms injury, serious traffic Anxiety accident, earthquake, and Attrition witnessing the death of a loved one. (Carlson et al 1998) High Male war veterans Outpatient setting, 22 PTSD diagnosis United States Severity of PTSD Depressive symptoms Anxiety Attrition
There is limited evidence favouring EMDR over treatment as usual on reducing the likelihood of having a PTSD diagnosis at posttreatment (k=1, n=22; RR 0.6 95% CI 0.21, 1.68)
There is limited evidence favouring EMDR over treatment as usual on reducing the severity of clinician-rated PTSD symptoms at post-treatment (k=1, n=20; SMD =-1.24 95% CI -2.20, -0.28)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between EMDR and treatment as usual on reducing the severity of self-rated PTSD symptoms at post-treatment (k=2, n=42; SMD =-0.41 95% CI -1.02, 0.21)
221
There is evidence favouring EMDR over treatment as usual for reducing depression at posttreatment (k=1, n=22; SMD -1.55 95% CI -2.51, -0.60)
There is limited evidence favouring EMDR over treatment as usual for reducing anxiety at posttreatment (k=1, n=22; SMD -1.09 95% CI -1.99, -0.19)
Box 78 Evidence statement matrix for RCT comparing EMDR and treatment as usual for adults with PTSD Component Rating Description Evidence base C One level II study with a moderate risk of bias, one with a high level of bias and one study that did not provide sufficient data to allow results to be included, all results based on completer data only Consistency A Studies consistent in favouring EMDR
Clinical impact C Limited evidence favouring EMDR over TAU.; however based on very small samples
Generalisability B Female victims of psychological trauma and male combat veterans; similar to target population for guidelines
Applicability C Studies set in the US; probably applicable to Australian healthcare context with some caveats
Summary of evidence
One small study with a moderate risk of bias and one with a high risk of bias found limited evidence for clinically important effects favouring EMDR over treatment as usual, but the studies were very small and should be interpreted carefully. One further study, from which effect sizes were unable to be calculated, also found statistically significant improvement in PTSD measures for the group who received EMDR. (Grade C).
Analysis of EMDR versus treatment as usual studies according to ITT status
Neither of the included studies analysed their data according to ITT principles.
EMDR VERSUS TREATMENT AS USUAL IN CHILDREN
One low-quality randomised controlled trial investigated EMDR compared with usual care in adolescents with conduct disorders and externalising (eg aggression and delinquency) and internalising (eg anxiety/depression, somatic difficulties and retreat) behaviour problems who had been exposed to maltreatment (Farkas et al 2010). Participants were randomised to receive either a treatment package (MASTR) including EMDR (and other interventions such as motivational interviewing) plus varying forms of usual care (N=33) or usual care only (N=32). Outcome assessors were blinded to the treatment allocation. The dropout rates during 3-month treatment period and 3-month follow-up period were 26.2% (17/65) and 12.3% (8/65), respectively. The two treatment groups’ completers (n=19 in the MASTR/EMDR group vs n=21 in the usual care group) were comparable with respect to patient demographic and disease characteristics at baseline.
Table 73 Study profiles for RCT comparing EMDR and treatment as usual for children with PTSD Reference Risk of bias Population Setting N Outcomes measured
222 (Farkas et al 2010) High Adolescents exhibiting Youth Protection 65 Severity of PTSD symptoms conduct problems and Services, Canada Depressive symptoms internalising and Anxiety externalising behaviours and Conduct disorder who had been exposed to Attrition maltreatment
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between EMDR and usual care on reducing the severity of PTSD symptoms at post-treatment in adolescents (k=1; n=40; SMD=-0.41; 95% CI -1.03, 0.22).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between EMDR and usual care on reducing the severity of PTSD symptoms at 3-month follow-up in adolescents (k=1; n=40; SMD=-0.36; 95% CI -0.99, 0.26).
There is limited evidence favouring EMDR over usual care on reducing depression symptoms at post-treatment in adolescents (k=1; n=40; SMD=-0.88; 95% CI -1.53, -0.23).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between EMDR and usual care on reducing depression symptoms at 3-month follow-up in adolescents (k=1; n=40; SMD=-0.19; 95% CI -0.81, 0.43).
There is limited evidence favouring EMDR over usual care on reducing anxiety symptoms at post-treatment in adolescents (k=1; n=40; SMD=-0.66; 95% CI -1.30, -0.03).
There is limited evidence favouring EMDR over usual care on reducing anxiety symptoms at post-treatment in adolescents (k=1; n=40; SMD=-0.72; 95% CI -1.36, -0.08).
There is limited evidence favouring EMDR over usual care on resolving externalising behaviour problems at post-treatment in adolescents (k=1; n=40; SMD=-0.84; 95% CI -1.48, -0.19).
There is limited evidence favouring EMDR over usual care on resolving externalising behaviour problems at 3-month follow-up in adolescents (k=1; n=40; SMD=-1.00; 95% CI -1.65, -0.34).
There is limited evidence favouring EMDR over usual care on resolving externalising behaviour problems at post-treatment in adolescents (k=1; n=40; SMD=-0.51; 95% CI -1.14, -0.12).
There is limited evidence favouring EMDR over usual care on resolving externalising behaviour problems at post-treatment in adolescents (k=1; n=40; SMD=-0.50; 95% CI -1.12, -0.13).
There is limited evidence favouring usual care over EMDA on attrition at post-treatment in adolescents (k=1; n=40; RR=2.33; 95% CI 0.93, 5.86).
223 Box 79 Evidence statement matrix for RCT comparing EMDR and treatment as usual for children with PTSD Component Rating Description Evidence base D One level II study with a high risk of bias
Consistency NA Only one study
Clinical impact C Clinically important point estimates favouring EMDR over usual care on outcomes of depression (only at post-treatment), anxiety, externalising behaviours and internalising behaviours and favouring usual care over EMDR on attrition (only at post-treatment). However, the full ranges of estimates included clinically irrelevant effects. Generalisability C Likely generalisable to adolescents with conduct disorders and externalising/internalising behaviour problems. Unclear how generalisable to broader target population.
Applicability C Study conducted in Canada, so evidence probably applicable to Australian healthcare context with some caveats.
Summary of evidence
Limited evidence suggests that EMDR is more beneficial than usual care in regards to improving depression symptom at post-treatment and resolving anxiety, externalising behaviour problems and internalising behaviour problems at post-treatment and at 3-month follow-up in adolescents. Limited evidence suggests that usual care is associated with lower dropout rate at post-treatment in adolescents when compared with EMDR. No significant benefit was found on reducing the severity of PTSD symptoms in children. (Grade C).
NARRATIVE EXPOSURE THERAPY (TRAUMA-FOCUSED) VERSUS TREATMENT AS USUAL One RCT of moderate quality (Neuner et al 2010) compared narrative exposure therapy (NET) and treatment as usual (TAU). Thirty-two asylum seekers with PTSD were allocated evenly to the two treatment groups. Follow-up was at six months and outcomes on PTSD and depression symptom severity were assessed according to the Post-traumatic Stress Diagnostic Scale (PDS) and the Hopkins Symptom Checklist (HSCL), respectively. Measures of effect size for severity of both PTSD and depression symptoms showed limited evidence, based on clinically significant point estimates with confidence intervals that included both clinically important and clinically unimportant values.
Table 74: Study profiles for RCTs comparing narrative exposure therapy and treatment as usual for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Neuner et al 2010) Moderate Asylum seekers Outpatient clinic for 32 Severity of PTSD refugees, Germany Depression
There is limited evidence favouring narrative exposure therapy over treatment as usual on reducing the severity of PTSD symptoms at 6 months follow-up (k = 1; n = 34; SMD = -1.02 95% CI, -1.79, -0.26).
There is limited evidence favouring narrative exposure therapy over treatment as usual on reducing the severity of depression symptoms at 6 months follow-up (k = 1; n = 34; SMD = - 0.53 95% CI, -1.26, 0.20).
224 Box 80: Evidence statement matrix for RCT comparing trauma focused narrative exposure therapy and treatment as usual for adults with PTSD Component Rating Description Evidence base C One level II study with moderate risk of bias
Consistency NA One study only
Clinical impact C Moderate
Generalisability C Evidence not directly generalisable to the target population but could be sensibly applied
Applicability C Evidence probably applicable to the Australian healthcare system with some caveats
Summary of evidence The one study available for this comparison showed limited evidence favouring NET over TAU. It was conducted in a high income country and is therefore likely to be applicable to the Australian context. It is unlikely that the patients in the study are so different from the asylum seeker population to be considered within the proposed guideline that the results cannot be generalised (Grade C).
“THE COUNTING METHOD” vs TREATMENT AS USUAL
A study by Johnson & Lubin (2006) compared ‘the counting method’ with treatment as usual (TAU). This study also compared ‘the counting method’ to EMDR and prolonged exposure; these comparisons are considered in the intervention vs intervention section. ‘The counting method’ is an imaginal exposure technique, where the subject remembers their traumatic memory chronologically as the therapist counts from one to 100. It is different to EMDR as it does not rely on cognitive restructuring, and does not have homework or in vivo exposure like prolonged exposure. The subject remembers the traumatic event privately, without detailed verbal communication to the therapist.
This study was of fair quality and had only small numbers in each arm of the trial (n=9 in ‘the counting method’ and n=11 in TAU).
Table 75: Study profiles for RCTs comparing ‘the counting method’ and treatment as usual for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Johnson & Lubin Moderate Female victims of University clinic, United 51 Severity of PTSD 2006) psychological trauma States (including all 4 arms)
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between ‘the counting method’ and treatment as usual on reducing the severity of clinician-measured PTSD symptoms at post-treatment (k=1, n=20, SMD=-0.38, 95%CI -1.27, 0.51).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between ‘the counting method’ and treatment as usual on reducing the severity of self-reported PTSD symptoms at post-treatment (k=1, n=20, SMD=0.27, 95%CI -
225 0.61, 1.16).
Box 81: Evidence statement matrix for RCT comparing ‘the counting method’ and treatment as usual for adults with PTSD Component Rating Description Evidence base C One level II study with moderate risk of bias
Consistency NA One study only
Clinical impact D Limited: only inconclusive findings
Generalisability C Evidence not directly generalisable to the target population but could be sensibly applied
Applicability C Evidence probably applicable to the Australian healthcare system with some caveats
Summary of evidence One small study with a moderate risk of bias found no difference between the effectiveness of ‘the counting method’ and treatment as usual. (Grade C).
TRAUMA-FOCUSED CBT VS STRESS MANAGEMENT THERAPIES
There were nine studies that compared TF-CBT with a stress management therapy ((Foa et al 1999; Marks et al 1998; Foa et al 1991; Taylor et al 2003; Vaughan et al 1994; McDonagh et al 2005; Echeburua et al 1997; Hinton et al 2011; Echeburua et al 1996). The TF-CBT component of these studies was similar in that it included cognitive restructuring and exposure therapy. The stress management therapies included muscle relaxation (Marks 1998, Taylor 2003, Vaughan 1994, Echuburua 1997, Hinton 2011, Echuburua 1996), stress inoculation therapy (Foa 1991, Foa 1999) and Present Centred Therapy (PCT, McDonagh 2005). The Echuburua 1996 study was originally included in the NICE review under early interventions, however it did not fit the criteria for this review for early intervention but was able to be included in this section.
These studies ranged in quality from poor to good, with six studies with a moderate risk of bias and three with a high risk. The trauma populations were mixed, and the studies were set in a range of countries including the UK, Spain, the US and Australia. All the studies but one (Hinton 2011) provided individual therapy. As this method of treatment delivery is quite different, this study was not included in the meta-analysis.
Table 76 Study profiles for RCTs comparing trauma-focused CBT and stress management for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Marks et al 1998) Moderate Unspecified trauma Outpatient setting, 87 PTSD diagnosis United Kingdom Severity of PTSD Attrition (Taylor et al 2003) Moderate Unspecified trauma (road Outpatient setting, 30 Severity of PTSD accidents, sexual or non- United States Depressive symptoms sexual assault, witnessing Attrition traumatic death)
226 (Vaughan et al Moderate Victims of violent crime, rape, Outpatient PTSD clinic, 24 PTSD diagnosis 1994) child abuse or motor accident Australia Depressive symptoms Attrition
(Echeburua et al Moderate Women aged 16 years and Outpatient setting, Spain 20 PTSD diagnosis 1997) over who were victims of Severity of PTSD sexual aggression Depressive symptoms Anxiety (Hinton et al 2011) Moderate Mixed trauma population of Outpatient setting, 24 Severity of PTSD Carribbean-Latino subjects United States Anxiety
(Echeburua et al Moderate Women aged 16 years and Outpatient setting, Spain 20 Severity of PTSD 1996) over who were victims of Depressive symptoms sexual aggression Anxiety (Foa et al 1999) High Female victims of sexual and Outpatient setting, 64 PTSD diagnosis nonsexual assault United States Severity of PTSD Depressive symptoms Anxiety Attrition (McDonagh et al High Women with PTSD Outpatient setting, 51 Severity of PTSD 2005) secondary to Child Sexual United States Depressive symptoms Abuse Anxiety Quality of life (Foa et al 1991) High Women who had Outpatient setting, 24 PTSD diagnosis experienced sexual assault, United States Severity of PTSD aggravated assault, or Depressive symptoms assault with a weapon, aged Anxiety over 16 Attrition
There is limited evidence favouring TF-CBT over stress management therapies for reducing the likelihood of a PTSD diagnosis at post-treatment (k=6, n=284; RR 0.78 95% CI 0.61, 0.99)
227
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between TF-CBT and stress management therapies for reducing the severity of clinician-rated PTSD symptoms at post-treatment (k=8, n=310; SMD -0.25 95% CI -0.61, 0.12)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between TF-CBT and stress management therapies for reducing the severity of clinician-rated PTSD symptoms at 2-5 months follow up (k=5, n=127; SMD -0.48 95% CI -0.84, -0.12)
228
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between TF-CBT and stress management therapies for reducing the severity of self-rated PTSD symptoms at post-treatment (k=3, n=127; SMD - 0.37 95% CI -0.74, 0.01)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between TF-CBT and stress management therapies for reducing the severity of self-rated PTSD symptoms at 2-5 months follow up (k=2, n=54; SMD -0.44 95% CI -0.99, 0.10)
229
There is evidence suggesting there is unlikely to be a clinically important difference between TF-CBT and stress management therapies for reducing depression at post-treatment (k=7, n=232; SMD-0.12 95% CI -0.36, 0.15)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between TF-CBT and stress management therapies for reducing depression at 2-5 months follow up (k=5, n=147; SMD -0.28 95% CI -0.62, 0.06)
230
There is evidence suggesting there is unlikely to be a clinically important difference between TF-CBT and stress management therapies for reducing anxiety at post-treatment (k=6, n=198; SMD -0.09 95% CI -0.39, 0.20)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between TF-CBT and stress reduction therapies for reducing anxiety at 2-5 months follow up (k=4, n=117; SMD -0.17 95% CI -0.56, 0.21)
231
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between TF-CBT and stress reduction therapies for improving quality of life at post-treatment (k=2, n=71; SMD -0.21 95% CI -0.68, 0.27)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between TF-CBT and stress reduction therapies on attrition (k=6, n=284; RR 1.17 95% CI 0.69, 2.00)
The study that conducted TF-CBT and applied muscle relaxation in groups was a very small study, and the publication failed to provide detail about randomisation and group comparisons. This study only used self-report outcomes, and with its high risk of bias, the results should be interpreted with caution. The study found clinically important differences in favour of TF-CBT on its outcomes of PTSD severity, and clinically important point estimates for anxiety.
232
There is evidence favouring group TF-CBT over group muscle relaxation training on reducing the severity of PTSD symptoms at post-treatment (k=1, n=24; SMD -1.53(-2.44, - 0.62)
There is evidence favouring group TF-CBT over group muscle relaxation training on reducing the severity of PTSD symptoms at 12 weeks follow up (k=1, n=24; SMD -1.58(-2.50 -0.66)
There is limited evidence favouring group TF-CBT over group muscle relaxation training for reducing anxiety at post-treatment (k=1, n=24; SMD -0.84 95% CI -1.68, -0.01)
There is limited evidence favouring group TF-CBT over group muscle relaxation training for reducing anxiety at 12 weeks follow up (k=1, n=24; SMD -0.96 95% CI -1.80, -0.11)
Box 82 Evidence statement matrix for RCTs comparing trauma-focused CBT and stress management therapies for adults with PTSD Component Rating Description Evidence base C Six level II studies with a moderate risk of bias and three with a high risk.
Consistency A Studies consistent in showing no clinically important differences between therapies.
Clinical impact D No clinically important differences between treatments
Generalisability C Varied populations of mixed ethnicities with mixed trauma experiences, some of which will be generalisable to the guidelines population
Applicability C Applicable to Australian healthcare context with some caveats
Summary of evidence
Nine studies of poor to average quality found no clinically important differences on any outcomes with the exception of limited evidence favouring TF-CBT for PTSD diagnosis. (Grade C)
TRAUMA-FOCUSED CBT VERSUS STRESS MANAGEMENT IN WOMEN WHO HAD PTSD SECONDARY TO SEXUAL OR PHYSICAL ABUSE AS AN ADULT, OR CHILD SEXUAL ABUSE
Five of the studies in the TF-CBT versus stress management comparison considered women who had experienced sexual or physical abuse as an adult, or child sexual abuse (Foa 1999, McDonagh 2005, Foa 1991, Echeburua 1996 and Echeburua 1997). Most of these studies were rated as having a high risk of bias, and most were published pre 2000. In general, the results for this subgroup mirrored the results for the main analysis, however two of the point estimates managed to reach clinical importance (although the confidence intervals also included clinically unimportant effects).
233 Table 77 Study profiles for RCTs comparing trauma-focused CBT and stress management for women with PTSD secondary to physical or sexual abuse, or child sexual abuse Reference Risk of bias Population Setting N Outcomes measured (Echeburua et al Moderate Women aged 16 years and Outpatient setting, Spain 20 PTSD diagnosis 1997) over who were victims of Severity of PTSD sexual aggression Depressive symptoms Anxiety
(Echeburua et al Moderate Women aged 16 years and Outpatient setting, Spain 20 Severity of PTSD 1996) over who were victims of Depressive symptoms sexual aggression Anxiety
(Foa et al 1999) High Female victims of sexual and Outpatient setting, 64 PTSD diagnosis nonsexual assault United States Severity of PTSD Depressive symptoms Anxiety Attrition (McDonagh et al High Women with PTSD Outpatient setting, 51 Severity of PTSD 2005) secondary to Child Sexual United States Depressive symptoms Abuse Anxiety Quality of life (Foa et al 1991) High Women who had Outpatient setting, 24 PTSD diagnosis experienced sexual assault, United States Severity of PTSD aggravated assault, or Depressive symptoms assault with a weapon, aged Anxiety over 16 Attrition
There is limited evidence favouring trauma-focused CBT over stress management for abused women on the likelihood of having a PTSD diagnosis at posttreatment (k=3, n=132; RR 0.78 95% CI 0.37, 1.66)
234
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between trauma-focused CBT and stress management for abused women for reducing the severity of clinician-rated PTSD symptoms at posttreatment (k=5, n=179; SMD -0.22 95% CI -0.80, 0.36)
There is limited evidence favouring trauma-focused CBT over stress management for abused women for reducing the severity of clinician-rated PTSD symptoms at 2-5months follow up (k=3, n=73; SMD -0.55 95% CI -1.02, -0.07)
235
There is evidence suggesting there is unlikely to be a clinically important difference between trauma-focused CBT and stress management for abused women on reducing the severity of depression at posttreatment (k=5, n=178; SMD -0.05 95% CI -0.35, 0.26)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between trauma-focused CBT and stress management for abused women on reducing the severity of depression at 2-5 months follow up (k=3, n=93; SMD -0.46 95% CI -0.90, -0.02)
236
There is evidence suggesting there is unlikely to be a clinically important difference between trauma-focused CBT and stress management for abused women on reducing the severity of anxiety at posttreatment (k=5, n=174; SMD -0.11 95% CI -0.42, 0.21)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between trauma-focused CBT and stress management for abused women on reducing the severity of anxiety at 2-5 months follow up (k=3, n=93; SMD -0.33 95% CI -0.77, 0.11)
237
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between trauma-focused CBT and stress management for abused women on study attrition (k=3, n=132; RR 0.89 95% CI 0.45, 1.76)
Box 83 Evidence statement matrix for RCTs comparing trauma-focused CBT and stress management therapies for women with PTSD secondary to physical or sexual abuse, or child abuse Component Rating Description Evidence base C Two level II studies with a moderate risk of bias and three with a high risk.
Consistency A Studies consistent in showing no clinically important differences between therapies.
Clinical impact D No clinically important differences between treatments, with the exception of clinically important point estimates on PTSD diagnosis and clinician-rated PTSD at 2-5 months follow up
Generalisability B Women who had experienced various types of physical and sexual abuse as adults and children; broadly generalisable to the guidelines population
Applicability C Applicable to Australian healthcare context with some caveats
Summary of evidence
Five studies of poor to average quality found few clinically important differences between TF-CBT and stress management for women with PTSD secondary to physical or sexual abuse or child abuse. Results favoured TF-CBT for PTSD diagnosis and clinician-rated PTSD severity at 2-5 months, but only the point estimate was clinically important. In general the results for this subgroup mirror the results for the comparison as a whole. (Grade C)
238 TRAUMA-FOCUSED CBT VERSUS SUPPORTIVE COUNSELLING There were six studies that compared trauma-focused CBT (TF-CBT) with supportive counselling (SC) (Blanchard et al 2003; Bryant et al 2003b; Cottraux et al 2008; Foa et al 1991; Litz et al 2007; Schnurr et al 2007), plus one that followed-up Blanchard et al (2003) (Blanchard et al 2004). One of these studies (Litz et al 2007) compared each of these therapies delivered over the internet with therapist assistance; this study will be considered separately to the others.
The TF-CBT was similar in all studies, and involved some form of exposure and cognitive restructuring. The supportive counselling involved psychoeducation and supportive listening, without the cognitive restructuring or exposure aspects of the TF-CBT. The studies considered various trauma populations, and were conducted in the USA, France and Australia. One study was good quality with a low risk of bias and good sample size; the other studies were smaller with a high risk of bias.
The internet-based study treatment was similar in its approach, with both arms of the study assisted by therapists, but the therapy was self-managed. This was a small study with a high risk of bias. As this therapy had a different delivery method, it was not entered into the meta- analysis.
Table 78 Study profiles for RCTs comparing trauma-focused CBT and supportive counselling for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Schnurr et al 2007) Low Female veterans with mixed Veterans’ Affairs Medical 284 PTSD diagnosis trauma experiences Centres, 9 sites in US Severity of PTSD Depressive symptoms Anxiety Quality of life Attrition
(Bryant et al 2003a) High Nonsexual assault or a motor PTSD clinic, Australia 24 PTSD diagnosis vehicle accident Severity of PTSD Depressive symptoms Anxiety Attrition
(Foa et al 1991) High Women who had experienced Outpatient setting, 24 PTSD diagnosis sexual assault, aggravated United States Severity of PTSD assault, or assault with a Depressive symptoms weapon, aged over 16 Anxiety Attrition (Blanchard et al High Motor vehicle accident Outpatient setting, 73/52 PTSD diagnosis 2003) followed up survivors United States Severity of PTSD in(Blanchard et al Depressive symptoms 2004) Anxiety Attrition
(Cottraux et al 2008) High Men and women aged 18-65 Outpatient setting, 60 PTSD diagnosis who were mixed trauma France Severity of PTSD survivors Depressive symptoms Anxiety Quality of life
239 (Litz et al 2007) High Department of Defence Internet-based study, 45 PTSD diagnosis service members who had USA Severity of PTSD PTSD related to Sept 11 Depressive symptoms attack on Pentagon or Anxiety combat in Iraq or Afghanistan
There is limited evidence favouring TF-CBT over supportive counselling for reducing the likelihood of a PTSD diagnosis at post-treatment (k=5, n=485; RR 0.76 95% CI 0.67, 0.86)
There is limited evidence favouring TF-CBT over supportive counselling for reducing the severity of clinician-rated PTSD symptoms at post-treatment (k=4, n=404; SMD -0.61 95% CI -1.13, -0.09)
240
There evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between TF-CBT and supportive counselling for reducing the severity of clinician-rated PTSD symptoms at 3 months follow up (k=3, n=354; SMD -0.28 95% CI - 0.49, -0.07)
There is limited evidence favouring TF-CBT over supportive counselling for reducing the severity of clinician-rated PTSD symptoms at 6-12 months follow up (k=3, n=381; SMD - 0.69 95% CI -1.56, 0.18)
241
There is limited evidence favouring TF-CBT over supportive counselling for reducing the severity of self-rated PTSD symptoms at post-treatment (k=5, n=502; SMD -0.74 95% CI - 1.33, -0.15)
There is evidence suggesting there is unlikely to be a clinically important difference between TF-CBT and supportive counselling for reducing the severity of self-rated PTSD symptoms at 2-5 months follow up (k=3, n=415; SMD -0.25 95% CI -0.44, -0.05)
242
There is limited evidence favouring TF-CBT over supportive counselling for reducing the severity of self-rated PTSD symptoms at 6-12 months follow up (k=3, n=381; SMD -0.67 95% CI -1.45, 0.11)
There is evidence suggesting there is unlikely to be a clinically important difference between TF-CBT and supportive counselling for reducing depression at post-treatment (k=5, n=446; SMD -0.31 95% CI -0.50, -0.12)
243
There is evidence suggesting there is unlikely to be a clinically important difference between TF-CBT and supportive counselling for reducing depression at 2-5 months follow up (k=3, n=356; SMD -0.27 95% CI -0.48, -0.06)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between TF-CBT and supportive counselling for reducing depression at 6-12 months follow up (k=3, n=381; SMD -0.43 95% CI -0.95, 0.09)
244
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between TF-CBT and supportive counselling for reducing anxiety at post-treatment (k=5, n=446; SMD -0.39 95% CI -0.58, -0.20)
There is evidence suggesting there is unlikely to be a clinically important difference between TF-CBT and supportive counselling for reducing anxiety at 2-5 months follow up (k=3, n=356; SMD -0.19 95% CI -0.40, 0.02)
245
There is limited evidence favouring TF-CBT over supportive counselling for reducing anxiety at 6-12 months follow up (k=3, n=381; SMD -0.67 95% -1.48, 0.13)
The evidence is inconclusive so it is not possible to determine whether there is a clinically important difference between TF-CBT and supportive counselling in study attrition (k=5, n=493; RR 0.90 95% CI 0.63, 1.31)
One study compared TF-CBT with supportive counselling (Litz et al 2007), both delivered over the internet. Each therapy arm was therapist-assisted and self-managed and lasted for 8 weeks. The study was small and of poor quality, with a lack of detail given in the study report and high dropout rates, especially in the CBT group (42%). The study utilised only self-report measures.
There is limited evidence favouring internet-based TF-CBT over internet-based supportive counselling on the likelihood of having a PTSD diagnosis at post-treatment (k=1, n=31; RR 0.45 (0.24, 0.83)
246 The evidence is inconclusive so it is not possible to determine whether there is a clinically important difference between internet-based TF-CBT and internet-based supportive counselling on reducing the severity of PTSD symptoms at post-treatment (k=1, n=31; SMD - 0.40(-1.12, 0.31)
The evidence is inconclusive so it is not possible to determine whether there is a clinically important difference between internet-based TF-CBT and internet-based supportive counselling on reducing depression post-treatment (k=1, n=31; SMD -0.49(-1.21, 0.22)
The evidence is inconclusive so it is not possible to determine whether there is a clinically important difference between internet-based TF-CBT and internet-based supportive counselling on reducing anxiety post-treatment (k=1, n=31; SMD -0.38(-1.09, 0.37)
Box 84 Evidence statement matrix for RCTs comparing trauma-focused CBT and supportive counselling for adults with PTSD Component Rating Description Evidence base B One level II study with a low level of bias; rest with high level of bias
Consistency A All outcomes favour TF-CBT over supportive counselling
Clinical impact C Several point estimates clinically important favouring CBT over supportive counselling, with many outcomes inconclusive.
Generalisability B Mixed trauma populations that are similar to target populations for Australian guidelines.
Applicability C Probably applicable to Australian healthcare context with some caveats
Summary of evidence
To investigate the comparison TF-CBT vs supportive counselling, there was one good quality, large trial with a low risk of bias, and several smaller studies with a high level of bias. The results are consistent in favouring TF-CBT over supportive counselling for all outcomes, with some of these differences being clinically important on the point estimate. (Grade B)
247 TF-CBT vs SUPPORTIVE COUNSELLING (CHILD CENTRED THERAPY) IN CHILDREN
There was one study that compared TF-CBT to Child Centred Therapy (CCT) in children aged 8-14 years ((Cohen et al 2004b), followed up in (Deblinger et al 2006)). CCT was similar to the supportive counselling described in the adult studies above, in that it provided active listening and support without any cognitive restructuring or exposure therapy. Both therapies in this trial were administered individually and separately to both child and parent, whilst the TF-CBT arm also included three combined parent-child sessions. Each arm of the trial involved 12 weeks of therapy.
A lack of detail about the methodology of this study limited its quality; overall it had a high level of bias. Although it had good numbers in each arm and dropout rates were around 22% at post-treatment, only completer analyses were presented.
At post-treatment, this study showed clinically important evidence for PTSD diagnosis favouring TF-CBT. It was consisted in showing greater improvement in PTSD symptoms, anxiety, and depression for those children and parents receiving TF-CBT, although none of these differences were clinically important.
Table 79 Study profiles for RCTs comparing trauma-focused CBT and supportive counselling for children with PTSD Reference Risk of bias Population Setting N Outcomes measured (Cohen et al 2004b), High Children aged 8-14 years Outpatient setting, 229 PTSD diagnosis who had experienced sexual United States Severity of PTSD (Deblinger et al abuse and a parent or care- Depressive symptoms 2006) giver Anxiety Child behaviour
There is evidence favouring TF-CBT over CCT on the likelihood of having a PTSD diagnosis at post-treatment (k=1, n=180; RR 0.46 95% CI 0.29, 0.73)
The evidence is inconclusive and so it is not possible to determine whether or not there is a clinically important difference between TF-CBT and CCT on reducing the severity of the PTSD symptom reexperiencing at post-treatment (k=1, n=180; SMD -0.49 95% CI -0.78, - 0.19), at 6 months follow up (k=1, n=147; SMD -0.48 95% CI -0.81, -0.15) or at 12 months follow up (k=1, n=153; SMD -0.26 95% CI -0.58, 0.06)
There is limited evidence favouring TF-CBT over CCT on reducing the severity of the PTSD symptom avoidance at post-treatment (k=1, n=180; SMD -0.72 95% CI -1.02, -0.42)
The evidence is inconclusive and so it is not possible to determine whether or not there is a clinically important difference between TF-CBT and CCT on reducing the severity of the PTSD symptom avoidance at 6 months follow up (k=1, n=147; SMD -0.29 95% CI -0.62, 0.03) and 12 months follow up (k=1, n=153; SMD -0.38 95% CI -0.70, -0.06)
The evidence is inconclusive and so it is not possible to determine whether or not there is a clinically important difference between TF-CBT and CCT on reducing the severity of the PTSD symptom hypervigilance at post-treatment (k=1, n=180; SMD -0.37 95% CI -0.67, -
248 0.08), at 6 months follow up (k=1, n=147; SMD -0.22 95% CI -0.54, 0.11) and at 12 months follow up (k=1, n=153; SMD -0.21 95% CI -0.53, 0.11)
The evidence is inconclusive and so it is not possible to determine whether or not there is a clinically important difference between TF-CBT and CCT on reducing depression at post- treatment (k=1, n=183; SMD -0.40 95% CI -0.69, -0.11), and at 6 months follow up (k=1, n=151; SMD -0.29 95% CI -0.61, 0.03)
There is evidence suggesting there is unlikely to be a clinically important difference between TF-CBT and CCT on reducing depression at 12 months follow up (k=1, n=155; SMD -0.17 95% CI -0.49, 0.11)
The evidence is inconclusive and so it is not possible to determine whether or not there is a clinically important difference between TF-CBT and CCT on reducing anxiety at post- treatment (k=1, n=183; SMD -0.25 95% CI -0.54, 0.04), at 6 months follow up (k=1, n=151; SMD -0.24 95% CI -0.56, 0.08) or at 12 months follow up (k=1, n=155; SMD -0.19 95% CI - 0.51, 0.12).
The evidence is inconclusive and so it is not possible to determine whether or not there is a clinically important difference between TF-CBT and CCT on reducing child problem behaviour at post-treatment (k=1, n=179; SMD -0.26 95% CI -0.56, 0.04)
There is evidence suggesting there is unlikely to be a clinically important difference between TF-CBT and CCT on reducing child problem behaviour at 6 months follow up (k=1, n=142; SMD -0.07 95% CI -0.40, 0.25) or 12 months follow up (k=1, n=146; SMD -0.08 95% CI - 0.40, 0.25)
Box 85 Evidence statement matrix for RCTs comparing trauma-focused CBT and supportive counselling for children with PTSD Component Rating Description Evidence base D One study with a high level of bias
Consistency NA Only one study
Clinical impact D One clinically important difference on PTSD diagnosis and a clinically important point estimate on the outcome of the avoidance subscale of PTSD, but all other outcomes were either inconclusive or found no difference.
Generalisability C Population of children with multiple trauma experiences and had a variety of psychological and behavioural problems: expect children in Australia who had experienced the same would be similar and thus would be a target for the Australian guidelines. Applicability C Probably applicable to Australian healthcare context with some caveats
Summary of evidence One poor quality study found a clinically important difference in the diagnosis of PTSD post- treatment favouring children in the TF-CBT group, and a clinically important difference on one dimension of PTSD (avoidance) but not others. Although all the results favoured TF- CBT, for each symptom measure and for each other follow up time point there were no clinically important differences between TF-CBT and child-centred therapy. (Grade D)
249 TRAUMA-FOCUSED CBT VS WOMENS HEALTH EDUCATION
One study, Hien 2009, was conducted in a population of women with co-occuring PTSD and substance abuse. It compared a trauma-focused CBT that addressed both PTSD and substance abuse (Seeking Safety, SS) with Women’s Health Education (WHE), which was designed to provide equivalent therapeutic attention, expectancy of benefit and issue-oriented focus, but without theory driven techniques and with no explicit focus on substance abuse or trauma. All subjects were enrolled at and recruited from community-based substance abuse treatment programs, and continued to receive standard substance abuse treatment throughout the trial.
This was a good quality study with a moderate level of bias, limited only by its high dropout rates of around 40%. However ITT was conducted and the outcome measures included clinician-rated and self-rated PTSD severity measures. Follow up was conducted at 3, 6 and 12 months post-treatment, however only the mean over this whole follow-up period was presented.
Table 80 Study profiles for RCTs comparing trauma-focused CBT (Seeking Safety) and Women’s Health Education for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Hien et al 2009) Moderate Women aged 18-65 years Outpatient setting, 353 Severity of PTSD (clinican and who had past exposure to United States self-rated) traumatic event and met Attrition current diagnosis for drug or alcohol abuse or dependence
There is evidence suggesting there is unlikely to be a clinically important difference between SS and WHE on reducing the severity of clinician-rated PTSD symptoms at post-treatment (k=1, n-353; SMD -0.04 95%CI -0.26, 0.17)
There is evidence suggesting there is unlikely to be a clinically important difference between SS and WHE on reducing the severity of clinician-rated PTSD symptoms between 3 and 12 months follow up (k=1, n-353; SMD -0.12 95%CI -0.33, 0.09)
There is evidence suggesting there is unlikely to be a clinically important difference between SS and WHE on reducing the severity of self-rated PTSD symptoms at post-treatment (k=1, n-353; SMD -0.08 95%CI -0.28, 0.13)
There is evidence suggesting there is unlikely to be a clinically important difference between SS and WHE on reducing the severity of self-rated PTSD symptoms at between 3 and 12 months follow up (k=1, n-353; SMD -0.14 95%CI -0.35, 0.07)
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between SS and WHE on study attrition at post-treatment (k=1, n=353: RR 1.07 95% CI 0.82-1.40)
Box 86 Evidence statement matrix for RCTs comparing Seeking Safety and Women’s Health Education for adults with PTSD Component Rating Description Evidence base C One study with moderate risk of bias
250 Consistency NA One study only
Clinical impact D No clinically important differences between treatments
Generalisability D Very specific population with combined PTSD and substance-abuse; difficult to judge whether it is sensible to generalise to target population
Applicability C Applicable to Australian healthcare context with some caveats
Summary of evidence
One good size study with a moderate risk of bias found no clinically important differences between trauma-focused CBT and education for women with co-occurring PTSD and substance abuse. (Grade C)
TRAUMA-FOCUSED CBT VERSUS HYPNOTHERAPY One small study compared TF-CBT and hypnotherapy in survivors of mixed trauma (Brom et al 1989). The TF-CBT was trauma desensitisation, which involved a two factor approach of conditioning and cognitive learning, whilst the goal of hypnotherapy was to bring the patient in contact with the reality of the traumatic event and to bring about a decrease in the conditioned responses triggered by the event. The study also considered two other treatments which are assessed in other sections. This study was judged to have a high risk of bias due to a lack of detail about randomisation, group differences and blinding, although it did conduct ITT analysis and had a low dropout rate of 11%.
Table 81 Study profiles for RCTs comparing trauma-focused CBT and hypnotherapy for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Brom et al 1989) High Experienced a violent crime, Outpatient setting, the 60 Severity of PTSD traffic accident, or lost a Netherlands Anxiety loved one due to murder/suicide, traffic accident, or illness
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between trauma-focused CBT and hypnotherapy on reducing the severity of self-reported PTSD symptoms at post-treatment (k=1, n=54; SMD=-0.26, 95%CI -0.80, 0.27). There is evidence suggesting that there is unlikely to be a clinically important difference between trauma-focused CBT and hypnotherapy on reducing the severity of self- reported PTSD symptoms at 3 months’ follow-up (k=1; n=54, SMD=-0.02, 95%CI - 0.55, 0.51). There is evidence suggesting that there is unlikely to be a clinically important difference between trauma-focused CBT and hypnotherapy on reducing anxiety at post-treatment (k=1; n=54, SMD=-0.01, 95%CI -0.52, 0.54). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between trauma-focused CBT and hypnotherapy on reducing anxiety at 3 months’ follow-up (k=1, n=54; SMD=-0.136, 95%CI -0.67, 0.39).
251
Box 87 Evidence statement matrix for RCTs comparing trauma-focused CBT and hypnotherapy for adults with PTSD Component Rating Description Evidence base D One Level II study with a high risk of bias due to lack of description regarding randomisation, baseline patient characteristics and blinding Consistency NA Only one study
Clinical impact D No clinically important difference detected between CBT and hypnotherapy
Generalisability A Evidence likely to be directly generalisable to the target population (a mix of trauma types, in patients from a European country)
Applicability B Evidence applicable to the Australian healthcare context with few caveats
Summary of evidence The evidence was too limited to make any conclusions regarding the comparative efficacy of trauma-focused CBT and hypnotherapy for adults with PTSD. (Grade D)
TRAUMA-FOCUSED CBT VERSUS PSYCHODYNAMIC THERAPY
The study by Brom, as described above, also compared the TF-CBT treatment (trauma desensitization) to psychodynamic therapy. The aim of the psychodynamic therapy is limited to the solving of the intrapsychic conflicts resulting from the traumatic experience, with the therapist playing an active role. The limitation of this study are described above.
Table 82 Study profiles for RCTs comparing trauma-focused CBT and psychodynamic therapy for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Brom et al 1989) High Experienced a violent crime, Outpatient setting, the 60 Severity of PTSD traffic accident, or lost a Netherlands Anxiety loved one due to murder/suicide, traffic accident, or illness
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between trauma-focused CBT and psychodynamic therapy on reducing the severity of PTSD symptoms at post-treatment (k=1, n=54, SMD=-0.25, 95%CI -0.796, 0.27) or at 3 months’ follow-up (k=1, n=54; SMD=0.22, 95%CI -0.31, 0.76). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between trauma-focused CBT and psychodynamic therapy on reducing anxiety post-treatment (k=1, n=54, SMD=0.37, 95%CI -0.16, 0.91) or at 3 months’ follow-up (k=1, n=54; SMD=0.21, 95%CI -0.32, 0.74).
Box 88 Evidence statement matrix for RCTs comparing trauma-focused CBT and psychodynamic therapy for adults with PTSD Component Rating Description Evidence base D One Level II study with a high risk of bias due to lack of description regarding randomisation, baseline patient characteristics and blinding
252 Consistency NA Only one study
Clinical impact D No clinically important difference detected between CBT and psychodynamic therapy
Generalisability A Evidence likely to be directly generalisable to the target population (a mix of trauma types, in patients from a European country)
Applicability B Evidence applicable to the Australian healthcare context with few caveats
Summary of evidence The evidence was too limited to make any conclusions regarding the comparative efficacy of trauma-focused CBT and psychodynamic therapy for adults with PTSD. (Grade D)
TRAUMA-FOCUSED CBT VERSUS PSYCHODYNAMIC THERAPY IN ADOLESCENTS One study with a moderate level of bias compared a form of trauma-focused CBT (prolonged exposure) against time-limited psychodynamic psychotherapy. Adolescents in both treatment conditions responded significantly to treatment, with some outcome measures showing that prolonged exposure was more effective than psychodynamic psychotherapy, although the full range of plausible outcomes outlined by the confidence intervals include effects in the opposite direction. {Gilboa-Schechtman, 2010, 20855048} Table 83 Study profiles for RCTs comparing trauma-focused CBT and psychodynamic therapy for adolescents with PTSD Reference Risk of bias Population Setting N Outcomes measured (Gilboa-Schectman Moderate Adolescents with PTSD due Outpatient setting, 38 PTSD diagnosis et al 2010) to a single trauma (imotor Israel Severity of PTSD vehicle accident, sexual or Depressive symptoms nonsexual assault, terrorist Functioning attack or other)
There is limited evidence favouring trauma-focused CBT over psychodynamic therapy on the likelihood of having a PTSD diagnosis post-treatment (k=1, n=38, RR=0.5, 95%CI 0.24, 1.05) and at 6 months’ follow-up (k=1, n=38, RR=0.5, 95%CI 0.26, 0.96).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between trauma-focused CBT and psychodynamic therapy on the severity of PTSD symptoms (self-report) post-treatment (k=1, n=38, SMD=-0.48, 95%CI -1.12, 0.17).
There is limited evidence favouring trauma-focused CBT over psychodynamic therapy on the severity of PTSD symptoms (self-report) at 6 months’ follow-up (k=1, n=38, SMD=-0.53, 95%CI -1.17, 0.12).
253 The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between trauma-focused CBT and psychodynamic therapy on depressive symptoms post-treatment (k=1, n=38, SMD=-0.08, 95%CI -0.72, 0.56) or at 6 months’ follow-up (k=1, n=38, SMD=-0.19, 95%CI -0.83, 0.44).
There is limited evidence favouring trauma-focused CBT over psychodynamic therapy on global functioning post-treatment (k=1, n=38, SMD=0.64, 95%CI -0.01, 1.29) and at 6 months’ follow-up (k=1, n=38, SMD=0.62, 95%CI -0.02, 1.28).
Box 89 Evidence statement matrix for RCTs comparing trauma-focused CBT and psychodynamic therapy for adolescents with PTSD Component Rating Description Evidence base C One level II study with a moderate risk of bias
Consistency NA Only one study
Clinical impact C Clinically relevant point estimates on the outcomes of diagnosis of PTSD at both time-points, severity of PTSD symptoms at 6 months, and functioning. Little difference between treatments on the final levels of depressive symptoms, although baseline levels were considerably lower in psychodynamic therapy condition. Generalisability B Trauma types highly generalisable to target population – adolescents with PTSD due to predominantly motor vehicle accidents, or sexual or nonsexual assault
Applicability C Limited applicability given healthcare setting in Israel likely to differ to Australian healthcare setting.
Summary of evidence One average quality study found that limited evidence in favour of trauma-focused CBT over psychodynamic psychotherapy in adolescents on PTSD outcome measures, but not measures of depressive symptoms. (Grade C)
TRAUMA-FOCUSED CBT VS ‘THE COUNTING METHOD’
A study by Johnson & Lubin (2006) compared prolonged exposure to ‘the counting method’, which is detailed in the comparison ‘the counting method’ vs TAU above. This was a small study of average quality; other comparisons examined in this study are reported elsewhere.
Table 84 Study profiles for RCTs comparing trauma-focused CBT and ‘the counting method’ for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Johnson & Lubin Moderate Women (mean age 38.9 years) who Outpatient 51 Severity of PTSD, clinician rated 2006) had experienced trauma either as an setting, United and self-report adult or child (rape, physical abuse, States sexual abuse or MVA)
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between prolonged exposure and ‘the counting method’ on reducing the severity of clinician–rated PTSD symptoms at post-treatment (k=1, n=18, SMD=-0.18, 95%CI -1.11, 0.74) or at 3 months follow-up (k=1, n=18, SMD=-0.13, 95%CI -1.06, 0.79).
254 There is limited evidence favouring prolonged exposure over ‘the counting method’ on reducing the severity of self-reported PTSD symptoms post-treatment (k=1, n=18, SMD=- 0.70, 95%CI -1.65, 0.26 and at 3 months follow-up (k=1, n=18, SMD=-0.58, 95%CI -1.52, 0.36).
Box 90 Evidence statement matrix for RCT comparing trauma-focused CBT and ‘the counting method’ for adults with PTSD Component Rating Description Evidence base C One level II study at a moderate risk of bias.
Consistency NA Only one study.
Clinical impact D Limited evidence favouring PE over ‘the counting method’ on the self-report measures, but not the clinician-rated measures; small sample sizes meant the confidence intervals also included clinically unimportant effects. Generalisability C Population who had experienced mixed traumas, although only females; generalisable to a proportion of the target audience for the guidelines.
Applicability C Study performed in the United States; evidence probably applicable to the Australian healthcare context with some caveats.
Summary of evidence This small, average quality study found limited evidence favouring PE over ‘the counting method’ on the self-report PTSD symptom measures. However there is greater potential for bias in the self-reported outcomes than in the clinician-rated outcomes, which were not clinically important, so this should be interpreted with caution. (Grade C)
COGNITIVE BEHAVIOURAL THERAPY ADMINISTERED TO DIFFERENT PEOPLE, FOR CHILDREN WITH PTSD
Two studies study compared CBT given to different people (child, parent or both) to treat PTSD in children who had been sexually abused ((Deblinger et al 1996; Deblinger et al 1999; King et al 2000). These studies are also both considered in Question 23, and the interventions against waitlist in Question 10. The King study compared CBT for children alone to CBT for children and a non-offending parent. This comparison is considered in Question 23. The Deblinger 1996 study, followed up in Deblinger 1999, compared child-only CBT with parent- only CBT and child-and-parent CBT.
The study was limited by small sample sizes and did not blind the outcomes assessors to group allocation. Whilst the study claimed to be randomised, no details about the randomisation procedure were given, the differences between groups were not detailed, although it was stated that no significant differences on any variables of interest were found between the groups. At post-treatment, loss to follow-up was 11% (11/100); however the study followed participants up for up to 2 years, and loss to follow-up varied over that time period, up to as much as 50% in the community control group. The study only reported completer data.
The comparisons assessed in this section are: CBT for mothers only vs CBT for children only, and CBT for mothers only vs CBT for mother-and-child. The comparisons between child-only and child-parent CBT are presented in Question 23. Due to five follow-up time points, there are many comparisons, increasing the chances of finding a difference by chance.
255
Table 85 Study profiles for RCTs comparing CBT to a different form of CBT. Reference Risk of bias Population Setting N Outcomes measured Deblinger 1996, Moderate Children aged 7-13 Clinic within University 100 PTSD Deblinger 1999 years who had been medical school, USA Anxiety sexually abused Depression Child behaviour
Child-only CBT vs mother-only CBT:
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between child -only CBT and mother-only CBT for sexually abused children with PTSD on reducing the severity of PTSD symptoms at post-treatment (k=1; n=46; SMD=-0.36 95% CI -0.94, 0.22), at 3 months follow-up (k=1; n=41; SMD=- 0.18 95% CI -0.79, 0.43), at 6 months follow-up (k=1; n=41; SMD=-0.48 95% CI -1.10, 0.14), at 1 year follow-up (k=1; n=41; SMD=-0.22 95% CI -0.83, 0.40) or at 2 years follow- up (k=1; n=41; SMD=0.20 95% CI -0.41, 0.81)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between child -only CBT and mother-only CBT for sexually abused children with PTSD on reducing depression at post-treatment (k=1; n=46; SMD=- 0.21 95% CI -0.79, 0.37), at 3 months follow-up (k=1; n=41; SMD=-0.37 95% CI -0.98, 0.25), at 6 months follow-up (k=1; n=41; SMD=-0.36 95% CI -0.98, 0.26), at 1 year follow- up (k=1; n=41; SMD=-0.20 95% CI -0.81, 0.42) or at 2 years follow-up (k=1; n=41; SMD=0.19 95% CI -0.42, 0.81)
There is limited evidence favouring mother-only CBT over child-only CBT for sexually abused children with PTSD on reducing externalising behaviour at post-treatment (k=1; n=46; SMD=0.72 95% CI 0.13, 1.32)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between child -only CBT and mother-only CBT for sexually abused children with PTSD on reducing externalising behaviour at 3 months follow-up (k=1; n=38; SMD=0.22 95% CI -0.42, 0.86), at 6 months follow-up (k=1; n=38; SMD=0.21 95% CI -0.43, 0.85), at 1 year follow-up (k=1; n=38; SMD=0.25 95% CI -0.39, 0.89) or at 2 years follow-up (k=1; n=38; SMD=0.27 95% CI -0.37, 0.91)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between child -only CBT and mother-only CBT for sexually abused children with PTSD on reducing internalising behaviour at post-treatment (k=1; n=46 SMD=0.25 95% CI -0.33, 0.83)
There is limited evidence favouring child-only CBT over mother-only CBT for sexually abused children with PTSD on reducing anxiety at post-treatment (k=1; n=46; SMD=-0.61 95% CI -1.20,-0.02)
Mother only CBT vs child and mother CBT:
256 The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between child and mother CBT and mother-only CBT for sexually abused children with PTSD on reducing the severity of PTSD symptoms at post- treatment (k=1; n=44; SMD=-0.32 95% CI -0.92, 0.27), at 3 months follow-up (k=1; n=39; SMD=-0.17 95% CI -0.80, 0.46), at 6 months follow-up (k=1; n=39; SMD=-0.23 95% CI - 0.86, 0.40), at 1 year follow-up (k=1; n=39; SMD=-0.47 95% CI -1.10, 0.17) or at 2 years follow-up (k=1; n=39; SMD=0.05 95% CI -0.58, 0.67).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between child and mother CBT and mother-only CBT for sexually abused children with PTSD on reducing depression at post-treatment (k=1; n=44; SMD=-0.27 95% CI -0.86, 0.33), at 3 months follow-up (k=1; n=39; SMD=-0.04 95% CI - 0.67, 0.59), at 6 months follow-up (k=1; n=39; SMD=0.12 95% CI -0.51, 0.75), at 1 year follow-up (k=1; n=39; SMD=0.19 95% CI -0.44, 0.82) or at 2 years follow-up (k=1; n=39; SMD=0.26 95% CI -0.37, 0.89)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between child and mother CBT and mother-only CBT for sexually abused children with PTSD on reducing anxiety at post-treatment (k=1; n=44; SMD=-0.10 95% CI -0.70, 0.49)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between child and mother CBT and mother-only CBT for sexually abused children with PTSD on reducing internalising behaviour at post-treatment (k=1; n=44; SMD=0.07 95% CI -0.52, 0.66)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between child and mother CBT and mother-only CBT for sexually abused children with PTSD on reducing externalising behaviour at post-treatment (k=1; n=44; SMD=0.29 95% CI -0.30, 0.89)
There is limited evidence favouring mother-only CBT over child and mother CBT for sexually abused children with PTSD on reducing externalising behaviour at 3 months follow-up (k=1; n=36; SMD=0.53 95% CI -0.14, 1.19)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between child and mother CBT and mother-only CBT for sexually abused children with PTSD on reducing externalising behaviour at 6 months follow- up (k=1; n=36; SMD=0.37 95% CI -0.29, 1.03), at 1 year follow-up (k=1; n=36; SMD=0.27 95% CI -0.39, 0.93) or at 2 years follow-up (k=1; n=36; SMD=0.28 95% CI -0.38, 0.94)
Box 91: Evidence statement matrix for RCTs comparing CBT to CBT delivered to different people, for PTSD in children Component Rating Description Evidence base C One small level II study with a moderate risk of bias
Consistency NA Only one study
Clinical impact D Very few clinically important differences found for any comparison on any outcome
257 Generalisability C Results probably generalisable to Australian population of children who have experienced sexual abuse Applicability C Evidence probably applicable to Australian healthcare context with some caveats
Summary of evidence One small study with a moderate risk of bias found very few clinically important differences between CBT given to child-only, mother-only and mother and child. (Grade C)
258 NARRATIVE EXPOSURE THERAPY (TRAUMA-FOCUSED) VERSUS SUPPORTIVE COUNSELLING One RCT (Neuner et al 2004a) investigated the effectiveness of narrative exposure therapy (NET) compared to supportive counselling (SC) in adults. Participants in the study by Neuner and colleagues received four sessions of either NET or SC. Briefly, NET involved the participant in a detailed reconstruction of their own biography, which was refined over the treatment period to connect fragmented memories and attain habituation, while SC was specifically non-trauma focused, centring discussions on coping with symptoms, and dealing with problems in the present.
This study was found to be at a moderate risk of bias, due to a suspect method of randomisation, a small loss to follow-up, but only completer-data presented (not ITT). The trauma population included adult Sudanese refugees living in a settlement in Uganda (Neuner et al 2004). While the overall effect size estimates at 12 months provided evidence of a clinically important difference between the treatments, the range of values (95% CI) included clinically significant and insignificant effects, indicating limited evidence favouring NET over SC.
Table 86: Study profiles for RCTs comparing narrative exposure therapy and supportive counselling for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Neuner et al 2004a) Moderate Sudanese refugees Refugee camp, Uganda 31 PTSD diagnosis Severity of PTSD
There is limited evidence favouring narrative exposure therapy over supportive counselling on the likelihood of having a PTSD diagnosis at 12 months follow-up (k=1, n=31, RR=0.48, 95%CI -.26, 0.88). There is limited evidence favouring narrative exposure therapy over supportive counselling on reducing the severity of PTSD symptoms (clinician-rated) at 12-month follow-up (k = 1; n = 27; SMD = -1.22; 95% CI, -2.05 to -0.38). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between narrative exposure therapy and supportive counselling on reducing the severity of PTSD symptoms (self-rated) post-treatment (k = 1; n = 28; SMD =-0.05, 95%CI -0.80, 0.68) or at 4 months follow-up (k=1, n=27, SMD=0.29, 95%CI - 0.45, 1.04). There is limited evidence favouring narrative exposure therapy over supportive counselling on the severity of PTSD symptoms (self-rated) at 12 months follow-up (k=1, n=27, SMD=- 1.06, -1.87, -0.25).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between narrative exposure therapy and supportive counselling on reducing the severity of depression symptoms at 12-month follow-up (k = 1; n = 48; SMD = - 0.16; 95% CI, -0.73 to 0.41).
There is limited evidence favouring narrative exposure therapy over supportive counselling on reducing functional impairment (CAPS - clinician) at 12-month follow-up (k = 1; n = 48; SMD = -0.53 95% CI, -1.10 to 0.05).
259 Box 92: Evidence statement matrix for RCT comparing trauma focused narrative exposure therapy and supportive counselling for adults with PTSD Component Rating Description Evidence base C One level II studies with a moderate risk of bias
Consistency NA Only one study
Clinical impact D Limited evidence favoured narrative exposure therapy over supportive counselling on all outcome measures at 12 months follow-up, but not for post-treatment or at 4 months follow-up.
Generalisability C Evidence not directly generalisable to the target population but could be sensibly applied
Applicability D Setting of study was in developing African nation and therefore recommendations for clinical practice need to take into account the limited applicability of this evidence to the Australian healthcare context.
Summary of evidence One small study of average quality showed some limited evidence favouring NET over SC in adults with PTSD. (Grade C).
NARRATIVE EXPOSURE THERAPY (TRAUMA-FOCUSED) VERSUS SUPPORTIVE COUNSELLING IN ADOLESCENTS/YOUNG ADULTS One further study compared narrative exposure therapy (NET) to supportive counselling (SC) in a population of adolescents/young adults aged between 12 and 25 (mean age 18 years) from Uganda who were formerly child soldiers (Ertl et al 2011). Participants in the study by Ertl and co-workers had eight sessions of either treatment. This study was determined to have a moderate risk of bias as the method of randomisation was not stated, and only completer- data were analysed (not intention-to-treat).
Overall there appears very little difference between narrative exposure therapy and supportive counselling in adolescents/young adults who were former child soldiers.
Table 87: Study profiles for RCTs comparing narrative exposure therapy and supportive counselling for adolescents/young adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Ertl et al 2011) Moderate Former Ugandan child Participants homes, 57 Severity of PTSD symptoms soldiers Uganda Depressive symptoms Functional impairment
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between narrative exposure therapy and supportive counselling on the severity of PTSD symptoms (clinician-rated) at 3 months follow-up (k=1, n=50, SMD=0.05, 95%CI -0.50, 0.60), 6 months’ follow-up (k=1, n=49, SMD=-0.11,95%CI - 0.67, 0.45) or at 12 months follow-up (k = 1; n = 48; SMD = -0.40; 95% CI, -0.97 to 0.17). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between narrative exposure therapy and supportive counselling on the severity of depressive symptoms at 3 months’ follow-up (k=1, n=50, SMD=0.26, 95%CI -0.29, 0.82), 6 months’ follow-up (k=1, n=49, SMD=-0.07, 95%CI -0.63, 0.49) or 12 months’ follow-up (k=1, n=48, SMD=-0.16, 95%CI -0.73, 0.41). The evidence is inconclusive and so it is not possible to determine if there is a clinically
260 important difference between narrative exposure therapy and supportive counselling on functional impairment at 3 monhts’ follow-up (k=1, n=50, SMD=-0.03, 95%CI -0.58, 0.53), or 6 months’ follow-up (k=1, n=49, SMD=0.23, 95%CI -0.33, 0.79). There is limited evidence favouring narrative exposure therapy over supportive counselling on reducing functional impairment at 12 months’ follow-up (k=1, n=48, SMD=-0.53, 95%CI -1.10, 0.05).
Box 93: Evidence statement matrix for RCT comparing trauma focused narrative exposure therapy and supportive counselling for adults with PTSD Component Rating Description Evidence base C One level II studies with a moderate risk of bias
Consistency NA Only one study
Clinical impact D Vast majority of outcomes/time points found no clinically important point estimates. The confidence intervals were wide enough to include effects in either direction.
Generalisability D Evidence not directly generalisable to the target population and hard to judge whether it is sensible to apply (former child soldiers in Uganda)
Applicability D Setting was in developing African nations and therefore recommendations for clinical practice need to take into account the limited applicability of this evidence to the Australian healthcare context
Summary of evidence One small study with a moderate risk of bias was too inconclusive on which to make any statements regarding the comparative effectiveness of narrative exposure therapy and supportive counselling in adolescents/young adults (Grade D).
NARRATIVE EXPOSURE THERAPY (TRAUMA-FOCUSED) VERSUS BRIEF PSYCHOEDUCATION Two RCTs (Bichescu et al 2007; Neuner et al 2004a) compared narrative exposure therapy (NET) with brief psychoeducation. Both trials delivered treatment on an individual basis. In terms of the treatment conditions, both studies provided one session of psychoeducation (defined by Neuner and colleagues as an intervention which “served as a control... to monitor the development of refugees who received only minimal intervention” following diagnosis). Bichescu et al (2007) provided no further details on the PE provided to their study participants. The NET was described similarly in both studies, however patients treated under the Bichescu protocol received an additional session to the four that Neuner’s group received.
Both studies were determined to be at a moderate risk of bias. The trauma populations included ethnic Sudanese residing in a refugee camp in Uganda (Neuner et al 2004) and Romanian nationals who were former political detainees (Bichescu et al 2007). Clinician rated PTSD severity after 6 months (Bichescu et al 2007) and 12 months (Neuner et al 2004) were combined in a meta-analysis, the results of which are show in below. The overall effect size estimate showed a large, clinically important difference in the direction favouring NET over brief psychoeducation.
Table 88: Study profiles for RCTs comparing narrative exposure therapy and psychoeducation for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured
261 (Bichescu et al Moderate Former political detainees Subsidiaries of 18 Change in symptoms of PTSD 2007) Association of Former and depression Political Detainees, Romania
(Neuner et al 2004a) Moderate Sudanese refugees Refugee camp, Uganda 29 PTSD diagnosis Severity of PTSD
Outcomes for PTSD diagnosis were reported at 6-month (Bichescu et al 2007) and 12-month (Neuner et al 2004) follow-up and were combined in the meta-analysis shown below. Again, the overall effect size estimate showed a large, clinically important difference in the direction favouring NET over brief psychoeducation.
There is limited evidence favouring narrative exposure therapy over brief psychoeducation on reducing the likelihood of having a PTSD diagnosis at 6-12 months follow up(k = 2; n = 47; RR = 0.53; 95% CI, 0.32, 0.87).
262 There is evidence favouring narrative exposure therapy over brief psychoeducation on reducing the severity of PTSD symptoms at 12-month follow-up (k = 2; n = 43; SMD = - 1.44; 95% CI, -2.13 to -0.75).
Bichescu also reported on depression severity as measured by the Beck Depression Inventory (BDI) at six months. No other studies reported on depression outcomes for the comparison between NET and psychoeducation. The point estimate of effect size for both outcomes was found to be clinically important while confidence interval included both clinically important and unimportant effects.
There is limited evidence favouring narrative exposure therapy over psychoeducation on reducing the severity of depression symptoms at 6-month follow-up (k = 1; n = 18; SMD = - 1.41; 95% CI, -2.44 to -0.38).
Box 94: Evidence statement matrix for RCT comparing trauma narrative exposure therapy and pscyhoeducation for adults with PTSD Component Rating Description Evidence base C Two level II studies with a moderate risk of bias
Consistency A Both studies consistent in favouring NET over brief psychoeducation
Clinical impact C Moderate; evidence suggests a clinically important finding favouring NET for PTSD symptoms, and limited evidence favouring NET for other outcomes
Generalisability C Evidence not directly generalisable to the target population but could be sensibly applied
Applicability D Evidence not applicable to the Australian healthcare context
Summary of evidence Two studies provided evidence favouring NET over PE for reducing the severity of PTSD at six to twelve month follow-up, and limited evidence for PTSD diagnosis. There was also limited evidence favouring NET over PE for reducing severity of depression symptoms as 6- month follow-up. These findings are from small studies and it is unknown how generalisable they would be to the Australian population. (Grade C).
NARRATIVE EXPOSURE THERAPY (TRAUMA-FOCUSED) VERSUS STRESS INOCULATION TRAINING One RCT (Hensel-Dittmann et al 2011) investigated the effectiveness of NET compared to stress inoculation training (SIT) in a PTSD population who had been victims of war and/or torture (n=28). Patients were randomised to 10 sessions of either NET (n=15) or SIT (n=13). Both NET and SIT sessions were approximately 90 minutes in duration and were delivered over an average of 13 weeks. The NET protocol required that patients construct detailed chronological biographies in cooperation with the therapists. Patients were encouraged to relive the emotions of their traumatic experience during their narrative, while therapists recorded their autobiographical accounts. During subsequent sessions, patients worked with the therapists to correct and refine the narratives. Sessions for SIT were based a semi- structured treatment originally intended for rape victims which was modified to the needs of survivors of organised violence. The treatment involved teaching patients a range of coping strategies that involved breathing techniques, relaxation training, cognitive restructuring, thought stopping, guided self-dialogue, covert modelling and role play. In order to keep SIT
263 distinct from NET, the focus was on situations in the present, thus discouraging inadvertent reliving of traumatic events.
The authors concluded on the basis of their treatment over time analysis that PTSD symptoms were significantly decreased for the NET group, but not for the SIT group. They reported that depression scores did not change significantly over time in either treatment group.
Table 89: Study profiles for RCTs comparing narrative exposure therapy and stress inoculation training for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Hensel-Dittmann et High Victims of war/torture University outpatient 28 Severity of PTSD symptoms al 2011) clinic for refugees, Depression Germany
There is limited evidence favouring narrative exposure therapy over stress inoculation training for reducing the severity of clinician-rated PTSD symptoms at 12 months follow up. (k = 1; n = 28; SMD = -0.52; 95% CI, -1.55 to 0.51).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between narrative exposure therapy and stress inoculation training on reducing the severity of depression symptoms at 12 months follow up (k = 1; n = 28; SMD = -0.29; 95% CI, -1.31 to 0.72).
Box 95: Evidence statement matrix for RCT comparing trauma narrative exposure therapy and stress inoculation training for adults with PTSD Component Rating Description Evidence base D One level II study with high risk of bias
Consistency NA One study only
Clinical impact D Limited evidence favouring NET over SIT for PTSD symptoms, but not for depression
Generalisability B Evidence directly generalisable to the target population with some caveats
Applicability C Evidence probably applicable to the Australian healthcare context with some caveats
Summary of evidence One very small study of low quality showed limited evidence in favour of NET over SIT for reduction of PTSD symptoms, but not depression, but given its small size and high risk of bias it should be interpreted with caution. (Grade D).
NARRATIVE EXPOSURE (TRAUMA FOCUSED) VERSUS COGNITIVE PROCESSING THERAPY One RCT (Resick et al 2008) compared the effectiveness of cognitive processing therapy (CPT) with its individual components in a sample of physically and/or sexually assaulted women. The comparison addressed in this sub-section is trauma focused written accounts (with exclusion of all cognitive components of CPT) and full CPT (including trauma focused written accounts and cognitive based therapy). For the purpose of this review, the trauma focused written accounts have been determined to be for the most part the same as narrative exposure therapy (NET), the only difference being that “written accounts” as described by
264 Resick et al are undertaken by the patient, whereas NET traditionally involves the therapist in taking a written record of the patient’s verbal narrative. Accordingly, “written accounts” are identified in all subsequent discussion as NET.
Trauma focused NET was delivered with the exclusion of all other therapy components. During NET sessions, therapists were allowed to make nondirective, supportive comments and occasional educational statements, but they were not allowed to engage in any cognitive therapy or challenges to the client’s dysfunctional statements. Full CPT included both cognitive restructuring/processing components and exposure based NET
Mean end-point values obtained by the study investigators at post-treatment and after six months follow-up indicated similar reductions in PTSD and depression symptom severity for NET and CPT. Effect size measures calculated for self and clinician-rated PTSD symptoms, depressive symptoms and anxiety symptoms showed inconclusive evidence at both time points for a clinically important difference between NET and CPT, i.e. clinically unimportant point estimates and confidence intervals which included important and unimportant effects (Resick et al 2008).
Table 90: Study profiles for RCTs comparing narrative exposure therapy and CPT for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Resick et al 2008) High Women with history of Unspecified setting in 162 Change in symptoms of PTSD physical or sexual abuse the United States and depression
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between narrative exposure therapy and cognitive processing therapy on reducing the severity of clinician-rated PTSD symptoms at post-treatment (k = 1; n = 80; SMD = -0.34; 95% CI, -0.78, 0.11).
There is evidence suggesting that there is unlikely to be a clinically important difference between narrative exposure therapy and cognitive processing therapy on reducing the severity of clinician-rated PTSD symptoms at 6 months follow up (k = 1; n = 85; SMD = - 0.14; 95% CI, -0.57, 0.29).
There is evidence suggesting that there is unlikely to be a clinically important difference between narrative exposure therapy and cognitive processing therapy on reducing the severity of self-report PTSD symptoms at post-treatment (k = 1; n = 80; SMD = -0.35; 95% CI, -0.80, 0.09).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between narrative exposure therapy and cognitive processing therapy on reducing the severity of self-report PTSD symptoms at 6 months follow up (k = 1; n = 83; SMD = -0.20; 95% CI, -0.64 to 0.23).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between narrative exposure therapy and cognitive processing therapy on reducing the severity of depression symptoms at post-treatment (k = 1; n = 81; SMD = 0.11; 95% CI, 0.55 to 0.32) or at 6 months follow up (k = 1; n = 82; SMD = -0.08; 95% CI, -0.51 to 0.36).
265 The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between narrative exposure therapy and cognitive processing therapy on reducing the severity of anxiety symptoms at post-treatment (k =1; n = 78; SMD = -0.29; 95% CI, -0.74, 0.16) or at 6 months follow up (k =1; n = 81; SMD = 0.10; 95% CI, -0.34, 0.53.).
Box 96: Evidence statement matrix for RCT comparing trauma narrative exposure therapy and CPT for adults with PTSD Component Rating Description Evidence base D One level II study with high risk of bias
Consistency NA One study only
Clinical impact D Slight/restricted- no clinically important differences between treatments
Generalisability B Evidence directly generalisable to the target population with some caveats
Applicability C Evidence probably applicable to Australian healthcare context with some caveats
Summary of evidence This low quality study with high risk of bias provides inconclusive evidence to determine if there are clinically important differences between NET and CPT in terms of reduction in PTSD, depressive and anxiety symptoms. (Grade D).
NARRATIVE EXPOSURE THERAPY (TRAUMA FOCUSED) VERSUS COGNITIVE PROCESSING THERAPY (COGNITIVE COMPONENTS) Resick et al 2008 , as described above, also compared the effectiveness of NET (n=55) and the cognitive components of cognitive processing therapy without the NET (CPT-C; n=51) in physically/sexually assaulted women. The form of NET studied in this trial is usually part of a full CPT protocol, which includes trauma focused and cognitive elements. However, the current comparison focuses on outcomes for separate delivery of the two main components of the full therapy. The trauma focused NET component was provided with exclusion of all cognitive components but permitted therapists to make nondirective, supportive comments and occasional educational statements. During NET, therapists could not engage patients in challenges aimed at changing the patients’ dysfunctional beliefs about their trauma. The CPT-C protocol used only cognitive restructuring or re-processing component, with strict exclusion of any exposure based therapy.
Table 91: Study profiles for RCTs comparing narrative exposure therapy and CPT-C for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Resick et al 2008) High Women with history of Unspecified setting in 162 Change in symptoms of PTSD physical or sexual abuse the United States and depression
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between narrative exposure therapy and cognitive processing therapy (cognitive components only) on reducing the severity of clinician-rated PTSD
266 symptoms at post-treatment (k = 1; n = 75; SMD = -0.39; 95% CI, -0.84, 0.06) or at 6 months follow up (k = 1; n = 76; SMD = -0.17; 95% CI, -0.62, 0.27).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between narrative exposure therapy and cognitive processing therapy (cognitive components only) on reducing the severity of self-reported PTSD symptoms at post-treatment (k = 1, n = 76; SMD = -0.43; 95% CI, -0.88, 0.03) or at 6 months follow up (k = 1; n = 75; SMD = -0.20; 95% CI, -0.66 to 0.26).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between narrative exposure therapy and cognitive processing therapy (cognitive components only) on reducing the severity of depression symptoms at post- treatment (k =1; n = 76; SMD = -0.42; 95% CI, -0.87, 0.04) or at 6 months follow up (k = 1; n = 74; SMD = -0.24; 95% CI, -0.70 to 0.21).
There is limited evidence favouring cognitive processing therapy (cognitive components only) over narrative exposure therapy on reducing the severity of anxiety symptoms at post- treatment (k = 1; n = 74; SMD = -0.51; 95% CI, -0.98, -0.05).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between narrative exposure therapy and cognitive processing therapy (cognitive components only) on reducing the severity of anxiety symptoms at 6 months follow up (k = 1; n = 74; SMD = -0.13; 95% CI, -0.59, 0.33).
Box 97: Evidence statement matrix for RCT comparing trauma narrative exposure therapy and CPT-C for adults with PTSD Component Rating Description Evidence base D One level II study with high risk of bias
Consistency NA One study only
Clinical impact D Slight/restricted; few clinically important differences found
Generalisability B Evidence directly generalisable to the target population with some caveats
Applicability C Evidence probably applicable to Australian healthcare context with some caveats
Summary of evidence From one reasonable size study with a high risk of bias it is not possible to determine if there are clinically important differences between NET and CPT-C in terms of reduction of PTSD and depressive symptoms. (Grade C).
SUPPORTIVE COUNSELLING VERSUS BRIEF PSYCHOEDUCATION
The final comparison to consider in the Neuner 2004 study, described above, was the supportive counselling treatment versus the brief psychoeducation treatment. For the purposes of this comparison, supportive counselling is considered the intervention and psychoeducation the control.
267 Table 92 Study profiles for RCTs comparing supportive counselling and brief psychoeducation for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Neuner et al 2004a) Moderate Sudanese refugees Refugee camp, Uganda 25 PTSD diagnosis Severity of PTSD
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between supportive counselling and brief psychoeducation on reducing the likelihood of having a PTSD diagnosis at 12 month follow up (k = 1; n = 26; RR = 1.14; 95% CI, 0.77 to 1.69).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between supportive counselling and brief psychoeducation on reducing the severity of clinician-rated PTSD symptoms at 12 month follow up (k = 1; n = 24; SMD = -0.24; 95% CI, -1.04 to 0.57).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between supportive counselling and brief psychoeducation on reducing the severity of self-reported PTSD symptoms at post-treatment (k = 1; n = 25; SMD = -0.13; 95% CI, - 0.92 to 0.65).
There is limited evidence favouring supportive counselling over brief psychoeducation on reducing the severity of self-reported PTSD symptoms at 4 month follow up (k = 1; n = 25; SMD = -0.55; 95% CI, -1.35 to 0.25).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between supportive counselling and brief psychoeducation on reducing the severity of self-reported PTSD symptoms at 12 month follow up (k = 1; n = 24; SMD = - 0.10; 95% CI, -0.91 to 0.7).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between supportive counselling and brief psychoeducation on improving quality of life at post-treatment (k = 1; n = 25; SMD = 0; 95% CI, -0.78 to 0.78), at 4 month follow up (k = 1; n = 25; SMD = 0.28; 95% CI, -0.51 to 1.07) or at at 12 month follow up (k = 1; n = 24; SMD = -0.06; 95% CI, -0.87 to 0.74)
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between supportive counselling and brief psychoeducation on reducing the likelihood of leaving the study early due to any reason (k = 1; n = 26; RR = 0.86; 95% CI, 0.06 to 12.28).
Box 98 Evidence statement matrix for RCT comparing narrative exposure therapy and supportive counselling for adults with PTSD Component Rating Description Evidence base C One level II study at a moderate risk of bias.
Consistency NA Only one study.
Clinical impact D No clinically important differences between the treatments
268 Generalisability D Very specific population in a very specific setting; hard to judge whether it is sensible to generalise to target population (Sudanese refugees in refugee camp).
Applicability D Study performed in refugee camp in Africa; not applicable to Australian healthcare context.
Summary of evidence One small study with a moderate risk of bias found no clinically important differences between supportive counselling and brief psychoeducation. (Grade D).
AFFECT REGULATION THERAPY VS PRESENT CENTRED THERAPY
One study compared trauma affect regulation- guide for education and therapy (target) with Present Centred Therapy (PCT) (Ford et al 2011). TARGET is a CBT based on recognising, modulating and recovering from negative emotion states and accessing and sustaining positive emotion states, but with no trauma processing. PCT is a problem-solving therapy, also without trauma memory processing that does not address affect regulation, but teaches social problem-solving skills designed to enhance coping with PTSD symptoms. The therapies were tested amongst mothers with a history of victimisation and children under 5 years; the study population was particularly underprivileged and had multiple mental health issues. These treatments were also compared to waitlist and these comparisons are considered in Question 10.
This was an average quality study with reasonable numbers and a moderate level of bias. The study provided ITT results for the PTSD remission outcome at all time points, however for the other outcomes, at the 3 and 6 month follow ups, more than 50% of the same had dropped out of the study and so these outcomes are not presented.
Table 93 Study profiles for RCTs comparing affect regulation therapy and present centred therapy for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Ford et al 2011) Moderate Women aged 18-50 years Outpatient setting, 101 PTSD diagnosis who had past exposure to United States Severity of PTSD (clinican and victimisation or incarceration self-rated) Anxiety Depression Attrition
There is limited evidence favouring TARGET over PCT for reaching full PTSD remission at post-treatment (k=1, n=101; RR 1.38 95% CI 0.59, 3.21), at 3 months follow up (k=1, n=101; RR 1.55 95% CI 0.76, 3.15) and at 6 months follow up (k=1, n=101; RR 1.36 95% CI 0.73, 2.52).
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between TARGET and PCT for reducing the severity of clinician-rated PTSD symptoms at post-treatment (k=1, n=101; SMD -0.04 95% CI -0.43, 0.35).
269 The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between TARGET and PCT for reducing the severity of self-reported PTSD symptoms at post-treatment (k=1, n=101; SMD -0.32 95% CI -0.71, 0.07)
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between TARGET and PCT for reducing anxiety at post-treatment (k=1, n=101; SMD -0.48 95% CI -0.88, -0.08)
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between TARGET and PCT for reducing depression at post-treatment (k=1, n=101; SMD -0.03 95% CI -0.42, 0.36)
Box 99 Evidence statement matrix for RCTs comparing non-trauma-focused CBT and PCT for adults with PTSD Component Rating Description Evidence base C One study with moderate risk of bias
Consistency NA One study only
Clinical impact D No clinically important differences between treatments
Generalisability D Population was particularly underprivileged with multiple mental health issues from urban American area with high rates of violence; hard to judge how generalisable it is to guidelines population
Applicability C Applicable to Australian healthcare context with some caveats
Summary of Evidence One average quality study found no difference on any of the outcomes between two different types of non-trauma focused CBT. (Grade D)
AFFECT REGULATION THERAPY VS ENHANCED TREATMENT AS USUAL IN CHILDREN
One study by Ford (in press) compared a non-trauma focused CBT (TARGET) with what the authors described as ‘enhanced treatment as usual’ in adolescent girls with delinquency issues. TARGET, Trauma Affect Regulation: Guide for Education and Therapy, is a CBT that teaches participants to prevent and manage PTSD symptoms in current life events, but without a trauma focus. Enhanced treatment as usual was described as a manualised relational therapy in which therapists assisted participants to develop their own definition of and solutions to goals or problems of greatest important to them. Both treatments were delivered in 12 50 minute sessions. The study included girls with delinquent behaviours (about half of whom were living in residential treatment facilities due to severe behavioural problems) and full or partial PTSD. The girls were extensively exposed to trauma, with 100% of the sample experiencing a traumatic separation or loss of caregiver, and over half of the sample experiencing an accident, disaster or illness, physical assault or abuse, and traumatic community or family violence.
This relatively small study was judged to have a high overall level of bias due to a lack of blinding of outcomes assessor, no detailing of the randomization procedure or comparison of groups and no intention-to-treat analysis (although this was claimed, the data provided was
270 only those who completed assessments).
Table 94 Study profiles for RCTs comparing affect regulation therapy and enhanced treatment as usual for children with PTSD Reference Risk of bias Population Setting N Outcomes measured Ford: in press High Girls aged 13-17 years with Outpatient setting, 101 PTSD diagnosis delinquent behaviours and United States Severity of PTSD (clinican and extensive trauma histories self-rated) Anxiety Depression
The study found a clinically important point estimate favouring TARGET for PTSD diagnosis, but no other conclusive evidence to show superior effectiveness of TARGET over enhanced treatment as usual.
There is limited evidence favouring TARGET over enhanced treatment as usual on PTSD diagnosis at posttreatment (k=1, n=46; RR 0.69 95% CI 0.35-1.38)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between TARGET and enhanced treatment as usual for reducing the severity of clinician-rated PTSD symptoms at post-treatment (k=1, n=46; SMD 0.24 95% CI -0.35, 0.82)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between TARGET and enhanced treatment as usual on reducing depression at posttreatment (k=1, n=46; SMD 0.22 95% CI -0.37, 0.80)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between TARGET and enhanced treatment as usual on reducing anxiety at posttreatment (k=1, n=46; SMD -0.18 95% CI -0.76, 0.41)
Box 100 Evidence statement matrix for RCTs comparing non-trauma-focused CBT and enhanced treatment as usual for children with PTSD Component Rating Description Evidence base D One level II study with high risk of bias
Consistency NA One study only
Clinical impact D A clinically important difference favouring TARGET on the point estimate for PTSD diagnosis, but no other clinically important differences between treatments
Generalisability D Population of adolescent girls was severely disadvantaged with multiple trauma exposures and mental health issues; hard to judge how generalisable it is to guidelines population
Applicability C Applicable to Australian healthcare context with some caveats
Summary of evidence One small study with a high risk of bias showed that a CBT treatment without a trauma focus, TARGET, could decrease the chances of having a PTSD diagnosis at posttreatment, however the confidence intervals also included non-clinically important effects. No other clinically important differences were found between treatments. (Grade D)
271
PROLONGED EXPOSURE THERAPY VERSUS COGNITIVE THERAPY Four studies (five articles) compared the effectiveness of different components of CBT: exposure therapy and cognitive therapy (Tarrier et al 1999a; Marks et al 1998; Resick et al 2008; Resick et al 2002; Resick et al In press). One further study was identified which compared group CBT (trauma-focused) versus group CBT (non-trauma-focused), but this is analysed separately, as individual CBT is considered a different treatment to individual CBT for the purposes of this review (Schnurr et al 2003).
Tarrier et al (1999) compared the effectiveness of imaginal exposure (without discussion of throughts and emotions) against the effectiveness of cognitive therapy (without any exposure elements). The trial was limited to people who had spent four weeks documenting their symptoms and attending weekly appointments, and who still met the criteria of PTSD at the end of the four weeks, to reduce the likelihood of including people who would spontaneously remit due to nonspecific factors of treatment. The study by Tarrier et al (1999) was considered to be at a moderate risk of bias due to providing only analysis by treatment received (not intention-to-treat). Marks et al (1998) compared TF-CBT with its two components - exposure therapy and cognitive restructuring, as well as relaxation. The TF- CBT and relaxation comparison is considered elsewhere. The Marks 1998 study was of good quality with a moderate risk of bias, limited by only providing completer data, although the dropout rate was low.
Three articles (two studies) by Resick et al (2002, 2008 and In press) were included. Resick 2008 study was also a dismantling study, comparing TF-CBT with its two components, cognitive restructuring alone and the exposure therapy alone, in this case written accounts. The written accounts arm of the trial was considered to be equivalent to narrative exposure therapy and thus those comparisons are considered in that section. Both studies were considered to be at high risk of bias due to lack of details about methodology, and due to a high loss to follow-up. Resick et al (in press) reported two clinically important findings: being randomised to prolonged exposure was associated with a reduced chance of having PTSD at 5 – 10 years post-treatment, whereas cognitive therapy was associated with a reduced chance of having a panic disorder in the 5 – 10 years since treatment. However, the full range of plausible estimates (outlined by the confidence intervals) also included findings which favoured the alternative treatment and these findings are therefore not statistically significant.
Table 95 Study profiles for RCTs comparing prolonged exposure and cognitive therapy for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Tarrier et al 1999a) Moderate Crime, accident or other Outpatient setting, 62 PTSD diagnosis trauma, but NOT child United Kingdom Severity of PTSD (Tarrier et al 1999b) sexual abuse Depressive symptoms Anxiety Attrition
(Marks et al 1998) Moderate Unspecified trauma, Outpatient setting, 42 Severity of PTSD including physical assault, United Kingdom Social and occupational road accidents, non-road functioning accidents, sexual assault, hostage, bombing, combat
272 (Resick et al 2008) High Females who had Outpatient setting, 162 Severity of PTSD experienced sexual or United States Depression physical assault in childhood or adulthood
(Resick et al 2002) High Raped or physically Outpatient setting, 124 Severity of PTSD assaulted women United States Depressive symptoms
(Resick et al In High Raped or physically Outpatient setting, 126 PTSD diagnosis press) assaulted women United States Severity of PTSD Depressive symptoms 5-10 year follow-up Depression diagnosis of (Resick et al Alcohol problem diagnosis 2002) Panic disorder diagnosis
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between prolonged exposure and cognitive therapy on the likelihood of having a PTSD diagnosis post-treatment (k=2, n=179; RR 1.05 95% CI 0.77, 1.44)
There is limited evidence favouring prolonged exposure over cognitive therapy on the likelihood of having a PTSD diagnosis at 5-10 years follow-up (k=1, n=126, RR=0.79, 95%CI 0.39, 1.6).
273
There is evidence suggesting there is unlikely to be a clinically important difference between prolonged exposure and cognitive therapy on clinician-rated PTSD severity post-treatment (k=4, n=303; SMD -0.01 95% CI -0.24, 0.21)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between prolonged exposure and cognitive therapy on clinician-rated PTSD severity at 6 months follow up (k=3, n=159; SMD -0.36 95% CI -1.12, 0.40)
274
There is evidence suggesting there is unlikely to be a clinically important difference between prolonged exposure and cognitive therapy on clinician-rated PTSD severity at 9 – 12 months follow-up (k=2, n=178, SMD=0.01, 95%CI -0.29, 0.30).
There is evidence suggesting there is unlikely to be a clinically important difference between prolonged exposure and cognitive therapy on clinician-rated PTSD severity at 5-10 years follow-up (k=1, n=126, SMD=0.00, 95%CI -0.35, 0.35).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between prolonged exposure and cognitive therapy on self- rated PTSD –avoidance subscale at post-treatment (k=1, n=62; SMD -0.48 95% CI -0.99, 0.02)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between prolonged exposure and cognitive therapy on self- rated PTSD at post-treatment (k=1, n=80; SMD 0.09 95% CI -0.35, 0.53)
There is evidence suggesting there is unlikely to be a clinically important difference between prolonged exposure and cognitive therapy for self-rated PTSD at 6 months follow up (k=1, n=80: SMD -0.01 95% CI -0.45, 0.43)
275
There is evidence suggesting there is unlikely to be a clinically important difference between prolonged exposure and cognitive therapy on depression at post-treatment (k=3, n=265; SMD 0.20 95% CI -0.05, 0.44)
There is evidence suggesting there is unlikely to be a clinically important difference between prolonged exposure and cognitive therapy on depressive symptoms at 6 months follow up (k=2, n=136; SMD 0.09 95% CI -0.25, 0.43)
276
There is evidence suggesting there is unlikely to be a clinically important difference between prolonged exposure and cognitive therapy on depressive symptoms at 12 months follow up (k=2, n=176: SMD= 0.12, 95% CI -0.18, 0.41)
There is evidence suggesting there is unlikely to be a clinically important difference between prolonged exposure and cognitive therapy on depressive symptoms at 5 – 10 years follow up (k=1, n=110, SMD=0.22, 95%CI -0.15, 0.60)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between prolonged exposure and cognitive therapy on the likelihood of having a depression diagnosis over 5 – 10 years post-treatment (k=1, n=83, RR=0.97, 95%CI 0.64, 1.42).
PE vs CT
There is evidence suggesting there is unlikely to be a clinically important difference between prolonged exposure and cognitive therapy on anxiety at post-treatment (k=2, n=142; SMD 0.13 95% CI -0.20, 0.46)
277 PE vs CT
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between prolonged exposure and cognitive therapy on anxiety at 6 months follow up (k=2, n=135; SMD 0.21 95% CI -0.13, 0.55)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between prolonged exposure and cognitive therapy on anxiety at 12 months follow up (k=1, n=54; SMD -0.07 95% CI -0.60, 0.47)
There is limited evidence favouring cognitive therapy over prolonged exposure on the likelihood of having a panic disorder in the 5 – 10 years post-treatment (k=1, n=78, RR=2.56, 95%CI 0.75, 9.09).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between prolonged exposure and cognitive therapy on the likelihood of being diagnosed with an alcohol use disorder in the 5 – 10 years post-treatment (k=1, n=82, RR=0.95, 95%CI 0.26, 3.57).
PE vs CT
278
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between prolonged exposure and cognitive therapy study attrition (k=2, n=179; RR 1.05 95% CI 0.60, 1.84)
Box 101 Evidence statement matrix for RCTs comparing prolonged exposure and cognitive therapy for adults with PTSD Component Rating Description Evidence base C Two level II studies with a moderate risk of bias; three studies (four articles) with a high risk of bias.
Consistency A All studies consistent in showing very little difference between therapies on all outcomes
Clinical impact D Very few clinically important differences between therapies. There was a clinically important point estimate favouring prolonged exposure over cognitive for likelihood of having PTSD at long-term follow- up, but this difference was not statistically significant. Generalisability A Mixed trauma populations similar to those who are targets of guidelines.
Applicability C Studies performed in the United Kingdom and United States, leading evidence to probably be applicable to the Australian healthcare context with some caveats.
Summary of evidence Four studies with a moderate or high risk of bias showed few clinically important differences between prolonged exposure and cognitive therapy. There was a clinically important point difference found favouring prolonged exposure for reducing the likelihood of having a PTSD diagnosis 5 – 10 years since treatment, but this was not statistically significant. (Grade C)
CBT WITH AN EXPOSURE COMPONET VS CBT WITHOUT AN EXPOSURE COMPONENT IN CHILDREN
There were two studies that compared CBT with an exposure component to CBT without an exposure component, one in children who had been sexually abused ((Deblinger et al 2011), and one in children exposed to single incident trauma (but not sexual abuse (Nixon et al 2011)).
The Deblinger 2011 study compared two different types of trauma-focused CBT, one including a trauma narrative and one without it, over two time periods, 8 sessions and 16 sessions. Each arm of the trial included parents in the CBT, with therapy for children and non-offending parent separately, and together. The difference between the two treatments was the trauma narrative, where the child was encouraged to develop a detailed account of their abuse and related experiences, which they processed and reviewed with the therapist and parent. The groups without the trauma narrative were not encouraged to talk or write in detail about their experiences, but the course of the CBT did lead to some exposure and processing of their experiences, and where specific problems presented, therapists conducted in vivo exposure and processing to help children overcome these issues. Thus it cannot be strictly said that the comparison groups were CBT with and without exposure therapy. This study report did not provide enough to detail to assess its quality, including a lack of information about randomisation and blinding of outcomes assessor, and no ITT analysis. However it did have low drop out rates (15%). It is complex to interpret as it answered four different questions: 1) is CBT with the trauma narrative was better than without it over 8 sessions? 2) is CBT with the trauma narrative better than without it over 16 sessions?
279 3) is CBT without the trauma narrative better over 16 sessions than 8? 4) is CBT with trauma narrative better over 16 sessions than 8?
The Nixon study also compared TF-CBT with an exposure component to cognitive therapy without a trauma component. This study also included parents in the therapy, and was conducted over 9 sessions. Although this study was small, it was well designed, let down by high dropout rates.
The Nixon study and the 8 session arms of the Deblinger 2011 study were considered similar enough to enter into meta-analyses; the other arms of the Deblinger 2011 study are reported separately. Following the methodology in the NICE guidelines report, the PTSD subscale means and standard deviations in the Deblinger 2011 study were added together to give an overall PTSD severity rating, which was then entered into meta-analysis with the Nixon 2011 study.
Table 96: Study profiles of RCTs comparing CBT to CBT in children Reference Risk of bias Population Setting N Outcomes measured (Nixon et al 2011) Moderate Children aged 7-17 years Outpatient setting, 33 Symptoms of PTSD who had experienced Australia Diagnosis of PTSD single incident trauma, but Depression not sexual abuse Anxiety Child behaviour Deblinger 2011 High Children aged 4-11 years Two states in USA 210 Symptoms of PTSD who had been sexually Depression abused Child behaviour
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between CBT with exposure therapy and CBT without exposure therapy PTSD in children given in 9 sessions on the diagnosis of PTSD at post- treatment (k=1; n=33; RR= 0.81 95% CI 0.34, 1.89), at 6 months follow up (k=1; n=33; RR= 1.04 95% CI 0.62, 1.74).
280 There is evidence suggesting that there is unlikely to be a clinically important difference between CBT with exposure therapy and CBT without exposure therapy for children with PTSD given in 8-9 sessions on reducing the severity of clinician-rated PTSD symptoms at post-treatment (k=2, n=112; SMD -0.03 95% CI -0.41, 0.34)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between CBT with exposure therapy and CBT without exposure therapy for children with PTSD given in 9 sessions on reducing the severity of clinician-rated PTSD symptoms at 6 months follow up (k=1; n=33; SMD= 0.10 95% CI - 0.59, 0.78)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between CBT with exposure therapy and CBT without exposure therapy for children with PTSD given in 9 sessions on reducing the severity of self- rated PTSD symptoms at post-treatment (k=1; n=33; SMD= 0.00 95% CI -0.68, 0.68) or at 6 months follow up (k=1; n=33; SMD= 0.07 95% CI -0.61, 0.75)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between CBT with exposure therapy and CBT without exposure therapy for children with PTSD given in 16 sessions on reducing the severity of clinician-rated PTSD symptoms (k=1; n=79; SMD=0.33 95% CI -0.12, 0.77)
There is evidence suggesting that there is unlikely to be a clinically important difference between CBT with exposure therapy and CBT without exposure therapy for children with PTSD given in 8-9 sessions on reducing depression (k=2, n=87; SMD -0.03 95% CI -0.45, 0.40)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between CBT with exposure therapy and CBT without exposure therapy given in 16 sessions for sexually abused children with PTSD on reducing depression (k=1; n=58; SMD=-0.27 95% CI -0.79, 0.25)
281
There is limited evidence favouring CBT with exposure therapy over CBT without exposure therapy for children with PTSD given in 8-9 sessions on reducing anxiety (k=2, n=87; SMD - 1.78 95% CI -5.15, 1.58)
The evidence is inconclusive so it is not possible to determine whether there is a clinically important difference between CBT with exposure therapy and CBT without exposure therapy for children with PTSD given in 16 sessions on reducing anxiety (k=1, n=57; SMD 0.33 95% CI -0.20, 0.85)
There is evidence suggesting there is unlikely to be a clinically important difference between CBT with exposure therapy and CBT without exposure therapy for children with PTSD given in 8-9 sessions on reducing internalising behaviour (k=2, n=111; SMD 0.03 95% CI -0.34, 0.41)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between CBT with exposure therapy and CBT without exposure therapy for sexually abused children with PTSD given in 16 sessions on reducing internalising behaviour (k=1; n=78; SMD=0.44 95% CI -0.01, 0.89)
282
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between CBT with exposure therapy and CBT without exposure therapy for children with PTSD given in 8-9 sessions on reducing externalising behaviour (k=2; n=111; SMD=0.24 95% CI -0.14, 0.61)
There is limited evidence favouring CBT without exposure therapy over CBT with exposure therapy for children with PTSD given in 16 sessions on reducing externalising behaviour (k=1; n=78; SMD=0.68 95% CI 0.22, 0.89)
Box 102: Evidence statement matrix for RCT comparing TF-CBT with CBT in children Component Rating Description Evidence base C One level II study with moderate level of bias, one with high level of bias Consistency C Some inconsistency amongst different outcomes Clinical impact D Slight/restricted. There were few clinically important differences between TF-CBT with and without exposure therapy, given over 8-9 or 16 sessions.. Generalisability A Population consisted of children who had experienced mixed traumas, which are a target population of the guidelines. Applicability A One study set in Australia and directly applicable to healthcare context.
Summary of evidence Two small studies, one with moderate risk of bias and one with a high risk of bias, comparing CBT with and without an exposure focus for 8-9 sessions, or 16 sessions, found no clinically important differences between the therapies. (Grade C)
TRAUMA-FOCUSED CBT VERSUS OTHER THERAPIES
There were two studies that compared TF-CBT with other therapies (Cloitre 2010, Bryant 2008). These studies were each different in their intervention and control arms and so are addressed separately. In addition, there were two other studies which could be included in this comparison; the Beidel 2011 study, which compared a multicomponent exposure therapy to exposure therapy only, and the Foa 2005 study which compared prolonged exposure with prolonged exposure plus cognitive restructuring; as these studies do not have the same comparators as the others in this section and could not be entered into meta-analyses, these studies are considered in Question 20.
283 Table 97 Study profiles for RCTs comparing TF CBT to other therapies. Reference Risk of bias Population Setting N Outcomes measured (Cloitre et al 2010) Moderate Women aged 18-65 Outpatient setting, 104 PTSD symptom severity with PTSD related to United States PTSD diagnosis childhood sexual abuse Depression Anxiety
(Bryant et al 2008b) Moderate Civilian survivors of Outpatient setting, 118 PTSD symptom severity nonsexual assault or Australia Depression anxiety motor vehicle accident trauma
The Cloitre 2010 study compared three different therapy types added together in different combinations: skills training plus exposure; skills training plus supportive counselling, and supportive counselling plus exposure. The study was conducted in adult women who had been sexually abused as children. The skills training (ST) was based on dialectical behaviour therapy and focused on aspects of emotion management and revision of maladaptive schemas. The exposure (E) was based on prolonged exposure therapy. Supportive counselling (SC) was client directed discussion of life problems related to abuse history. This study was of good quality but received a moderate risk of bias rating due to dropouts. The study found skills training plus exposure to be better than supportive counselling plus exposure, but no better than skills training plus supportive counselling; and skills training plus supportive counselling was better than supportive counselling plus exposure, although few of the outcomes were clinically important.
There is limited evidence favouring ST/E over SC/E for reducing the likelihood of having a PTSD diagnosis at post-treatment (k=1, n=66: RR 0.59 95% CI 0.36-0.96)
There is limited evidence favouring ST/E over ST/SC for reducing the likelihood of having a PTSD diagnosis at post-treatment (k=1, n=66: RR 0.59 95% CI 0.36-0.96)
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between SC/E and ST/SC on the likelihood of a PTSD diagnosis at post-treatment (k=1, n=71; RR 1.23 95% CI 0.86-1.86)
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between ST/E and SC/E on clinician rated PTSD symptoms at post-treatment (k=1, n=66: SMD -0.37 95% CI -0.85, 0.12)
There is limited evidence favouring ST/E over SC/E on clinician rated PTSD symptoms at 3 months follow up (k=1, n=66: SMD -0.82 95% CI -1.33, -0.32)
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between ST/E and SC/E on clinician rated PTSD symptoms at 6 months (k=1, n=66: SMD -0.40 95% CI -0.89, 0.09)
There is evidence suggesting there is unlikely to be a clinically important difference between ST/E and ST/SC on clinician rated PTSD symptoms at post-treatment (k=1, n=75; SMD 0.02 95% CI -0.45, 0.48)
284 The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between ST/E and ST/SC on clinician rated PTSD symptoms at 3 months follow up (k=1, n=75: SMD -0.34 95% CI -0.81, 0.13)
There is limited evidence favouring ST/E over ST/SC on clinician rated PTSD symptoms at 6 months follow up (k=1, n=75: SMD -0.57 95% CI -1.04, -0.09)
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between SC/E and ST/SC on clinician rated PTSD symptoms at post-treatment (k=1, n=75: SMD 0.35 95% CI -0.12, 0.82)
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between SC/E and ST/SC on clinician rated PTSD symptoms at 3 months follow up (k=1, n=75: SMD 0.37 95% CI -0.10, 0.85)
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between SC/E and ST/SC on clinician rated PTSD symptoms at 6 months follow up (k=1, n=75: SMD -0.18 95% CI -0.65, 0.29)
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between ST/E and SC/E on self rated PTSD symptoms at post-treatment (k=1, n=75: SMD -0.46 95% CI -0.95, 0.03)
There is limited evidence favouring ST/E over SC/E on self rated PTSD symptoms at 3 months follow up (k=1, n=75: SMD -0.77 95% CI -1.27, -0.27)
There is limited evidence favouring ST/E over SC/E on self rated PTSD symptoms at 6 months follow up (k=1, n=75: SMD -0.97 95% CI -1.48, -0.46)
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between ST/E and ST/SC on self rated PTSD symptoms at post-treatment (k=1, n=75: SMD -0.04 95% CI -0.51, 0.43)
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between ST/E and ST/SC on self rated PTSD symptoms at 3 months follow up (k=1, n=75: SMD -0.44 95% CI -0.91, 0.03)
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between ST/E and ST/SC on self rated PTSD symptoms at 6 months follow up (k=1, n=75: SMD -0.39 95% CI -0.87, 0.08)
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between SC/E and ST/SC on self rated PTSD symptoms at post-treatment (k=1, n=75: SMD 0.39 95% CI -0.08, 0.86)
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between SC/E and ST/SC on self rated PTSD symptoms at 3 months follow up (k=1, n=75: SMD 0.38 95% CI -0.09, 0.85)
285 The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between SC/E and ST/SC on self rated PTSD symptoms at 6 months follow up (k=1, n=75: SMD 0.49 95% CI 0.02, 0.97)
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between ST/E and SC/E on depression symptoms at post-treatment (k=1, n=66: SMD -0.46 95% CI -0.95, 0.03)
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between ST/E and SC/E on depression symptoms at 3 months follow up (k=1, n=66: SMD-0.43 95% CI -0.92, 0.05)
There is limited evidence favouring ST/E over SC/E on depression symptoms at 6 months follow up (k=1, n=66: SMD -0.56 95% CI -1.06, -0.07)
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between ST/E and ST/SC on depression symptoms at post-treatment (k=1, n=75: SMD -0.36 95% CI -0.83, 0.11)
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between ST/E and ST/SC on depression symptoms at 3 months follow up (k=1, n=75: SMD-0.23 95% CI -0.70, 0.23)
There is limited evidence favouring ST/E over ST/SC on depression symptoms at 6 months follow up (k=1, n=66: SMD -0.56 95% CI -1.03, -0.08)
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between SC/E and ST/SC on depression symptoms at post-treatment (k=1, n=75: SMD 0.11 95% CI -0.36, 0.58)
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between SC/E and ST/SC on depression symptoms at 3 months follow up (k=1, n=75: SMD 0.23 95% CI -0.24, 0.70)
There is evidence suggesting there is unlikely to be a clinically important difference between SC/E and ST/SC on depression symptoms at 6 months follow up (k=1, n=75: SMD 0.02 95% CI -0.44, 0.49)
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between ST/E and SC/E on anxiety symptoms at post-treatment (k=1, n=66: SMD - 0.17 95% CI -0.65, 0.31)
There is evidence favouring ST/E over SC/E for anxiety symptoms at 3 months follow up (k=1, n=66: SMD -1.22 95% CI -1.74, -0.69)
There is limited evidence favouring ST/E over SC/E on anxiety symptoms at 6 months follow up (k=1, n=66: SMD -0.85 95% CI -1.35, -0.35)
286 The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between ST/E and ST/SC on anxiety symptoms at post-treatment (k=1, n=75: SMD -0.32 95% CI -0.79, 0.15)
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between ST/E and ST/SC on anxiety symptoms at 3 months follow up (k=1, n=75: SMD -0.25 95% CI -0.72, 0.22)
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between ST/E and ST/SC on anxiety symptoms at 6 months follow up (k=1, n=75: SMD -0.42 95% CI -0.89, 0.05)
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between SC/E and ST/SC on anxiety symptoms at post-treatment (k=1, n=75: SMD- 0.15 95% CI -0.61, 0.32)
There is limited evidence favouring ST/SC over SC/E on anxiety symptoms at 3 months follow up (k=1, n=75: SMD 0.79 95% CI 0.31, 1.28)
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between SC/E and ST/SC on anxiety symptoms at 6 months follow up (k=1, n=75: SMD 0.40 95% CI -0.07, 0.87)
The Bryant 2008 study compared four types of exposure therapy: imaginal exposure (IE), in vivo exposure (IVE), imaginal plus in vivo exposure (I/IVE), and imaginal and in vivo exposure with cognitive therapy (I/IVE/CR) in civilian trauma survivors. The comparisons of imaginal plus in vivo exposure vs imaginal exposure alone and in vivo exposure alone, and imaginal, in vivo and cognitive restructuring vs imaginal exposure alone and in vivo exposure alone are considered in Question 20. This was a good quality study with a moderate risk of bias, again due to dropouts. There were no clinically important differences between imaginal exposure and in vivo exposure, however imaginal/in vivo/cognitive restructuring together was more effective than imaginal and in vivo exposure together.
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between IE and IVE on clinician rated PTSD symptoms at post-treatment (k=1, n=59: SMD -0.01 95% CI -0.53, 0.50)
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between IE and IVE on clinician rated PTSD symptoms at 6 months follow up (k=1, n=59: SMD -0.02 95% CI -0.49, 0.53)
There is limited evidence favouring I/IVE/CR over I/IVE for clinician rated PTSD symptoms at post-treatment (k=1, n=59; SMD 0.76 95% CI 0.24, 1.29)
There is limited evidence favouring I/IVE/CR over I/IVE for clinician rated PTSD symptoms at 6 months follow up (k=1, n=59; SMD 0.72 95% CI 0.19, 1.25)
287 The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between IE and IVE on depression symptoms at post-treatment (k=1, n=59: SMD - 0.14 95% CI -0.37, 0.65)
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between IE and IVE on depression symptoms at 6 months follow up (k=1, n=59: SMD 0.06 95% CI -0.45, 0.57)
There is limited evidence favouring I/IVE/CR over I/IVE for depression symptoms at post- treatment (k=1, n=59; SMD 0.58 95% CI 0.06, 1.10)
There is limited evidence favouring I/IVE/CR over I/IVE for depression symptoms at 6 months follow up (k=1, n=59; SMD 0.82 95% CI 0.29, 1.35)
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between IE and IVE on anxiety symptoms at post-treatment (k=1, n=59: SMD - 0.02 95% CI -0.49, 0.53)
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between IE and IVE on anxiety symptoms at 6 months follow up (k=1, n=59: SMD -0.29 95% CI -0.22, 0.81)
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between I/IVE and I/IVE/CR on anxiety symptoms at post-treatment (k=1, n=59: SMD 0.16 95% CI -0.35, 0.67)
The evidence is inconclusive so it is not possible to determine if there is a clinically important difference between I/IVE and I/IVE/CR on anxiety symptoms at 6 months follow up (k=1, n=59: SMD 0.39 95% CI -0.13, 0.90
Box 103: Evidence statement matrix for RCTs comparing trauma-focused CBT with other therapies Component Rating Description Evidence base C Two level II studies with a moderate risk of bias
Consistency C Consistency hard to judge given multiple comparisons on many outcomes; tended towards favouring treatments that had exposure and cognitive restructuring aspects, but not consistently. Clinical impact D Restricted impact; mostly inconclusive findings but some clinically important point estimates. Generalisability A Similar populations to the target populations for the guidelines.
Applicability C Probably applicable to Australian context with some caveats.
Summary of evidence Two small, average quality studies used multiple comparisons to compare different aspects of TF-CBT. Whilst the results tended to favour treatments that included an exposure component and a cognitive restructuring component, this was not consistent. (Grade D)
288 EMDR VERSUS TRAUMA-FOCUSED CBT
There were six studies that compared EMDR to trauma-focused CBT. These studies were conducted in various outpatient settings in the US, Australia and Europe, with a range of populations who had experienced traumas such as sexual assault, motor vehicle accidents, physical assaults, and child abuse. Three of these studies were of average quality with a moderate risk of bias, whilst the rest had a high risk of bias. These studies compared EMDR with various forms of TF-CBT: prolonged exposure (Taylor 2003, Johnson 2006, Rothbaum 2005, Ironson 2002), CBT (Power 2005) and image habituation training (Vaughan 1994). The EMDR protocols were very similar in all the studies.
Table 98 Study profiles for RCTs comparing trauma-focused CBT and EMDR for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Taylor et al 2003) Moderate Unspecified trauma (road Outpatient setting, 41 Severity of PTSD accidents, sexual or non- United States Depressive symptoms sexual assault, witnessing Attrition traumatic death)
(Vaughan et al Moderate Victims of violent crime, rape, Outpatient PTSD clinic, 25 PTSD diagnosis 1994) child abuse or motor accident Australia Severity of PTSD Depressive symptoms Anxiety Attrition (Johnson & Lubin Moderate Females who had Outpatient setting, 38 Severity of PTSD 2006) experienced physical or United States sexual abuse, rape or a motor vehicle accident
(Power et al 2002) High Unspecified trauma (road Outpatient setting, 48/76 PTSD diagnosis accidents, occupational Scotland Severity of PTSD accidents, sexual or non- Depressive symptoms sexual assault, witnessing Anxiety traumatic death, real/implied Attrition physical threat) (Rothbaum et al High Adult rape victims Outpatient setting, 40 PTSD diagnosis 2005) United States Depressive symptoms Anxiety Functioning
(Ironson et al 2002) High Adults who had experienced Outpatient setting, 22 PTSD severity a single trauma, past United States Depressive symptoms spousal abuse or were survivors of child sexual abuse
289
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between TF-CBT and EMDR on PTSD diagnosis at post- treatment (k=5 n=204; RR 0.87 95% CI 0.66, 1.15)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between TF-CBT and EMDR on clinician-rated PTSD severity at post-treatment (k=4, n=121; SMD -0.24 95% CI -0.89, 0.41)
290
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between TF-CBT and EMDR on clinician-rated PTSD severity at 3 months follow up (k=4, n=94; SMD -0.39 95% CI -1.11, 0.32)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between TF-CBT and EMDR on self-rated PTSD severity at post-treatment (k=5, n=140; SMD -0.47 95% CI -0.81,-0.13)
There is limited evidence favouring EMDR over TF-CBT on self-rated PTSD severity at 3 months follow up (k=1, n=18; SMD -1.10 95% CI -2.09, -0.11)
291
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between TF-CBT and EMDR on depression at post-treatment (k=5, n=162; SMD -0.39 95% CI -1.15, 0.37)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between TF-CBT and EMDR on depression at 2-6 months follow up (k=5, n=128; SMD -0.08 95% CI -0.66, 0.49)
292
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between TF-CBT and EMDR on anxiety at post-treatment (k=3, n=113; SMD -0.21 95% CI -0.58, 0.17)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between TF-CBT and EMDR on anxiety at 2-6 months follow- up (k=1, n=25; SMD 0.01 95% CI -0.78, 0.79)
There is limited evidence favouring EMDR over TF-CBT on study attrition at post-treatment (k=5, n=204; RR 0.68 95% CI 0.43, 1.08)
293 Box 104 Evidence statement matrix for RCTs comparing trauma-focused CBT and EMDR for adults with PTSD Component Rating Description Evidence base C Three studies with a moderate risk of bias,3 with high risk
Consistency A Nearly all comparisons consistent in showing no difference between the therapies.
Clinical impact D Nearly all comparisons unable to show EMDR or TF-CBT superior to the other
Generalisability A Mixed trauma populations similar to those targeted by the guidelines
Applicability C Various outpatient settings around the world; applicable to Australian healthcare context with some caveats.
Summary of evidence Six small trials of poor to average quality found no clinically important differences between TF-CBT and EMDR. (Grade C).
Analysis of EMDR versus Waitlist studies according to ITT status Only one of the included studies (Vaughan 1994) in this comparison analysed their results using intention to treat; thus it was not possible to analyse separately.
EMDR vs TRAUMA-FOCUSED CBT IN CHILDREN
There were two studies of children with PTSD that compared EMDR to exposure-based CBT (Jaberghaderi 2004, de Roos 2011). The first study, Jaberghaderi 2004, was a very small, poor quality study of girls aged 12-13 in Iran who had been sexually abused. Subjects, identified through a screening process conducted at a school, were randomised to EMDR (n=9) or exposure-based CBT (n=9). Parents also received one session of psychoeducation, the same for all parents regardless of their child’s assignment. The study used child and parent reports of PTSD symptoms, and a measure of the child’s behaviour at school by her teachers; no clinician or objective measures of any outcomes were undertaken. The second study, de Roos 2011, included children who had been affected by a fireworks factory explosion in the Netherlands, and was conducted at a disaster mental health after-care centre. This study included boys and girls aged between four and 18 years, and randomised them to EMDR (n=26) or CBT (n=26). The study was of good quality including appropriate assignment and blinding of outcomes assessors. These two studies had different treatment lengths (4 sessions in the de Roos study and 12 sessions in the Jaberghaderi study) however the treatments were comparable.
Both studies found improvement in their outcome measures for both treatments, but neither of them demonstrated an advantage for one treatment over another, on any outcome. These studies shared two outcomes (Parent Report of Posttraumatic Symptoms and Child Report of Posttraumatic Symptoms, at post-treatment), and these were entered into a metaanalysis. All other outcomes were unique to just one of the studies.
Table 99: Study profiles of RCTs comparing EMDR to TF-CBT in children Reference Risk of bias Population Setting N Outcomes measured
294 Jaberghaderi 2004 High Iranian girls aged 12- University clinic in 14 PTSD symptoms by parent and child 13 years who had urban setting in Iran report; behaviour at school by teacher trauma symptoms report related to sexual abuse de Roos 2011 Moderate Children aged 4-18 Disaster mental health 52 PTSD symptoms by parent and child years who had trauma after-care centre in report; PTSD reaction index; depression; symptoms related to a Enschede, the anxiety; child behaviour fireworks factory Netherlands explosion
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between EMDR and CBT for children with PTSD on PTSD symptoms by parent report at post-treatment (k=2; n=66; SMD=-0.17 95% CI -0.65, 0.32)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between EMDR and CBT for children with PTSD on PTSD symptoms by parent report at 3 months follow up (k=1; n=26; SMD=-0.16 95% CI -0.70, 0.39)
295
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between EMDR and CBT for children with PTSD on PTSD symptoms by child report at post-treatment (k=2; n=54; SMD=-0.15 95% CI -0.68, 0.39)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between EMDR and CBT for children with PTSD on PTSD symptoms by child report at 3 months follow up (k=1; n=40; SMD=-0.08 95% CI -0.71, 0.54)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between EMDR and CBT for children with PTSD on depression symptoms at post-treatment (k=1; n=40; SMD=0.04 95% CI -0.58, 0.66)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between EMDR and CBT for children with PTSD on depression symptoms at 3 months follow up (k=1; n=40; SMD=-0.36 95% CI -0.99, 0.26)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between EMDR and CBT for children with PTSD on anxiety symptoms at post-treatment (k=1; n=40; SMD=-0.04 95% CI -0.66, 0.58)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between EMDR and CBT for children with PTSD on anxiety symptoms at 3 months follow up (k=1; n=40; SMD=0.09 95% CI -0.53, 0.71)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between EMDR and CBT for children with PTSD on child behaviour problems at 3 months follow up (k=1; n=52; SMD=-0.20 95% CI -0.75, 0.34)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between EMDR and CBT for children with PTSD on child behaviour problems at school, as measured by teachers, at post-treatment (k=1; n=14; SMD=0.40 95% CI -0.66, 1.46)
296 Box 105: Evidence statement matrix of RCTs comparing EMDR with CBT in children Component Rating Description Evidence base C Two small level II studies, one with a moderate risk of bias, one with a high risk of bias
Consistency A Studies consistent in finding no conclusive differences between the treatments
Clinical impact D Very few clinically important differences found for any comparison on any outcome
Generalisability D One study in Iran which is culturally very different to Australia; one in the Netherlands but with a large ethnic minority component; difficult to generalise Applicability C Methods used in the studies probably applicable to Australian healthcare context.
Summary of evidence Although in these two small studies, both EMDR and CBT in children resulted in improvements to symptoms, both studies failed to demonstrate any benefit of one treatment over the other. (Grade D).
EMDR VERSUS STRESS MANAGEMENT THERAPIES
There were three studies that compared EMDR to stress management (Vaughan et al 1994; Carlson et al 1998; Taylor et al 2003). The stress management therapies were all relaxation focused: biofeedback assisted relaxation (Carlson), applied muscle relaxation (Vaughan) and relaxation training (Taylor). All three studies were small, and two had a moderate risk of bias whilst the other had a high risk. All the studies had multiple arms and two also compared the EMDR and relaxation therapy to treatment as usual or waitlist controls. The trauma populations were mixed, and one of the studies was set in Australia whilst the others were from the United States.
Table 100 Study profiles for RCTs comparing EMDR and stress management for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Vaughan et al Moderate Victims of violent crime, rape, Outpatient PTSD clinic, 23 PTSD diagnosis 1994) child abuse or motor accident Australia Severity of PTSD Depressive symptoms Anxiety Attrition (Taylor et al 2003) Moderate Unspecified trauma (road Outpatient setting, 30 Severity of PTSD accidents, sexual or non- United States Depressive symptoms sexual assault, witnessing Attrition traumatic death) (Carlson et al 1998) High Male war veterans Outpatient setting, 22 PTSD diagnosis United States Severity of PTSD Depressive symptoms Anxiety Attrition
297
There is limited evidence favouring EMDR over stress management on reducing the likelihood of having a PTSD diagnosis at post-treatment (k=3, n=84; RR 0.71 95% CI 0.41, 1.22)
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between EMDR and stress management therapy on reducing the severity of clinician-rated PTSD symptoms at post-treatment (k=2, n=53; SMD -0.35, 95% CI –0.90, 0.19).
298
There is limited evidence favouring EMDR over stress management for reducing the severity of clinician-rated PTSD symptoms at 2-5 months follow-up (k=3, n=71; SMD -0.74 95% CI - 1.64, 0.15)
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between EMDR and stress management on reducing the severity of self- reported PTSD symptoms at post-treatment (k=3, n=75; SMD -0.40, 95% CI -0.86 to 0.06)
299
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between EMDR and stress management on reducing the severity of self- reported PTSD symptoms at 2-5 months follow up (k=2, n=54; SMD -0.44, 95% CI -0.99 to 0.10)
There is limited evidence favouring EMDR over stress management therapy for reducing depression at post-treatment (k = 3, n =75; SMD = -0.67; 95% CI, -1.14, -0.2).
300
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between EMDR and stress management therapy for reducing depression at 2-5 months follow up (k = 3, n = 75; SMD = -0.23; 95% CI, -0.7, 0.23).
There is limited evidence favouring EMDR over stress management for reducing anxiety at post-treatment (k = 2, n = 45; SMD = -0.75; 95% CI, -1.36 ,- 0.13). I
301
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between EMDR and stress management for reducing anxiety at 2-5 months follow up (k=2, n=45; SMD -0.42 95% CI -2.21, 1.37)
Box 106 Evidence statement matrix for RCT comparing EMDR and stress management therapies for adults with PTSD Component Rating Description Evidence base C Two small level II studies with a moderate risk of bias, one small study with high risk.
Consistency A All outcomes in all studies favour EMDR.
Clinical impact C Some clinically important point estimates for effect favouring EMDR; others inconclusive
Generalisability B Mixed trauma populations including veterans; generalisable to guidelines population
Applicability B One study performed in Australian outpatient setting, although study is quite old now; others in United States, leading evidence to probably be applicable to the Australian healthcare context with some caveats.
Summary of evidence Three small studies with a moderate to high risk of bias found consistent treatment effects favouring EMDR over stress management, some of which were clinically important at the point estimate. (Grade C).
EMDR VERSUS SUPPORTIVE COUNSELLING Scheck et al (1998) compared EMDR against an active listening control group, designed to control for non-specific treatment effects such as rapport, sympathetic attention, and expectancy of treatment benefit. It appeared to be a well designed trial, but there was a high rate of drop-out of the study, and although the authors compared the baseline values of those who dropped out, compared with those who completed the study, there is still the possibility that the high drop-out rate may have biased the results, although it is unclear which direction the results would have been influenced. There were statistically significant benefits detected on all the outcome measures focused on symptoms (ie, all except attrition), favouring EMDR
302 over active listening.
Table 101 Study profiles for RCTs comparing EMDR and active listening for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Scheck et al 1998) High Young women aged between 16 and Outpatient 60 Severity of PTSD 25, who had a recent history of setting, United Depressive symptoms dysfunctional behaviours, such States Anxiety sexual promiscuity, running away, Attrition drug and alcohol misuse (77% PTSD) 90% had physical or emotional abuse as child
There is limited evidence favouring EMDR over supportive counselling for reducing the severity of self-reported PTSD symptoms at post-treatment (k=1, n=57, SMD=-0.75, 95%CI - 1.21, -0.47)
There is limited evidence favouring EMDR over supportive counselling for reducing depression at post-treatment (k=1, n=60; SMD -0.72, 95%CI -1.24, -0.19).
There is limited evidence favouring EMDR over supportive counselling for reducing anxiety at post-treatment (k=1, n=59; SMD -0.66, 95%CI 0.66, -1.18, -0.13).
There is limited evidence favouring supportive counselling over EMDR on study attrition (k=1, n=57; RR 2.00, 95%CI 0.19, 20.90).
Box 107 Evidence statement matrix for RCT comparing EMDR and active listening for adults with PTSD Component Rating Description Evidence base D One level II study at a high risk of bias.
Consistency NA Only one study.
Clinical impact C Limited evidence favouring EMDR over supportive counselling on PTSD symptom severity, depressive symptoms and anxiety. Fewer people dropped out of supportive counselling than EMDR.
Generalisability A Population directly generalisable to a proportion of the target audience for the guidelines, with a high rate of physical or emotional abuse as children.
Applicability C Study performed in the United States, leading evidence to probably be applicable to the Australian healthcare context with some caveats.
Summary of evidence One small study with a high risk of bias found that if EMDR was superior to supportive counselling. (Grade D)
EMDR VS ‘THE COUNTING METHOD’
One study by Johnson 2006 compared EMDR to ‘the counting method’ (Johnson & Lubin 2006). This study is described in the comparison ‘the counting method’ vs TAU. This was a small, average quality study, which compared three treatment arms to eachother and to TAU; the other comparisons are included in the relevant sections.
303 Table 102 Study profiles for RCTs comparing EMDR and ‘the counting method’ for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Johnson & Lubin Moderate Women (mean age 38.9 years) who Outpatient 51 Severity of PTSD, clinician rated 2006) had experienced trauma either as an setting, United and self-report adult or child (rape, physical abuse, States sexual abuse or MVA)
There is limited evidence favouring EMDR over ‘the counting method’ on reducing the severity of clinician-measured PTSD symptoms at post-treatment (k=1; n=18; SMD -0.60 95% CI -1.54, 0.35) and at 3 months follow-up (k=1; n=18; SMD -1.10 95% CI -2.10, -0.11)
There is limited evidence favouring EMDR over ‘the counting method’ on reducing the severity of self-reported PTSD symptoms at post-treatment (k=1; n=18; SMD -0.51 95% CI - 1.45, 0.43) and at 3 months follow-up (k=1; n=18; SMD -1.10 95% CI -2.09, 0.11)
Box 108 Evidence statement matrix for RCT comparing EMDR and ‘the counting method’ for adults with PTSD Component Rating Description Evidence base D One level II study at a moderate risk of bias.
Consistency NA Only one study.
Clinical impact C Evidence of clinically important point estimates all favouring EMDR over ‘the counting method’, but small sample sizes meant the confidence intervals also included clinically unimportant effects.
Generalisability C Population who had experienced mixed traumas, although only females; generalisable to a proportion of the target audience for the guidelines.
Applicability C Study performed in the United States; evidence probably applicable to the Australian healthcare context with some caveats.
Summary of evidence One small, average quality study showed that EMDR was more effective than ‘the counting method’ at reducing clinician-measured and self-reported symptoms of PTSD, but the study was limited by the very small sample size and the confidence intervals around the point estimates of clinical importance included effects that were clinically unimportant. (Grade C)
EMDR vs EMOTIONAL FREEDOM TECHNIQUES
One study (Karatzias et al 2011) explored the effectiveness of EMDR compared to Emotional Freedom Techniques (EFT). EFT is an exposure-based therapy that elicits “imagery, narrative and in vivo arousal related to the distressing memory” accompanied by light tapping on various meridian points on the face and body. This relatively small study (n=46) was conducted with a general population of trauma survivors with PTSD in Scotland, and was well designed with regard to randomisation, allocation concealment and blinding of outcomes assessment. The analysis was ITT, however high dropout rates (43% in the EMDR arm and 39% in the EFT arm) suggest that caution should be exercised in interpreting the results. Reasons for loss to follow up were not detailed and so it is not possible to tell if the treatments themselves were unacceptable, or if there was some other reason for such large numbers not completing treatment and outcomes assessment.
304 Table 103: study profiles for RCTs comparing EMDR to emotional freedom techniques Reference Risk of bias Population Setting N Outcomes measured (Karatzias et al 2011) Moderate Adults 18-65 years with Public psychotherapy 46 PTSD symptoms PTSD from general service in Scotland Anxiety; depression trauma (accidents, assault, other)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between EMDR and EFT on reducing the severity of clinician- rated PTSD symptoms at post-treatment (k=1; n=43; SMD=-0.08 95% CI -0.50, 0.65) or at 3 months follow up (k=1; n=43; SMD=0.17 95% CI -0.41, 0.75).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between EMDR and EFT on reducing the severity of self- reported PTSD symptoms at post-treatment (k=1; n=43; SMD=-0.02 95% CI -0.60, 0.56) or at 3 months follow up (k=1; n=43; SMD=0.10 95% CI -0.47, 0.68).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between EMDR and EFT on reducing depression symptoms at post-treatment (k=1; n=43; SMD=0.07 95% CI -0.51, 0.65) or at 3 months follow up (k=1; n=43; SMD=0.11 95% CI -0.47, 0.69)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between EMDR and EFT on reducing anxiety symptoms at post-treatment (k=1; n=43; SMD=0.16 95% CI -0.42, 0.73) or at 3 months follow up (k=1; n=43; SMD=0.06 95% CI -0.51, 0.64)
Box 109: evidence statement matrix for RCTs comparing EMDR to emotional freedom techniques Component Rating Description Evidence base C One small level II study with a moderate risk of bias
Consistency NA One study only
Clinical impact D No clinically important differences found for any outcome
Generalisability A Study with adult survivors of general trauma in Scotland; generalisable to target population
Applicability A Study in public setting in Scotland; directly comparable to Australian healthcare context.
Summary of evidence One small but well designed study found no difference between the effectiveness of EMDR and EFT for treatment of PTSD. The study had high dropout rates in both arms of the study, but as no reasons for dropout were recorded, it is difficult to assess whether dropouts were due to the acceptability of these treatments or other reasons. (Grade C).
STRESS MANAGEMENT VERSUS SUPPORTIVE COUNSELLING
One study compared stress management to supportive counselling for treating women who had experienced sexual or physical assault. In this study, the stress management treatment
305 was stress inoculation training, involving instruction in coping skills, deep muscle relaxation, controlled breathing and thought stopping to counter ruminative or obsessive thinking. The supportive counselling treatment involved teaching the subject a general problem solving technique, focusing on everyday problems, not the assualt. This small study was considered to have a high risk of bias due to a lack of detail about methodology and a completer only analysis, with drop outs of 17.6% in the stress inoculation arm and 21% in the supportive counselling arm. For the purposes of judging the clinical importance of effect sizes in this study, the supportive counselling is considered both an active and inactive treatment arm.
Table 104 Study profiles for RCTs comparing stress management and supportive counselling for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Foa et al 1991) High Women who had experienced rape or Outpatient 31 PTSD diagnosis attempted rape setting, United Severity of PTSD States Depressive symptoms Anxiety Attrition
There is limited evidence favouring stress management therapy over supportive counselling on reducing the likelihood of having a PTSD diagnosis after treatment (k=1; n=31; RR=0.58, 95% CI 0.3 to 1.11). There is limited evidence favouring stress management therapy over supportive counselling on reducing the severity of clinician-rated PTSD symptoms at post-treatment (k=1; n=25; SMD=–1.22, 95% CI –2.09 to –0.35). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between stress management therapy and supportive counselling on reducing the severity of clinician-rated PTSD symptoms at 3 months follow up (k = 1; n = 18; SMD = -0.38; 95% CI, -1.31 to 0.55). There is limited evidence favouring stress management therapy over supportive counselling on reducing depression at post-treatment (k = 1; n = 25; SMD = -0.51; 95% CI, -1.31 to 0.3). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between stress management therapy and supportive counselling on reducing depression at 3 months follow up (k = 1; n = 18; SMD = -0.48; 95% CI, -1.42 to 0.46). There is limited evidence favouring stress management therapy over supportive counselling on reducing anxiety at post-treatment (k = 1; n = 25; SMD = -0.51; 95% CI, -1.32 to 0.29) and at 3 months follow up (k = 1; n = 18; SMD = -0.68; 95% CI, -1.64 to 0.28) The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between stress management therapy and supportive counselling on reducing the likelihood of leaving treatment early for any reason (k=1; n=31; RR=0.82, 95% CI 0.2 to 3.46).
Box 110 Evidence statement matrix for RCT comparing stress management and supportive counselling for adults with PTSD Component Rating Description Evidence base D One small study with a high risk of bias
306 Consistency NA One study only
Clinical impact C Clinically important point estimates favouring stress management therapy over supportive counselling on reducing likelihood of PTSD, PTSD severity, depressive symptoms and anxiety in the short term. No clinically important differences found for PTSD severity or depression after 3 months. Generalisability A Female rape victims who are a target population of the guidelines
Applicability C Study from the US; applicable to Australian healthcare setting with some caveats
Summary of evidence One small, poor quality study of female rape victims provided limited evidence for some clinically important effects favouring stress management over supportive counselling in the short term. (Grade D).
MINDFULNESS VS PSYCHOEDUCATION DELIVERED IN PERSON AND VIA TELEPHONE
One study compared a mindfulness treatment with psychoeducation for subjects with combat- related PTSD. Both treatments were delivered via two in-person sessions and six telephone sessions, and participants also had a handbook to guide their therapy. The mindfulness intervention included teaching participants to notice sensations, thoughts and emotions, and mindfulness exercises. The psychoeducation involved education on a range of topics such as trust, effects of trauma, and coping and healing. Subjects were all males who had experienced combat in war or peace-keeping missions. This was a small, poor quality study. Although the randomisation procedure appeared to be thorough, there were significant differences between the two groups on the PTSD outcome measures at baseline, which means the results should be interpreted with caution due to the likelihood of selection bias. Moreover, the study did not blind the outcomes assessors or conduct an ITT analysis.
Table 105 Study profiles for RCTs comparing mindfulness and psychoeducation delivered in-person and via telephone for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured Niles: in press High Male combat veterans aged 23-66 Outpatient 33 Severity of PTSD years setting, United States
This study found strong evidence favouring the mindfulness intervention, however due to the size of the study, the poor quality and the lack of comparability of the two treatment groups at baseline, these findings should be interpreted with caution.
There is evidence favouring mindfulness over psychoeducation for reducing the severity of clinician-rated PTSD symptoms at posttreatment (k=1, n=27; SMD -1.23 95% CI -2.06, - 0.41)
There is evidence favouring mindfulness over psychoeducation for reducing the severity of self-rated PTSD symptoms at posttreatment (k=1, n=27; SMD -1.90 95% CI -2.80, -0.99)
There is limited evidence favouring mindfulness over psychoeducation for reducing the
307 severity of self-rated PTSD symptoms at 6 weeks follow up (k=1, n=24; SMD -0.86 95% CI -1.70, -0.03)
Box 111 Evidence statement matrix for RCT comparing mindfulness and psychoeducation delivered in person and via telephone for adults with PTSD Component Rating Description Evidence base D One small study with a high risk of bias
Consistency NA One study only
Clinical impact D Clinically important evidence favouring mindfulness but due to problems with the study should be interpreted with caution
Generalisability A Combat veterans who are a target population of the guidelines
Applicability C Study from the US; applicable to Australian healthcare setting with some caveats
Summary of evidence One small, poor quality study found large, clinically important effects favouring mindfulness over psychoeducation for treating PTSD in combat veterans. However, this study has a large chance of selection bias given large differences in the outcome measures at baseline, and so these results should be interpreted with caution. (Grade D)
GROUP CBT (TRAUMA-FOCUSED) VERSUS GROUP CBT (NON-TRAUMA FOCUSED)
One study compared trauma-focused group CBT with non-trauma focused group CBT (present-centred therapy) in Vietnam veterans. This long term study (30 weeks plus booster sessions) compared group psychotherapy that included exposure components with group therapy based on education about PTSD and associated feelings, and problem solving. The study was large, and well designed, but reported only completer analysis and so was assessed to have a high level of bias.
Table 106 Study profile for RCT comparing group CBT (trauma-focused) and group CBT (non-trauma focused) for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Schnurr et al 2003) High Vietnam veterans Outpatient 360 PTSD diagnosis setting, United Severity of PTSD symptoms States Attrition
There is evidence suggesting there is unlikely to be a clinically important difference between group CBT (trauma-focused) and group CBT (non-trauma-focused) on reducing the likelihood of having a PTSD diagnosis after treatment (k=1; n=360; RR=0.98, 95% CI 0.83 to 1.16). There is evidence suggesting there is unlikely to be a clinically important difference between group CBT (trauma-focused) and group CBT (non-trauma-focused) on reducing the severity of PTSD symptoms (k=1; n=325; SMD=0.12, 95% CI –0.34 to 0.1). There is limited evidence suggesting a difference favouring group CBT (non-trauma- focused) over group CBT (trauma-focused) on reducing the likelihood of leaving
308 treatment early for any reason (k=1; n=360; RR=1.38, 95% CI 1 to 1.9).
Box 112 Evidence statement matrix for RCT comparing group CBT (trauma-focused) and group CBT(non-trauma focused) for adults with PTSD Component Rating Description Evidence base D One study with a high risk of bias
Consistency NA Only one study
Clinical impact D No clinically important differences found
Generalisability A Combat veterans; similar to a target population for guidelines
Applicability C Study conducted in the United States; probably applicable to Australian healthcare context with some caveats
Summary of evidence Evidence from one average quality study of good size but with a high risk of bias found no clinically important differences between trauma-focused group CBT and group therapy without trauma focus for combat veterans. (Grade D)
GROUP CBT (VIDEOCONFERENCE) VERSUS GROUP CBT (SAME ROOM) One study was identified which compared a group CBT delivered via videoconference facilities, and a group CBT delivered face-to-face in the same room (Frueh et al 2007). The treatment was called ‘Social and Emotional Rehabilitation’, and involved 14 sessions of social skills training, and activities to increase social participation. All participants were male veterans with combat-related trauma.
Those who participated in the same-room group expressed more comfort with talking to their therapist post-treatment than those who participated in the videoconference group. Adherence to treatment was the same in both groups, but the videoconference group was less likely to perform the homework assignments (Frueh et al 2007).
Table 107 Study profiles for RCTs comparing group non-trauma-focused CBT delivered via videoconference or in the same room for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Frueh et al 2007) High Male veterans with combat-related Outpatient 21/38 Severity of PTSD symptoms trauma setting, United Depressive symptoms States (video- Attrition conference or face-to-face)
There is limited evidence favouring face-to-face group CBT over video-conference group CBT at reducing the severity of PTSD symptoms at post-treatment (k=1, n=21, SMD=1.06; 95%CI 0.13, 1.98).
309 The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between video-conference group CBT and face-to-face group CBT on reducing depressive symptoms at post-treatment (k=1, n=21, SMD=0.23, 95%CI - 0.63, 1.11).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between video-conference group CBT and face-to-face group CBT on attrition at post-treatment (k=1, n=21, RR=1.09, 95%CI 0.54, 2.22).
Box 113 Evidence statement matrix for RCT comparing non-trauma-focused CBT delivered via videoconference or in the same room for adults with PTSD Component Rating Description Evidence base D One level II study with a high risk of bias due to high drop-out and analyses of completer-only data
Consistency NA Only one study
Clinical impact D One clinically important point estimate favouring face-to-face group CBT (non-trauma focused) over group CBT (non-trauma-focused) via videoconference, on the outcome of severity of PTSD symptoms post-treatment. However, the full range of estimates included clinically irrelevant effects. Generalisability C Likely generalisable to male veterans with combat-related PTSD. Unclear how generalisable to broader target population.
Applicability C Study performed in United States, so evidence probably applicable to Australian healthcare context with some caveats.
Summary of evidence One small suggests that non-trauma-focused group CBT is more beneficial in regards to severity of PTSD symptoms post-treatment when delivered face-to-face rather than via videoconferencing. (Grade D).
GROUP CBT (NON-TRAUMA FOCUSED) VERSUS GROUP PSYCHOEDUCATION
One RCT ((Dunn et al 2007)) compared group CBT and group psychoeducation for males with post-combat related PTSD patients at three Veterans Affairs centres in the United States. A total of 111 veterans were randomised to CBT (n=55) or psychoeducation (n=56), with 29 and 37 patients included in the final follow-up assessment at 12 months for the respective groups. The CBT treatment was non-trauma focused and called ‘self management’ by the authors; the psychoeducation treatment did not include instruction that was designed to create behaviour change. This study was of average quality, and although the randomisation and blinding seemed adequate, only completers were included in the analysis and 41% of the sample were lost to follow up.
Table 108: Study profiles for RCTs comparing written emotion disclosure and control writing condition for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Dunn et al 2007) High Male veterans with combat- Veterans Affairs(VA) 111 PTSD and depression symptom related PTSD Medical Center and two severity VA outreach centers, United States
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between group CBT and group psychoeducation on reducing the
310 severity of clinician-rated PTSD symptoms at post-treatment (k = 1; n = 77; SMD = -0.21; 95% CI, -0.66 to 0.25), at 3-month follow-up (k = 1; n = 70; SMD = -0.15; 95% CI, -0.62 to 0.32), at 6-month follow-up (k = 1; n = 71; SMD = -0.13; 95% CI, -0.60 to 0.34), or at 12- month follow-up (k = 1; n = 66; SMD = -0.37; 95% CI, -0.89 to 0.12).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between group CBT and group psychoeducation on reducing the severity of self-reported PTSD symptoms at post-treatment (k = 1; n = 77; SMD = -0.16; 95% CI, -0.61 to 0.29), at 3-month follow-up (k = 1; n = 70; SMD = -0.12; 95% CI, -0.59 to 0.35) or at 12-month follow-up (k = 1; n = 66; SMD = -0.06; 95% CI, -0.55 to 0.42).
There is evidence suggesting that there is unlikely to be a clinically important difference between group CBT and group psychoeducation on reducing the severity of self-reported PTSD symptoms at 6-month follow-up (k = 1; n = 71; SMD = 0.02; 95% CI, -0.45 to 0.49).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between group CBT and group psychoeducation on reducing the severity of depression at post-treatment (k = 1; n = 77; SMD = -0.23; 95% CI, -0.69 to 0.22), at 3-month follow-up (k = 1; n = 70; SMD = -0.18; 95% CI, -0.65 to 0.29), ) at 6-month follow-up (k = 1; n = 71; SMD = -0.07; 95% CI, -0.54 to 0.40) or at 12-month follow-up (k = 1; n = 66; SMD = 0.21; 95% CI, -0.28 to 0.69).
Evidence statement matrix for RCT comparing trauma written emotional disclosure and control writing condition for adults with PTSD Component Rating Description Evidence base D One level II study with high risk of bias
Consistency NA One study only
Clinical impact D Slight/restricted; no clinically important differences between the treatments on any of the outcomes over any of the time periods
Generalisability B Evidence directly generalisable to the target population with some caveats
Applicability C Evidence probably applicable to Australian healthcare context with some caveats
Summary of evidence The evidence from this RCT is inconclusive, with no clinically important differences between emotional disclosure and control writing conditions. The results are likely to be generalisable to the Australian veteran population suffering from PTSD. (Grade D).
GROUP IMAGERY REHEARSAL THERAPY VS GROUP SLEEP AND NIGHTMARE MANAGEMENT
One study compared group imagery rehearsal against a non-exposure based group therapy for sleep and nightmare problems for combat veterans with PTSD who were having nightmares (Cook et al 2010). The imagery rehearsal treatment was based on the premise taht waking mental activity can influence the content of dreams; subjects altered their nightmare script via imagery techniques and mentally rehearsed their revised script. The alternative treatment, sleep and nightmare management, consisted of psychoeducation about PTSD nightmares and contained elements of standard CBT for insomnia, and whilst content of nightmares was not
311 discussed, the effect of nightmares on daily functioning was. Both treatments consisted of weekly 90minute sessions for six weeks.
This study was of a reasonable size and methodology, but was rated a high risk of bias due to presenting only completer analysis. Nightmares were not an outcome of interest for this review and so the results are not reported, however the study found no difference between the two treatments on the nightmare frequency or sleep quality outcomes.
Table 109: study profiles for RCTs comparing group imagery rehearsal and group sleep and nightmare management Reference Risk of bias Population Setting N Outcomes measured (Cook et al 2010) High Male Vietnam combat Veterans’ Affairs 124 PTSD symptoms veterans with PTSD medical centres, United Depression related nightmares States
There is evidence suggesting there is unlikely to be a clinically important difference between group imagery rehearsal and group sleep and nightmare management on reducing the severity of clinician-rated PTSD symptoms at post-treatment (k=1, n=101; SMD -0.04 95% CI -0.43, 0.35)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between group imagery rehearsal and group sleep and nightmare management on reducing the severity of self-rated PTSD symptoms at post- treatment (k=1, n=101; SMD -0.17 95% CI -0.56, 0.22)
There is evidence suggesting there is unlikely to be a clinically important difference between group imagery rehearsal and group sleep and nightmare management on reducing the severity of self-rated PTSD symptoms at 3 months follow up (k=1, n=99; SMD -0.08 95% CI -0.48, 0.31) or at 6 months follow up (k=1, n=95; SMD -0.05 95% CI -0.45, 0.36)
There is evidence suggesting there is unlikely to be a clinically important difference between group imagery rehearsal and group sleep and nightmare management on reducing depression at post-treatment (k=1, n=101; SMD 0.14 95% CI -0.25, 0.53) or at 3 months follow up (k=1, n=99; SMD 0.08 95% CI -0.32, 0.48)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between group imagery rehearsal and group sleep and nightmare management on reducing depression at 6 months follow up (k=1, n=95; SMD 0.13 95% CI -0.28, 0.53)
312 Box 114: Evidence statement matrix of RCTs comparing group imagery rehearsal to group sleep and nightmare management Component Rating Description Evidence base D One level II study with a high risk of bias
Consistency NA One study only
Clinical impact D No clinically important differences found for any outcome
Generalisability A Study with male combat veterans; generalisable to one of the target populations of guidelines Applicability C Study in Veterans’ Affairs medical centres in United States; probably applicable to Australian healthcare context with some caveats.
Summary of evidence One average quality study with a high risk of bias found no differences between group imagery rehearsal and group sleep and nightmare management for reducing the symptoms of PTSD or depression in combat veterans. (Grade D).
PARENT AND CHILD GROUP CBT VS PARENT-ONLY GROUP CBT
One study compared group CBT for parents who had physically abused their child, and their child, with parent-only group CBT, with the aim of helping the abused children (Runyon et al 2010). In this study, the subjects in the parent and child CBT received group therapy just for parents or children, as well as group therapy with parents and children. The parent-only CBT group received group therapy just for the offending parent. The parent and child CBT focused on children recounting their trauma and the feelings and emotions it elicited, the parents taking full responsibility for the abuse and understanding the child’s feelings about it, and the parents also learnt some behaviour management strategies. The parent-only CBT group focused on parent training without the involvement of the child.
This study was of poor quality and lacked detail in the methodology, and failed to address some differences in the baseline characteristics of the groups. It found a clinically important point estimate for PTSD severity favouring parent and child CBT at post-treatment, but no other differences.
Table 110 Study profiles for RCTs comparing group parent-child CBT to group parent-only CBT. Reference Risk of bias Population Setting N Outcomes measured (Runyon et al 2010) High Children 7-13 years Clinic within University 60 Severity of PTSD symptoms who had experienced medical school, USA Child behaviour physical abuse and their abusing parent.
There is limited evidence favouring parent and child group CBT over parent-only group CBT for reducing the severity of PTSD symptoms at post-treatment (k=1, n=60: SMD -0.61 95% CI -1.13, -0.09)
The evidence is inconclusive and so it is not possible to determine whether or not there is a clinically important difference between parent and child group CBT and parent-only group CBT on reducing child internalising behaviour at post-treatment (k=1, n=60: SMD 0.14 95% CI -0.37, 0.66)
313 The evidence is inconclusive and so it is not possible to determine whether or not there is a clinically important difference between parent and child group CBT and parent-only group CBT on reducing child externalising behaviour at post-treatment (k=1, n=60: SMD 0.20 95% CI -0.32, 0.71)
Box 115: evidence statement matrix for RCTs comparing parent and child group CBT to parent-only group CBT Component Rating Description Evidence base D One small level II study with a high risk of bias
Consistency NA Only one study
Clinical impact C Possibly clinically important difference on PTSD but none on child behaviour.
Generalisability C American urban setting; results probably generalisable to Australian population of children who have experienced physical abuse Applicability C Evidence probably applicable to Australian healthcare context with some caveats.
Summary of evidence One small, poor quality study found limited evidence for improving PTSD severity in children who had been physically abused with parent and child group CBT compared to parent-only group CBT. (Grade D)
314 Box 116 Study selection criteria for research question 12
Research Question 12. For people with PTSD, is individual therapy more effective than group therapy? Selection criteria Inclusion criteria Population People with PTSD Intervention Individual therapy (eg psychodynamic psychotherapy, individual cognitive behavioural therapies, EMDR, narrative exposure therapy, image rehearsal therapy, supportive counselling, hypnosis) Comparator Group therapy (eg supportive therapy, psychoeducation, psychodynamic therapy, group CBT such as anxiety management, stress inoculation, assertiveness training, prolonged exposure, cognitive restructuring) Outcome Primary outcome: resolution of symptoms of PTSD Secondary outcomes: symptoms of depression, anxiety and substance misuse/ social and occupational function/ quality of life/ treatment refusal/ dropout over 12 months/ side-effects/ posttraumatic growth/ physical comorbidity Additional outcomes for children: attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies are found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies Search Period 8/2005-10/2011 for adultsa ; 1966-10/2011 if requiredb 1966–10/2011 for children and adolescentsc Language English
a Updated search from 2007 Guidelines b Expanded search period if fewer than two Level II studies are found c New research questions CBT = cognitive behavioural therapy; EMDR = eye movement desensitisation and reprocessing
Box 117 Study selection criteria for research question 13
Research Question 13. For people with PTSD, is the combination of individual therapy and group therapy more effective than either alone? Selection criteria Inclusion criteria Population People with PTSD Intervention Individual therapy and group therapy (see Box 116 for examples) Comparator Individual therapy or group therapy (see Box 116 for examples) Outcome Primary outcome: resolution of symptoms of PTSD Secondary outcomes: symptoms of depression, anxiety and substance misuse/ social and occupational function/ quality of life/ treatment refusal/ dropout over 12 months/ side-effects/ posttraumatic growth/ physical comorbidity Additional outcomes for children: attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies are found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies Search Period 8/2005-10/2011 for adultsa ; 1966-10/2011 if requiredb 1966–10/2011 for children and adolescentsc Language English
a Updated search from 2007 Guidelines b Expanded search period if fewer than two Level II studies are found c New research questions
Two RCTs were identified meeting the inclusion criteria for question 12 (Salloum & Overstreet 2008; Trowell et al 2002), whereas no studies were identified addressing question 13. One additional study comparing individual and group therapy in school children was identified, but it was subsequently excluded as data could not be extracted (Chemtob et al 2002b).
315 GROUP INTERVENTIONS VERSUS INDIVIDUAL INTERVENTIONS
Two RCTs (Salloum & Overstreet 2008; Trowell et al 2002) compared a group intervention to individual intervention. Salloum & Overstreet (2008) randomised 56 primary school-age children equally to 10 weeks of group or individual therapy, which were both based on CBT and narrative exposure techniques. The other study recruited 75 sexually abused girls aged 6 to 14 years who were allocated to either individual psychotherapy, delivered in up to 30 sessions per patient, or psychoeducational group therapy with as many as 18 sessions per group. Due to heterogeneity of the populations and the outcomes reported (Salloum & Overstreet reported total PTSD symptom severity at three weeks follow-up, while Trowell and colleagues reported on change in symptom subscales of PTSD severity after at least one year of follow-up) no meta-analysis was possible.
Table 111: Study profiles for RCTs comparing group interventions to individual interventions for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Salloum & Moderate Children exposed to natural 3 elementary schools, 45 Severity of PTSD symptoms Overstreet 2008) disaster (Hurricane Katrina) United States (Trowell et al 2002) High Sexually abused girls Outpatient clinics in the 75 Severity of PTSD symptoms United Kingdom subscale measures (re- experiencing, avoidance)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between group intervention and individual intervention on reducing the severity of PTSD symptoms at 3 weeks follow-up (k = 1; n = 45; SMD = -0.23 95% CI, -0.82, 0.36).
There is limited evidence favouring individual over group interventions on the reduction of severity of PTSD re-experiencing symptoms between baseline and 1 year follow-up (k=1, n= 56, SMD=-0.76, 95%CI -1.31, -0.22), 2 years follow-up (k=1, n=49, SMD=-0.79, 95%CI - 1.37, -0.20) and 3-4 years follow-up (k=1, n=64, SMD=-0.58, 95%CI -1.08, -0.08).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between group intervention and individual intervention on reducing the severity of PTSD avoidance symptoms between baseline and 1 year follow-up (k=1, n= 56, SMD=-0.44, 95%CI -0.97, 0.09), 2 years follow-up (k=1, n=49, SMD=-0.28, 95%CI -0.85, 0.28) and 3-4 years follow-up (k=1, n=64, SMD=-0.39, 95%CI -0.88, 0.10).
Box 118: Evidence statement matrix for RCT comparing group interventions to individual interventions for adults with PTSD Component Rating Description Evidence base C One level II study with moderate risk of bias and one level II study with high risk of bias
Consistency C Consistent in direction of effect
Clinical impact D Slight/restricted
Generalisability B Evidence directly generalisable to the target population with some caveats
Applicability C Evidence probably applicable to Australian healthcare context with some caveats
316
Summary of evidence There is limited evidence suggesting there may be a benefit in individual interventions compared to group interventions at reducing re-experiencing symptoms of PTSD. (Grade C).
317
Box 119 Study selection criteria for research question 14
Research Question 14. Are established interventions for PTSD effective when self-delivered or self-delivered with practitioner support compared to practitioner delivered intervention or no intervention? Selection criteria Inclusion criteria Population People with PTSD Intervention Self-delivered psychological intervention with/without face-to-face practitioner support (eg web-based interapy or telephone support) Comparator 1. Practitioner delivered psychological intervention 2. No treatment (eg assessment only) Outcome Primary outcome: resolution of symptoms of PTSD Secondary outcomes: symptoms of depression, anxiety and substance misuse/ social and occupational function/ quality of life/ treatment refusal/ dropout over 12 months/ side-effects/ posttraumatic growth/ physical comorbidity. Additional outcomes for children: attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies are found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies Search Period 8/2005-10/2011 for adultsa ; 1966-10/2011 if requiredb 1966-10/2011 for children and adolescentsc Language English aupdated search from 2007 Guidelines. b Expanded search period if fewer than two Level II studies are found c New research questions
Four studies were included under the assessment of Question 14. Three studies compared the use of an internet-delivered CBT treatment, against either a waitlist condition, or a control condition, while one study compared the use of a self-help booklet outlining CBT principles, against both a CBT condition (practitioner delivered), and a waitlist condition.
One study compared telepsychiatry against face-to-face contact as methods of delivering CBT, was considered to be practitioner delivered, rather than self-delivered, so was considered under Question 11 (Frueh et al 2007).
In addition, there were two studies which included self-guided treatment for those exposed to trauma as an early intervention, and were considered under Questions 3 and 4 (Beatty et al 2010; Cox et al 2010).
SELF-HELP BOOKLET VERSUS WAITLIST
One moderate quality randomised controlled trial was which compared the effectiveness of a self-help booklet versus a waitlist control, in a population of motor vehicle accident survivors (Ehlers et al 2003). Approximately 4 weeks after their accident, patients received a brochure about PTSD, explaining that help may be available, inviting them to participate in the study comparing cognitive therapy, a self help book, or repeated assessments. If patients met the inclusion criteria and were interested in participating, they were required to spend 3 weeks monitoring symptoms, and only those who still met the criteria for PTSD after this monitoring stage were entered into the trial, with both the self-help group and waitlist group being told they could receive cognitive therapy after 9 months if they still needed help with their symptoms. Comparisons between cognitive therapy and waitlist are included under Question 10.
318 Table 112 Study profiles for RCTs comparing self help and supportive psychotherapy for people with acute PTSD or ASD Reference Risk of bias Population Setting N Outcomes measured (Ehlers et al 2003) Moderate Motor vehicle accident United Kingdom 52 PTSD diagnosis survivors Symptoms of PTSD Depressive symptoms Anxiety Quality of life
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between self-help booklet and waiting list on reducing the likelihood of having a PTSD diagnosis post-treatment (k=1; n=57; RR=1.09, 95% CI 0.81 to 1.46) or at 6 months’ follow-up (k=1; n=57; RR=1.1, 95% CI 0.71 to 1.71). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between self-help booklet and waiting list on reducing the severity of self-report PTSD symptoms at post-treatment (k=1; n=52; SMD=–0.27, 95% CI –0.81 to 0.28). There is evidence suggesting there is unlikely to be a clinically important difference between self-help booklet and waiting list on reducing the severity of clinician-rated PTSD symptoms at 6 months’ follow-up (k=1; n=52; SMD=0.07, 95% CI –0.47 to 0.62). There is evidence suggesting there is unlikely to be a clinically important difference between self-help booklet and waiting list on reducing the severity of depressive symptoms at post- treatment (k=1; n=52; SMD=-0.12, 95% CI –0.66 to 0.43). The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between self-help booklet and waiting list on reducing the severity of depressive symptoms at 6 months’ follow-up (k=1; n=52; SMD=0.36, 95% CI –0.18 to 0.91). There is evidence suggesting there is unlikely to be a clinically important difference between self-help booklet and waiting list on reducing the severity of anxiety at post-treatment (k=1; n=52; SMD=-0.15, 95% CI –0.70 to 0.39) and at 6 months’ follow-up (k=1; n=52; SMD=0.16, 95%CI -0.38, 0.71). There is evidence suggesting there is unlikely to be a clinically important difference between self-help booklet and waiting list on improving quality of life at post-treatment (k=1; n=52; SMD=0.04 95% CI –0.50 to 0.59). There is limited evidence favouring waiting list over self help booklet on reducing work, social and family impairment at 6 months’ follow-up (k=1; n=52; SMD=1.31 95% CI 0.70 to 1.91).
Box 120 Evidence statement matrix for RCTs comparing self help booklet and waistlist for people with acute PTSD Component Rating Description Evidence base C One level II study with a moderate risk of bias due to lack of intention-to-treat analyses and drop-out
Consistency NA Only one study. However, different outcome measures were consistent in the absence of any clear difference between treatment conditions. Clinical impact D No clear differences detected between a self-help booklet outlining CBT principles and a repeated assessments condition. Results were mixed between showing either no difference, a slight trend towards favouring self help, or a trend towards favouring waitlist.
319 Generalisability C Only one trauma type, but highly generalisable to Australians involved in motor vehicle accidents. Likely to be generalisable to other trauma types.
Applicability B Study performed in the United Kingdom with a healthcare system similar to Australia.
Summary of evidence Limited evidence suggests no beneficial impact of a self help booklet outlining CBT principles for treating PTSD, compared to a waitlist group. (Grade C).
INTERNET DELIVERED CBT VERSUS WAITLIST
A study by Lange et al (2003) was the initial study to combine a manual-based cognitive- behavioural writing therapy with the internet. Treatment participants received emails twice a week with 45 minute writing assignments involving writing about the trauma, self confrontation, cognitive reappraisal and social sharing, and were given feedback on their assignments via email by a therapist. This study was performed in the Netherlands, and found that interapy was superior to waitlist in reducing severity of PTSD symptoms, depressive symptoms and anxiety. However, the results of this study are at risk of being biased, due to a lack of intention-to-treat analyses, and a high loss to follow-up (45%). A study by Knaevelsrud et al (2007) used the same approach as Lange et al (2003) in a German population, and found the same direction of effect in favour of interapy, although the only clinically important finding was for one subscale (Intrusion) of the Impact of Events Scale (IES).
Spence et al (2011) assessed the benefit of an internet-based CBT therapy in Australia, which included psychoeducation on PTSD, instructions about controlling physical symptoms, principles of cognitive therapy, education and guidance on graded exposure (imaginal and written exposure and/or audio-recording), challenging dysfunctional beliefs and information about relapse prevention. This occurred over seven online lessons, with the addition of homework assignments, an online discussion forum, automatic reminder emails and an instant messenger service allowing private communication with the clinician. This well designed trial (at risk of bias due to using only self report measures, which are unable to be blinded) reported no clinically important differences between internet CBT and a control group.
Table 113 Study profiles for RCTs comparing internet-delivered CBT and control/waitlist for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Knaevelsrud & Moderate Unspecified trauma: sudden or violent Internet, 95/96 Severity of PTSD symptoms Maercker 2007) death of a close person or sexual Germany Depressive symptoms abuse, incest, or rape Anxiety Attrition
(Spence et al 2011) Moderate Unspecified trauma: physical assault, Internet, 42 Severity of PTSD symptoms other unwanted sexual experience, Australia Depressive symptoms sexual assault, transportation Anxiety accidents, and other stressful Attrition experiences
320 (Lange et al 2003) High Unspecified trauma: loss of loved Internet, the 131/184 Severity of PTSD symptoms one, sexual abuse, physical abuse Netherlands Depressive symptoms and/or robbery, loss of health, house Anxiety or job, traffic accident, divorce or Attrition other traumatic event with the family
There is limited evidence favouring internet CBT over control/waitlist on reducing the severity of PTSD symptoms at post-treatment (k=3, n=238, SMD=-0.84, 95%CI -1.33, -0.34).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between internet CBT and control/waitlist on reducing depressive symptoms at post-treatment (k=3, n=238, SMD=-0.70, 95%CI -0.97, -0.43).
321
There is evidence suggesting that there is unlikely to be a clinically important difference between internet CBT and control/waitlist on reducing anxiety at post-treatment (k=3, n=238, SMD=-0.54, 95%CI -0.80, -0.27).
There is evidence suggesting there is unlikely to be a clinically important difference between internet CBT and control/waitlist on attrition at post-treatment (k=3, n=324, RR=1.03, 95%CI 0.75, 1.42).
Box 121 Evidence statement matrix for RCT comparing internet CBT and control/waitlist for adults with PTSD Component Rating Description Evidence base C Three level II studies, two with a moderate risk of bias due to self-report measures which cannot be blinded, and one with a high risk of bias due to lack of intention to treat analyses and high drop-out.
Consistency B All studies consistent in the direction of effect, and the difference in the size of effect may be explained by the potential for bias in the studies which provided completer-only data.
322 Clinical impact D Internet CBT resulted in a clinically important point estimate compared to control/waitlist, although the confidence interval also included clinically unimportant effects. The benefits on depressive symptoms and anxiety were too small to be considered clinically important. Generalisability A Samples all included a mix of trauma types, and one of the studies was based in Australia.
Applicability A Internet therapy highly applicable in Australia, particularly given one of the studies was performed in Australia.
Summary of evidence Limited evidence suggests that internet CBT (online or via email) is slightly beneficial over a control/waitlist condition. However, the size of the effect is only considered clinically important for the outcome measure of PTSD symptoms, and was too small to be considered clinically important on depressive symptoms or anxiety. (Grade C).
SELF-HELP BOOKLET VERSUS CBT
Ehlers et al (2003) also compared the effectiveness of cognitive therapy against a self-help booklet condition, which contained information on the principles of using CBT to treat PTSD, including some specific information relating to trauma symptoms after a motor vehicle accident.
Table 114 Study profiles for RCTs comparing self help and CBT for people with acute PTSD Reference Risk of bias Population Setting N Outcomes measured (Ehlers et al 2003) Moderate Motor vehicle accident United Kingdom 56 PTSD diagnosis survivors Symptoms of PTSD Depressive symptoms Anxiety Quality of life
There is evidence favouring CBT over self-help booklet on reducing the likelihood of having a PTSD diagnosis post-treatment (k=1, n=56, RR=0.27, 95%CI 0.13, 0.57) and at 6 months’ follow-up (k=1, n=56, RR=0.18, 95%CI 0.06, 0.54). There is limited evidence favouring CBT over self-help booklet on reducing the severity of clinician-rated PTSD symptoms at post-treatment (k=1, n=56, SMD=-1.00, 95%CI -1.55, - 0.44) and at 6 months’ follow-up (k=1, n=56, SMD=-1.52, 95%CI -1.52, -0.41). There is limited evidence favouring CBT over self-help booklet on reducing the severity of self-rated PTSD symptoms at post-treatment (k=1, n=56, SMD=-1.35, 95%CI -1.93, -0.77) and at 6 months’ follow-up (k=1, n=56, SMD=-1.94, 95%CI -1.94, -0.78). There is limited evidence favouring CBT over self-help booklet on reducing depressive symptoms at post-treatment (k=1, n=56, SMD= -1.34, 95%CI -1.92, -0.76) and at 6 months’ follow-up (k=1, n=56, SMD=-1.23, 95%CI -1.81, -0.66). There is limited evidence favouring CBT over self-help booklet on reducing anxiety at post- treatment (k=1, n=56, SMD= -1.08, 95%CI -1.64, -0.52) and at 6 months’ follow-up (k=1, n=56, SMD= -1.16, 95%CI -1.72, -0.59) The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between CBT and self-help booklet on reducing work, social and family impairment at post-treatment (k=1, n=56, SMD=-0.74, 95%CI -1.28, -0.20)
323 There is limited evidence favouring CBT over self-help booklet on reducing work, social and family impairment at 6 months’ follow-up (k=1, n=56, -0.80, 95%CI -1.34, -0.25).
Box 122 Evidence statement matrix for RCTs comparing self help booklet and waistlist for people with acute PTSD Component Rating Description Evidence base C One level II study with a moderate risk of bias due to lack of intention-to-treat analyses and drop-out
Consistency NA Only one study. However, different outcome measures were consistent in direction of effect and similar in size of effect Clinical impact C Moderate clinical impact – all outcome measures showed at a clinically important point difference on at least one time point clearly demonstrating that face-to-face CBT was superior to providing a booklet with CBT principles in it to patients with PTSD following a motor vehicle accident.
Generalisability C Only one trauma type, but highly generalisable to Australians involved in motor vehicle accidents. Likely to be generalisable to other trauma types.
Applicability B Study performed in the United Kingdom with a healthcare system similar to Australia.
Summary of the evidence Limited evidence (one study) showed consistent benefits in CBT over providing a self help booklet outlining CBT principles to patients who have PTSD secondary to a motor vehicle accident. Clinically important point estimates were found on all outcome measures, although the full range of estimates included in the confidence intervals also include clinically unimportant differences on most outcome measures. (Grade C)
324 Pharmacological interventions
Box 123 Study selection criteria for research questions 15 and 16
Research Question 15. For people with PTSD, do pharmacological interventions improve outcomes compared with placebo? 16. For people with PTSD, does any pharmacological intervention confer any advantage over other pharmacological interventions? Selection criteria Inclusion criteria Population People with PTSD Intervention Pharmacological intervention (eg SSRIs, other second-generation antidepressants, tricyclic antidepressants, monoamine oxidase inhibitors, benzodiazepines, mood stabilisers, anti-convulsants, and some non- benzodiazepine hypnotics and anti-anxiety medications) Comparator 1. Placebo 2. Other pharmacological intervention Outcome Primary outcome: resolution of symptoms of PTSD Secondary outcomes: symptoms of depression, anxiety and substance misuse/ social and occupational function/ quality of life/ treatment refusal/ dropout over 12 months/ side-effects/ posttraumatic growth/ physical comorbidity. Additional outcomes for children: attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies are found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies Search Period 8/2005-10/2011 for adultsa , 1996-10/2011 for children and adolescentsc Language English a Updated search from 2007 Guidelines c New research questions SSRIs = selective serotonin reuptake inhibitors
Pharmacological interventions used to treat PTSD, and for which there was evidence identified in this systematic review, fall into 8 different categories: x Selective serotonin reuptake inhibitors (SSRIs) x Norepinephrine reuptake inhibitors (NRI) x Tricyclic antidepressants (TCAs) x Monoamine oxidase inhibitors (MOAIs) x Other antidepressants x Atypical antipsychotics x Anticonvulsants x Noradrenergic agents x Nonbenzodiazepine hypnotics x Other drugs
Studies identified addressing questions 15 and 16 are distributed throughout these categories. SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRI) PAROXETINE VERSUS PLACEBO The systematic review identified four studies on paroxetine that met the inclusion criteria. All four studies included a mixed trauma population. One of the studies was a continuation/relapse prevention study. Studies providing results in the format of mean post-
325 treatment scores (Fani et al 2011, 2009) were separated from studies which provided results in terms of change of baseline (Marshall et al 2001; Tucker et al 2001). Both Marshall et al (2001) and Tucker et al (2001) stated that their data were intention-to-treat, but required at least one post-baseline efficacy assessment. This is not considered true ITT, as it may result in systematically excluding patients who have adverse events in the initial weeks of treatment, and refuse further participation in the trial.
Table 115 Study profiles for RCTs comparing paroxetine and placebo for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Fani et al 2011) Moderate Unspecified trauma (childhood sexual Outpatient , 13 Severity PTSD symptoms abuse, adult sexual assault, adult United States (CAPS) physical assault, motor vehicle accident, combat exposure)
(Fani et al 2009) Moderate Unspecified trauma Outpatient, 18 Severity PTSD symptoms United States (CAPS)
(Tucker et al 2001) Moderate Unspecified trauma (physical or Outpatient 323 Severity of PTSD symptoms sexual assault, seeing someone hurt setting, United Depressive symptoms or die, serious accident or injury, States Quality of life combat) Attrition
(Marshall et al 2001) High Unspecified trauma (physical or Outpatient 551 Severity of PTSD symptoms sexual assault, witnessing setting, Depressive symptoms injury or death, serious accident or multicentre, Quality of life injury and combat) United States Attrition
Two small studies by Fani et al (2011 and 2009) assessed the effectiveness of paroxetine on the treatment of PTSD. Fani et al (2011) randomized 7 participants to intervention and 6 to placebo. Fani et al (2009) included a slightly larger sample with 8 participants in the intervention and 10 in the placebo group. The intervention groups in both studies received paroxetine, which started at 12.5 mg per day increasing to a maximum of 62.5 mg per day over a 12 week period. At the end of this period participants were measured with the Clinical Administered PTSD Scale (CAPS) to determine the mean end score in each group and found a trend towards lower PTSD severity in the placebo groups.
326
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between paroxetine and placebo on reducing the severity of clinician-rated PTSD symptoms (k = 2; n = 29; SMD = 0.29; 95% CI, -0.42, 1.00)
Marshall et al (2001) investigated the effectiveness of paroxetine for the treatment of PTSD in a three arm trial; placebo (n=186), 20 mg per day paroxetine (n=183) and 40 mg per day paroxetine (n=182). The effect of the treatment was expressed in the mean change in score on the CAPS, Treatment Outcome PTSD Scale, self-rated Davidson Trauma Scale (DTS), Montgomery-Åsberg Depression Rating Scale and Sheenan Disability Scale. Data for the 20 mg group and the 40 mg group could not be combined for the purposes of meta-analysis, so for the purpose of the comparison against placebo, outcomes on the 40 mg per day group are taken into account as it is more similar to doses administered in the other three studies than the 20 mg group. All patients started at 20 mg per day, which was increased to 30 mg and 40mg per day in week 2 and 3, respectively, for those randomized to the 40 mg group.
Participants (n=307) in the study by Tucker et al (2001) were randomized to either 20 to 50 mg paroxetine or placebo and assessed on the change in PTSD symptoms, depression and quality of life over a 12 week period. The mean dosage of paroxetine during the study was 27.6 mg per day (SD 6.72). The majority of the participants had been exposed to physical or sexual assault (51% in placebo and 48% in intervention)..
There is evidence suggesting that there is unlikely to be a clinically important difference between paroxetine and placebo on reducing the severity of clinician-rated PTSD symptoms (k = 2; n = 858; SMD = -0.45; 95% CI, -0.59, -0.31)
327 There is evidence suggesting that there is unlikely to be a clinically important difference between paroxetine and placebo on reducing the severity of self-rated PTSD symptoms (k = 2; n = 858; SMD = -0.41; 95% CI, -0.55, -0.27)
328 There is evidence suggesting that there is unlikely to be a clinically important difference between paroxetine and placebo on reducing depression (k = 2; n = 858; SMD = -0.47; 95% CI, -0.51, -0.33)
There is evidence suggesting that there is unlikely to be a clinically important difference between paroxetine and placebo on increasing the quality of life (k = 2; n = 858; SMD = - 0.29; 95% CI, -0.43, -0.16)
Box 124 Evidence statement matrix for RCT comparing paroxetine and placebo for adults with PTSD Component Rating Description Evidence base C Three level II studies with moderate risk of bias and one level II study with a high risk of bias
Consistency A All studies are consistent
Clinical impact D None of the results indicated a clinically important difference
Generalisability B The populations in the four studies all had mixed trauma. The majority of the sample was of Caucasian ethnic background, except for Fani 2009 study which included more African Americans.
Applicability C The studies were performed in the USA, which has comparable health care to the Australian system, with some caveats.
Summary of evidence The evidence provided suggests there is no clinical benefit from paroxetine in comparison to placebo for the treatment of PTSD in a population with a mix of trauma experiences. (Grade C)
Paroxetine vs placebo ITT analysis
Two very small studies were considered to present ITT data as they had no loss to follow-up (Fani et al 2011; Fani et al 2009). The only relevant outcome measure presented in these studies was severity of PTSD symptoms (clinician-rated), which found a non-clinically important trend towards favouring placebo over paroxetine.
329 Table 116 Study profiles for RCTs comparing paroxetine and placebo for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Fani et al 2011) Moderate Unspecified trauma (childhood sexual Outpatient , 13 Severity PTSD symptoms abuse, adult sexual assault, adult United States (CAPS) physical assault, motor vehicle accident, combat exposure)
(Fani et al 2009) Moderate Unspecified trauma Outpatient, 18 Severity PTSD symptoms United States (CAPS)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between paroxetine and placebo on reducing the severity of clinician-rated PTSD symptoms (k = 2; n = 29; SMD = 0.29; 95% CI, -0.42, 1.00)
PAROXETINE 20MG VERSUS PAROXETINE 40MG Marshall and colleagues (2001) compared the effectiveness of paroxetine dosed at 20mg/day or 40mg/day with a placebo arm over 12 weeks. The double-blind RCT of 563 PTSD patients initiated both active treatments at a dose of 20mg/day, and patients allocated to 40mg/day treatment were titrated up to 30mg/day during week 2, and finally 40mg/day from the beginning of week 3. Patients were recruited from 59 outpatient centres in the United States.
Effect sizes were calculated for primary and secondary outcomes as determined for the purpose of this review, and the evidence suggests that there is unlikely to be a clinically important difference between the two doses of paroxetine for either of these outcomes.
In terms of safety considerations, Marshall and co-workers reported that the most common adverse events associated with paroxetine (incidence ≥10% and twice that of placebo) were asthenia, diarrhoea, abnormal ejaculation, impotence, nausea and somnolence. The majority of ‘treatment-emergent’ adverse events were rated as mild or moderate in severity and serious adverse events occurred in nine patients who received paroxetine. There were 21 patients
330 randomised to 20mg/day paroxetine who withdrew and 28 patients withdrew from the 40mg/day treatment arm.
Table 117 Study profile for RCT comparing 20mg and 40mg fluoxetine for treatment of PTSD patients Reference Risk of bias Population Setting N Outcomes measured (Marshall et al 2001) High PTSD patients diagnosed according 59 outpatient 376 Severity of PTSD symptoms to DSM-IV criteria centres, United Depression symptoms States Quality of life Attrition
There is evidence suggesting there is unlikely to be a clinically important difference between paroxetine 20mg and paroxetine 40mg on reducing the severity of clinician-rated PTSD symptoms at post-treatment (k = 1; n= 365; SMD = -0.06; 95% CI, -0.27 to 0.14).
There is evidence suggesting there is unlikely to be a clinically important difference between paroxetine 20mg and paroxetine 40mg on reducing the severity of PTSD symptoms reducing the severity of self-reported PTSD symptoms at post-treatment (k = 1; n = 365; SMD = - 0.08; 95% CI, -0.29 to 0.12).
There is evidence suggesting there is unlikely to be a clinically important difference between paroxetine 20mg and paroxetine 40mg on reducing depression symptoms at post-treatment (k = 1; n = 365; SMD = -0.08; 95% CI, -0.29 to 0.12).
There is evidence suggesting there is unlikely to be a clinically important difference between paroxetine 20mg and paroxetine 40mg on increasing quality of life at post-treatment (k = 1; n = 365; SMD = -0.08; 95% CI, -0.28 to 0.13).
There is evidence suggesting there is unlikely to be a clinically important difference between paroxetine 20mg and paroxetine 40mg on attrition post-treatment (k = 1; n = 375; RR = 0.89; 95% CI, 0.68 to 1.15).
Box 125 Evidence statement matrix for RCT comparing 20mg and 40mg fluoxetine for treatment of PTSD patients Component Rating Description Evidence base D One level II study with high risk of bias
Consistency NA One study only
Clinical impact D Slight/restricted
Generalisability B Evidence directly generalisable to the target population with some caveats
Applicability C Evidence applicable to the Australian healthcare context with some caveats.
Summary of evidence Treatment of PTSD patients with 20mg or 40mg paroxetine results in outcomes with no statistical or clinically important differences (Grade D).
SERTRALINE VERSUS PLACEBO
331
Eight studies were identified that examined the effectiveness of sertraline for the treatment of PTSD (Friedman et al 2007, Brady et al 2000A, Brady et al 2005, Davidson et al 2001, Davidson et al 2004, Davidson et al 2006, Tucker et al 2004 and Zohar et al 2002). The majority of the study included a mixed trauma population, except for Zohar et al (2002) and Friedman et al (2007).
Three studies (Friedman et al 2007, Brady et al 2005 and Davidson et al 2004) could not be combined in the meta analysis due to the format of data provided. These studies are summarised narratively.
The good quality study by Friedman et al (2007) assessed the effectiveness of sertraline (mean dose 135 mg/day) for the treatment of PTSD in mainly (more than 80%) participants exposed to combat. Besides the diagnosis of PTSD, the population also showed a high percentage of major depression. The results were presented as mean change with a standard error. No statistically significant difference was found for sertraline in comparison to placebo for CAPS (F = 1.28, p = 0.26) for intention to treat analyses. Similarly no statistically significant difference was found on the Impact Event Scale and CGI-I (F = 1.20, p = 0.28 and F = 0.69, p = 0.41, respectively). The authors also stated that there were no significant differences found between sertraline and placebo on the outcomes of depressive symptoms (on the HAM-D) or anxiety (on the HAM-A), but did not provide any data for these outcomes.
Brady et al (2005), in their good quality trial, found no statistically significant difference between sertraline and placebo in reducing clinician rated PTSD severity on the CAPS (F(2,68)=2.68, p=0.08) for intention to treat analyses. Mean scores of the treatment groups were not provided, nor were mean change scores, so it is unclear whether the difference was clinically important in this study. However, these results are in line with the results of Friedman et al (2007), indicating no clinically important difference between sertraline and placebo for a reduction in PTSD symptoms.
Davidson et al (2004) used data obtained from two previous clinical trials of sertraline versus placebo (Davidson et al 2001 and Brady et al 2000), and reported a statistically significant difference in the rate of remission of PTSD symptoms between the sertraline group and placebo group as rated by clinicians on the CAPS (chi squared = 5.32, 1 df, p = 0.021), or self-rated on the DTS (chi squared = 5.79, 1 df, p = 0.016). Remission was determined by more than 20 points difference on the CAPS, and more than 18 points difference on the DTS, between baseline and follow up. However, with the data provided it is not possible to determine the clinical importance of the difference between sertraline and placebo on remission.
Table 118 Study profiles for RCTs comparing sertraline and placebo for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Friedman et al Low Unspecified trauma (serious Out patients 166 Severity of PTSD symptoms 2007) accident, physical or sexual assault, psychiatric Depressive symptoms combat, seeing someone hurt or die) clinic at medical Anxiety centres in USA
332 (Brady et al 2005) Low Civilian trauma (sexual assault, Outpatient 94 Severity of PTSD symptoms physical assault, serious accident) setting, United Depressive symptoms States
(Davidson 2004) Moderate Unspecified trauma type (serious Outpatient 395 PTSD diagnosis unintentional injury or fire, physical or setting, multi- Combines study 1 sexual assault, seeing someone hurt centre, United and study 2 or die, being in war or combat, or States miscellaneous event such as kidnapping)
(Davidson et al Moderate Unspecified trauma type (nonsexual Outpatient 352 PTSD diagnosis 2006b) abuse, adult sexual abuse, childhood setting, United Severity of PTSD sexual abuse, unexpected death, States Attrition Different study to 1 accidental injury, and combat) or 2
(Davidson et al Moderate Unspecified trauma type (physical or Outpatient 202 Severity of PTSD Symptoms 2001) sexual assault, seeing someone hurt setting, multi- Depressive symptoms or die, serious accident/fire/injury, centre, United Anxiety Study 2 being in war or combat or other States Quality of life trauma) Attrition (Zohar et al 2002) Moderate Military veterans (combat-related Outpatient 42 Severity of PTSD symptoms violence, motor vehicle accident, setting, Israel captivity) (Brady et al 2000) High Unspecified trauma type (serious Outpatient 187 Severity of PTSD symptoms unintentional injury or fire, physical or setting, multi- Depressive symptoms Study 1 sexual assault, seeing someone hurt centre, United Quality of life or die, being in war or combat, or States Attrition miscellaneous event such as kidnapping) (Tucker et al 2004) High Unspecified trauma type (childhood Outpatient, 50 Severity of PTSD symptoms physical or sexual abuse, witnessing United States violent death, tornado, combat, motor vehicle accident, bomb, life threatening event)
The results of the five remaining studies were able to be meta-analysed.
333 The funnel plot (Appendix H) shows that there may possibly be publication bias for this outcome, favouring a significant result in either direction, given the high proportion of data points that fall outside of the pseudo 95% confidence limits.
There is limited evidence favouring sertraline over placebo on reducing the severity of clinician-rated PTSD symptoms (k = 5; n =794; SMD = -0.94; 95% CI, -2.07 to 0.19).
There is evidence suggesting that there is unlikely to be a clinically important difference between sertraline and placebo on reducing self-reported PTSD symptoms severity as measured by Impact of Event Scale (k = 2; n = 383; SMD = -0.30; 95% CI, -0.50, -0.10)
There is evidence suggesting that there is unlikely to be a clinically important difference between sertraline and placebo on the reduction of self-reported PTSD symptoms as measured with the Davidson Trauma Scale (k = 3; n = 737; SMD = -0.29; 95%CI, -0.44, - 0.15)
334
There is evidence suggesting that there is unlikely to be a clinically important difference between sertraline and placebo on reducing depression as measured by Hamilton Rating Scale for Depression (k = 2; n = 385; SMD = -0.21; 95% CI, -0.41, -0.01).
There is evidence suggesting that there is unlikely to be a clinically important difference between sertraline and placebo on reducing depression as measured by Montgomery-Åsberg Depression Rating Scale. (k = 2; n = 384; SMD = -0.19; 95% CI, -0.39, 0.01)
335
There is evidence suggesting that there is unlikely to be a clinically important difference between sertraline and placebo for improving quality of life as measured by Quality of Life Enjoyment and Life Satisfaction short form. (k = 3; n =385; SMD = -0.23; 95% CI, -0.37, - 0.08)
There is evidence suggesting that there is unlikely to be a clinically important difference between sertraline and placebo for improving quality of life as measured by Sheenan Disability Scale. (k = 1; n =352; SMD = 0.19; 95% CI, -0.01, 0.40)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between sertraline and placebo for study attirition (k=3, n=437; RR 1.09 95% CI 0.73, 1.63)
Two studies reported on adverse events as a result of treatment with sertraline or placebo. Friedman et al (2007) noted a larger proportion of patients in the sertraline group suffering from nausea, diarrhoea and fatigue than in the placebo group. Similarly, Davidson reported
336 double the proportion of diarrhoea sufferers in the sertraline group than placebo and almost twice for nausea and fatigue.
Table 119 Side effects of sertraline and placebo in people with PTSD Reference Treatment emergent Sertraline (n=84) Placebo (n=82 side effects (Friedman et al 2007) Headache 22 patients (26.7%) 20 patients (24.1%) Nausea 18 patients (20.9%) 8 patients (9.6%) Diarrhoea 26 patients (31.4%) 15 patients (18.1%) Somnolence 12 patients (14%) 7 patients (8.4%) Fatigue 9 patients (10.5%) 1 patients (1.2%) Insomnia 12 patients (14%) 8 patients (9.6%) (Davidson et al 2006b) Headache 55 patients (32%) 52 patients (29%) Nausea 40 patients (23%) 25 patients (14%) Diarrhoea 19 patients (26%) 23 patients (13%) Dizziness 17 patients (10%) 14 patients (8%) Dry mouth 26 patients (15%) 27patients (15%) Constipation 12 patients (7%) 18 patients (10%) Fatigue 24 patients (14%) 16 patients (9%) Insomnia 17 patients (10%) 23 patients (13%) Somnolence 17 patients (10%) 23 patients (13%) NB: side effects which occurred at twice or more the rate of the other treatment are bolded
Box 126 Evidence statement matrix for RCT comparing sertraline and placebo for adults with PTSD Component Rating Description Evidence base B Two level II studies with low risk of bias, four level II studies with moderate risk of bias and two level II studies with high risk of bias Consistency B The majority of the studies were consistent for all outcomes. However for attrition and PTSD symptoms severity, two studies showed inconsistent results which could be explained. Clinical impact D No clinically important differences had been found.
Generalisability B The populations included are mixed trauma PTSD patients, which is generalisable to the target population.
Applicability C All studies, except Zohar et al (2002) were conducted in the USA, which has a similar health care context to Australia
Summary of evidence There is relatively strong evidence suggesting there is no clinically important benefit of sertraline over placebo for the treatment of PTSD. (Grade B) Sertraline vs placebo ITT analyses
Brady et al (2005) was the only study which provided data on all patients randomised (as they had no loss to follow-up). Every other study comparing sertraline and placebo required at least one post-baseline assessment to be included (modified ITT). Brady et al (2005) reported a non-statistically significant trend favouring sertraline over placebo for reducing PTSD symptom severity (clinician-rated). Summary data were not provided, so it is unknown whether this difference was clinically important. There were no between-group differences on either patient-rated PTSD severity or depressive symptoms.
Table 120 Study profiles for RCTs comparing sertraline and placebo for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured
337 (Brady et al 2005) Low Civilian trauma (sexual assault, Outpatient 94 Severity of PTSD symptoms physical assault, serious accident) setting, United Depressive symptoms States
SERTRALINE VERSUS PLACEBO IN COMBAT VETERANS The study by Zohar et al (2002) included Israeli military veterans who had experienced combat-related violence, a motor vehicle accident or captivity and reported on the effectiveness of sertraline compared to plecabo for PTSD symptom reduction, decrease in depression and attrition. Table 121 Study profiles for RCTs comparing sertraline and placebo for military veterans with PTSD Reference Risk of bias Population Setting N Outcomes measured (Zohar et al 2002) Moderate Military veterans (combat-related Outpatient 42 Severity of PTSD symptoms violence, motor vehicle accident, setting, Israel captivity)
There is evidence favouring sertraline over placebo on reducing the severity of clinician- rated PTSD symptoms in combat veterans (k = 1; n = 32; SMD = -1.78; 95% CI, -2.51, - 0.94)
There is limited evidence favouring sertraline over placebo on reducing depression in combat veterans (k = 1; n = 32; SMD = -0.97; 95% CI, -1.71, -0.23)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between sertraline and placebo on attrition ( k = 1; n = 32; RR = 1.24; 95% CI, 0.41, 3.76)
Box 127 Evidence statement matrix for RCT comparing sertraline and placebo for adults with PTSD Component Rating Description Evidence base C One level II study with moderate risk of bias
Consistency N/A Only one study
Clinical impact C Evidence was found that sertraline does make a clinically important difference in the treatment of PTSD symptom severity compared to placebo. Limited evidence was found for clinically important differences in depression reduction and attrition. Generalisability B The population included were veterans with combat related PTSD, which is generalisable to the target population.
Applicability C The study was conducted in Israel, which is applicable to the Australian system with some caveats.
Summary of evidence One small study indicated that treatment with sertraline in veterans with combat related PTSD reduces PTSD symptoms. However, no such results were found for depression or attrition. (Grade C)
SERTRALINE VERSUS PLACEBO IN CHILDREN/ADOLESCENTS A study by Robb et al (2010) examined the effectiveness of sertraline in the treatment of PTSD in children and adolescents. In addition to the psychoeducational/ cognitive behavioral therapy, patients received either placebo or sertraline. The results were presented in the
338 format of Least-Square means (SE) from which no effect size could be calculated for this review. However, none of the results indicated a statistically significant difference in outcome effect between sertraline and placebo. Furthermore, no significant increased risk was found for possible adverse events between the two treatment groups.
Based on the absence of effect size data, no statement has been made for the evidence.
Table 122 Study profile for RCT comparing sertraline and placebo for treatment of PTSD patients Reference Risk of bias Population Setting N Outcomes measured (Robb et al 2010) High Children and adolescents with mixed Outpatient 129 Change in PTSD symptoms trauma (sexual abuse, traumatic centres, United depression news, victum physical States quality of life abuse/violence, accident, witness violence, fire or natural disaster)
FLUOXETINE VERSUS PLACEBO Six studies were identified that examined the effectiveness of fluoxetine for the treatment of PTSD (Table 123). Four of these studies included a population with combat related PTSD. Two studies reported on a relapse prevention stage following an initial acute treatment stage (Davidson et al 2005 and Martenyi et al 2002). Martenyi et al (2002) included a subpopulation of Martenyi et al (2002A), that responded to the first 12 week acute treatment with fluoxetine and placebo, defined as a 50% reduction in Treatment Outcome PTSD score. Data from Martenyi et al (2006) could not be included in any meta-analyses due to the format their data was presented in (least square means with standard error).
Table 123 Study profiles for RCTs comparing fluoxetine and placebo for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Martenyi & Low Male and female with combat related Outpatient 144 Severity of PTSD symptoms Soldatenkova 2006) PTSD setting, Bosnia Depression Herzegovina, Anxiety Croatia and Relapse Yugoslavia
(Hertzberg et al Low Male combat veterans with severe, Outpatient 12 Severity of PTSD symptoms 2000) chronic PTSD setting, United Quality of life States Attrition (Connor et al 1999) Moderate Unspecified trauma type (rape; other Outpatient 50 Severity of PTSD symptoms sexual trauma; physical abuse; setting, United Quality of life traumatic bereavement; violent crime; States Attrition accident; other) (predominantly female civilian traumas)
(Davidson et al Moderate Unspecified trauma type Outpatient 62 Attrition 2005a) setting, United Side effects States
(Martenyi et al Moderate Adults who experienced combat Outpatient 301 Severity of PTSD symptoms 2002b) trauma and/or victims of war or setting, Europe, Depressive symptoms witness of war event (mostly male, Israel and South Anxiety Acute phase young and recent trauma) Africa
339 (Martenyi et al Moderate Adults who experienced combat Outpatient 98 Relapse prevention (severity of 2002a) trauma and/or victims of war or setting, Europe, PTSD symptoms) witness of war event, and responded Israel and South Attrition Subgroup of to acute phase of treatment Africa responders from (Martenyi et al 2002b)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between fluoxetine and placebo on reducing the severity of clinician-rated PTSD symptoms (k = 1; n = 301; SMD = -0.28; 95% CI, -0.54, -0.02)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between fluoxetine and placebo reducing the severity of self- reported PTSD symptoms (k=2, n=62, SMD=-0.74; 95%CI -1.26, -0.22)
340 The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between fluoxetine and placebo in improving quality of life (k=2, n=62, SMD=-0.62; 95%CI -1.12, -0.10)
There is limited evidence favouring fluoxetine over placebo for study attrition (k=4, n=254, RR=0.55; 95%CI 0.37, 0.80)
Box 128 Evidence statement matrix for RCT comparing fluoxetine and placebo for adults with PTSD Component Rating Description Evidence base B Two level II studies with low risk of bias and four level II studies with moderate risk of bias
Consistency B One of the three studies reported contradicting results, however the effect on the result in the meta- analysis is minimal and can be explain by the small sample size in the particular study. Clinical impact D The result from the meta analysis indicates a slight to limited clinical impact as the confidence interval incorporated none clinically important effect sizes.
Generalisability B Four studies included veterans with combat related PTSD and two with mixed trauma. The majority of the populations was male and of Caucasian ethnic background. Therefore, the population was generalisable to the target population with some caveats.
Applicability B The studies were performed in the USA and Europe, which have comparable health care to the Australian system.
Summary of evidence There is inconclusive or limited evidence favouring fluoxetine over placebo for the treatment of PTSD. (Grade B)
Fluoxetine vs placebo ITT analysis
Four studies provided intention-to-treat data comparing fluoxetine and placebo. No meta- analyses were able to be performed as Martenyi et al (2002a, 2002b, 2006) provided the majority of data in the form of least square means and standard errors, Martenyi et al (2002a, 2002b) provided CAPS data in the form of mean change scores for both the acute and treatment maintenance phases, whereas Herzberg et al (2000) provided data in the form of mean post-treatment scores. All evidence statements are therefore from single studies. No
341 differences between fluoxetine and placebo for either acute treatment or maintenance therapy were considered clinically important.
Table 124 Study profiles for RCTs comparing fluoxetine and placebo for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Martenyi & Low Male and female with combat related Outpatient 144 Severity of PTSD symptoms Soldatenkova 2006) PTSD setting, Bosnia Depression Herzegovina, Anxiety Croatia and Relapse Yugoslavia
(Hertzberg et al Low Male combat veterans with severe, Outpatient 12 Severity of PTSD symptoms 2000) chronic PTSD setting, United Quality of life States Attrition (Martenyi et al Moderate Adults who experienced combat Outpatient 301 Severity of PTSD symptoms 2002b) trauma and/or victims of war or setting, Europe, Depressive symptoms witness of war event (mostly male, Israel and South Anxiety Acute phase young and recent trauma) Africa
(Martenyi et al Moderate Adults who experienced combat Outpatient 98 Relapse prevention (severity of 2002a) trauma and/or victims of war or setting, Europe, PTSD symptoms) witness of war event, and responded Israel and South Attrition Subgroup of to acute phase of treatment Africa responders from (Martenyi et al 2002b)
There is evidence suggesting that there is unlikely to be a clinically important difference between fluoxetine and placebo on reducing the severity of clinician-rated PTSD symptom severity post-treatment (k=1, n=301, SMD=-0.28, -0.54, -0.02)
There is evidence suggesting that there is unlikely to be a clinically important difference between fluoxetine and placebo on reducing the severity of clinician-rated PTSD symptom severity post-maintenance therapy (k=1, n=98, SMD=-0.28, -0.69, 0.12)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between fluoxetine and placebo on the severity of self-rated PTSD symptom severity post-treatment (k=1, n=205, SMD=0.04, 95%CI -1.09, 1.17).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between fluoxetine and placebo on attrition post-acute treatment (k=1, n=12, RR=3.00, 95%CI 0.15, 61.74).
There is limited evidence favouring fluoxetine over placebo on attrition post-maintenance therapy (k=1, n=131, RR=0.57, 95%CI 0.31, 1.03).
FLUOXETINE VERSUS PLACEBO IN COMBAT VETERANS
Four studies were identified that included participants with combat related PTSD (Hertzberg et al 2000, Martenyi et al 2002A, Martenyi et al 2002B and Martenyi et al 2006). As described earlier, the study by Martenyi et al (2006) was not included in the meta-analyses due to the least square mean data provided.
342
Hertzberg et al (2000) included twelve predominantly African American male veterans in their trial. Six participants received fluoxetine of a mean dose of 48 mg/day (range of 10 mg to 60 mg) fluoxetine at the of the 12 week treatment period.
Table 125 Study profiles for RCTs comparing fluoxetine and placebo for combat veterans with PTSD Reference Risk of bias Population Setting N Outcomes measured (Martenyi & Low Male and female with combat related Outpatient 144 Severity of PTSD symptoms Soldatenkova 2006) PTSD setting, Bosnia Depression Herzegovina, Anxiety Croatia and Relapse Yugoslavia
(Hertzberg et al Low Male combat veterans with severe, Outpatient 12 Severity of PTSD symptoms 2000) chronic PTSD setting, United Quality of life States Attrition (Martenyi et al Moderate Adults who experienced combat Outpatient 301 Severity of PTSD symptoms 2002b) trauma and/or victims of war or setting, Europe, Depressive symptoms witness of war event (mostly male, Israel and South Anxiety Acute phase young and recent trauma) Africa
(Martenyi et al Moderate Adults who experienced combat Outpatient 98 Relapse prevention (severity of 2002a) trauma and/or victims of war or setting, Europe, PTSD symptoms) witness of war event, and responded Israel and South Attrition Subgroup of to acute phase of treatment Africa responders from (Martenyi et al 2002b)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between fluoxetine and placebo for reducing the severity of self-rated PTSD symptoms over 12 weeks (k = 1; n = 12; SMD = -0.04; 95% CI, -1.09, 1.17)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between fluoxetine and placebo for an improvement in quality of life over 12 weeks (k = 1; n = 12; SMD = -0.17; 95% CI, -1.30, 0.97)
343
There is limited evidence favouring fluoxetine over placebo for attrition. (k = 2; n = 143; RR = 0.57; 95% CI, 0.31, 1.03)
Box 129 Evidence statement matrix for RCT comparing fluoxetine and placebo for people with combat related PTSD Component Rating Description Evidence base B Two level II studies with low risk of bias and four level II studies with moderate risk of bias
Consistency B One of the three studies reported contradicting results, however the effect on the result in the mate analysis is minimal and can be explain by the small sample size in the particular study. Clinical impact D The result from the meta analysis indicates a slight to limited clinical impact as the confidence interval incorporated none clinically important effect sizes.
Generalisability B Four studies included veterans with combat related PTSD. The majority of the populations were male and of Caucasian ethnicity .
Applicability B The studies were performed in the USA and Europe, which have comparable health care systems to the Australian system.
Summary of evidence No evidence was found for a clinically important difference between treatment with fluoxetine and placebo for a reduction in PTSD symptoms or improvement in quality of life in combat veterans. However, some evidence suggests there might be benefit of fluoxetine over placebo at minimising attrition. (Grade B) FLUOXETINE 20MG VERSUS FLUOXETINE 40MG The effectiveness of fluoxetine dosed at 20mg/day or 40mg/day over twelve weeks, plus a placebo, was tested in an RCT of 411 PTSD patients (Martenyi et al 2007). Specifically, all patients were initiated at a dose of 20mg/day, and those randomised to the 40mg/day were titrated up to the higher dose after two weeks. Patients were recruited from 43 investigational sites across the United States.
Martenyi and colleagues provided mean change scores as their measure of PTSD, depression and anxiety outcomes, with no statistically significant differences. Respective measurement tools were the Clinician Administered PTSD scale (CAPS), Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM-A). Our effect size
344 estimates provided evidence that there is unlikely to be any clinically meaningful differences on any outcomes between the different dosing regimens.
Side effect profiles are summarised below in (Table 126).
Table 126 Side effect profiles for patients treated with 20mg and 40mg fluoxetine Reference Adverse event, 20mg fluoxetine , % patients 40mg fluoxetine, % patients (Martenyi et al Any 67.5 77.5 2007) Headache 16.0 18.8 Nausea 12.9 13.8 Somnolence 9.2 11.9 Rhinitis 7.4 11.3 Serious adverse events, n patients Thoughts of self-mutilation 1 0 Anxiety 0 2 Chest pain 0 1 Suicidal ideation 0 1 Gastritis 0 1 Self-harm related events 2 4 aBold text denotes a side effect for which the number/% of patients with that side effect or number of events (also in bold) is at least two times greater than the number for the comparison drug.
Table 127 Study profile for RCT comparing 20mg and 40mg fluoxetine for treatment of PTSD patients Reference Risk of bias Population Setting N Outcomes measured (Martenyi et al 2007) High PTSD patients diagnosed according 43 323 Change in PTSD, depression to DSM-IV criteria investigational and anxiety symptoms sites across the United States
There is evidence suggesting that there is unlikely to be a clinically important difference between 20mg fluoxetine and 40mg fluoxetine on reducing the severity of clinician-rated PTSD symptoms at post-treatment (k = 1; n = 323; SMD = 0.00; 95% CI, -0.24, 0.22).
There is evidence suggesting that there is unlikely to be a clinically important difference between 20mg fluoxetine and 40mg fluoxetine on reducing severity of depression symptoms at post-treatment (k = 1; n = 323; SMD = -0.01; 95% CI, -0.24, 0.22).
There is evidence suggesting that there is unlikely to be a clinically important difference between 20mg fluoxetine and 40mg fluoxetine on reducing severity of anxiety symptoms at post-treatment (k = 1; n = 323; SMD = 0.06; 95% CI, -0.17, 0.30).
Box 130 Evidence statement matrix for RCT comparing 20mg and 40mg fluoxetine for treatment of PTSD patients Component Rating Description Evidence base D One level II study with high risk of bias
Consistency NA One study only
Clinical impact D Slight/restricted
Generalisability B Evidence directly generalisable to the target population with some caveats
Applicability C Evidence applicable to the Australian healthcare context with some caveats
345 Summary of evidence Treatment of PTSD patients with 20mg or 40mg fluoxetine results in similar outcomes, with evidence that it is unlikely that a clinically important difference exists between these treatments (Grade D). FLUOXETINE VERSUS MOCLOBEMIDE
Onder et al 2006 compared the effectiveness of fluoxetine and moclobemide (a reversible monoamine oxidase inhibitor), plus tianeptine (a serotonin reuptake enhancer), over twelve weeks in a three-arm, open-label RCT of 103 patients. Patients from outpatient clinics providing psychiatric and psychological services were eligible for inclusion if diagnosed with PTSD according to DSM-IV criteria following the 1999 Marmara earthquake in Turkey. For patients randomised to receive fluoxetine (n=38), the treatment regime involved a daily oral dose initiated at 20mg and increased to 40mg/day if no response had occurred by week eight of the study. Patients allocated to moclobemide (n=35) were initiated at a dose of 450mg/day, which was increased to 900mg/day if no response had occurred by week eight.
Based on mean end-point scores on the Clinician Administered PTSD Scale, the authors concluded that fluoxetine and moclobemide show similar efficacy in the treatment of PTSD. The effect size estimate calculated for these end-point data revealed a clinically significant difference favouring fluoxetine over moclobemide, however, over the range of possible values (95% CI), both clinically and non-clinically significant values were included (limited evidence favouring fluoxetine over moclobemide) (Onder et al 2006).
Side effect profiles (number of patients who dropped out due to side effects) are summarised below in (Table 128).
Table 128 Side effect profiles for patients who dropped out of fluoxetine and moclobemide Reference Side effect Fluoxetine (n of drop-outs) Moclobemide (n of drop-outs) (Onder et al 2006) Insomnia 1 1 Nausea 2 0 aBold text denotes a side effect for which the number of patients with that side effect (also in bold) is at least two times greater than the number for the comparison drug.
Table 129 Study profile for RCT comparing fluoxetine and moclobemide for post-earthquake PTSD patients Reference Risk of bias Population Setting N Outcomes measured (Onder et al 2006) High PTSD patients diagnosed according University 73 Change in PTSD symptoms to DSM-IV criteria following exposure outpatient to earthquake psychiatric unit and psychological trauma centre, Turkey
There is limited evidence favouring fluoxetine over moclobemide for reducing the severity of clinician-rated PTSD symptoms (k=1, n=73, SMD=-0.78, 95%CI -1.26, -0.31).
Box 131 Evidence statement matrix for RCT comparing fluoxetine and moclobemide for post-earthquake PTSD patients Component Rating Description Evidence base D One level I study with high risk of bias
346 Consistency NA One study only
Clinical impact D Slight/restricted
Generalisability C Evidence not directly generalisable to the target population but could be sensibly applied
Applicability D Evidence not applicable to the Australian healthcare context
Summary of evidence The available evidence for the effectiveness of fluoxetine compared to moclobemide among patients with PTSD following a natural disaster (earthquake) was of low quality with high risk of bias. In terms of the change in clinician-rated PTSD symptoms, there is limited evidence favouring fluoxetine over moclobemide (Grade D).
FLUOXETINE VERSUS TIANEPTINE
The RCT by Onder et al (2006) also compared the effectiveness of fluoxetine and tianeptine (an anxiolytic serotonin reuptake enhancer) over the twelve week study period. For patients randomised to receive fluoxetine (n=38), the treatment regime was also the same as described previously. Patients allocated to tianeptine (n=30) were initiated at a dose of 37.5mg/day, which was increased to 50mg/day if no response had occurred by week eight.
The mean end-point scores on the CAPS indicated that the effectiveness of fluoxetine and tianeptine were similar for the treatment of PTSD. The effect size point estimate based calculated from the study data revealed a clinically non-significant difference favouring tianeptine over fluoxetine, while the confidence contained both clinically and non-clinically significant values (inconclusive evidence for difference between the treatments) (Onder et al 2006).
Side effect profiles (number of patients who dropped out due to side effects) are summarised below in (Table 130).
Table 130 Side effect profiles for patients who dropped out, by treatment group Reference Side effect Fluoxetine (n of drop-outs) Taineptine (n of drop-outs) (Onder et al 2006) Insomnia 1 0 Over sedation 0 1 Nauseaa 2 0 aBold text denotes a side effect for which the number of patients with that side effect (also in bold) is at least two times greater than the number for the comparison drug
Table 131 Study profile for RCT comparing fluoxetine and tianeptine for post-earthquake PTSD patients Reference Risk of bias Population Setting N Outcomes measured (Onder et al 2006) High PTSD patients diagnosed according University 68 Change in PTSD symptoms to DSM-IV criteria following exposure outpatient to earthquake psychiatric unit and psychological trauma centre, Turkey
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between fluoxetine and tianeptine for reducing the severity of
347 clinician-rated PTSD symptoms (k=1, n=68, SMD=0.48, 95%CI 0.00, 0.97).
Box 132 Evidence statement matrix for RCT comparing fluoxetine and tianeptine for post-earthquake PTSD patients Component Rating Description Evidence base D One level I study with high risk of bias
Consistency NA One study only
Clinical impact D Slight/restricted
Generalisability C Evidence not directly generalisable to the target population but could be sensibly applied
Applicability C Probably applicable to Australian healthcare context with some caveats. (From Turkey)
Summary of evidence The available evidence for the effectiveness of fluoxetine compared to tianeptine for treating PTSD symptoms developed post-earthquake was of low quality with high risk of bias. In terms of change in CAPS rated symptoms, there is no conclusive evidence to suggest a difference between treatment with fluoxetine or tianeptine (Grade D).
CITALOPRAM VERSUS PLACEBO The study by Tucker et al (2004) assessed the effectiveness of citalopram and placebo on reducing the symptoms of PTSD and depression. During the trial, patients did not receive any psychotropic medications apart from occasional diphenhydramine for sleep within 2 weeks from baseline.
Table 132 Study profiles for RCTs comparing citalopram and placebo for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Tucker et al 2004) High Unspecified trauma type (childhood Outpatient, 35 Severity of PTSD symptoms physical or sexual abuse, witnessing United States violent death, tornado, combat, motor vehicle accident, bomb, life threatening event)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between citalopram and placebo for reducing the severity of PTSD symptoms (k = 1; n =35; SMD = -0.40; 95% CI, -1.27 to 0.47).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between citalopram and placebo for reducing depression (k = 1; n =35; SMD = -0.51; 95% CI, -1.39 to 0.37).
Box 133 Evidence statement matrix for RCT comparing citalopram and placebo for adults with PTSD Component Rating Description Evidence base D One level II study with high risk of bias
Consistency NA One study only
348 Clinical impact D The evidence indicated no/ limited clinical important difference between active and placebo treatment for both PTSD symptom severity and depression.
Generalisability B The sample included was a mixed trauma population with a slight overrepresentation of females.
Applicability C The study was conducted in the USA, which has a comparable health system to Australia.
Summary of evidence One small study with a high risk of bias found that there was a trend towards favouring citalopram over placebo for reducing symptoms of PTSD and depression, but these differences were not large enough to be considered clinically important. (Grade D)
NOREPINEPHRINE REUPTAKE INHIBITORS
REBOXETINE VERSUS FLUVOXAMINE Spivak et al 2006 conducted a trial in which 40 victims of motor vehicle accident (MVA) with PTSD were randomised to treatment with either reboxetine (n=20) or fluvoxamine (n=20). The trial operated over 8 weeks and patients received drugs as fixed doses of reboxetine and fluvoxamine at 8mg/day and 150mg/day, respectively.
Based on their mean end-point data, the study authors concluded that the efficacy of reboxetine and fluvoxamine were comparable. An effect size analysis of the study data showed no clinically meaningful differences across the range of outcomes including the CAPS, Clinician-Rated Treatment Outcome PTSD Scale (TOP-8) and the Hamilton Scale for Anxiety. The confidence intervals, however, could not completely exclude clinically important effects, and it is therefore impossible to determine whether an important clinical difference exists between the two treatments for any of these outcomes. A clinically meaningful effect size was observed for depression symptoms as rated on the Hamilton Depression scale, but the confidence interval could not exclude clinically unimportant effects, leading to the conclusion that there is limited evidence favouring fluvoxamine over reboxetine for the treatment of depressive symptoms in PTSD patient (Spivak et al 2006).
In terms of safety outcomes for the reboxetine group, it was reported that one patient experienced mild side effects including concentration difficulties, depression, increased sleep duration, emotional indifference, reduced salivation, palpitations, sweating, pruritis, weight loss, decreased libido and ejaculatory dysfunction. Moderate side effects included nausea/vomiting, constipation and erectile dysfunction in one patient, increased sweating in two patients, reduced sleep duration in four patients, tension in five patients and palpitations in five patients. Severe side effects included nausea and constipation in one patient, headache in one patient and tension and palpitations in three patients. Fluvoxamine patients experienced mild side effects including reduced salivation and sedation (one patient); moderate side effects including sedation, tension, orthostatis and weight gain (one patient), fatigue nausea and vomiting (one patient), headache (one patient), and erectile dysfunction (one patient); and severe side effects included fatigue, constipation, palpitations and increased sweating (one patient) and headache (one patient).
Table 133: Study profile for RCT comparing reboxetine and fluvoxamine for PTSD patients Reference Risk of bias Population Setting N Outcomes measured
349 (Spivak et al 2006) High PTSD patients diagnosed according Community 40 Change in PTSD symptoms to DSM-IV criteria mental health Change in depression symptoms outpatient clinic, Change in anxiety symptoms Israel
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between mirtazapine and paroxetine for reducing the severity of clinician-rated PTSD symptoms (CAPS) at post-treatment (k=1, n=40, SMD=0.17, 95%CI -0.59, 0.93).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between mirtazapine and paroxetine for reducing the severity of clinician-rated PTSD symptoms (TOP-8) at post-treatment (k=1, n=40, SMD=0.11, 95%CI -0.64, 0.88).
There is limited evidence favouring fluvoxamine over reboxetine for reducing depression symptoms at post-treatment (k=1, n=40, SMD=0.67, 95%CI -0.11, 1.45).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between reboxetine and fluvoxamine for reducing anxiety symptoms at post-treatment (k=1, n=40, SMD=0.43, 95%CI -0.33, 1.20).
Box 134: Evidence statement matrix for RCT comparing reboxetine and fluvoxamine for PTSD patients Component Rating Description Evidence base D One level I study with high risk of bias
Consistency NA One study only
Clinical impact D Slight/Restricted; one clinically important point estimate but all other findings inconclusive
Generalisability C Evidence not directly generalisable to the target population but could be sensibly applied
Applicability D Community setting in Israel; difficult to judge applicability to the Australian healthcare context
Summary of evidence Available evidence from one small, low quality trial does not allow determination of whether a clinically meaningful difference exists between reboxetine and fluvoxamine for reducing symptoms PTSD and anxiety, while there is limited evidence favouring fluvoxamine over reboxetine for reducing symptoms of depression (Grade D).
TRICYCLIC ANTIDEPRESSANTS Tricyclic antidepressants were historically used treating PTSD, even though they are not licensed for this indication. The current update of the systematic review identified no new evidence. AMITRIPTYLINE VERSUS PLACEBO IN COMBAT VETERANS
350 Davidson et al (1990) reported on the use of amitriptyline for the treatment of combat related PTSD.
Table 134 Study profiles for RCTs comparing amitriptyline and placebo for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Davidson et al High Trauma due to military conflict Inpatient or 36 Severity of PTSD symptoms 1990) outpatient Depressive symptoms setting, US Anxiety Attrition
There is limited evidence favouring amitriptyline over placebo on reducing the severity of self-reported PTSD symptoms (k = 1; n = 33; SMD = -0.90; 95% CI, -1.62 to -0.18).
There is limited evidence favouring amitriptyline over placebo on reducing depression symptoms (k = 1; n = 33; SMD = -1.16; 95% CI, -1.90 to –0.41).
There is limited evidence favouring amitriptyline over placebo on reducing anxiety symptoms (k = 1; n= 33; SMD = -0.99; 95% CI, -1.72 to -0.26).
There is limited evidence favouring placebo over amitriptyline on reducing the likelihood of leaving the study early for any reason (k = 1; n = 46; RR =1.34; 95% CI, 0.52 to 3.49).
Box 135 Evidence statement matrix for RCT comparing amitriptyline and placebo for people with combat related PTSD Component Rating Description Evidence base D One level II study with high risk of bias
Consistency NA only one study
Clinical impact D There is limited evidence for a clinically important difference.
Generalisability B The sample included veterans with combat related PTSD, which is generalisable to the target population.
Applicability C The study was conducted in the USA, which has a comparable health system to Australia, with some caveats.
Summary of evidence The evidence suggests that the use of amitriptyline for the reduction of PTSD symptoms, depression, anxiety or attrition was more effective than placebo. (Grade C) AMITRIPTYLINE VERSUS PAROXETINE
One open-label RCT (Celik et al 2011) investigated the effectiveness of amitryptiline compared to paroxetine within a combat-related PTSD population (n=42) over 12 weeks. Paroxetine was delivered at a dosage of 10mg/day during the first week of treatment and sequentially increased to 20mg/day during weeks two to three, 30mg/day during weeks four to five, 40mg/day during weeks six to seven and 60mg/day during weeks eight to twelve, if tolerated and clinically indicated. Amitryptiline was initially dosed at 25mg/day for the first three days, then increased in steps to 50mg/day on days four through seven, 75mg/day for the next two weeks, and then to 100mg/day after week 3 as necessary. After week five the
351 amitryptiline dose could be increased to a maximum of 200mg/day or lowered to 75mg/day, according to patient response. The study setting was an inpatient psychiatric clinic for the military, located in Turkey. Patients were eligible for study inclusion if they had been diagnosed with PTSD according to the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I).
The authors concluded that while no statistically significant differences were found between amitryptiline and paroxetine, treatment response with amitryptiline seemed to be higher. In terms of PTSD symptom reduction (measured by CAPS), comparison of the post-test continuous data provided point estimates of effect size that indicated slight superiority of amitryptiline over paroxetine. However, the confidence intervals associated with these effect size analyses included both clinically important and unimportant effects. For depression and anxiety outcomes (Beck Depression Inventory, Beck Anxiety Inventory) point estimates did not indicate a clinically meaningful effect size, while confidence intervals included both clinically important and unimportant values (Celik et al 2011).
In terms of safety outcomes, Celik and co-workers reported that three patients randomised to paroxetine and five patients in the amitryptiline treatment group were lost to follow-up due to side effects. The most common side effects were nausea, sexual aversion, drowsiness and yawning for paroxetine patients and dry mouth, constipation, nausea, drowsiness and sexual aversion for amitriptyline patients.
Table 135 Study profiles for RCTs comparing amitryptiline and paroxetine for soldiers with combat-related PTSD Reference Risk of bias Population Setting N Outcomes measured (Celik et al 2011)} High Soldiers with combat-related PTSD Psychiatry 42 Symptoms of PTSD, depression diagnosed according to DSM-IV inpatient clinic and anxiety criteria for the military, Turkey
There is limited evidence favouring amitryptiline over paroxetine for reducing the severity of clinician-rated PTSD symptoms (k=1, n=42, SMD=0.55, 95%CI -0.07, 1.16).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between amitryptiline and paroxetine for reducing depression symptoms (k=1, n=42, SMD=0.06, 95%CI -0.55, 0.66).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between amitryptiline and paroxetine for reducing anxiety symptoms (k=1, n=42, SMD=0.25, 95%CI -0.36, 0.85).
Box 136 Evidence statement matrix for RCT comparing amitryptiline and paroxetine for soldiers with combat- related PTSD Component Rating Description Evidence base D One level I study with high risk of bias
Consistency NA One study only
Clinical impact D Slight/restricted; limited evidence favouring amitryptiline over paroxetine for PTSD outcomes but not for others
352 Generalisability C Evidence not directly generalisable to the target population but could be sensibly applied
Applicability D Evidence not applicable to the current Australian healthcare context
Summary of evidence The evidence available to assess the effectiveness of amitryptiline compared to paroxetine among soldiers with combat-related PTSD diagnosed according to DSM-IV criteria was of low quality. In terms of clinician and investigator-rated PTSD symptoms, there is limited evidence favouring amitryptiline over paroxetine, while in terms of anxiety and depression symptoms it cannot be determined whether there is a clinically important difference between amitryptiline and paroxetine (Grade D).
IMIPRAMINE PLUS PSYCHOTHERAPY VERSUS PLACEBO PLUS PSYCHOTHERAPY IN COMBAT VETERANS
One trial of imipramine met the inclusion criteria. Kosten et al (1991) combined imipramine and psychodynamic therapy in a population of Vietnam war veterans, to determine the clinical effectiveness on the reduction of PTSD symptoms. Imipramine was administered over 8 weeks at a mean dose of 225 mg per day (±55 mg/per day). Psychodynamic therapy included a one weekly individual session with a Masters level psychologist during the same trial time.
Table 136 Study profiles for RCTs comparing imipramine plus psychotherapy and placebo plus psychotherapy for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Kosten et al 1991) Moderate Male combat veterans Outpatient 41 Severity of PTSD symptoms setting, United Depressive symptoms States Anxiety Attrition
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between imipramine and placebo on reducing the severity of self- reported PTSD symptoms at post-treatment (k = 1; n = 41; SMD = -0.24 ; 95% CI, -0.86, 0.38).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between imipramine and placebo on reducing depression symptoms at post-treatment (k =1; n = 41; SMD = -0.22; 95% CI, -0.84, 0.40).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between imipramine and placebo on reducing anxiety symptoms at post- treatment (k = 1; n = 41; SMD = -0.46; 95% CI, -1.08, 0.17).
There is limited evidence favouring imipramine over placebo on reducing the likelihood of leaving the study early for any reason (k = 1; n = 41; RR = 0.78; 95% CI, 0.47, 1.30).
353
Box 137 Evidence statement matrix for RCT comparing imipramine plus psychotherapy and placebo plus psychotherapy for adults with PTSD Component Rating Description Evidence base C One level II study with moderate risk of bias
Consistency NA Only one study
Clinical impact D No clinically important differences were found for PTSD symptoms, depression and anxiety. However, limited clinical important difference was found for attrition.
Generalisability B The population consisted of Vietnam war veterans, which is generalisable to the subgroup target population.
Applicability C The study was conducted in the USA, which has a comparable health system to Australia, with some caveats.
Summary of evidence The evidence suggests there is no benefit of imipramine in addition to psychotherapy over psychotherapy alone for a reduction in PTSD symptoms, depression or anxiety. Furthermore, limited evidence was found indicating that additional imipramine reduces the likelihood of attrition compared to psychotherapy alone. (Grade C)
MONOAMINE OXIDASE INHIBITORS BROFAROMINE VERSUS PLACEBO The study by Katz et al (1994) assessed the effectiveness of brofaromine for the reduction of PTSD symptoms in a population with mixed trauma. At the time of the trial, bofaromine was an experimental drug and was not commercially available.
Table 137 Study profiles for RCTs comparing brofaromine and placebo for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Katz et al 1994) Moderate Unspecified trauma type (sexual Outpatient 66 Severity of PTSD symptoms assault, physical assault, accident, setting, 9 sites, Attrition combat-related) France, UK
There is limited evidence favouring brofaromine over placebo on reducing the severity of clinician-assessed PTSD symptoms (k = 1; n = 45; SMD = -0.58; 95% CI, -1.18 to 0.02).
There is limited evidence favouring placebo over brofaromine on reducing the likelihood of leaving the study early due to any reason (k = 1; n = 66; RR =1.44; 95% CI, 0.69 to 3.01).
Box 138 Evidence statement matrix for RCT comparing brofaromine and placebo for adults with PTSD Component Rating Description Evidence base C One level II study with moderate risk of bias
Consistency NA only one study
Clinical impact D Limited evidence was found that favoured brofaromine over placebo.
Generalisability B The study sample included patients with mixed trauma which resulted in PTSD.
354 Applicability B The study was performed in multiple centre in Europe and is therefore applicable to the Australian context
Summary of evidence Evidence for the effectiveness of brofaromine in the treatment of PTSD is limited (Grade C)
PHENELZINE PLUS PSYCHOTHERAPY VERSUS PLACEBO PLUS PSYCHOTHERAPY IN COMBAT VETERANS One trial assessed the use of phenelzine in addition to psychotherapy for the treatment of combat related PTSD (Kosten et al 1991).
Table 138 Study profiles for RCTs comparing phenelzine plus psychotherapy versus placebo plus psychotherapy for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Kosten et al 1991) Moderate Male combat veterans Outpatient 37 Severity of PTSD symptoms setting, United Depressive symptoms States Anxiety Attrition
There is limited evidence favouring phenelzine over placebo on reducing the severity of self- report PTSD symptoms (k = 1; n = 37; SMD = -1.06; 95% CI, -1.75 to -0.36).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between phenelzine and placebo on reducing depression symptoms (k = 1; n = 37; SMD = -0.4; 95% CI, -1.06 to 0.25).
There is limited evidence favouring phenelzine over placebo on reducing anxiety symptom (k = 1; n = 37; SMD = -0.67; 95% CI, -1.34 to -0.01).
There is evidence favouring phenelzine over placebo on reducing the likelihood of leaving the study early due to any reason (k = 1; n = 37; RR =0.32; 95% CI, 0.12 to 0.8).
Box 139 Evidence statement matrix for RCT comparing phenelzine plus psychotherapy versus placebo plus psychotherapy for adults with PTSD Component Rating Description Evidence base C One level II study with moderate risk of bias
Consistency NA Only one study
Clinical impact D There is limited evidence for clinically important differences in outcomes on PTSD symptoms, Anxiety and attrition. There is no conclusive evidence for depression as an outcome.
Generalisability B Population consisted of combat veterans which is generalisble to the subgroup target population.
Applicability C The study was conducted in the USA, which has a comparable health system to Australia, with some caveats.
Summary of evidence There is limited evidence suggesting that combat veterans might benefit from phenelzine in addition to psychotherapy over psychotherapy alone for the treatment of PTSD. (Grade C)
355
OTHER ANTIDEPRESSANTS
MIRTAZAPINE VERSUS PLACEBO One study met the inclusion criteria that assessed the effectiveness of mirtazapine in a mixed trauma population (Davidson et al 2003).
Table 139 Study profiles for RCTs comparing mirtazapine and placebo for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Davidson et al Moderate Unspecified trauma type (rape, Outpatient 26 Severity of PTSD symptoms 2003) childhood sexual abuse, physical setting, United Depressive symptoms abuse, criminal assault. military States Anxiety combat, accidental injury, witnessing Attrition a trauma, and unexpected death of a significant other)
There is evidence favouring mirtazipine over placebo on reducing the severity of clinician- rated PTSD symptoms at post-treatment (k = 1; n = 21; SMD = -1.89; 95% CI, -3 to -0.78).
There is limited evidence favouring mirtazipine over placebo on reducing the severity of self- report PTSD symptoms at post-treatment (k = 1; n = 26; SMD = -0.76; 95% CI, -1.6 to 0.08).
There is limited evidence favouring mirtazipine over placebo on reducing depression symptoms at post-treatment (k = 1; n = 25; SMD = -0.92; 95% CI, -1.81 to -0.04).
There is limited evidence favouring mirtazipine over placebo on reducing anxiety symptoms at post-treatment (k = 1; n = 25; SMD = -0.88; 95% CI, -1.77 to 0).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between mirtazipine and placebo on reducing the likelihood of leaving treatment early (k = 1; n = 29; RR = 0.9; 95% CI, 0.29 to 2.82).
Box 140 Evidence statement matrix for RCT comparing mirtazapine and placebo for adults with PTSD Component Rating Description Evidence base C One level II study with moderate risk of bias
Consistency NA Only one study
Clinical impact D There is limited evidence for clinically important differences in outcomes on PTSD symptoms, depression and anxiety. There is no conclusive evidence indicating a decrease in attrition.
Generalisability B Population had experienced mixed trauma.
Applicability C The study was conducted in the USA, which has a comparable health system to Australia, with some caveats.
Summary of evidence There is limited evidence suggesting that mirtazapine is more beneficial than placebo for the treatment of PTSD. (Grade C)
356 MIRTAZAPINE VERSUS SERTRALINE IN COMBAT VETERANS A poor quality open label trial by Chung et al (2004) compared the effectiveness of mirtazapine with sertraline in a group of Korean veterans. Prior to the study, participants were required to have a seven day washout period of any medications except for Zopliclone for insomnia. It was not stated whether patients were also receiving psychotherapy for PTSD or not. The mean daily dose of mirtazapine was 34.1 mg and for sertraline was 101.5 mg. Data were not provided in such a format as to allow effect sizes to be calculated so results are discussed narratively. In the mirtazapine group who completed treatment, PTSD symptom severity scores on the CAPS-2 were reduced by 43.4% compared to baseline, whereas in the sertraline group who completed treatment, CAPS-2 scores were reduced by 37.4% compared to baseline. There were no statistically significant differences in PTSD symptom severity for patients receiving mirtazapine compared to sertraline (t=-0.73, p=0.47).
Depressive symptoms, as measured on the Hamilton depression rating scale, were reduced by 58.5% in the mirtazapine group, and 59.1% in the sertraline group (t=1.00, p=0.32). This would correspond to evidence that there is unlikely to be any clinically important difference between mirtazapine and sertraline.
Patient drop-outs were fairly evenly distributed between the two groups (13.7% from the mirtazapine group, and 12.2% in the sertraline group). Mirtazapine was associated with dry mouth (19.6%), constipation (19.6%), somnolence (15.7%) and weight gain (1.96%), while the sertraline group reported indigestion (14.3%), palpitation (6.1%), agitation (2.0%), epigastric soreness (2.0%) and sexual dysfunction (2.0%).
Table 140 Study profiles for RCTs comparing mirtazapine and sertraline for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Chung et al 2004) High Elderly male veterans of the Korean Inpatient and 113 Severity of PTSD symptoms or Vietnam war with PTSD and outpatient Depressive symptoms possible comorbid major depression setting, Seoul Side-effects or dysthymia Veterans Attrition Hospital, Korea
There is evidence suggesting that there is unlikely to be a clinically important difference between mirtazapine and sertraline for treatment dropout rate (k = 1; n =100; RR = 0.98; 95% CI, 0.30 to 1.02).
Box 141 Evidence statement matrix for RCT comparing mirtazapine and sertraline for adults with PTSD Component Rating Description Evidence base D One level II study at a high risk of bias due to lack of any blinding, no details of randomisation, and lack of any intention-to-treat analyses.
Consistency NA Only one study
Clinical impact D No clinically important differences detected on measures of efficacy. Side effects differed between mirtazapine and sertraline, and were marginally more frequent in the mirtazapine group.
Generalisability C Population in the study were elderly male veterans who had both PTSD and either MDD, dysthymia or a combination of both. The generalisability of the study is therefore restricted, but it is clinically sensible to still apply this evidence to the target population. .
Applicability C Korean healthcare system differs from Australian healthcare setting, but is probably applicable with some caveats.
357 Summary of evidence Limited evidence suggests there is little difference in the efficacy of mirtazapine and sertraline at reducing PTSD symptom severity or depressive symptoms. The side-effects profiles of the two drugs differ, with slightly more side-effects being reported in the mirtazapine group. (Grade D).
MIRTAZAPINE VERSUS PAROXETINE In an open-label trial design, Seo et al 2010 compared the effectiveness of mirtazapine (n=20 patients) and paroxetine (n=20 patients) treatment over eight weeks. To be included in the study, patients were required to have a PTSD diagnosis based on the Structured Clinical Interview for DSM-IV Axis I Disorders, Clinician Version (SCID-CV) and be within the age range of 18 to 65 years. The dosing regime for mirtazapine and paroxetine was initiated at 15mg/day and 10mg/day, respectively, and both drugs could be titrated upwards at the discretion of the treating clinician to a maximum of 60mg/day.
End-point mean scores on PTSD symptoms (CAPS, CGI-S) and depression symptoms (Beck Depression Inventory) suggested that the effectiveness of fluoxetine and tianeptine were similar for the treatment of PTSD. Effect size estimates calculated from the continuous data revealed no clinically significant differences on PTSD and depression outcomes for the two drugs. (Seo et al 2010).
Side effect profiles are summarised below in Table 141.
Table 141 Side effect profiles for patients treated with mirtazapine and paroxetine Reference Side-effects among drop-outs Mirtazapine, n (%) patients Paroxetine, n (%) patients (Seo et al 2010) Agitation 1 (5) 0 Dry mouth 1 (5) 0 Constipation/gastrointestinal upset 0 1 (5) Total side effects Agitationa 4 (20) 0 Nervousness/anxiety 3 (15) 3 (15) Fatigue 3 (15) 2 (10) Dry mouth 1 (5) 0 Weight gain 1 (5) 0 Insomnia 0 2 (10) Indigestion 0 1 (5) Constipation/GI upset 0 1 (5) aBold text denotes a side effect for which the number of patients with that side effect (also in bold) is at least two times greater than the number for the comparison drug
Table 142 Study profile for RCT comparing mirtazapine and paroxetine for PTSD patients Reference Risk of bias Population Setting N Outcomes measured (Seo et al 2010) Moderate PTSD patients diagnosed according Korea 40 Change in PTSD symptoms to DSM-IV criteria Change in depression symptoms
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between mirtazapine and paroxetine for reducing the severity of clinician-rated PTSD symptoms (k=1, n=40, SMD=0.18, 95%CI -0.44, 0.80).
358 The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between mirtazapine and paroxetine for reducing the severity of PTSD symptoms as measured by CGI-S (k=1, n=40, SMD=0.13, 95%CI -0.49, 0.75).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between mirtazapine and paroxetine for reducing depression (k=1, n=40, SMD=0.21, 95%CI -0.40, 0.84).
Evidence statement matrix for RCT comparing mirtazapine and paroxetine for PTSD patients Component Rating Description Evidence base C One level I study with moderate risk of bias
Consistency NA One study only
Clinical impact D Slight/restricted: no clinically important differences found
Generalisability D Korean population; hard to judge whether it is sensible to generalise to the target population
Applicability D Evidence not applicable to the Australian healthcare context
Summary of evidence Available evidence from one small study of moderate quality does not allow determination of whether a clinically meaningful difference exists between mirtazapine and paroxetine for treatment of PTSD and depression symptoms among DSM-IV diagnosed PTSD patients (Grade D).
VENLAFAXINE VERSUS PLACEBO There are two studies of venlafaxine that met the inclusion criteria; (Davidson et al 2006a; Davidson et al 2006b) the trauma population was unspecified. The studies reported inconsistent results for PTSD symptom severity, depressive symptoms and social/work functioning, which could be ascribed to the length of follow up (12 weeks versus 6 months). This is also reflected in the by the significant heterogeneity.
Table 143 Study profiles for RCTs comparing venlafaxine and placebo for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Davidson et al Moderate Unspecified trauma type (nonsexual Outpatient 358 Severity of PTSD 2006b) abuse, adult sexual abuse, childhood setting, United Depression sexual abuse, unexpected death, States Quality of life accidental injury, and combat Disability Attrition
(Davidson et al Moderate Unspecified trauma type (nonsexual Outpatient 329 Severity of PTSD 2006a) abuse, adult sexual abuse, childhood setting, multi- Depression sexual abuse, unexpected death, centre, Europe, Quality of life accidental injury, and combat South America, Disability South Africa Attrition and United Kingdom
359
There is evidence suggesting that there is unlikely to be a clinically important difference between venlafaxine and placebo on reducing the severity of PTSD symptoms (k = 2; n = 687; SMD = 0.03; 95% CI, -0.54, 0.60)
There is evidence suggesting that there is unlikely to be a clinically important difference between venlafaxine and placebo on reducing depressive symptoms (k = 2; n = 687; SMD = -0.01; 95% CI, -0.42, 0.40)
360
There is evidence suggesting that there is unlikely to be a clinically important difference between venlafaxine and placebo on increasing social/work functioning (k = 2; n = 687; SMD = 0.01; 95% CI, -0.45, 0.46)
There is evidence suggesting that there is unlikely to be a clinically important difference between venlafaxine and placebo on a increase in quality of life (k = 2; n = 687; SMD = - 0.25; 95% CI, -0.40,- 0.10)
Box 142 Evidence statement matrix for RCT comparing venlafaxine and placebo for adults with PTSD Component Rating Description Evidence base C Two level II studies with moderate risk of bias
Consistency B Studies are inconsistent for three out of the four putcomes, this could be explained by the length of follow up. Clinical impact D The evidence indicates that there is limited evidence for a better outcome when treated with venlafaxine than with placebo.
361 Generalisability B Population had a history of mixed trauma.
Applicability B The studies were conducted in the USA, South Africa and Europe, which have a comparable health system to Australia.
Summary of evidence There is no clinically important benefit of venlafaxine over placebo for the treatment of PTSD in a mixed trauma population. (Grade C)
VENLAFAXINE VERSUS SERTRALINE Davidson et al (2006) reported on a large double-blind trial which was performed in 59 outpatient psychiatric clinics inUSA. Although the trial was well designed, it was classified as having a moderate risk of bias, as there was a drop-out rate of 34% across the three arms of the trial (venlafaxine, sertraline and placebo).
As outlined in the evidence statements below Table 144, there were no clinically important differences detected between venlaxafine and sertraline on measures of efficacy. Side effects which occurred in at least 10% of patients in one treatment arm are listed in Table 145. Over twice as many people receiving sertraline reported diarrhoea than in the venlafaxine group (26% vs 12%), but there were no other large differences in the rate of side effects between the two drugs.
Table 144 Study profiles for RCTs comparing venlafaxine and sertraline for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Davidson et al Moderate Unspecified trauma type Outpatient setting in 352 PTSD diagnosis 2006b) (nonsexual abuse, adult sexual the USA Severity of PTSD abuse, childhood sexual abuse, Quality of life unexpected death, accidental Attrition injury, and combat
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between venlafaxine and sertraline on reducing the likelihood of having a post-treatment PTSD diagnosis (k = 1; n = 352; RR = 0.92; 95% CI, 0.81 to 1.05).
There is evidence suggesting there is unlikely to be a clinically important difference between venlafaxine and sertraline on reducing the severity of clinician-rated PTSD symptoms (k = 1; n = 352; SMD = -0.01; 95% CI, -0.22 to 0.2).
There is evidence suggesting there is unlikely to be a clinically important difference between venlafaxine and sertraline on reducing the severity of self-reported PTSD symptoms (k = 1; n = 352; SMD = -0.1; 95% CI, -0.31 to 0.11).
There is evidence suggesting there is unlikely to be a clinically important difference between venlafaxine and sertraline on improving quality of life (k = 1; n = 352; SMD = -0.02; 95% CI, -0.23 to 0.19).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between venlafaxine and sertraline on reducing the likelihood of leaving treatment early (k = 1; n = 352; RR = 0.84; 95% CI, 0.62 to 1.14).
362
Table 145 Side effects of venlafaxine and sertraline in people with PTSD Reference Treatment emergent Venlafaxine (n=179) Sertraline (n=173) side effects (Davidson et al 2006b) Headache 53 patients (29%) 57 patients (32%) Nausea 45 patients (24%) 39 patients (23%) Diarrhoea 22 patients (12%) 47 patients (26%) Dizziness 24 patients (13% ) 21 patients (10%) Dry mouth 34 patients (18%) 26 patients (15%) Somnolence 21patients (12%) 18 patients (10%) Fatigue 19 patients (11%) 24 patients (14%]) Constipation 21 patients (12%) 12 patients (7%) Insomnia 24 patients (13%) 18 patients (10%) NB: side effects which occurred at twice or more the rate of the other treatment are bolded
Box 143 Evidence statement matrix for RCT comparing venlafaxine and sertraline for adults with PTSD Component Rating Description Evidence base C One large RCT (level II evidence) with a moderate risk of bias due to high levels of drop-out.
Consistency NA Only one study
Clinical impact D Venlafaxine and sertraline appeared to be similarly effective at reducing likelihood of having PTSD, severity of PTSD symptoms, and improving quality of life. The side effects profiles were similar, with the exception of diarrhoea, which was over twice as frequent in the group receiving sertraline. Generalisability A Very good generalisability, given the broad range of trauma types experienced, and the broad range of countries the study participants were from.
Applicability B Applicable to the Australian healthcare context with few caveats. Some of the participants were from Europe and the United Kingdom, with similar healthcare systems to the Australia.
Summary of evidence No clinically important differences were detected between venlafaxine and sertraline in a large trial with a mixed-trauma population. They appeared to be equally effective on measures of efficacy, and very similar in their side effects profile with the exception of diarrhoea being more frequent in those receiving sertraline. (Grade C).
NEFAZODONE VERSUS PLACEBO IN COMBAT VETERANS One average-to-good quality trial assessed the effect of Nefazodone on PTSD symptoms, compared to placebo (Davis et al 2004). It was not stated whether participants were receiving any concurrent psychological treatment. Patients were required to be free of any psychotropic medication in the 2 weeks prior to the intervention (Davis et al 2004). An intention to treat analysis was conducted.
Table 146 Study profiles for RCTs comparing nefazodone and placebo for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Davis et al 2004) Moderate Male veterans (combat trauma) and 1 Outpatient 42 Severity of PTSD symptoms female with civilian trauma (sexual setting, United Depressive symptoms trauma) States Side effects Attrition
There was a slightly higher patient dropout rate for those receiving the active treatment, with 19 per cent experiencing side effects of dizziness, gastro-intestinal symptoms, and headaches.
363
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between nefazodone and placebo on reducing the severity of clinician-rated PTSD symptoms at post-treatment (k = 1; n =41; SMD = -0.23; 95% CI - 0.86, 0.41)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between nefazodone and placebo on reducing the severity of self-rated PTSD symptoms at post-treatment (k = 1; n =41; SMD = 0.49; 95% CI -0.15,1.13)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between nefazodone and placebo on a reduction in depression at post-treatment (k = 1; n =41; SMD = -0.27; 95% CI -0.91, 0.37)
Box 144 Evidence statement matrix for RCT comparing nefazodone and placebo for adults with PTSD Component Rating Description Evidence base C One level II study with moderate risk of bias
Consistency NA Only one study
Clinical impact D There was no clinical important difference between the treatments for all outcomes, as the evidence was inconclusive.
Generalisability B The population consisted of veterans with combat related PTSD, which is generalisable to the subgroup target population.
Applicability C The study was conducted in the USA, which has a comparable health system to Australia, with some caveats.
Summary of evidence The evidence provided was inconclusive, suggesting that there is no additional benefit from treatment with nefazodone over placebo for PTSD in combat veterans. (Grade C)
NEFAZODONE VERSUS SERTRALINE McRae et al (2004) compared the effectiveness of nefazodone with sertraline in an outpatient setting in a sample of people with PTSD due to a mix of trauma types, predominantly women who had suffered sexual or physical abuse, either as a child or adult. Participants were required to have a wash-out period if receiving any psychotropic drugs, and also could not receive psychotherapy during the trial. The average final daily dose of nefazodone patients received was 463 mg, and the average daily dose of sertraline patients received was 153 mg.
Table 147 Study profiles for RCTs comparing nefazodone and sertraline for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (McRae et al 2004) Moderate Unspecified trauma type (childhood Outpatient 37 Severity of PTSD symptoms physical or sexual abuse, physical setting, United Depressive symptoms assault, sexual assault, accident or States Anxiety other) 77% female Functioning
The study by McRae et al (2004) had a relatively high rate of drop out, with only 23/37 (62.2%) of patients completing the 12 week trial. Effectiveness data provided were for 26 patients who provided at least one post-randomisation CAPS assessment. No statistically
364 significant differences were detected on any efficacy outcome measures between the patients receiving nefazodone and those receiving sertraline.
Those receiving sertraline were more than twice as likely to report fatigue, anorgasmia/delayed ejaculation, dry mouth, nervousness, blurred vision and a rash/itching than those taking nefazodone, while those on nefazodone were more than twice as likely to report difficulty concentrating and nausea than those taking sertraline (see Table 148).
Table 148 Side effects of venlafaxine and sertraline in people with PTSD Reference Treatment emergent side Nefazodone (n=19) Sertraline (n=18) effects (McRae et al 2004) drowsiness 26.3% 27.8% headache 26.3% 22.2% insomnia 21.1% 16.7% dizziness 21.1% 21.1% fatigue 5.3% 16.7% anorgasmia/delayed ejaculation 0% 16.7% restlessness 10.5% 11.1% nightmares 5.3% 11.1% dry mouth 0% 11.1% difficulty concentrating 10.5% 0% nausea 10.5% 0% increased appetite 5.3% 5.6% nervousness 0% 5.6% blurred vision 0% 5.6% rash/itching 0% 5.6% decreased appetite 5.3% 5.3% muscle tension 5.3% 5.3%
NB: side effects which occurred at twice or more the rate of the other treatment are bolded
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between Nefazodone and Sertraline for reducing the severity of clinician-rated PTSD symptoms (clinician administered PTSD interview scale) (k = 1; n =26; SMD = -0.01; 95% CI, -0.78 to 0.76).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between Nefazodone and Sertraline for reducing the severity of clinician-rated PTSD symptoms ( TOP-8 investigator rated scale of PTSD) (k = 1; n =26; SMD = -0.02; 95% CI, -0.79 to 0.75).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between Nefazodone and Sertraline for reducing the severity of self-reported PTSD symptoms (k = 1; n =26; SMD = -0.09; 95% CI, -0.86 to 0.68).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between Nefazodone and Sertraline for reducing anxiety (k = 1; n =26; SMD = -0.31; 95% CI, -1.08 to 0.46).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between Nefazodone and Sertraline for reducing depression (k = 1; n =26; SMD = -0.12; 95% CI, -0.89 to 0.65).
365 The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between Nefazodone and Sertraline for improving functioning (k = 1; n =26; SMD = 0.13; 95% CI, -0.64 to 0.90).
Box 145 Evidence statement matrix for RCT comparing nefazodone and sertraline for adults with PTSD Component Rating Description Evidence base C One small level II study with a moderate risk of bias.
Consistency NA Only one study
Clinical impact D Both nefazodone and sertraline treatment groups showed significant improvements on a number of clinician- and self-rated outcome measures, but there were no clinically important differences detected between the two. Side effects were common in both groups, the most common being drowsiness and headaches. Generalisability B Good generalisability given the mixed trauma population.
Applicability C Study performed in the United States. Probably applicable to the Australian healthcare context with comes caveats.
Summary of evidence No statistically significant or clinically important differences were found between nefazodone and sertraline in adults with PTSD on reducing PTSD symptom severity, depressive symptoms, anxiety, or levels of disability. (Grade C)
ATYPICAL ANTIPSYCHOTICS OLANZAPINE VERSUS PLACEBO Two studies were identified that assessed the effectiveness of olanzapine for the treatment of PTSD. Butterfield et al (2001) assessed olanzapine alone versus placebo for a mixed- trauma population, which consisted predominantly of female rape victims. The study by Stein et al (2002) assessed the effectiveness of olanzapine in addition to SSRIs in male combat veterans. This study was included under Question 21.
Table 149 Study profiles for RCTs comparing olanzapine and placebo for adults with PTSD Reference Risk of bias Population Setting N Outcome measures (Butterfield et al High Unspecified trauma type (domestic Outpatient 15 Severity of PTSD symptoms 2001) violence, military harassment, rape in setting, United Quality of life military, combat trauma, physical States Attrition assault, childhood physical or sexual abuse), 90% women
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between olanzapine and placebo on reducing the severity of clinician- rated PTSD symptoms (k = 1; n = 11; SMD = 0.16; 95% CI, -1.07 to 1.39).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between olanzapine and placebo on reducing the severity of self- reported PTSD symptoms (k = 1; n = 11; SMD = 0.04; 95% CI, -1.19 to 1.26).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between olanzapine and placebo on improving quality of life (k = 1; n = 11; SMD = - 0.17; 95% CI, -1.4 to 1.06).
366
There is limited evidence favouring placebo over olanzapine on reducing the likelihood of leaving treatment early (k = 1; n = 15; RR = 1.5; 95% CI, 0.2 to 11).
Box 146 Evidence statement matrix for RCT comparing olanzapine and placebo for adults with PTSD Component Rating Description Evidence base D One level II study with high risk of bias
Consistency NA Only one study
Clinical impact D No conclusive evidence was found for PTSD symptom or quality of life improvement. However, limited evidence was found for a reduction in attrition.
Generalisability B Population consisted of people with mixed trauma experiences.
Applicability C Study performed in the United States. Applicable to the Australian healthcare context with some caveats.
Summary of evidence The evidence suggest there is no clinically important difference between olanzapine and placebo for the treatment of PTSD in a mixed trauma population (Grade C)
RISPERIDONE VERSUS PLACEBO Four studies were identified that examined the effectiveness of riperidone as treatment for PTSD.
The good quality study by Krystal et al (2011) ran a trial with war veterans who suffered from combat related PTSD. Risperidone was administered to 133 participants who starting off with 1mg per day, increasing to a maximum of 3mg per day over 6 months. The other participants received placebo (n = 134).
Riperidone was administered to patients with chronic combat related PTSD in the average quality study by Bartzokis et al (2005). Thirty-three patients received a starting dose of 1 mg per day increasing to a maximum of 3 mg per day over 16 weeks. Both the intervention (92%) and placebo group (92%) maintained the stable pre trial psychotropic medication regimens.
The poor quality trial by Reich et al (2004) assessed the effectiveness of risperidone as a treatment for patients with PTSD secondary to child sexual abuse. Nine participants were taking other psychiatric medications during the study. Five participants randomised to risperidone were also receiving an SSRI (n=1), tricyclic antidepressant (n=1), and benzodiazepines (n=1). Four participants randomised to placebo were on an SSRI (n=2), a tricyclic antidepressant (n=1), a benzodiazepine (n=1) and trazodone (n=1). These medications were kept stable throughout the study (Reich et al 2004).
Risperidone was found to be statistically significantly better at reducing PTSD symptoms than placebo after 8 weeks of treatment in patients who completed the trial. This was largely due to a reduction on the intrusion symptoms subscale of the Clinician Administered PTSD Scale.
367 Depressive symptoms and anxiety results from Krystal et al (2011) and Bartzokis et al (2005) could not be combined as one provided data in the form of post-treatment means, whereas the other provided data in the form of change from baseline. Results were consistent for depressive symptoms, but inconsistent on anxiety, with the better quality study finding no difference (Krystal et al 2011), contrasting against Bartzokis et al (2005), who reported a clinically important change from baseline.
Table 150 Study profiles for RCTs comparing risperidone and placebo for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Krystal et al 2011) Low War veterans with combat related Outpatient in 267 Severity of PTSD symptoms PTSD Medical clinics, Anxiety United States Depression Quality of life
(Bartzokis et al Moderate Males with combat related PTSD Outpatient, 65 Severity of PTSD symptoms 2005) United States Anxiety Depression
(Reich et al 2004) High Women with PTSD secondary to child Outpatient 21 Severity of PTSD symptoms abuse (sexual, physical, emotional, or setting, United verbal) States
(Hamner et al 2003) High War veterans with combat related Outpatient 37 Severity of PTSD symptoms PTSD setting, USA
There is evidence suggesting that there is unlikely to be a clinically important difference between risperidone and placebo on reducing the severity of clinician-rated PTSD symptoms at post-treatment (k=1, n=267, SMD=-0.19, 95% CI -0.43, 0.05).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between risperidone and placebo on reducing the severity of
368 clinician-rated PTSD symptoms (change from baseline) at post-treatment (k = 2; n = 56; SMD = -0.58; 95% CI -1.02, -0.15)
There is evidence suggesting that there is unlikely to be a clinically important difference between risperidone and placebo for reducing depressive symptoms at post-treatment (k=1, n=267, SMD = -0.19, 95% CI -0.43, 0.05) or on change from baseline at post-treatment (k=1, n=65, SMD=-0.27, 95%CI -0.76, 0.21).
There is evidence suggesting that there is unlikely to be a clinically important difference between risperidone and placebo for reducing anxiety at post-treatment (k=1, n=267, SMD = -0.21, 95% CI (-0.45, 0.03)
There is limited evidence favouring risperidone over placebo for reducing anxiety (change from baseline) at post-treatment (k=1, n=65, SMD= -0.87, 95%CI -1.34, -0.33).
There is evidence suggesting that there is unlikely to be a clinically important difference between risperidone and placebo on improving physical functioning post-treatment (k=1, n=267, SMD = 0.19, 95% CI -0.05, 0.43)
Box 147 Evidence statement matrix for RCT comparing risperidone and placebo for adults with PTSD Component Rating Description Evidence base B One level II study with a low risk of bias, one level II study with moderate risk of bias and two level II studies with high risk of bias Consistency A Studies were consistent
Clinical impact D No clinical important difference detected.
Generalisability B Populations consisted of war veterans and women with history of childhood sexual abuse, which are both generalisable to the target population.
Applicability C Both studies were performed in the United States. Applicable to the Australian healthcare context with some caveats.
Summary of evidence The evidence suggests there is no clinically important difference between risperidone and placebo for the treatment of PTSD in a mixed trauma population. (Grade B)
RISPERIDONE VERSUS PLACEBO IN COMBAT VETERANS
Three studies (Hamner et al 2003, Bartzokis et al 2005 and Krystal et al 2011) included a population of veterans with combat related PTSD in their trail.
On PTSD symptom severity as an outcome, Krystal et al (2011) and Hamner et al (2003) found contradicting results. Hamner et al (2003) reported that placebo was favoured over risperidone, while Krystal et al (2011) reported the opposite. This might be explained by the difference in length of treatment and the much smaller sample size of Hamner et al (2003). However, both indicated insignificant differences between both treatments on mean endpoint. There was no heterogeneity.
369 Table 151 Study profiles for RCTs comparing risperidone and placebo for combat veterans with PTSD Reference Risk of bias Population Setting N Outcomes measured (Krystal et al 2011) Low War veterans with combat related Outpatient in 267 Severity of PTSD symptoms PTSD Medical clinics, Anxiety United States Depression Quality of life
(Bartzokis et al Moderate Males with combat related PTSD Outpatient, 65 Severity of PTSD symptoms 2005) United States Anxiety Depression
(Hamner et al 2003) High War veterans with combat related Outpatient 37 Severity of PTSD symptoms PTSD setting, USA
There is evidence suggesting that there is unlikely to be a clinically important difference between risperidone and placebo on reducing the severity of clinician-rated PTSD symptoms at post-treatment (k = 2; n =304; SMD = -0.15; 95% CI, -0.38, 0.07).
The evidence is inconclusive so it is not possible to determine whether there is a clinically important difference between risperidone and placebo on reducing the severity of clinician- rated PTSD symptoms (change from baseline) at post-treatment (k=1, n=65, SMD=-0.65, 95%CI -1.13, -0.14).
There is evidence suggesting that there is unlikely to be a clinically important difference between risperidone and placebo on reducing depression at post-treatment (k = 1; n =267; SMD = -0.19; 95% CI, -0.43, 0.05) or on reducing depression (change from baseline) at post-treatment (k = 1; n = 35; SMD = -0.22; 95% CI, -0.71, 0.27).
There is evidence suggesting that there is unlikely to be a clinically important difference between risperidone and placebo on reducing anxiety at post-treatment (k = 1; n =267; SMD
370 = -0.21; 95% CI, -0.45, 0.03) or on reducing anxiety (change from baseline) at post- treatment (k = 1; n = 35; SMD = -0.05; 95% CI, -0.54, 0.43).
There is evidence suggesting that there is unlikely to be a clinically important difference between risperidone and placebo on improving quality of life at post-treatment (k = 1; n =267; SMD = 0.02; 95% CI, -0.22, 0.26)
Box 148 Evidence statement matrix for RCT comparing risperidone and placebo for people with combat related PTSD Component Rating Description Evidence base B One level II study with low risk of bias, one level II studies with moderate risk of bias and one level II study with high risk of bias Consistency A Studies were consistent
Clinical impact D No clinical important difference detected.
Generalisability B All three studies included veterans with combat related PTSD.
Applicability C All studies were performed in the United States. Applicable to the Australian healthcare context with some caveats.
Summary of evidence The evidence indicates there are no clinically important differences between risperidone and placebo for the treatment of combat related PTSD. (Grade B)
ANTICONVULSANTS
TOPIRAMATE VERSUS PLACEBO One study was identified in the searches that reported on topiramate for the treatment of PTSD. Tucker et al (2007) included a population with non combat related PTSD. Participants randomised to toparimate, started treatment at 25 mg per day which was titrated by 25 to 50 mg per week during an 8 week period and maintained for more than 4 weeks. The authors reported a percentage change on PTSD symptom severity (CAPS) of -59.5±25.9 for topiramate and -45.5±34.3 for placebo, which was not found to be a significant difference between group (p = 0.23). Similar results were found for anxiety (HAM-A, p = 0.33), depression (HAM-D, p = 0.25) and quality of life (Sheenan Disability Scale, p = 0.80). In the topiramate group, four patients discontinued treatment due to adverse events compared to three in the placebo group. The most common adverse event were headache, sinusitis and taste perversion (see Table 153). One additional study assessing topiramate versus placebo in 40 male Vietnam war veterans was identified by the systematic review (Lindley et al 2007), but was excluded due to having 55% loss to follow-up in the treatment arm. However, this high rate of loss to follow-up was determined to be due to side-effects of topiramate. The side-effects from this study have therefore also been outlined here.
Due to the absence of mean end score or mean change scores, no clinical important difference could be determined. As a result, no statement has been made on the evidence.
371 Table 152 Study profiles for RCTs comparing topiramate and placebo Reference Risk of bias Population Setting N Outcomes measured (Tucker et al 2007) Moderate Adult Outpatient, USA 40 Severity of PTSD symptoms Non–combat-related Depressive symptoms trauma Anxiety Social and occupational function Side-effects
Table 153 Adverse events from topiramate or placebo occurring in ≥20% of patients Reference Side effects Topiramate n (%) Placebo n (%) (Tucker et al Headache 7 (37) 5 (26) 2007) Sinusitis 5 (26) 2 (11) Taste perversion 5 (26) 0 (0) Language problems 4 (21) 3 (16) Insomnia 4 (21) 3 (16) Dyspepsia 4 (21) 2 (11) Paresthesia 4 (21) 1 (5) Nervousness 4 (21) 1 (5) Fatigue 4 (21) 0 (0) Hypertension 2 (11) 4 (21) Difficulty with concentration/attention 2 (11) 4 (21)
(Lindley et al Treatment-emergent events causing N events N events 2007) discontinuation in study, CNS related impaired cognition/paresthesias/dyarthia 1 - visual illusion/confusion/headache 1 - abnormal dreams/sedation 1 - paresthesias/dizziness/sedation/ataxia 1 - fatigue/vertigo 1 - increased anxiety/patient perception of pale skin 1 - anxiety/blurred vision - 1
Treatment-emergent events causing discontinuation in study, non-CNS related rash 1 - elevated liver enzymes 1 -
Non treatment-emergent events causing discontinuation study, non-CNS related urinary tract infection 1 -
Total treatment-emergent events, CNS-related 11 12
Total treatment-emergent events, non-CNS related plus CNS related 16 17 NB: side effects which occurred at twice or more the rate of the other treatment are bolded; CNS= central nervous system
TIAGABINE VERSUS PLACEBO Davidson et al (2007) compared the effectiveness of tiagabine (n=116 patients) and placebo (n=116 patients) in a randomised trial. The study population included adults with mixed trauma types across 38 centres in the United States. The dosing regimen for tiagabine was
372 initiated at 4mg daily for one week, after which the dosage was titrated in 4mg increments through to week six, with a maximum allowable dose of 16mg per day. This dose was maintained until week 12 of the study, unless there was an indication for reducing the dose.
Drop-out rate for the trial was 39 per cent overall (91/232 patients). The primary outcome for the purpose of this review was clinician-rated PTSD symptom severity, as measured by the Clinician Administered PTSD Scale (CAPS). Secondary outcomes included anxiety symptom severity as per the Montgomery-Asberg Depression Rating Scale (MADRS) and social and occupational functional impairment as measured on the Sheenan Disability Scale (SDS). Post-hoc effect size analysis by the evaluators provided evidence suggesting that there is unlikely to be a clinically important difference between the treatments on any of these outcomes (Davidson et al 2007).
Table 154: Study profiles for RCTs comparing tiagabine and placebo for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Davidson et al Moderate Adult population with mixed trauma Outpatient, 232 Severity of PTSD symptoms 2007) United States Depressive symptoms Anxiety Social and occupational functioning
In terms of safety outcomes, patients who received tiagabine experienced dizziness and somnolence at twice the rate of placebo patients, while other common adverse events occurred with similar frequency in both groups (Table 155) Most events were considered to be mild to moderate severity. One event was considered severe by the study investigators and involved one patient who experienced dizziness and nausea with loss of consciousness following an 8mg dose of tiagabine without food.
Table 155 Adverse events for comparison of tiagabine and placebo in people with PTSD Reference Adverse events Tiagabine (n=116) Placebo (n=116) % % (Davidson et al 2007) dizziness 32 13 headache 25 27 somnolence 20 10 nausea 18 20 Note: adverse events which occurred at twice or more the rate of the other treatment are in bold text
There is evidence suggesting that there is unlikely to be a clinically important difference between tiagabine and placebo on reducing the severity of clinician-rated PTSD symptoms at 12 weeks follow-up (k = 1; n = 232; SMD = 0.02; 95% CI, -0.24 to 0.28).
There is evidence suggesting that there is unlikely to be a clinically important difference between tiagabine and placebo on reducing anxiety symptom severity at 12 weeks follow-up (k = 1; n = 232; SMD = 0.01; 95% CI, -0.25 to 0.26).
There is evidence suggesting that there is unlikely to be a clinically important difference between tiagabine and placebo on reducing social and occupational functional impairment at 12 weeks follow-up (k = 1; n = 232; SMD = 0.05; 95% CI, -0.20 to 0.31).
Box __ Evidence statement matrix for RCT comparing tiagabine and placebo for adults with PTSD Component Rating Description
373 Evidence base C One level II study with a moderate risk of bias.
Consistency NA Only one study
Clinical impact D Slight/restricted
Generalisability B Good mix of trauma types, and so generalisability is good
Applicability C Study performed in the United States. Probably applicable to the Australian healthcare context with some caveats.
Summary of evidence No clinically important differences were found between tiagabine and placebo on reducing PTSD symptom severity, anxiety symptoms or functional impairment (Grade C).
DIVALPROEX VERSUS PLACEBO One study compared the effectiveness of divalproex sodium against placebo over an 8 week period (Davis et al, 2008). One further study was identified assessing the same comparison, but was excluded from the systematic review as there was a greater than 50% loss to follow-up in the placebo arm (Hamner et al 2009). The mean divalproex dose received by participants by week 8 was 2309±508 mg/day. No clinically important benefits were found from divalproex compared to placebo. Side effects were more common in divalproex than placebo (see Table 157), although only three patients (7%) in the divalproex arm withdrew treatment due to adverse events, compared with one (2%) in the placebo arm. However, due to some inconsistencies within the text of the article, it is unclear whether the percentages provide in Table 157 are the rates of adverse events experienced per treatment arm, or overall (ie, the rate of side effects may potentially be double what is stated if the wrong denominator was used).
Table 156 Study profiles for RCTs comparing divalproex and placebo for military veterans with PTSD Reference Risk of bias Population Setting N Outcomes measured (Davis et al 2008) Moderate Military veterans, 98% male Outpatient 82 PTSD severity (clinician) setting, United Depressive symptoms States Anxiety Attrition Side effects
There is evidence suggesting that there is unlikely to be a clinically important difference between divalproex and placebo on reducing the severity of clinician-rated PTSD symptoms at post-treatment (k=1, n=82, SMD=-0.22, 95%CI -0.66, 0.21).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between divalproex and placebo on reducing depressive symptoms at post-treatment (k=1, n=82, SMD=-0.47, 95%CI -0.91, -0.03)
There is evidence suggesting that there is unlikely to be a clinically important difference between divalproex and placebo on reducing anxiety at post-treatment (k=1, n=82, SMD= - 0.07, 95%CI -0.50, 0.36)
374 The evidence is inconclusive and so it not possible to determine whether there is a clinically important difference between divalproex and placebo on attrition (RR=1.33, 95%CI 0.56, 3.17).
Table 157 Side effects for divalproex and placebo in greater than 6% of patients Reference Side effect Divalproex Placebo (Davis et al 2008) Dizziness 24% - Nausea 14% - Gastrointestinal tract upset 12% - Drowsiness 12% - Increased urinary frequency 10% - Headache 10% - Memory deficit 10% - Abnormal vision 7% - Muscle weakness/myalgias - 7% NB: side effects which occurred at twice or more the rate of the other treatment are bolded
Box 149 Evidence statement matrix for RCT comparing divalproex and placebo for adults with PTSD Component Rating Description Evidence base C One level II study with a moderate risk of bias
Consistency N/A Only one study
Clinical impact D No clinically important differences detected between divalproex and placebo on measures of effect. Side effects were much more common in the divalproex arm.
Generalisability B Sample was from military veterans, predominantly male. Likely to be generalisable to target population.
Applicability C Study from the United States. Likely to be applicable to the Australian healthcare setting with some caveats.
Summary of evidence Divalproex was not found to be beneficial compared to placebo for treatment PTSD, and had a higher side-effects profile. (Grade C)
NORADRENERGIC AGENTS
GUANFACINE VERSUS PLACEBO
One study by Neylan et al (2006) was identified that examined the effectiveness of guanfacine for the treatment of chronic PTSD in veterans. Participants received a target dose ranging between 1 mg and 3 mg per day of guanfacine over an 8 week period. The primary effectiveness outcome was measured with the CAPS. The results did not indicate a statistically significant improvement between the intervention and placebo group on all outcomes.
Table 158 Study profiles for RCTs comparing guanfacine with placebo Reference Risk of bias Population Setting N Outcomes measured (Neylan et al 2006) High Veterans with PTSD Outpatient, USA 63 PTSD severity Type of trauma: not Depressive symptoms stated, possibly Quality of life combat-related
375 Side effects
Significant adverse events were reported for the use of guanfacine compared to placebo as outlined in Table 159.
Table 159 Side effects of guanfacine vs placebo in people with PTSD Reference Treatment emergent side guanfacine (n=29) Placebo (n=34) effects (Neylan et al 2006) Dry mouth 17 patients (59%) 5 patients (15%) Light headedness 7 patients (24%) 1 patient (3%) Somnolence 14 patients (48%) 8 patients (23%)
NB: side effects which occurred at twice or more the rate of the other treatment are bolded
There is evidence suggesting that there is unlikely to be a clinically important difference between guanfacine and placebo on reducing the severity of clinician-rated PTSD symptoms (k = 1; n = 63; SMD = -0.02; 95% CI, -0.57 to 0.51)
There is evidence suggesting that there is unlikely to be a clinically important difference between guanfacine and placebo on reducing the severity of PTSD symptoms (SCL-90-R) (k = 1; n = 63; SMD = -0.24; 95% CI, -0.78 to 0.31)
There is evidence suggesting that there is unlikely to be a clinically important difference between guanfacine and placebo on reducing depression (k = 1; n = 63; SMD = -0.04; 95% CI, -0.59 to 0.50)
There is evidence suggesting that there is unlikely to be a clinically important difference between guanfacine and placebo on improving quality of life (k = 1; n = 63; SMD = -0.08; 95% CI, -0.63 to 0.46)
Box 150 Evidence statement matrix for RCT comparing guanfaxine vs placebo for adults with PTSD Component Rating Description Evidence base D One small level II study with a high risk of bias.
Consistency NA Only one study
Clinical impact D The results indicated no statistically significant difference in effect between guanfaxine and placebo for the treatment of PTSD for all outcome measures. Therefore, no clinically important effects have been found. There were three significant adverse event in the intervention group vs placebo. Generalisability B Good generalisability given the population seem to be consisting of mainly veterans with assumed combat related PTSD. However, this was not stated directly.
Applicability C Study performed in the United States. Probably applicable to the Australian healthcare context with comes caveats.
Summary of evidence No statistically significant or clinically important differences were found between guanfaxine and placebo in veterans with chronic PTSD on reducing PTSD symptom severity, depressive symptoms, and increasing quality of life. (Grade D)
376 PRAZOSIN VS PLACEBO
Two moderate quality studies compared the effectiveness of prazosin versus placebo in samples of patients with PTSD who were having sleep disturbances. One study by Raskind et al (2007) was in a sample of military veterans, while the Taylor et al (2008) included patients with a history of childhood sexual abuse, childhood physical abuse, adult assault, rape or life- threatening motor vehicle accident. The majority of participants in both studies were receiving ongoing psychotherapy, and some were receiving maintenance psychotropic medication, which was unaltered during the study. Both studies used a starting dose of prazosin of 1 mg per day, which was titrated up to a maximum of 6 mg per day.
Taylor et al used a crossover trial design. After 3 weeks and a wash out period of one week, the groups crossed over to receive the alternate treatment for another 3 weeks. After three weeks on prazosin, the severity of PTSD symptoms, as measured on the PCL-C, were reduced an average of 7 points on a scale of 17 to 85 (to 51±14), whereas after three weeks on placebo, the same patients had reductions on the PCL-C of only 1 point (to 55±15).
In a slightly larger study, Raskind et al (2007) compared the effectiveness of prazosin and placebo over 8 weeks. Side effects from both prazosin and placebo are reported in Table 161. Raskind et al (2007) reported that on the PTSD Dream Rating Scale, there was a statistically significant difference favouring prazosin, however, this outcome was added at mid-study (i.e. not an outcome specified prior to study commencement) and the analyses were based on only 22 of the original 40 participants randomised, so conclusions should be very limited.
Table 160 Study profiles for RCTs comparing prazosin with placebo (in addition to ongoing psychotherapy) Reference Risk of bias Population Setting N Outcomes measured (Raskind et al 2007) Moderate Military veterans who Outpatient, United 34 Severity of PTSD symptoms {Raskind, 2007 suffer from trauma States Depressive symptoms #823} nightmares and sleep Global functioning disturbance (Taylor et al 2008) Moderate Adult PTSD patients Outpatient, United 13 Severity of PTSD symptoms with sleep disturbance States Type of trauma: childhood sexual abuse, physical abuse, adult assault etc
Table 161 Side effects of prazosin vs placebo in adults with PTSD Reference Treatment emergent side effects Prazosin (n=17) Placebo (n=17)
(Raskind et al 2007) Transient dizziness upon standing 9 6 Nasal or sinus congestion 7 1 Headache 3 1 Initial insomnia 1 1 Dry mouth 2 0 Sweating, depression and lower 0 1 oedema Upper gastrointestinal bleeding 1 0 (considered unrelated) resulting in discontinuation
377 Uncomfortable orthostatic dizziness 1 0 resulting in discontinuation NB: side effects which occurred at twice or more the rate of the other treatment are bolded
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between prazosin and placebo on reducing the severity of clinician-rated PTSD symptoms post-treatment (k=1; n=34; SMD=-0.37; 95%CI -1.05, 0.31).
There is evidence suggesting that there is unlikely to be a clinically important difference between prazosin and placebo on reducing the severity of self-reported PTSD symptoms post- treatment (k = 1; n = 13; SMD = -0.27; 95% CI, -1.04 to 0.51)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between prazosin and placebo on depressive symptons post- treatment (k=1; n=34; SMD= -0.26; 95%CI -0.94, 0.41).
There is limited evidence favouring prazosin over placebo on improvement in global functioning post-treatment (k=1; n=34; SMD=-1.03, 95%CI-1.55, -0.52).
Box 151 Evidence statement matrix for RCT comparing Prazosin vs placebo for adults with PTSD Component Rating Description Evidence base C Two level II studies with a moderate risk of bias.
Consistency C Studies consistent on the one outcome in common
Clinical impact D The results indicated that there was no clinical important benefit of prazosin over placebo for PTSD symptoms or depression, and limited evidence favouring prazosin on global functioning functioning. Adverse events more frequent in prazosin group. Generalisability B Reasonable generalisability given the mixed trauma population and military veteran population from the US. Applicability C Studies performed in the United States. Probably applicable to the Australian healthcare context with comes caveats.
Summary of evidence Two moderate quality studies found no clinically important differences between prazosin and placebo for the treatment of PTSD symptoms (self-rated or clinician-rated) or depressive symptoms, although one study found improvement in global functioning was greater in those receiving prazosin. (Grade C)
NONBENZODIAZEPINE HYPNOTIC ESZOPICLONE VERSUS PLACEBO Pollack et al (2011) compared eszopiclone dosed at 3mg daily over three weeks with placebo. The patient population comprised an adult trauma population with concomitant sleep disturbance and the study was carried out in an outpatient setting in the United States. Participant inclusion required a wash-out period of one week.
Drop-out rate was 11 per cent (3/27 patients), and effectiveness data were provided for the remaining 24 patients who were followed up at three weeks. Primary outcomes were clinician
378 and self-rated PTSD symptom severity, as measured by the Clinician Administered PTSD Scale (CAPS) and Short PTSD Rating Interview (SPRINT) at follow-up. Sleep quality, as an important quality of life component, has been included here as a secondary outcome and was measured on the Pittsburgh Sleep Quality Index (PSQI). Post-hoc effect size analysis by the evaluators provided estimates that were inconclusive as to whether there is a clinically meaningful difference between eszopiclone and placebo on reducing PTSD severity (clinician and self report), whilst there was limited evidence in favour of the active drug over placebo (Pollack et al 2011).
Table 162 Study profiles for RCTs comparing eszopiclone and placebo for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Pollack et al 2011) Moderate Adult trauma population with sleep Outpatient, 24 Severity of PTSD symptoms disturbance United States Quality of life (sleep)
In terms of safety outcomes, only patients who received eszopiclone experienced adverse events, and these were considered to be mild to moderate severity (see Table 163).
Table 163 Adverse events for comparison of eszopiclone and placebo in people with PTSD Reference Adverse events Eszopiclone (n=14) Placebo (n=13) % % (Pollack et al 2011) unpleasant taste 32 - sedation 16 - headache 12 - Note: adverse events which occurred at twice or more the rate of the other treatment are in bold text
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between eszopiclone and placebo on reducing the severity of clinician-rated PTSD symptoms 3 weeks post-treatment (k = 1; n = 24; SMD = -0.70; 95% CI, -1.28 to -0.12).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between eszopiclone and placebo on reducing the severity of self-reported PTSD symptoms at 3 weeks post-treatment (SPRINT – self report) (k = 1; n = 24; SMD = -0.73; 95% CI, -1.32 to -0.15).
There is limited evidence favouring eszopiclone over placebo on improving quality of sleep at 3 weeks post-treatment (PSQI – self report)(k =1; n = 24; SMD = -0.82; 95% CI, -1.41, - 0.23).
Box 152 Evidence statement matrix for RCT comparing eszopiclone and placebo for adults with PTSD Component Rating Description Evidence base C One small level II study with a moderate risk of bias.
Consistency NA Only one study
Clinical impact D Slight/restricted
Generalisability C Some uncertainty regarding the mix of trauma types represented in this study
379 Applicability C Study performed in the United States. Probably applicable to the Australian healthcare context with some caveats.
Summary of evidence In the adult population assessed, no clinically important differences were found between eszopiclone and placebo on reducing PTSD symptom severity, while limited evidence favours the active drug on improving quality of life (sleep) (Grade C).
OTHER DRUGS SELECTIVE NEUROKININ-1 RECEPTOR ANTAGONIST GR205171 VERSUS PLACEBO Mathew et al (2011) compared the effectiveness of selective neurokinin-1 receptor antagonist GR2051717 (NK1RA GR2051717) with placebo in an unspecified US community setting. The population was predominantly comprised of civilians with clinically diagnosed PTSD due to a mix of trauma types. Participant inclusion required a wash-out period of at least a week, if receiving any psychotropic drugs, prior to placebo lead-in. The active drug was dosed at 5mg, once daily, over eight weeks.
The trial reported a drop-out, of 34 per cent (16/47 patients), and effectiveness data were provided for 39 patients. A range of secondary outcomes were assessed, however, the data presented could not be extracted for the purpose of this review‡. On the primary outcomes of interest, PTSD symptom severity and PTSD post-treatment diagnostic status as per the Clinician Administered PTSD Scale (CAPS), the study authors found no statistically significant differences between treatment groups. Post-hoc effect size analysis by the evaluators provided estimates that were inconclusive as to whether there is a clinically meaningful difference between GR205171 and placebo on reducing PTSD severity and on the likelihood of PTSD diagnosis post-treatment (Mathew et al 2011).
Table 164 Study profiles for RCTs comparing GR205171 and placebo for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Mathew et al 2011) High Majority civilian population with mixed Community 39 Severity of PTSD symptoms trauma types, predominantly non- setting, United PTSD diagnosis sexual abuse or violence States Depressive symptoms Anxiety Functioning
In terms of safety outcomes, there were no treatment related serious adverse events. The placebo group were more than twice as likely to report nausea and vomiting than the GR205171 group (Table 165).
Table 165 Adverse events for comparison of GR205171 and placebo in people with PTSD Reference Adverse events GR205171 (n=20) Placebo (n=19) n (%) n (%)
‡ Study authors reported results of Fisher’s exact test (F statistic) for significance of categorical outcomes based on improvement in symptoms over time. No mean change/post-treatment mean data for differences in symptom severity between study groups.
380 (Mathew et al 2011) headache 13 (65) 12 (63.2) tiredness/fatigue 11 (55) 15 (78.9) irritability 12 (60) 16 (84.2) appetite decrease 11 (55) 10 (52.6) nausea 3 (15) 10 (52.6) vomiting 0 (0) 3 (15.8) Note: adverse events which occurred at twice or more the rate of the other treatment are in bold text
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between GR205171 and placebo on reducing the severity of clinician-rated PTSD symptoms at post-treatment (CAPS) (k = 1; n = 39; SMD = -0.31; 95% CI, -0.94 to 0.32).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between GR205171 and placebo on the likelihood of having a PTSD diagnosis post-treatment (CAPS) (k = 1; n = 39; RR = 0.79; 95% CI, 0.60 to 1.04).
Box 153 Evidence statement matrix for RCT comparing GR205171 and placebo for adults with PTSD Component Rating Description Evidence base D One small level II study with a high risk of bias.
Consistency NA Only one study
Clinical impact D Slight/restricted
Generalisability B Good generalisability given the mixed trauma population
Applicability C Study performed in the United States. Probably applicable to the Australian healthcare context with some caveats.
Summary of evidence In the adult population assessed, no statistically significant or clinically important differences were found between GR205171 and placebo on reducing PTSD symptom severity or the likelihood of PTSD diagnosis at post-treatment (Grade C).
TIANEPTINE VERSUS MOCLOBEMIDE The final treatment comparison made by Onder et al 2006 was tianeptine (a serotonin reuptake enhancer) versus moclobemide (an MAOI) over 12 weeks.
End-point mean scores on the CAPS suggested that the effectiveness of fluoxetine and tianeptine were similar for the treatment of PTSD. However, effect size analysis of the continuous data revealed a clinically significant difference across all possible values, meaning that there is evidence favouring tianeptine over moclobemide for the reduction of PTSD symptoms (Onder et al 2006).
Side effect profiles (number of patients who dropped out due to side effects) are summarised below in (Table x).
Table 166 Side effect profiles for patients who dropped out, by treatment group Reference Side-effect Fluoxetine drop-outs, n Tianeptine drop-outs, n
381 (Onder et al 2006) Insomnia 1 0 Over sedation 0 1 Nausea 0 0
Table 167 Study profile for RCT comparing tianeptine and moclobemide for post-earthquake PTSD patients Reference Risk of bias Population Setting N Outcomes measured (Onder et al 2006) High PTSD patients diagnosed according University 35 Change in PTSD symptoms to DSM-IV criteria following exposure outpatient to earthquake psychiatric unit and psychological trauma centre, Turkey
There is evidence favouring tianeptine over moclobemide for reducing the severity of clinician-rated PTSD symptoms (k=1, n=65, SMD=1.18, 95%CI 0.65, 1.71).
Box 154 Evidence statement matrix for RCT comparing tianeptine and moclobemide for post-earthquake PTSD patients Component Rating Description Evidence base D One level I study with high risk of bias
Consistency NA One study only
Clinical impact C Moderate: clinically important difference but only one outcome.
Generalisability C Evidence not directly generalisable to the target population but could be sensibly applied
Applicability C Probably applicable to Australian healthcare context with some caveats.
Summary of evidence Available evidence of low-quality suggests that there is a clinically meaningful difference favouring tianeptine over moclobemide for treatment of PTSD symptoms related to earthquake (Grade C).
MDMA VERSUS PLACEBO One RCT (Mithoefer et al 2011) compared the effectiveness of ±3,4- methylenedioxymethamphetamine (MDMA) (n=12 patients) with placebo (n=8 patients) in a United States outpatient setting. Patients with clinically diagnosed, treatment resistant PTSD§ due to crime or war-related trauma were eligible for inclusion. The active drug and placebo were both administered during two eight-hour experimental psychotherapy sessions. MDMA was dosed at an initial morning dose of 125mg and could be supplemented with an extra 62.5mg at the discretion of the clinician.
Mithoefer and co-workers lost 13 per cent (3/23) of their patients to follow-up, leaving 20 patients for which primary effectiveness outcomes were reported. No secondary effectiveness outcomes as defined a priori by this review’s protocol were reported. Post-treatment mean
§ See the relevant study profile table for further details.
382 change scores reported by the study authors showed a statistically significant between treatment difference favouring MDMA over placebo on the severity of clinician and self- reported PTSD symptoms as per the Clinician Administered PTSD Scale (PTSD) and Impact of Events Scale-Revised (IES-R), respectively. In agreement with both the reported continuous measures, our effect size analysis provided limited evidence for a clinically meaningful difference favouring MDMA over placebo on reducing PTSD severity at all follow-up time points. Furthermore, categorical data on PTSD diagnostic status at post- treatment also provided limited evidence favouring MDMA over placebo.
Table 168 Study profiles for RCTs comparing MDMA and placebo for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Mithoefer et al Moderate Victims of crime-related (95%) and Outpatient 20 Severity of PTSD symptoms 2011) war-related (5%) trauma setting, United (clinician and self-report) States PTSD diagnosis
Secondary outcomes were available in terms of safety. On the day of the experimental sessions, the MDMA group were more than twice as likely as the placebo group to experience jaw tightness, nausea, feeling cold, dizziness, loss of appetite and impaired balance, while patients on placebo were more likely than patients receiving MDMA to report anxiety and insomnia, and found that headache and fatigue to be equally common. During the week following the experiments, irritability and loss of appetite were more common among MDMA patients, while incidence of fatigue, anxiety, low mood, headache and nausea was similar in both groups during this period (Table 169)
Table 169 Treatment emergent adverse events for comparison of MDMA and placebo in people with PTSD Reference Adverse events MDMA (n=12) Placebo (n=8) % % (Mithoefer et al 2011) On day of experimental sessions jaw tightness 79 19 nausea 50 13 feeling cold 42 19 dizziness 38 13 loss of appetite 33 6 impaired balance 25 0 anxiety 58 81 insomnia 54 63 headache 58 56 fatigue 46 50 During week after experiments irritability 33 19 loss of appetite 38 0 fatigue 75 75 anxiety 54 44 low mood 42 50 headache 25 25 nausea 29 25 Note: adverse events which occurred at twice or more the rate of the other treatment are in bold text
There is limited evidence favouring MDMA over placebo on reducing the severity of clinician rated PTSD symptoms at 2 months follow-up (CAPS) (k = 1; n = 20; SMD = -1.21; 95% CI, - 2.18 to -0.24).
383 There is limited evidence favouring MDMA over placebo on reducing the severity of self- reported PTSD symptoms at 2 months follow-up (IES-R) (k = 1; n = 20; SMD = -0.97; 95% CI, -1.92 to -0.03).
There is limited evidence favouring MDMA over placebo on the likelihood of having a PTSD diagnosis post-treatment (CAPS) (k = 1; n = 20; RR = 0.27; 95% CI, 0.07 to 0.98).
Box 155 Evidence statement matrix for RCT comparing MDMA and placebo for adults with PTSD Component Rating Description Evidence base C One small level II study with a moderate risk of bias.
Consistency NA Only one study
Clinical impact D Slight/restricted
Generalisability B Evidence directly generalisable with some caveats
Applicability C Study performed in the United States. Probably applicable to the Australian healthcare context with some caveats.
Summary of evidence This study of moderate quality provided consistent outcomes with limited evidence for a clinically important difference favouring MDMA over placebo on reducing PTSD symptom severity and the likelihood of PTSD diagnosis at post-treatment (Grade C).
CHINESE HERBAL FORMULA VERSUS PLACEBO Meng et al (2011) compared the effectiveness of a Chinese herbal formulation** (CHF) with placebo. The study was in a community setting with a population of Shanghai earthquake survivors aged 16 years or older. The active drug was dosed as a 12g package of granulated ingredients, twice daily, over eight weeks. The placebo, also containing granules of identical appearance, was dosed following the same regimen.
Meng and colleagues reported a loss to follow-up of 18 per cent (44/245 patients), and effectiveness data were provided on an intent-to-treat basis. The study authors provided their own measure of effect size (Cohen’s d statistic) for self-reported PTSD symptom severity based on the revised Symptom Check-List-90 Global Severity Index (SCL-90-R GSI) and concluded that the CHF conferred a significant treatment benefit over placebo. However, on the basis of our effect size measures interpreted within the context of cut-offs determined a priori for this review, the evidence suggests that there is unlikely to be a clinically important difference between the treatments.
Table 170 Study profiles for RCTs comparing Chinese herbal formulation and placebo for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Meng et al 2012) Moderate Chinese earthquake survivors Community 245 Severity of PTSD symptoms setting, China
** See the relevant study profile table for further details.
384 The study’s safety outcomes indicated that six patients (4.9%) in the CHF group and five patients in the placebo group withdrew due to adverse events. The most frequently reported adverse events were nausea, diarrhoea, and malaise. These events occurred at similar frequency in both groups (Table 171)
Table 171 Adverse events for comparison of Chinese herbal formulation and placebo in people with PTSD Reference Adverse events CHF (n=123) Placebo (n=122) n (%) n (%) (Meng et al 2012) nausea 18 (14.6) 11 (9) diarrhoea 13 (10.6) 8 (6.5) malaise 13 (10.6) 15 (12.3)
There is evidence suggesting that there is unlikely to be a clinically important difference between Chinese herbal formulation and placebo on reducing the severity of self-reported PTSD symptoms at post-treatment (SCL-90-R GSI) (k = 1; n = 245; SMD = 0.44; 95% CI, 0.19 to 0.69).
Box 156 Evidence statement matrix for RCT comparing Chinese herbal formulation and placebo for adults with PTSD Component Rating Description Evidence base C One level II study with a moderate risk of bias.
Consistency NA Only one study
Clinical impact D Slight/restricted
Generalisability D Restricted to earthquake survivors
Applicability D Study performed in China. Not applicable to the Australian healthcare context.
Summary of evidence No evidence for a clinically important difference between the Chinese herbal formula and placebo was found (Grade D).
GLUCOCORTICOID VERSUS PLACEBO One RCT (Suris et al 2010) was available for comparison of intravenous glucocorticoid (hydrocortisone sodium succinate, 4mg/kg body mass) and placebo in the form of intravenous saline. A total of 22 combat veterans in a United States outpatient setting were randomised evenly, and received a once-off dose of either treatment during a memory reactivation task using established imagery techniques. The research aim was to assess the potential effectiveness of glucocorticoid in augmenting traumatic memory extinction, thereby reducing PTSD symptom severity.
The PTSD outcomes were measured using the Impact of Event Scale-Revised (IES-R), a self- report questionnaire tool. The secondary outcome was reduction in self-reported depression symptom severity, as measured on the Quick Inventory of Depressive Symptomology (QIDS- SR). While PTSD outcomes were reported separately for worst and second worst traumatic events, an overall measure representing both traumas was reported for depression symptom scores at one-week follow-up. Although the total follow-up period extended to one month post-treatment, data were not reported for this time point. Two patients were reported as lost
385 to follow-up (9%), leaving 20 patients for which effectiveness outcomes were available. Post- treatment mean scores reported for PTSD outcomes showed no statistical differences between treatment groups, while the mean score for depression symptoms was statistically higher in the active treatment group. In agreement with both the reported continuous measures, our effect size analysis provided inconclusicve evidence for a clinically meaningful between treatment difference on reducing PTSD severity and limited evidence favouring placebo on reducing depression symptoms. The authors noted no side effects with either treatment (Suris et al 2010).
Table 172 Study profiles for RCTs comparing glucocorticoid and placebo for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Suns et al 2010) Moderate Combat veterans Outpatient, 20 Severity of PTSD symptoms United States (self-report) Severity of depression symptoms (self-report)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between glucocorticoid and placebo on reducing self-reported PTSD symptom severity, based on the worst reported trauma incident, at 1 week follow-up (IES-R) (k = 1; n = 20; SMD = -0.77; 95% CI, -1.68 to 0.14).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between glucocorticoid and placebo on reducing self-reported PTSD symptom severity, based on the second worst reported trauma incident, at 1 week follow-up (IES-R) (k = 1; n = 20; SMD = -0.79; 95% CI, -1.70 to 0.12).
There is limited evidence favouring placebo over glucocorticoid on reducing the severity of self-reported depression symptoms at 1 week follow-up (QIDS-SR) (k =1; n = 20; SMD = 1.06; 95% CI, 0.12, 1.99).
Box 157 Evidence statement matrix for RCT comparing glucocorticoid and placebo for adults with PTSD Component Rating Description Evidence base C One small level II study with a moderate risk of bias.
Consistency NA Only one study
Clinical impact D Slight/restricted
Generalisability C Restricted to patients with combat-related PTSD symptoms
Applicability C Study performed in the United States. Probably applicable to the Australian healthcare context with some caveats.
Summary of evidence This small study of moderate quality provided inconclusive evidence for a clinically important difference between glucocorticoid and placebo on reducing PTSD symptoms, while there was limited evidence favouring placebo over glucocorticoid for reducing symptoms of depression (Grade C).
386 Psychosocial rehabilitation
Box 158 Study selection criteria for research questions 17 and 18
Research Question 17. For people with PTSD, does psychosocial rehabilitation improve outcomes compared to no intervention? Selection criteria Inclusion criteria Population People with PTSD Intervention Psychosocial rehabilitation (eg teaching self-care and independent living skills techniques, providing supported housing, marital/family skills training, social skills training, vocational rehabilitation and case management) in addition to a psychological intervention or pharmacological intervention Comparator 1. No intervention (e.g. assessment only) Outcome Primary outcome: functional improvement, quality of life Secondary outcomes: symptoms of depression, anxiety and substance misuse/ social and occupational function/ quality of life/ treatment refusal/ dropout over 12 months/ side-effects/ posttraumatic growth/ physical comorbidity. Additional outcomes for children: attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies are found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies Search Period 8/2005-10/2011 for adultsa , 1966-10/2011 if requiredb 1966-10/2011 for children and adolescentsc Language English aUpdated search from 2007 Guidelines. b Expanded search period if fewer than two Level II studies are found cNew research questions
Two trials were identified that addressed question 17, assessing the impact of psychosocial rehabilitation versus no intervention (Dybdahl 2001; Weine et al 2008). Both of these trials were on populations who were displaced from their homes in Bosnia and Herzegovina.
The moderate quality trial by Dybdahl (2001) compared a psychosocial intervention for mothers with an assessments only group of mothers (all participants and their children also received a medical intervention, provided free basic health care once a month). The mothers in the intervention group were invited to participate in group discussions over 5 months of approximately 5 mothers per group, led by a trained preschool teacher. The discussions were semi-structured and related to psychoeducation about specific topics such as trauma and trauma reactions, coping strategies, child development, and the mother-child interaction. This program aimed to increase the caregiver’s positive experiences with the child, improving communication. Outcomes were not provided in a format that could be translated into the standard evidence statements for this review. Mothers’ mental health (as scored on the Impact of Events Scale; IES) was determined to be improved to a significantly larger degree in the intervention group compared to the control group (t(58)=1.99, p<0.05), but it is unknown whether this is due to baseline differences in the two groups. The difference in mean posttest scores (56.1 vs 59.2 = 3.1) is not considered clinically important on a scale of 0 to 110. Child functioning (mother-rated on an 11 item 7-point semantic differential scale) and depression (on the Birleson’s Depression Inventory) were not significantly different between intervention and control groups, although the direction of effect supported the use of the intervention. Weine et al (2008) assessed the benefit of a multiple family group intervention (n=110) versus assessment only (n=87) for refugees with PTSD from Bosnia-Herzegovina who had settled in Chicago. In the intervention group, families were invited to participate in nine
387 sessions of Coffee and Families Education and Support (CAFES) to discuss issues of mental health problems such as PTSD and depression, marital, parenting and school problems, and family beliefs addressing mental illness and the use of mental health treatments. The program aimed to strengthen family identity, family communication, and increase the use of mental health resources outside of the family. The key outcome measure of the study was the number of mental health visits made by the primary subject in each family. In the 18 months after the intervention, those people who were randomised to the CAFES group (regardless of attendance of the group) made an average of 17.53 mental health visits, compared with a mean of only 6.22 mental health visits per person in the control group. This significant difference was constant over time, and was observed in both the primary subjects and their family members (Weine et al 2008).
Table 173 Study profiles for RCTs comparing psychosocial interventions and assessment only for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (Dybdahl 2001) Moderate Mothers who were Outpatient setting, 75 Symptoms of PTSD internally displaced Bosnia from Bosnia- Herzegovina (Weine et al 2008) High Refugees from Community based, 197 Surrogate measure – number of mental Bosnia-Herzegovina Chicago health visits who had settled in Chicago
One further trial was identified that compared psychotherapy plus psychosocial rehabilitation against psychotherapy (i.e. single intervention versus multiple intervention) (Beidel et al 2011). This study has been included for question 20.
Box 159 Evidence statement matrix for cognitive behavioural therapy for indicated prevention in adolescents Component Rating Description Evidence base C One small RCT with a moderate risk of bias and one RCT with a high risk of bias.
Consistency A The two studies were consistent in the direction of effect
Clinical impact D A psychosocial support group for mothers improved trauma symptoms for mothers, but did not show any significant impact on their children’s functioning or depressive symptoms. A multiple-family group intervention significantly increased the number of mental health visits the primary participant and their family members made, but it is unknown to what degree this impacts the participants functioning or quality of life. Generalisability C Both studies were on refugees (either still within Bosnia, or settled in Chicago) from Bosnia or Herzegovina, who had experienced war and famine. Limited generalisability to the broader Australian population, but possible generalisable to refugees. Applicability C Probably applicable to the Australian healthcare system with some caveats
Summary of evidence Limited evidence found statistically significant benefits from psychosocial support groups compared to no intervention in regards to participant levels of trauma symptoms and number of mental health visits. No significant benefit was found for children of participants on level of functioning or depressive symptoms. (Grade C)
388 Exercise and physical therapies
Box 160 Study selection criteria for research questions 18 and 19
Research Question 18. For people with ASD or PTSD, do physical interventions or exercise improve outcomes compared to no intervention? 19. For people with ASD or PTSD, do physical interventions or exercise confer an advantage over psychological or pharmacological interventions? Selection criteria Inclusion criteria Population People with ASD or PTSD Intervention (1) Physical therapy (eg electroconvulsive therapy, transcranial magnetic stimulation, massage, acupuncture, acupressure, Healing Touch, CranioSacral therapy) (2) Exercise therapy (eg yoga, T’ai Chi, movement-to-music, rhythm activities, competitive sports, walking, jogging, swimming) Comparator 1. No intervention / placebo 2. Any psychological or pharmacological intervention (eg trauma-focused CBT, stress management therapy, EMDR, narrative exposure therapy, supportive counselling, interapy, SSRIs, other second-generation antidepressants, tricyclic antidepressants, monoamine oxidase inhibitors, benzodiazepines, mood stabilisers, anti-convulsants, and some non-benzodiazepine hypnotics and anti-anxiety medications) Outcome Primary outcome: resolution of symptoms of ASD or PTSD Secondary outcomes: symptoms of depression, anxiety and substance misuse/ social and occupational function/ quality of life/ treatment refusal/ dropout over 12 months/ side-effects/ posttraumatic growth/ physical comorbidity. Additional outcomes for children: attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies are found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies Search Period 8/2005-10/2011 for adultsa , 1966-10/2011 if requiredb 1966-10/2011 for children and adolescentsc Language English aupdated search from 2007 Guidelines bExpanded search period if fewer than two Level II studies are found cNew research questions CBT= cognitive behavioural therapy; EMDR = eye movement desensitisation and reprocessing; SSRIs = selective serotonin reuptake inhibitors
Six studies were identified that examined the effectiveness of exercise and physical therapies for the treatment of PTSD. These therapies included transcranial magnetic stimulation, acupuncture, body orientated therapy, muscle relaxation and massage and discussed below. One study reported on acupuncture in addition to CBT, which has been assessed under question 21.
REPEATED TRANSCRANIAL MAGNETIC STIMULATION (rTMS) VERSUS PLACEBO
One double blinded randomised controlled trial by Cohen et al (2004) was identified that compared repeated high and low frequency transcranial magnetic stimulation (rTMS) with placebo. The high frequency rTMS was applied at 10Hz for 2 seconds per train and the low frequency rTMS was applied at 1 Hz for 5 seconds per train. Both had an interval of 58 seconds between trains and were positioned at the right dorsolateral prefrontal cortex. The treatment was given for 20 minutes per day over 10 working days. The placebo group was treated in the same way; however no magnetic field was evoked except for auditory effect.
389
Table 174 Study profiles for RCTs comparing rTMS and placebo Reference Risk of Population Setting N Outcomes measured bias (Cohen et al Moderate Adults with DSM-IV In- and out- patient 14 Severity of PTSD symptoms 2004a) diagnostic criteria programs, university for PTSD based mental health research centre, trauma unspecified Israel
High-frequency rTMS versus control:
There is limited evidence favouring high frequency repetitive transcranial magnetic stimulation (rTMS) over control on reducing the severity of clinician-rated PTSD symptoms at 14 days’ follow-up (k = 1; n = 16; SMD = -0.72; 95% CI, -1.77 to 0.33).
There is limited evidence favouring high frequency repetitive transcranial magnetic stimulation (rTMS) over control on reducing the severity self-report PTSD symptoms at post- treatment (k = 1; n = 16; SMD = -1.5; 95% CI, -2.67 to -0.32) and at 14 days’ follow-up(k = 1; n = 16; SMD = -0.68; 95% CI, -1.73 to 0.36).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between high frequency repetitive transcranial magnetic stimulation (rTMS) and control on reducing depression symptoms at post-treatment (k = 1; n = 16; SMD = -0.3; 95% CI, -1.32 to 0.72) or at 14 days’ follow-up (k = 1; n = 16; SMD = -0.13; 95% CI, -1.14 to 0.89).
There is limited evidence favouring high frequency repetitive transcranial magnetic stimulation (rTMS) over control on reducing anxiety symptoms at post-treatment (k = 1; n = 16; SMD = -1.38; 95% CI, -2.53 to -0.23).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between high frequency repetitive transcranial magnetic stimulation (rTMS) and control on reducing anxiety symptoms at 14 days’ follow-up (k = 1; n = 16; SMD = 0; 95% CI, -1.01 to 1.01).
There is limited evidence favouring high frequency repetitive transcranial magnetic stimulation (rTMS) over control on reducing the likelihood of leaving the study early due to any reason prior to 14 days follow-up (k = 1; n =19; RR = 0.36; 95% CI, 0.04 to 3.35).
Box 161: Evidence statement matrix for RCTs comparing high frequency rTMS and placebo for people diagnosed with PTSD Component Rating Description Evidence base C One level II study with moderate risk of bias
Consistency N/A Only one study
390 Clinical impact D There is a slight clinical impact of high frequency rTMS for a reduction in PTSD symptoms (self-report PTSD checklist, Hamilton anxiety rating scale, drop out), however the evidence is limited due to the range of estimates defined by the confidence interval including clinically unimportant effects. The evidence was inconclusive for anxiety and depressive symptoms at 14 days post-treatment due to small effect size and confidence intervals which included non-clinically important effects. Generalisability B Population is generalisable to the target population with some caveats, as the trauma was not specified and the population came from Israel.
Applicability C As the study was conducted in Israel, the treatment might be applicable to the Australian health care system with some caveats
Low-frequency rTMS versus control: The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between low frequency repetitive transcranial magnetic stimulation (rTMS) and control on reducing the severity of clinician-rated PTSD symptoms at 14 days’follow-up (k = 1; n = 14; SMD = 0.12; 95% CI, -0.94 to 1.18). I
There is limited evidence favouring control over low frequency repetitive transcranial magnetic stimulation (rTMS) on reducing the severity of self-report PTSD symptoms at post- treatment (k = 1; n = 16; SMD = 0.82; 95% CI, -0.25 to 1.88). I
There is limited evidence favouring control over low frequency repetitive transcranial magnetic stimulation (rTMS) on reducing the severity of self-report PTSD symptoms at 14 days follow-up (k = 1; n = 14; SMD = 0.67; 95% CI, -0.43 to 1.77). I
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between low frequency repetitive transcranial magnetic stimulation (rTMS) and control on reducing depression symptoms at post-treatment (k = 1; n = 14; SMD = -0.09; 95% CI, -1.15 to 0.97) or at 14 days’follow-up (k = 1; n = 14; SMD = 0.36; 95% CI, -0.71 to 1.43
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between low frequency repetitive transcranial magnetic stimulation (rTMS) and control on reducing anxiety symptoms at post-treatment (k = 1; n = 14; SMD = 0.15; 95% CI, -0.91 to 1.21). I
There is limited evidence favouring control over low frequency repetitive transcranial magnetic stimulation (rTMS) on reducing anxiety symptoms at 14 days’follow-up (k = 1; n = 14; SMD = 0.57; 95% CI, -0.52 to 1.66). I
There is limited evidence favouring low frequency repetitive transcranial magnetic stimulation (rTMS) over control on reducing the likelihood of leaving the study early due to any reason prior to 14 days’follow-up (k = 1; n =18; RR = 0.8; 95% CI, 0.14 to 4.49). I
Box 162 Evidence statement matrix for RCTs comparing low frequency rTMS and placebo for people diagnosed with PTSD Component Rating Description Evidence base C One level II study withmoderate risk of bias
Consistency N/A Only one study
391 Clinical impact D There is a slight clinical impact of the introduction of low frequency rTMS in comparison to placebo for the treatment of PTSD. The effect sizes indicate a clinically important difference in severity of PTSD symptoms (self rated scale), anxiety (Hamilton Anxiety Rating Scale) and drop out between the two groups, however the confidence interval suggests uncertainty around the direction of the effect. The comparison did not provide sufficient evidence to favour low frequency rTMS over placebo, as the effect sizes were small and the confidence intervals included non-important results for anxiety and depression symptoms (clinician rated Hamilton scale) and clinician-rated PTSD symptoms (CAPS). Generalisability B Population is generalisable to the target population with some caveats, as trauma was no specified and the population came from Israel.
Applicability C As the study was conducted in Israel, the treatment might be applicable to the Australian health care system with some caveats
Summary of evidence Only one study was identified that examined the effectiveness of high and low frequency rTMS. There was limited evidence suggesting that high frequency rTMS was more effective over 14 days on a range of outcome measures, than control. The evidence for low frequency rTMS was inconclusive. (Grade C).
ACUPUNCTURE VERSUS WAITLIST
One study by Hollifield et al (2007) reported on the effectiveness of acupuncture in comparison to placebo for the treatment of patients with PTSD. Treatment with acupuncture consisted of one hour sessions twice per week in which 25 to 40 minutes were spend on needle insertion, manipulation and retention. All people diagnosed with PTSD, based on the DSM-IV, received needle placement at standard acupuncture points and with few flexible prescribed points added dependent on the individual patient characteristics. The comparison group was put on a waiting list.
Table 175 Study profiles for RCTs comparing acupuncture and waitlist in people with PTSD Reference Risk of bias Population Setting N Outcome measured (Hollifield et al Low Adults 17 % trauma during Outpatients, 56 Severity of PTSD symptoms Checklist 2007) adulthood; 38% trauma >3 USA Depressive symptoms events; 28% >5 Anxiety years of ongoing child abuse Functioning impairment
There is limited evidence favouring acupuncture treatment over waitlist on reducing the severity of self-reported PTSD symptoms at 3 months’ follow-up (k = 1; n = 56; SMD = - 0.99; 95% CI, -1.56 to -0.39).
There is limited evidence favouring acupuncture over waitlist on reducing depression at 3 months’ follow-up (k = 1; n = 56; SMD = -0.90; 95% CI, -1.49 to -0.31).
There is limited evidence favouring acupuncture over waitlist on reducing anxiety at 3 months’ follow-up (k = 1; n = 56; SMD = -0.81; 95% CI, -1.39 to -0.22).
There is limited evidence favouring acupuncture over waitlist on reducing impairment at 3 months’ follow-up (k = 1; n = 56; SMD = -0.97; 95% CI, -1.57 to -0.37).
392 Box 163 Evidence statement matrix for RCTs comparing acupuncture and waitlist for people diagnosed with PTSD Component Rating Description Evidence base B One RCT (level II evidence) with a low risk of bias
Consistency N/A Only one study included
Clinical impact C The clinical impact of acupuncture in the treatment of PTSD is moderate. The effect sizes suggest that there is clinically important difference between acupuncture and control, however the confidence interval indicate the uncertainty surrounding the effect due to inclusion of non-clinically important results. Generalisability B The population included patients with a clinical diagnosis of PTSD according to the DSM-IV and the majority were of Caucasian, White (non Hispanic) ethnic background. Therefore the population is generalisable to the Australian target population with some caveats. Applicability C The study was conducted in the United States. Therefore the results are likely to be applicable to the Australian context with some caveats.
Summary of evidence Only one study was identified. There was limited evidence to suggest that acupuncture is more effective than no treatment at 3 months’ follow-up for the various outcomes related to PTSD. (Grade B).
BODY ORIENTED THERAPY VERSUS WAITLIST
One moderate quality study by Price et al (2006) reported on the effects of body orientated therapy versus waitlist in a female population with a history of sexual abuse. The body orientated therapy involved a one hour session during which patient received massage for 25 minutes followed by body awareness education and body and mind integration session of 25 minutes. The results indicated that there was a statistically significant difference between the intervention group and control group on psychological symptoms score (SCL-90-R) (1.82 versus 1.10; p< 0.01), Crime Related Post Traumatic Stress Disorder scale (CR-PTSD) (1.82 versus 0.73; p< 0.01), total number of physical symptoms (1.84 versus 0.27; p<0.01) and physical symptom discomfort (1.82 versus 1.1; p< 0.01) at nine weeks follow-up. The study did not provide effect sizes or sufficient data to calculate effect sizes. Also, the sample size (n = 8) was very small suggesting a lack of power to support the results. It unknown whether the statistically significant differences were also clinically important.
Table 176 Study profiles for RCTs comparing body orientated therapy and waitlist Reference Risk of bias Population Setting N Outcome measured (Price 2006) Moderate Adult females with outpatient, Hospital, 8 PTSD symptoms ; Symptoms checklist report of childhood Seatle Revised (SCL-R90) sexual abuse history USA Dissociative experiences Scale (DES) Crime related Post Traumatic Stress Disorder Scale (CR-PTSD)
Box 164 Evidence statement matrix for RCTs comparing body orientated therapy and waitlist for people diagnosed with PTSD Component Rating Description Evidence base C One RCT (level II evidence) with moderate risk of bias
393 Consistency N/A Only one study included
Clinical impact D The clinical difference between body orientated therapy compared to waitlist was found to be statistically significant. However, information on the size of the effect or to calculate the effect size was not provided, therefore the clinical impact cannot be determined.
Generalisability C The population included only female patients with a childhood sexual abuse history. and originates from USA. Therefore the population can be sensibly applied to the Australian target population.
Applicability B The study was conducted in the USA, which has a comparable health system. Therefore the results are applicable to the Australian context with some caveats.
Summary of evidence One study was identified that favoured body orientated therapy over waitlist in a female population. However, based on the small size and the poor quality of the study a recommendation would not be advised.
ACUPUNCTURE VERSUS COGNITIVE BEHAVIOURAL THERAPY One study by Hollifield et al (2007) reported on the effectiveness of acupuncture in comparison to cognitive behaviour therapy (CBT) for the treatment of patients with PTSD. Treatment with acupuncture consisted of one hour sessions twice per week in which 25 to 40 minutes were spend on needle insertion, manipulation and retention. All people diagnosed with PTSD, based on the DSM-IV, received needle placement at standard acupuncture points and with few flexible prescribed points added dependent on the individual patient characteristics. The CBT group received group therapy for two hours weekly over 12 weeks and were encouraged to practice by themselves at home for 15 minutes each day.
Table 177 Study profiles for RCTs comparing acupuncture and CBT in people with PTSD Reference Risk of bias Population Setting N Outcomes measured (Hollifield et al Low Adults 17 % trauma Outpatient USA 56 change in PTSD symptoms (PSS-SR), 2007) during adulthood; depression and anxiety (self rated 38% trauma >3 Hopkins Symptom Checklist 25); daily events; 28% >5 functioning impairment (Sheenan years of ongoing Disability Inventory) child abuse. Trauma not further specified.
There is evidence suggesting that there is unlikely to be a clinically important difference between acupuncture and CBT on reducing the severity of self-reported PTSD symptoms at 3 months’ follow-up (k = 1; n = 57; SMD = -0.09; 95% CI, -0.65 to 0.47)
There is evidence suggesting that there is unlikely to be a clinically important difference between acupuncture and CBT on reducing depression at 3 months’ follow-up (k = 1; n = 57; SMD = -0.04; 95% CI, -0.60 to 0.52)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between acupuncture and CBT on reducing anxiety at 3 months’ follow-up (k = 1; n =57; SMD = -0.25; 95% CI, -0.81 to 0.31)
394 There is evidence suggesting that there is unlikely to be a clinically important difference between acupuncture and CBT on reducing impairment at 3 months’ follow-up (k = 1; n = 57; SMD = -0.16; 95% CI, -0.72 to 0.40)
Box 165 Evidence statement matrix for RCTs comparing acupuncture and waitlist for people diagnosed with PTSD Component Rating Description Evidence base B One RCT (level II) with low risk of bias
Consistency N/A Only one study included
Clinical impact D The clinical impact of acupuncture in the treatment of PTSD is slight/restricted. The effect sizes suggest that there is no clinically important difference between acupuncture and control on any outcome measure.
Generalisability B The population included patients with a clinical diagnosis of PTSD according to the DSM-IV . 28 % had exp[erienced child abuse for more than 5 years, other trauma’s are not specified. The majority of sample were of Caucasian, White (non Hispanic) ethnic background. Therefore the population is likely Applicability C The study was conducted in the United States. Therefore the results are probably applicable to the Australian healthcare context with some caveats.
Summary of evidence One study was identified that compared acupuncture with CBT. However, the results indicated that acupuncture is unlikely to be more effective than CBT in reducing PTSD symptoms. (Grade B)
MUSCLE RELAXATION VERSUS COGNITIVE BEHAVIOURAL THERAPY A poor quality study by Hinton et al (2011) examined the effect of muscle relaxation compared to CBT on PTSD symptoms. The trial included Caribbean-Latino women with a DSM-IV diagnosis of PTSD who were considered treatment resistant after receiving supportive counselling and selective serotonine reuptake inhibitors at a maximum tolerated dosage for at least 6 months prior to the study. Participants received applied muscle relaxation for 14 weekly sessions of one hour which consisted of psychoeducation about PTSD symptoms, anxiety and panic, how these produce somatic symptoms and how muscle relaxation can reduce these symptoms. The control group received CBT which was culturally adapted to the Carribean-Latino women.
Table 178 Study profiles for RCTs comparing muscle relaxation and CBT Reference Risk of Population Setting N Outcomes measured bias (Hinton et al 2011) Moderate Caribbean-Latino Community based 24 PTSD symptoms (PTSD checklist) females with out patient clinic, Anxiety (SCL-anxiety Scale) treatment resistant specialised in PTSD. Services to Caribbean-Latino trauma not patients specified
395 There is limited evidence favouring muscle relaxation over CBT on reducing the severity of clinician-rated PTSD symptoms at 12 weeks follow-up (k = 1; n = 24; SMD = -1.58; 95% CI, -2.50 to -0.66)
There is limited evidence favouring muscle relaxation over CBT on reducing anxiety at 12 weeks follow-up (k = 1; n = 24; SMD = -0.96; 95% CI, -1.80 to -0.11)
Box 166 Evidence statement matrix for RCTs comparing muscle relaxation and CBT for people diagnosed with PTSD Component Rating Description Evidence base C One RCT (level II evidence) with a moderate risk of bias
Consistency N/A Only one study included
Clinical impact C There was found to be a clinically important benefit of muscle relaxation over CBT on the severity of PTSD symptoms and anxiety. However, the confidence intervals also included clinically unimportant differences.
Generalisability C The study population included only Caribbean-Latino females with a diagnosis of PTSD according to the DSM-IV and who were considered treatment resistant. This treatment resistance might indicate a sample with more severe PTSD or other limitations. Therefore, the population is not directly generalisable to the broader target population. Applicability C The study was conducted in the USA, which has a comparable health system. Therefore the results are applicable to the Australian context with some caveats.
Summary of evidence One small study with a moderate risk of bias was identified that reported on the effectiveness of muscle relaxation in comparison to CBT. The results indicated that there is limited evidence favouring muscle relaxation over CBT for a reduction in PTSD symptoms and anxiety. (Grade C)
MASSAGE VERSUS VIDEO ATTENTION A study by Field et al (1996) examined the effectiveness of massage in children with PTSD after Hurricane Andrew. The study sample was randomly assigned to either the massage group or a video attention control group. The massage consisted of two 15 minute sequences of 30 back and forth strokes on designated area of the neck and back and was applied twice daily for eight days spread over a one month period. During the same time, the attention video control group viewed video tapes of ‘Milo and Otis’ or ‘Beauty and the beast’ together with a psychology graduate student who kept physical contact by having the child on their lap or an arm around the child. The final measure was performed one day before the last treatment at one month follow-up.
The results indicated that the massage intervention was more effective than attention video on measures of anxiety (F = 6.59, p < 0.01) and depression (F = 5.82, p <0.02) on immediate effect and long term (F = 12.87, p< 0.002 and F = 9.07, p< 0.005, respectively). However, the study did not provide effect sizes or sufficient data to calculate effect sizes, so the standard evidence sentences could not been written. It is therefore unclear whether the statistically significant results reported were also clinically important.
Table 179 Study profiles for RCTs comparing Massage and Attention Video Reference Risk of bias Population Setting N Outcomes measured
396 (Field et al 1996) Moderate Children experiencing Elementary school, 60 Immediate effects: State anxiety PTSD following Miami,United States inventory for children (STAIC), Happy Hurricane Andrew Faces Scale Long term effects: Children’s Manifest Anxiety Scale, Center for Epidemiological
Box 167 Evidence statement matrix for RCTs comparing massage and attention video for people diagnosed with PTSD Component Rating Description Evidence base C One RCT (level II evidence) with a moderate risk of bias
Consistency N/A Only one study included
Clinical impact D The clinical difference between massage compared to attention video was found to be statistically significant. However, information on the size of the effect or to calculate the effect size was not provided, therefore the clinical impact cannot be determined.
Generalisability B The study population included children with a mean age of 7.5 years, affected by Hurricane Andrew in the USA. The results could be directly generalised to the target population with same caveats. However, the results are not generalisable to an adult population.
Applicability C The study was conducted in the USA, which has a comparable health system. Therefore the results are applicable to the Australian context with some caveats.
Summary of evidence One moderate quality study reported on the effectiveness of massage compared to attention video for the reduction of depression and anxiety symptoms in children. However, the evidence provided did not allow determination of the clinical importance of the benefit of massage over watching a video. (Grade C).
CBT WITH ACUPUNCTURE VERSUS CBT Zhang et al (2011) reported on the effectiveness of acupuncture in addition to CBT for a reduction in PTSD symptoms in victims of an earthquake who suffered PTSD symptoms. All participants received CBT which included a daily 30 minute session in which the participant was asked to describe the earthquake scene and their experiences. The intervention group received additional acupuncture therapy, which involved 50Hz stimulation on the left Laogong for 30 minutes every other day. All patients were followed up at one week. Improvements in PTSD symptoms was measured with self evaluation Incident Effect Scale revised (IES-R) and self evaluated Impact of Mental Trauma scale. A high score on both these scale indicates a high level of symptoms.
Table 180 Study profiles for RCTs comparing CBT plus acupuncture and CBT Reference Risk of Population Setting N Outcomes measured bi (Zhang et al Moderate Adults suffering Tertiary setting, 91 IES-R score 0-4 to express no PTSD symptoms 2011)} from PTSD after an Wenchuan, China up to severe symptoms and earthquake Self score questionnaire for major post traumatic psychological condition
397 There is limited evidence favouring CBT plus acupuncture over CBT alone on reducing teh severity of self-reported PTSD symptoms at one week follow-up (k = 1; n =91; SMD = -1.21; 95% CI, -1.70 to -0.71)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between CBT plus acupuncture and CBT alone on reducing stress at one week follow-up (k = 1; n = 91; SMD = 0.59; 95% CI, 0.12 to 1.07)
Box 168 Evidence statement matrix for RCTs comparing massage and attention video for people diagnosed with PTSD Component Rating Description Evidence base C One RCT (level II evidence) with a moderate risk of bias
Consistency N/A Only one study included
Clinical impact D There was a clinically important difference favouring CBT plus acupuncture over CBT alone for reducing PTSD symptoms. However, the confidence interval also included clinically irrelevant differences. For stress as an outcome, there was a trend towards favouring CBT alone compared to CBT plus acupuncture, however the effect size was not large enough to be considered clinically important. Generalisability B The study population included victims of an earthquake in China who suffer from PTSD symptoms. The population is generalisable to the target population with some caveats.
Applicability C The study was conducted in China, which has a different health system in comparison to Australia. Therefore the results are probably applicable to the Australian context with some caveats.
Summary of evidence One study with a moderate risk of bias reported on the effectiveness of acupuncture in addition to CBT compared to CBT alone for a reduction in PTSD symptoms. Limited evidence was found in favour of CBT plus acupuncture for a reduction in severity of PTSD symptoms. However no conclusive evidence was found for stress as an outcome. (Grade C).
398 Combined Interventions
Box 169 Study selection criteria for research question 20
Research Question 20. For people with PTSD, is a single intervention more effective than multiple interventions? Selection criteria Inclusion criteria Population People with PTSD Intervention Single psychological or pharmacological intervention or psychosocial rehabilitation strategy Comparator Combined psychological interventions, combined pharmacological interventions, combined psychosocial interventions, or combined psychological, pharmacological, physical, exercise therapy, or psychosocial interventions Outcome Primary outcome: resolution of symptoms of PTSD Secondary outcomes: symptoms of depression, anxiety and substance misuse/ social and occupational function/ quality of life/ treatment refusal/ dropout over 12 months/ side-effects/ posttraumatic growth/ physical comorbidity. Additional outcomes for children: attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies are found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies Search Period 8/2005-10/2011 for adultsa , 1966-10/2011 if requiredb 1966-10/2011 for children and adolescentsc Language English
aUpdated search from 2007 Guidelines. bExpanded search period if fewer than two Level II studies are found c New research questions
Twelve studies were identified comparing a single intervention (or single intervention plus placebo) with multiple interventions for the treatment of adults with PTSD (Beidel et al 2011; Bryant et al 2008b; Bryant et al 2003a; Foa et al 1999; Foa et al 2005; Marks et al 1998; Mithoefer et al 2011; Otto et al 2003; Rothbaum et al 2006; Schneier et al 2011; Simon et al 2008; Stein et al 2002). One study in children and adolescents with PTSD symptoms (Cohen et al 2007) was identified that compared CBT plus pharmacotherapy with CBT plus placebo.
The identified studies assess comparisons that are categorised as follows: i. single versus multiple components of CBT ii. pharmacotherapy alone versus pharmacotherapy plus psychotherapy iii. psychotherapy plus pharmacotherapy versus psychotherapy plus placebo iv. pharmacotherapies versus pharmacotherapy plus placebo
399
i. Single versus multiple components of CBT
EXPOSURE THERAPY ALONE VERSUS EXPOSURE THERPAY PLUS COGNITIVE RESTRUCTURING Three studies were identified (Bryant et al 2003a; Foa et al 2005; Marks et al 1998) which compared a form of exposure therapy alone with exposure therapy plus cognitive restructuring. A 1998 publication by Marks et al(Marks et al 1998) described a well designed four armed trial with moderate risk of bias which compared prolonged exposure (PE) alone with PE plus cognitive restructuring (PE/CR) in a population of PTSD outpatients in the UK. An Australian three armed study by Bryant et al (Bryant et al 2003a) compared imaginal exposure therapy (IE) alone with IE plus CR (IE/CR) for people with PTSD. This study of moderate quality and moderate risk of bias was conducted with civilian victims of non-sexual violence or motor vehicle accidents. Thirdly, a US study by Foa et al (Foa et al 2005) compared PE alone with PE plus CR in a population of female rape or assault victims. The study was also assessed as moderate quality and with a moderate risk of bias.
Table 181 Study profiles for RCTs comparing exposure therapy with cognitive restructuring plus exposure therapy Reference Risk of bias Population Setting N Outcomes measured (Marks et al 1998) Moderate PTSD subjects UK, outpatients 47 PTSD severity (CAPS) referred through Work/social Adjustment (self-rated) professional and Global improvement (clinician-rated) community services. Global improvement (self-rated) Main problem (clinician-rated) Main problem (self-rated) Total of 4 goals (clinician-rated) Total of 4 goals (self-rated)
(Bryant et al 2003a) High Civilians with PTSD Australia, hospital 58 PTSD severity (CAPS-2) as a result of non- based PTSD Unit Impact of Events Scale (IES) sexual assault or Beck Depression Inventory (BDI) motor vehicle State-Trait Anxiety Inventory (STAI) accident Catastrophic Cognitions Questionnaire (CCQ) National Adult Reading Test (NART) (Foa et al 2005) High Women with PTSD US centre for 153 Primary: as a result of rape female rape and PTSD symptom scale (PSS-I) or assault. assault victims Secondary: Beck Depression Inventory (BDI) Social Adjustment Scale (SAS) PTSD Symptom Scale-Self report (PSS-SR)
Meta-analysis was conducted for clinician-rated PTSD severity and depression severity (BDI) which was measured in both the Bryant 2003 and Foa 2005 studies at the post treatment and six month follow up time points. For the purposes of the meta-analysis, following the methodology of the NICE review, the two reported subscales of the PSSI scale in the Foa 2005 study were added together to give an overall score for PTSD to enter into the meta- analysis. There were no other measures across the three studies which were sufficiently consistent to conduct meta-analysis.
400
There is evidence suggesting there is unlikely to be a clinically important difference between exposure therapy alone and exposure therapy plus cognitive restructuring on clinician-rated PTSD severity at post-treatment (k=2, n=193; SMD 0.11 95% CI -0.17, 0.40)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between exposure therapy alone and exposure therapy plus cognitive restructuring on clinician-rated PTSD severity at post-treatment (k=1, n=40; SMD -0.38 95% CI -1.00, 0.25)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between IE alone and IE/CR for improvement in impact of events scale (intrusion) score at post treatment (k=1, n=40; SMD= 0.24 95% CI -0.38, 0.86).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between IE alone and IE/CR for improvement in impact of events scale (avoidance) score at post treatment (k=1; n=40; SMD= 0.24, 95% CI -0.38, 0.86).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between exposure therapy alone and exposure therapy plus cognitive restructuring on clinician-rated PTSD severity at 1 month follow up (k=1, n=34; SMD -0.37 95% CI -1.04, 0.32)
There is limited evidence favouring exposure therapy plus cognitive restricting over exposure therapy alone on clinician-rated PTSD severity at 3 months follow up (k=1, n=27; SMD - 0.73 95% CI -1.51, 0.05)
There is evidence suggesting there is unlikely to be a clinically important difference between exposure therapy alone and exposure therapy plus cognitive restructuring on clinician-rated PTSD severity at 3 months follow up (k=1, n=89; SMD 0.04 95% CI -0.38, 0.45)
401
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between exposure therapy alone and exposure therapy plus cognitive restructuring on clinician-rated PTSD severity at 6 months follow up (k=2, n=129; SMD 0.24 95% CI -0.11, 0.59)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between exposure therapy alone and exposure therapy plus cognitive restructuring on clinician-rated PTSD severity at 6 months follow up (k=1, n=23; SMD -0.48 95% CI -1.31, 0.35)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between exposure therapy alone and exposure therapy plus cognitive restructuring for improvement in impact of events scale (intrusion) score at 6 month follow up (k=1; n=40; SMD 0.15 95% CI -0.47, 0.77).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between exposure therapy alone and exposure therapy plus cognitive restructuring for improvement in impact of events scale (avoidance) score at 6 month follow up (k=1; n=40; SMD 0.46 95% CI -0.17, 1.08).
402
There is evidence suggesting that there is unlikely to be a clinically important difference between IE alone and IE/CR for self-report depression severity (BDI score) at post treatment (k=2; n=191; Hedges’ g= 0.10, 95% CI -0.18, 0.39).
There is evidence suggesting that there is unlikely to be a clinically important difference between prolonged exposure alone and prolonged exposure plus cognitive restructuring for self-reported depression severity (BDI) at 3 month follow up (k=1, n=89, Hedges’ g= 0.04, 95% CI -0.38, 0.45).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between exposure therapy alone and exposure therapy plus
403 cognitive restructuring for self-reported depression severity (BDI score) at 6 month follow up (k=2; n=125; SMD 0.11 95% CI -0.24, 0.46).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between prolonged exposure alone and prolonged exposure plus cognitive restructuring for self-reported depression severity (BDI) at 12 month follow up (k=1, n=85, SMD -0.15 95% CI -0.58, 0.28).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between exposure therapy alone and exposure therapy plus cognitive restructuring anxiety at post treatment (k=1; n=40; SMD 0.11 95% CI -0.51, 0.73).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between exposure therapy alone and exposure therapy plus cognitive restructuring for anxiety at 6 month follow up (k=1; n=40; SMD -0.0, 95% CI - 0.66, 0.58).
Box 170 Evidence statement matrix for RCTs comparing exposure therapy with cognitive restructuring plus exposure therapy Component Rating Description Evidence base C One level II study with a moderate risk of bias and two level II studies with a high risk of bias
Consistency C Results vary favouring both treatments
Clinical impact D Slight/Restricted
Generalisability B Evidence directly generalisable to target population with some caveats
Applicability B Evidence applicable to Australian health context with some caveats
Summary of results The evidence from three studies with moderate risk to high risk of bias was unable to demonstrate greater effectiveness of either exposure therapy plus cognitive restructuring or exposure therapy alone. There were limited outcomes that showed any clinical importance favouring either treatment. It should be noted that follow up data tended to be reported as completer analysis only, rather than intention to treat analysis. (Grade C)
COGNITIVE RESTRUCTURING ALONE VERSUS COGNITIVE RESTRUCTURING PLUS EXPOSURE THERAPY The comparison of cognitive restructuring alone with cognitive restructuring plus exposure therapy was reported in a single identified study by Marks et al 1998 (Marks et al 1998) and constituted part of a four armed trial. Marks’ study assessed PTSD in a UK population and was well designed, with moderate risk of bias.
Table 182 Study profiles for RCTs comparing cognitive restructuring alone with cognitive restructuring plus exposure therapy Reference Risk of bias Population Setting N Outcomes measured
404 (Marks et al 1998) Moderate PTSD subjects UK, outpatients 43 PTSD severity (CAPS) referred through Work/social Adjustment (self-rated) professional and Global improvement (clinician-rated) community services. Global improvement (self-rated) Main problem (clinician-rated) Main problem (self-rated) Total of 4 goals (clinican-rated) Total of 4 goals (self-rated)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between cognitive restructuring alone and cognitive restructuring plus exposure therapy for clinician-rated PTSD severity at post treatment (k=1, n=39: SMD-0.33 95% CI -0.96, 0.31). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between cognitive restructuring alone and cognitive restructuring plus exposure therapy for clinician-rated PTSD severity at 1 month follow up (k=1, n=32 SMD 0.14 95% CI -0.56, 0.84). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between cognitive restructuring alone and cognitive restructuring plus exposure therapy for clinician-rated PTSD severity at 3 months follow up (k=1, n=27; SMD 0.41 95% CI -0.36, 1.17). There is limited evidence favouring cognitive restructuring plus exposure therapy over cognitive restructuring alone for the clinician-rated PTSD severity at 6 months follow up (k=1, n=23; SMD 0.83, 95% CI -0.02, 1.68).
Box 171 Evidence statement matrix for RCTs comparing cognitive restructuring alone with cognitive restructuring plus exposure therapy Component Rating Description Evidence base C One level I study with a moderate risk of bias
Consistency NA Not applicable (one study only)
Clinical impact D No clinically important differences found.
Generalisability B Evidence directly generalisable to target population with some caveats
Applicability B Evidence applicable to Australian health context with some caveats
Summary of evidence While the evidence from one small study of moderate bias risk was inconclusive, there was some evidence that suggested that exposure therapy plus cognitive restructuring was more effective than cognitive restructuring alone at the 6 month time point for PTSD severity. However at this time point there was a 41% drop out rate over both arms so the result should be viewed cautiously. (Grade C)
405 RELAXATION VERSUS EXPOSURE THERAPY PLUS COGNITIVE RESTRUCTURING Marks 1998 (Marks et al 1998) was the only study identified that reported data for this comparison as part of a four armed trial. Marks study assessed PTSD in a UK population and was well designed, with moderate risk of bias.
Table 183 Study profiles for RCTs comparing relaxation with exposure therapy plus cognitive restructuring Reference Risk of bias Population Setting N Outcomes measured (Marks et al 1998) Moderate PTSD subjects UK, outpatients 45 PTSD severity referred through Work/social Adjustment (self-rated) professional and Global improvement (clinician-rated) community services. Global improvement (self-rated) Main problem (clinician-rated) Main problem (self-rated) Total of 4 goals (clinican-rated) Total of 4 goals (self-rated)
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between relaxation and cognitive restructuring plus exposure therapy for clinician-rated PTSD severity at post treatment (k=1, n=38; SMD-0.24, 95% CI - 0.87, 0.40). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between relaxation and cognitive restructuring plus exposure therapy for clinician-rated PTSD severity at 1 month follow up (k=1, n=34; SMD 0.15, 95% CI -0.53, 0.82). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between relaxation and cognitive restructuring plus exposure therapy for clinician-rated PTSD severity at 3 months follow up (k=1, n=27; SMD 0.37, 95% CI -0.39, 1.13).
Box 172 Evidence statement matrix for RCTs comparing relaxation with exposure therapy plus cognitive restructuring Component Rating Description Evidence base C One level I study with a moderate risk of bias
Consistency NA Not applicable (one study only)
Clinical impact D No clinically important differences found.
Generalisability B Evidence directly generalisable to target population with some caveats
Applicability B Evidence applicable to Australian health context with some caveats
Summary of evidence There was no conclusive evidence regarding the effectiveness of relaxation compared with cognitive restructuring plus exposure therapy for PTSD symptom severity at post treatment, one, three or six month follow up time points. (Grade C)
406 SUPPORTIVE COUNSELLING VERSUS EXPOSURE THERAPY PLUS COGNITIVE RESTRUCTURING One Australian RCT was identified (Bryant et al 2003a) that fitted criteria for the comparison of supportive counselling with a form of exposure therapy (IE) plus cognitive restructuring. Bryant’s study recruited subjects with PTSD resulting from non-sexual assault or motor vehicle accident. The study was determined to be a well designed trial, but was classified as having a moderate risk of bias due to 22% loss to follow-up.
Table 184 Study profiles for RCTs comparing supportive counselling with exposure therapy plus cognitive restructuring Reference Risk of bias Population Setting N Outcomes measured (Bryant et al 2003a) Moderate Civilians with PTSD Australia, hospital 58 PTSD severity as a result of non- based PTSD Unit Depressive symptoms sexual assault or Anxiety motor vehicle accident
There is limited evidence favouring cognitive restructuring plus exposure therapy over supportive counselling for clinician-rated PTSD intensity score at post treatment (k=1; n=38; SMD 0.82, 95% CI 0.16, 1.48).
There is limited evidence favouring cognitive restructuring plus exposure therapy over supportive counselling for improvement in clinician-rated PTSD frequency score at post treatment (k=1; n=38; SMD 0.78, 95% CI 0.12, 1.44).
There is limited evidence favouring cognitive restructuring plus exposure therapy over supportive counselling for improvement in impact of events scale (intrusion) score at post treatment (k=1; n=38; SMD 0.73, 95% CI 0.08, 0.39).
There is limited evidence favouring cognitive restructuring plus exposure therapy over supportive counselling for improvement in impact of events scale (avoidance) score at post treatment (k=1; n=38; SMD 0.77, 95% CI 0.12, 1.44).
There is limited evidence favouring cognitive restructuring plus exposure therapy over supportive counselling for improvement in clinician administered PTSD intensity score at 6 month follow up (k=1; n=38; SMD 1.03, 95% CI 0.35, 1.70).
There is limited evidence favouring cognitive restructuring plus exposure therapy over supportive counselling for improvement in clinician administered PTSD frequency score at 6 month follow up (k=1; n=38; SMD 1.05, 95% CI 0.37, 1.72).
There is limited evidence favouring cognitive restructuring plus exposure therapy over supportive counselling for improvement in impact of events scale (intrusion) score at 6 month follow up (k=1; n=38; SMD 0.90, 95% CI 0.37, 1.57).
There is limited evidence favouring cognitive restructuring plus exposure therapy over supportive counselling for improvement in impact of events scale (avoidance) score at 6 month follow up (k=1; n=38; SMD 0.87, 95% CI -0.17 to 1.08).
407 There is limited evidence favouring cognitive restructuring plus exposure therapy over supportive counselling for improvement in BDI score at post treatment (k=1; n=38; SMD 0.73, 95% CI 0.07, 1.39).
There is limited evidence favouring cognitive restructuring plus exposure therapy over supportive counselling for improvement for improvement in BDI score at 6 month follow up (k=1; n=38; SMD 0.78, 95% CI 0.11, 1.44).
There is limited evidence favouring cognitive restructuring plus exposure therapy over supportive counselling for improvement in STAI anxiety score at post treatment (k=1; n=38; SMD 0.78, 95% CI 0.12, 1.44).
There is limited evidence favouring cognitive restructuring plus exposure therapy over supportive counselling for improvement in STAI anxiety score at 6 month follow up (k=1; n=40; SMD -0.04, 95% CI 0.23, 1.52).
Box 173 Evidence statement matrix for RCTs comparing supportive counselling with exposure therapy plus cognitive restructuring Component Rating Description Evidence base C One level II study with a moderate risk of bias
Consistency NA Not applicable (one study only)
Clinical impact B Consistent clinically important point estimates favouring cognitive restructuring plus exposure therapy
Generalisability B Evidence directly generalisable to target population with some caveats
Applicability A Evidence directly applicable to the Australian health care context
Summary of results There is consistent evidence of clinically important point estimates of effect from one Australian study favouring cognitive restructuring plus exposure therapy over supportive counselling for several clinician report and self report PTSD measures at both the post treatment and 6 month follow up time points. (Grade C)
IMAGINAL EXPOSURE VERSUS IMAGINAL EXPOSURE PLUS IN VIVO EXPOSURE One study was identified (Bryant et al 2008b) comparing imaginal exposure with imaginal exposure plus in vivo exposure, fitting search criteria. In Bryant’s four armed trial PTSD subjects were treated with one of the following single or multiple treatments: imaginal exposure (IE), in vivo exposure (IVE), IE plus IVE, (IE/IVE), or IE/IVE plus cognitive therapy (IE/IVE/CBT). While IE and IVE have similar exposure aspects, IVE has a greater learning component than IE. Overall therapy time was the same between all treatment groups. Bryant’s study was conducted in an Australian trauma clinic setting, in a population of patients with PTSD resulting from non-sexual assault or motor vehicle accident trauma. The study is of good quality and rated moderate for risk of bias.
408 Table 185 Study profiles for RCTs comparing imaginal exposure with imaginal exposure plus in vivo exposure Reference Risk of bias Population Setting N Outcomes measured (Bryant et al 2008b) Moderate Nonsexual assault Australia, hospital 62 PTSD severity and motor vehicle trauma clinic Depressive symptoms accident trauma Anxiety
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between IE and IE/IVE for clinician-rated PTSD severity at post-treatment (k=1, n=62, SMD 0, 95% CI cannot be calculated). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between IE and IE/IVE for clinician-rated PTSD severity at 6 months follow up (k=1, n=62, SMD 0.10, 95% CI -0.40, 0.60). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between IE and IE/IVE for depression at post-treatment (k=1, n=62, SMD -0.07, 95% CI -0.57, 0.43). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between IE and IE/IVE for depression at 6 months follow up (k=1, n=62, SMD -0.30, 95% CI -0.80, 0.20). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between IE and IE/IVE for anxiety at post-treatment (k=1, n=62, SMD 0.11, 95% CI -0.34, 0.61). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between IE and IE/IVE for anxiety at 6 months follow up (k=1, n=62, SMD 0.08, 95% CI -0.41, 0.58).
Box 174 Evidence statement matrix for RCTs comparing imaginal exposure with imaginal exposure plus in vivo exposure Component Rating Description Evidence base C One level II study with a moderate risk of bias
Consistency NA Not applicable (one study only)
Clinical impact D No clinically important differences between the treatments
Generalisability B Evidence directly generalisable to target population with some caveats
Applicability A Evidence directly applicable to the Australian health care context
Summary of results Evidence regarding the comparison of IE and IE/IVE was inconclusive and it was not possible to determine if there was a clinical difference between groups. (Grade C).
409 IN VIVO EXPOSURE VERSUS IMAGINAL EXPOSURE PLUS IN VIVO EXPOSURE Bryant’s 2008 study (Bryant et al 2008b) was the only RCT identified comparing in vivo exposure (IVE) and imaginal exposure plus in vivo exposure (IE/IVE). Bryant’s study was conducted in an Australian trauma clinic setting, in a population of patients with PTSD resulting from non-sexual assault or motor vehicle accident trauma. The study is of good quality and rated moderate for risk of bias.
Table 186 Study profiles for RCTs comparing in vivo exposure with imaginal exposure plus in vivo exposure Reference Risk of bias Population Setting N Outcomes measured (Bryant et al 2008b) Moderate Nonsexual assault Australia, hospital 59 PTSD severity and motor vehicle trauma clinic Depressive symptoms accident trauma Anxiety
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between IVE and IE/IVE for clinician-rated PTSD severity at post-treatment (k=1, n=59; SMD 0.02, 95% CI -0.49, 0.53). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between IVE and IE/IVE for clinician-rated PTSD severity at 6 months follow up (k=1, n=59; SMD 0.09, 95% CI -0.42, 0.60). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between IVE and IE/IVE for depression at post-treatment (k=1, n=59; SMD -0.20, 95% CI -0.72, 0.31). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between IVE and IE/IVE for depression at 6 months follow up (k=1, n=59; SMD -0.36, 95% CI -0.87, 0.15). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between IVE and IE/IVE for anxiety at post-treatment (k=1, n=59; SMD 0.08, 95% CI -0.43, 0.59). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between IVE and IE/IVE for anxiety at 6 months follow up (k=1, n=59, SMD -0.22, 95% CI -0.73, 0.30).
Box 175 Evidence statement matrix for RCTs comparing in vivo exposure with imaginal exposure plus in vivo exposure Component Rating Description Evidence base C One level II study with a moderate risk of bias
Consistency NA Not applicable (one study only)
Clinical impact D No clinically important differences found.
Generalisability B Evidence directly generalisable to target population with some caveats
Applicability A Evidence directly applicable to the Australian health care context
410 Summary of results Evidence regarding the comparison of IE and IE/IVE was inconclusive and it was not possible to determine if there was a clinical difference between groups. (Grade C).
IMAGINAL EXPOSURE VERSUS IMAGINAL EXPOSURE PLUS IN VIVO EXPOSURE AND COGNITIVE RESTRUCTURING One study (Bryant et al 2008b) was identified fitting search criteria that compared imaginal exposure (IE) with imaginal exposure plus in vivo exposure and cognitive restructuring (IE/IVE/CR). Bryant’s study was conducted in an Australian trauma clinic setting, in a population of patients with PTSD resulting from non-sexual assault or motor vehicle accident trauma. The study is of good quality and rated moderate for risk of bias.
Table 187 Study profiles for RCTs comparing imaginal exposure with imaginal exposure plus in vivo exposure and cognitive restructuring Reference Risk of bias Population Setting N Outcomes measured (Bryant et al 2008b) Moderate Nonsexual assault Australia, hospital 59 PTSD severity and motor vehicle trauma clinic Depressive symptoms accident trauma Anxiety
There is limited evidence favouring IE/IVE/CR over IE for clinician-rated PTSD severity at post-treatment (k=1, n=59; SMD 0.82, 95% CI 0.29, 1.35). There is limited evidence favouring IE/IVE/CR over IE for clinician-rated PTSD severity at 6 months follow up (k=1, n=59; SMD 0.91, 95% CI 0.36, 1.46). There is limited evidence favouring IE/IVE/CR over IE for depression at post-treatment (k=1, n=59; SMD -0.56, 95% CI 0.04, 1.08). There is limited evidence favouring IE/IVE/CR over IE for depression at 6 months follow up (k=1, n=59; SMD 0.56, 95% CI 0.04, 1.08). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between IE and IE/IVE/CR for anxiety at post-treatment (k=1, n=59; SMD 0.25, 95% CI -0.26, 0.76). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between IE and IE/IVE/CR for anxiety at 6 months follow up (k=1, n=59; SMD 0.45, 95% CI -0.07, 0.96).
Box 176 Evidence statement matrix for RCTs comparing imaginal exposure with imaginal exposure plus in vivo exposure and cognitive restructuring Component Rating Description Evidence base C One level I study with a moderate risk of bias
Consistency NA Not applicable (one study only)
Clinical impact C Moderate; several clinically important point estimates favouring the multicomponent intervention
Generalisability B Evidence directly generalisable to target population with some caveats
411 Applicability A Evidence directly applicable to the Australian health care context
Summary of results Bryant’s study provides limited evidence that there is a clinically important difference favouring IE/IVE/CR treatments over IE alone for reduction of PTSD symptoms and depression, but not for anxiety. The greater effectiveness of IE/IVE/CR was still evident at the 6 month follow up for both measures. (Grade C)
IN VIVO EXPOSURE VERSUS IMAGINAL EXPOSURE PLUS IN VIVO EXPOSURE AND COGNITIVE RESTRUCTURING One study (Bryant et al 2008b) was identified that compared imaginal exposure (IVE) with imaginal exposure plus in vivo exposure and cognitive restructuring (IE/IVE/CR). Bryant’s study was conducted in an Australian trauma clinic setting, in a population of patients with PTSD resulting from non-sexual assault or motor vehicle accident trauma. The study is of good quality and rated moderate for risk of bias.
Table 188 Study profiles for RCTs comparing in vivo exposure with imaginal exposure plus in vivo exposure and cognitive restructuring Reference Risk of bias Population Setting N Outcomes measured (Bryant et al 2008b) Moderate Nonsexual assault Australia, hospital 56 PTSD severity and motor vehicle trauma clinic Depressive symptoms accident trauma Anxiety
There is limited evidence favouring IE/IVE/CR over IVE for clinician-rated PTSD severity at post-treatment (k=1, n=56; SMD 0.99, 95% CI 0.44, 1.55). There is limited evidence favouring IE/IVE/CR over IVE for clinician-rated PTSD severity at 6 months follow up (k=1, n=56; SMD 0.99, 95% CI 0.44, 1.55). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between IVE and IE/IVE/CR for depression at post-treatment (k=1, n=56; SMD -0.46, 95% CI -0.07 , 0.99). There is limited evidence favouring IE/IVE/CR over IVE for depression at 6 months follow up (k=1, n=56; SMD 0.51, 95% CI -0.02, 1.04). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between IVE and IE/IVE/CR for anxiety at post-treatment (k=1, n=56; SMD 0.21, 95% CI -0.31, 0.74). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between IVE and IE/IVE/CR for anxiety at 6 months follow up (k=1, n=56; SMD 0.20, 95% CI -0.33, 0.72).
Box 177 Evidence statement matrix for RCTs comparing in vivo exposure with imaginal exposure plus in vivo exposure and cognitive restructuring Component Rating Description
412 Evidence base C One level I study with a moderate risk of bias
Consistency NA Not applicable (one study only)
Clinical impact D Slight/Restricted; limited clinically important point estimates of effect
Generalisability B Evidence directly generalisable to target population with some caveats
Applicability A Evidence directly applicable to the Australian health care context
Summary of results One Australian RCT provides limited evidence that there is a clinically important difference favouring IE/IVE/CR treatments over IVE alone for reduction of PTSD symptoms at post- treatment and at the 6 month follow up. While there was similar evidence of greater effectiveness of IE/IVE/CR for depression at the 6 month follow up, this difference was less significant at the post treatment time point. There was no conclusive evidence of clinical difference for anxiety at either post treatment or 6 month follow up. (Grade C)
PROLONGED EXPOSURE VERSUS PROLONGED EXPOSURE PLUS STRESS INNOCULATION TRAINING One four armed trial was identified (Foa et al 1999) fitting search criteria which compared prolonged exposure (PE) with prolonged exposure plus stress inoculation training (PE/SIT). In Foa’s 1999 trial PE consisted of 9 sessions based around imaginal exposure, and listening to a tape recording of the reliving of the traumatic memory as homework. SIT session focused on teaching coping skills, relaxation, cognitive restructuring and covert modelling, There was no exposure component of SIT and no homework was set. Study subjects were women who were victims of sexual or non-sexual assault (index assault after the age of 16 years). The study was well designed but there was a lack of intention to treat data reported, and greater than 15% loss to follow-up, so the study was therefore rated as having a high risk of bias.
Table 189 Study profiles for RCTs comparing prolonged exposure with prolonged exposure plus stress inoculation training Reference Risk of bias Population Setting N Outcomes measured (Foa et al 1999) High Female adult sexual US, mental health 55 Severity of PTSD and non-sexual centre Depressive symptoms assault victims Anxiety Social adjustment
At post-treatment: The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between PE and PE/SIT for clinician-rated PTSD severity (k=1, n=45; SMD 0.22, 95% CI -0.81, 0.37). There is limited evidence favouring PE over PE/SIT for depression (k=1, n=43; SMD -0.61, 95% CI -1.21, 0.00).
413 There is limited evidence favouring PE over PE/SIT for anxiety (k=1, n=43; SMD -0.60, 95% CI -1.21, 0.00). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between PE and PE/SIT for social adjustment (k=1, n=44; SMD -0.48, 95% CI -1.08, 0.12). At 3 months follow up: The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between PE and PE/SIT for clinician-rated PTSD severity (k=1, n=39; SMD 0.04, 95% CI-0.62, 0.67). There is limited evidence favouring PE over PE/SIT for depression (k=1, n=39; SMD -0.62, 95% CI -1.26, 0.02). The evidence is not conclusive and so it is not possible to determine whether there is a clinically important difference between PE and PE/SIT for anxiety (k=1, n=39; SMD -0.47, 95% CI -1.11, 0.17). There is limited evidence favouring PE over PE/SIT for social adjustment (k=1, n=38; SMD - 0.68, 95% CI -1.33, 0.02). At 6 months follow up: The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between PE and PE/SIT for clinician-rated PTSD severity (k=1, n=37; SMD -0.21, 95% CI -0.86, 0.44). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between PE and PE/SIT for depression (k=1, n=36; SMD - 0.40, 95% CI -1.06, 0.26). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between PE and PE/SIT for anxiety (k=1, n=36; SMD -0.46, 95% CI -1.12, 0.20). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between PE and PE/SIT for social adjustment (k=1, n=36; SMD -0.48, 95% CI -1.14, 0.18). At 1 year follow up: The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between PE and PE/SIT for clinician-rated PTSD severity (k=1, n=36; SMD -0.17, 95% CI -0.86, 0.52). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between PE and PE/S for depression (k=1, n=38; SMD -0.63, 95% CI -1.39, 0.13).
414 The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between PE and PE/SIT for anxiety (k=1, n=38; SMD -0.30, 95% CI -1.04, 0.45). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between PE and PE/SIT for social adjustment (k=1, n=32; SMD -0.28, 95% CI -0.97, 0.42).
Box 178 Evidence statement matrix for RCTs comparing prolonged exposure with prolonged exposure plus stress inoculation training Component Rating Description Evidence base D One level II study with a high risk of bias
Consistency NA Not applicable (one study only)
Clinical impact D Slight/Restricted; very few clinically important differences
Generalisability B Evidence directly generalisable to target population with some caveats
Applicability C Evidence probably applicable to Australian healthcare context with some caveats
Summary of results One study at high risk of bias was unable to demonstrate greater clinical effectiveness of PE or PE/SIT in treating PTSD. There was limited evidence that PE was more effective than PE/SIT for self reported measures BDI and STAI at the post treatment time point, and for the BDI measure at the 3 month time point. Results should be considered cautiously as data was reported from completer analysis only. (Grade D)
STRESS INNOCULATION TRAINING VERSUS PROLONGED EXPOSURE PLUS STRESS INNOCULATION TRAINING One trial by Foa et al (Foa et al 1999) fitted search criteria and compared Stress inoculation training (SIT) with prolonged exposure plus stress inoculation training (PE/SIT). PE consisted of nine sessions based around imaginal exposure, whereas SIT sessions focused on teaching coping skills, relaxation, cognitive restructuring and covert modelling, with no exposure component. Study subjects were women who were victims of sexual or non-sexual assault (index assault after the age of 16 years). The study was well designed but there was a lack of intention to treat data reported, and the risk of bias was moderate.
Table 190 Study profiles for RCTs comparing stress inoculation therapy with prolonged exposure plus stress inoculation training Reference Risk of bias Population Setting N Outcomes measured (Foa et al 1999) High Female adult sexual US, mental health 56 Severity of PTSD and non-sexual centre Depressive symptoms assault victims Anxiety Social adjustment
415 The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between SIT and PE/SIT for clinician-rated PTSD severity at post-treatment (k=1, n=41; SMD -0.07, 95% CI -0.68, 0.54). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between SIT and PE/SIT for depression at post-treatment (k=1, n=40; SMD -0.05, 95% CI-0.67, 0.57). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between SIT and PE/SIT for anxiety at post treatment (k=1, n=40; SMD -0.11, 95% CI -0.73, 0.52). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between SIT and PE/SIT for social adjustment (SAS) at post treatment (k=1, n=41; SMD -0.22, 95% CI -0.84, 0.39).
Box 179 Evidence statement matrix for RCTs comparing stress inoculation therapy with prolonged exposure plus stress inoculation training Component Rating Description Evidence base D One level II study with a high risk of bias
Consistency NA Not applicable (one study only)
Clinical impact D Slight/Restricted; no clinically important differences found
Generalisability B Evidence directly generalisable to target population with some caveats
Applicability C Evidence probably applicable to Australian healthcare context with some caveats
Summary of results One study comparing SIT and PE/SIT reported evidence that was inconclusive as to the greater clinical effectiveness of either treatment. (Grade D)
EXPOSURE THERAPY VERSUS TRAUMA MANAGEMENT THERAPY A single study was identified (Beidel et al 2011) meeting search criteria that compared exposure therapy (ET) with trauma management therapy (TMT). In Beidel’s trial, TMT is a combination of exposure therapy and social emotional rehabilitation, therefore meeting the criteria to be considered a multiple CBT component comparator. The US based RCT involved a population of male combat veterans with PTSD. The study was reported with minimal detail and was assessed as having high risk of bias.
Table 191 Study profiles for RCTs comparing exposure therapy with trauma management therapy Reference Risk of bias Population Setting N Outcomes measured (Beidel et al 2011) High Male combat US, referred from a 34 Severity of PTSD symptoms veterans VA centre and Vet Social adjustment centre in the north Depressive symptoms east Anxiety
416 The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between ET and TMT for reduction of PTSD symptoms (CAPS score) at post-treatment (k=1, n=30; SMD 0.15, 95% CI -0.56, 0.87). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between ET and TMT for reduction of PTSD symptoms (PCL- M score) at post-treatment (k=1, n=30; SMD -0.22, 95% CI -0.94, 0.50). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between ET and TMT for depression at post-treatment (k=1, n=30; SMD -0.26, 95% CI -0.98, 0.46). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between ET and TMT for anxiety at post-treatment (k=1, n=30; SMD -0.19, 95% CI -0.91, 0.53). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between ET and TMT for quality of life at post-treatment (k=1, n=30; SMD 0.49, 95% CI -0.24, 1.22).
Box 180 Evidence statement matrix for RCTs comparing exposure therapy with trauma management therapy Component Rating Description Evidence base D One level II study with a high risk of bias
Consistency NA Not applicable (one study only)
Clinical impact D Slight/Restricted; no clinically important differences
Generalisability B Evidence directly generalisable to target population with some caveats
Applicability C Evidence probably applicable to Australian healthcare context with some caveats
Summary of results From one study comparing ET and TMT the evidence was inconclusive regarding important clinical differences between the two interventions. (Grade D)
417 ii. Pharmacotherapy alone versus pharmacotherapy plus psychotherapy
SERTRALINE ALONE VERSUS SERTRALINE PLUS CBT
There were two studies identified that addressed the comparison of sertraline alone with sertraline plus CBT. A study by Rothbaum et al (Rothbaum et al 2006) randomised a broad sample of US outpatients with PTSD to sertraline plus CBT (PE) or sertraline alone. The randomised trial phase followed an open label sertraline phase during which participants’ doses were increased to maximum tolerated dose. While the trial was well designed, there were disparate dropouts rates between groups (Sertraline vs sertraline plus PE: 3% vs 18%) and the overall risk of bias was moderate. A second identified publication described a pilot study by Otto et al (Otto et al 2003) in US based Cambodian refugees from the Pol Pot period. In this trial CBT emphasised elements of education around PTSD symptoms and their distinction from culturally based fears and somatic sensations, exposure to memories of traumatic events, relaxation, breathing, and self-care skills. All participants were Khmer speaking women with PTSD who failed to respond adequately to treatment with clonazepam in combination with an SSRI other than sertraline. This small study was assessed as having a moderate risk of bias.
Table 192 Study profiles for RCTs comparing sertraline alone with sertraline plus CBT (PE) Reference Risk of bias Population Setting N Outcomes measured (Rothbaum et al Moderate Broad, recruited US, 3 university 65 Severity of PTSD 2006) through psychiatry Depressive symptoms advertisements and departments Anxiety professional referrals
(Otto et al 2003) Moderate Cambodian refugee US 23 Severity of PTSD Khmer speaking Depressive symptoms women Anxiety Somatisation
Outcomes from these two studies did not allow meta-analysis. While Rothbaum et al reported post treatment score means, Otto et al reported score change means. The evidence was inconclusive and so it is not possible to determine whether there is a clinically important difference between effectiveness of sertraline alone and sertraline plus CBT (PE) for clinician-rated PTSD severity at post-treatment (k=1, n=65; SMD 0.37, 95% CI -0.11, 0.87). The evidence was inconclusive and so it is not possible to determine whether there is a clinically important difference between effectiveness of sertraline alone and sertraline plus CBT (PE) for depression at post-treatment (k=1, n=65; SMD 0.20, 95% CI -0.29, 0.69). There is evidence suggesting that there is unlikely to be a clinically important difference between the effectiveness of sertraline alone and sertraline plus CBT (PE) for anxiety at post- treatment (k=1, n=65; SMD 0.01, 95% CI -0.48, 0.50).
418 There is limited evidence favouring sertraline plus CBT over sertraline alone in Cambodian refugee women for PTSD reexperiencing symptoms (CAPS mean change score) (k=1, n=10; SMD 0.74, 95% CI -0.54, 2.02). There is limited evidence favouring sertraline plus CBT over sertraline alone in Cambodian refugee women for PTSD avoidance/numbing symptoms (CAPS mean change score) (k=1, n=10; SMD 0.76, 95% CI -0.51, 2.06). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between effectiveness of sertraline plus CBT (PE) and sertraline alone for hyperarousal (CAPS mean change score)in Cambodian refugee women (k=1, n=10; SMD 0.42, 95% CI -0.84, 0.1.67). There is limited evidence favouring sertraline plus CBT over sertraline alone in Cambodian refugee women for anxiety (HSCL-90 mean change score) (k=1, n=10; SMD 0.53, 95% CI - 0.73, 7.79). The evidence is inconclusive and so it is not possible to determine whether there is a clinically important differences between sertraline plus CBT over sertraline alone in Cambodian refugee women for depression (HSCL-90 mean change score) (k=1, n=10; SMD unable to be calculated)
Box 181 Evidence statement matrix for RCTs comparing sertraline alone with sertraline plus CBT (PE) Component Rating Description Evidence base C Two level II studies with a moderate risk of bias.
Consistency C Some inconsistency, reflecting genuine uncertainty around question
Clinical impact D Slight/restricted; few of clinically importance and from very small study.
Generalisability C Evidence not directly generalisable to the target population but could be sensibly applied
Applicability C Evidence probably applicable to Australian healthcare context with some caveats
Summary of results Evidence from the larger study in this comparison suggested there were no clinically important differences between treatments, and whilst the small study with Cambodian refugee women (based on mean change scores) found that sertraline plus CBT was favoured over sertraline alone, this should be interpreted with caution given the small sample size and specific context of the trial population. (Grade C)
419 iii. Psychotherapy plus pharmacotherapy versus psychotherapy plus placebo
CBT (PE) PLUS PAROXETINE VERSUS CBT (PE) PLUS PLACEBO Two US based studies were identified that compared prolonged exposure (PE) plus the SSRI paroxetine with PE plus placebo. A study by Simon et al (Simon et al 2008) randomised 23 adult subjects with a primary diagnosis of PTSD recruited from 4 US academic centres. The trial had an initial phase of 8 sessions (90 to 120 minutes each) of PE for all participants. For the 10 week second phase participants who remained symptomatic after phase I were randomised to additional pharmacotherapy with paroxetine CR or placebo, while PE sessions continued every two weeks. The study was small and considered of moderate quality and risk of bias. A second identified study by Schneier et al (Schneier et al 2011) was a well designed trial, however a high dropout rate (30% dropout at post treatment) increased the risk of bias to moderate. The trial compared PE plus paroxetine with PE plus placebo, with PE consisting of 10 weekly 90 minute sessions conducted by psychiatrists experienced in CBT. Pharmacotherapy was administered concurrently with PE sessions.
Table 193 Study profiles for RCTs comparing paroxetine plus CBT with paroxetine plus placebo Reference Risk of bias Population Setting N Outcomes measured (Schneier et al Moderate World trade Centre US, New York 37 PTSD severity 2011) attack victims with victims of the Remission status PTSD 11/09/2001 terrorist Treatment response attack Depression Quality of Life
(Simon et al 2008) Moderate PE treatment US, 4 academic 23 Severity of PTSD refractory PTSD centres subjects
Reported measures were not sufficiently similar between studies to conduct a meta-analysis. The outcomes of the Schneier study showed some significant differences between groups favouring PE plus paroxetine for mean CAPS, HDRS and QoLESQ, however the data reported is from completer analysis only. The Simon study reported mean reduction in SPRINT and CGI-S scores and mean CGI-I score but the evidence was inconclusive based on effect size calculations. There is limited evidence favouring PE plus paroxetine over PE plus placebo for clinician- rated PTSD severity at post-treatment (k=1, n=37; SMD -0.52, 95% CI -1.30, 0.26). There is limited evidence favouring PE plus paroxetine over PE plus placebo for depression at post-treatment (k=1, n=37; SMD -0.66, 95% CI -1.43, 0.12). There is limited evidence favouring PE plus paroxetine over PE plus placebo for quality of life at post-treatment (k=1, n=37; SMD 0.68, 95% CI -0.25, 1.61). The evidence is inconclusive and so it is not possible to determine whether there is a clinically importance difference between PE plus paroxetine and PE plus placebo for the CGI – Improvement score (k=1, n=23; SMD 0.23, 95% CI -0.61, 1.07).
420 The evidence is inconclusive and so it is not possible to determine whether there is a clinically importance difference between PE plus paroxetine and PE plus placebo for the CGI – Severity reduction score (k=1, n=23; SMD -0.21, 95% CI -1.05, 0.63).
Box 182 Evidence statement matrix for RCTs comparing paroxetine plus CBT with paroxetine plus placebo Component Rating Description Evidence base C Two small Level II studies with a moderate risk of bias
Consistency B Results generally favour PE plus paroxetine
Clinical impact D Slight/Restricted; limited evidence for clinical importance on some outcomes
Generalisability B Evidence directly generalisable to target population with some caveats
Applicability C Evidence probably applicable to Australian healthcare context with some caveats
Summary of evidence Of the two small trials identified comparing PE plus paroxetine with PE plus placebo, the study with larger subject numbers (Schneier et al 2011)found limited evidence showing that the combined treatments were more effective than PE (with placebo) in reducing PTSD severity and depressive symptoms, and improving self-report quality of life aspects. These results should be considered with the understanding that they were calculated from completer data only, and that a smaller study (Simon et al 2008) found no conclusive evidence. (Grade C)
PSYCHOTHERAPY PLUS ± 3,4-METHYLENEDIOXYMETHAMPHETAMINE VERSUS PSYCHOTHERAPY PLUS PLACEBO A single recent study by Mithoefer et al (Mithoefer et al 2011) compared psychotherapy plus ±3,4-methylenedioxymethamphetamine (MDMA) to psychotherapy plus placebo in a small group of subjects with PTSD previously refractory to both psychotherapy and pharmacotherapy. This pilot study had two stages, the first of which was randomised. Subjects in the placebo group could elect to receive open label MDMA in the second stage of the trial. Psychotherapy in stage one consisted of two 90 minute ‘introductory’ sessions, two all day ‘experimental’ sessions (during which MDMA or placebo was administered), and three 90 minute sessions for ‘integration’ following each experimental session. Results favoured the MDMA group (CAPS and IES scores) at the post intervention time point and at 2 month follow up, however they should be viewed cautiously as although there was a low risk of bias the trial population was very small (n = 12 for MDMA vs n = 8 for placebo).
Table 194 Study profiles for RCTs comparing psychotherapy plus MDMA with psychotherapy plus placebo Reference Risk of bias Population Setting N Outcomes measured (Mithoefer et al Low Treatment refractory US 20 PTSD severity 2011) PTSD subjects recruited via letters to psychotherapists and internet dti t
421
There is evidence favouring psychotherapy plus MDMA over psychotherapy plus placebo for reducing clinician-rated PTSD severity at post-treatment (k=1, n=20; SMD -1.59, 95% CI -2.61, -0.57). There is limited evidence favouring psychotherapy plus MDMA over psychotherapy plus placebo for improving self-reported PTSD symptoms at post-treatment (k=1, n=20; SMD - 1.36, 95% CI -2.35, -0.37). There is limited evidence favouring psychotherapy plus MDMA over psychotherapy plus placebo for reducing clinician-rated PTSD severity at two months follow up (k=1, n=20; SMD -1.21, 95% CI -2.18, -0.24). There is limited evidence favouring psychotherapy plus MDMA over psychotherapy plus placebo for improving self-reported PTSD symptoms at two months follow up (k=1, n=20; SMD -0.97, 95% CI -1.92, -0.03).
Box 183 Evidence statement matrix for RCTs comparing psychotherapy plus MDMA with psychotherapy plus placebo Component Rating Description Evidence base C One very small study with a low risk of bias
Consistency NA Not applicable (one study only)
Clinical impact C Moderate; clinically important effects but very small sample
Generalisability B Evidence directly generalisable to target population with some caveats
Applicability C Evidence probably applicable to Australian healthcare context with some caveats
Summary of evidence One well designed but very small pilot study with a low risk of bias found evidence that psychotherapy plus MDMA treatment was better than psychotherapy (plus placebo) in reducing PTSD symptoms when measured by clinician assessed scale (CAPS) and by self assessed scale (IES-R). Results may support the conduct of larger trials to establish further data with higher power regarding this comparison. (Grade C)
TRAUMA-FOCUSSED CBT PLUS SERTRALINE VERSUS TRAUMA-FOCUSSED CBT PLUS PLACEBO IN CHILDREN One randomised controlled pilot study was identified for this comparison which was conducted in female children aged 10 to 17 years who experienced PTSD symptoms as a result of sexual abuse (Cohen et al 2007). A parent or caregiver participated with each child in the TF-CBT sessions which were administered to all trial subjects. TF-CBT included components of parenting skills, psychoeducation, relaxation, affect modulation, cognitive processing and trauma narrative. Sertraline was administered to the intervention group initially at 25 mg per day with subsequent doses adjusted for optimisation up to 200 mg per day. The intervention and control groups were found to be different at baseline in ‘hyperarousal’ scores, suggesting insufficient randomisation.
422
Table 195 Study profiles for RCTs comparing TF-CBT plus sertraline with TF-CBT plus placebo Reference Risk of bias Population Setting N Outcomes measured (Cohen et al 2007) Moderate Children aged 10 to US, community 24 Resolution of PTSD symptoms 17 years with sexual referrals Depression abuse-related PTSD Anxiety symptoms Social and occupational function Conduct disorder Side-effects
The evidence is inconclusive so it is not possible to determine whether there is a clinically important difference between TF-CBT plus sertraline and TF-CBT plus placebo for self- reported symptoms of reexperiencing at post treatment for girls affected by sexual abuse. (k=1, n=24; SMD= -0.39, 95% CI -1.23, 0.46) The evidence is inconclusive so it is not possible to determine whether there is a clinically important difference between TF-CBT plus sertraline and TF-CBE plus placebo for self- reported symptoms of avoidance at post treatment for girls affected by sexual abuse. (k=1, n=24; SMD= -0.47, 95% CI -1.31, 0.38) The evidence is inconclusive so it is not possible to determine whether there is a clinically important difference between TF-CBT plus sertraline and TF-CBE plus placebo for self- reported symptoms of hyperarousal at post treatment for girls affected by sexual abuse. (Note: baseline hyperarousal scores were statistically higher in the placebo group than the sertraline group.) (k=1, n=24; SMD -0.40, 95% CI -1.25, 0.44) There is limited evidence favouring TF-CBT plus sertraline over TF-CBT plus placebo for social and occupational function (CGAS) at post treatment for girls affected by sexual abuse. (k=1, n=24; SMD 0.69, 95% CI -0.17, 0.55)
Box 184 Evidence statement matrix for RCTs comparing TF-CBT plus sertraline with TF-CBT plus placebo Component Rating Description Evidence base C One small level II study with a moderate risk of bias
Consistency NA Not applicable (one study only)
Clinical impact D Slight/Restricted; no clinically important differences found with the exception of one outcome
Generalisability B Evidence directly generalisable to target population with some caveats
Applicability C Evidence probably applicable to Australian healthcare context with some caveats
Summary of evidence One small study with a moderate level of bias provided inconclusive evidence for improvement of PTSD symptoms in girls who were subjects of sexual abuse when TF-CBT plus sertraline was compared with TF-CBT plus placebo, using the self-report CPSS. Limited evidence showing TF-CBT plus sertraline is better than TF-CBT plus placebo for improvement of social and occupational function (CGAS) should be considered cautiously due to the small number in this trial and the moderate risk of bias. (Grade C)
423 iv. Pharmacotherapies versus pharmacotherapy plus placebo
SSRI PLUS OLANZAPINE VERSUS SSRI PLUS PLACEBO
One study (Stein et al 2002) compared treatment with olanzapine to placebo in a population of US combat veterans who were optimised on SSRI pharmacotherapy. The study aim was to determine if combination therapy of SSRI plus olanzapine was more effective in reducing PTSD symptoms than SSRI (plus placebo). In this small trial, randomised participants were taking a range of SSRIs (five were taking fluoxetine, seven were taking paroxetine, seven were taking sertraline) during the 12 week trial. Significant weight gain was a side effect in the olanzapine but not the placebo group (SSRI plus olanzapine vs SSRI plus placebo: mean=13.2 lb, SD=5.9 vs mean=-3.0 lb, SD=6.5).
Table 196 Evidence statement matrix for RCTs comparing SSRI plus olanzapine with SSRI plus placebo Reference Risk of bias Population Setting N Outcomes measured (Stein et al 2002) Moderate US combat veterans US healthcare system 19 PTSD severity (CAPS) Depressive symptoms (Centre for Epidemiological Studies Depression Scale –CES-D) Sleep symptoms (self-report Pittsburgh Sleep Quality Index) Number of responders ‘much improved’ or ‘very much improved’ relative to start of treatment (CGI)
Stein reported reduction in PTSD symptoms (as measured by the CAPS score), reduction in sleep disturbance (as measured by the global score on the Pittsburgh Sleep Quality Index), and reduction in depressive symptoms (as measured by the Centre for Epidemiological studies Depression Scale score, CES-D). Hedges’ g effect sizes are calculated from reduction scores.
There is limited evidence favouring SSRI plus olanzapine over SSRI plus placebo for reducing the severity of clinician-rated PTSD symptoms at post-treatment (k=1, n=19; SMD -0.92, 95% CI -1.87, 0.03).
There is limited evidence favouring SSRI plus olanzapine over SSRI plus placebo for reducing depression at post-treatment (k=1, n=19; SMD -1.20, 95% CI -2.18, -0.22)
There is evidence favouring SSRI plus olanzapine over SSRI plus placebo for reducing sleep disturbance at post-treatment (k=1, n=19; SMD -1.56, 95% CI -2.59, -0.53).
Box 185 Evidence statement matrix for RCTs comparing SSRI plus olanzapine with SSRI plus placebo Component Rating Description Evidence base C One small level II study with a moderate risk of bias
Consistency NA Not applicable (one study only)
Clinical impact C Moderate; evidence favours SSRI plus olanzapine, but based on very small sample and only three outcomes Generalisability B Evidence directly generalisable to target population with some caveats
424 Applicability C Evidence probably applicable to Australian healthcare context with some caveats
Summary of Evidence A single small trial of moderate bias risk found treatment with SSRI plus olanzapine was more effective than treatment with SSRI plus placebo for reducing PTSD symptoms, sleep disturbance and depressive symptoms in US combat veterans with PTSD, . There was significant weight gain in the SSRI plus olanzapine group. These results should be considered cautiously due to the small trial size, however larger RCTs may be warranted. (Grade C)
425
Box 186 Study selection criteria for research question 21
Research Question 21. For people with PTSD, is any intervention (pharmacotherapy, psychotherapy or psychosocial rehabilitation) more effective than any other intervention (pharmacotherapy, psychotherapy or psychosocial rehabilitation) Selection criteria Inclusion criteria Population People with PTSD Intervention (1) pharmacological intervention (2) psychological intervention (3) psychosocial rehabilitation intervention Comparator (1) psychological or psychosocial rehabilitation intervention (2) pharmacological or psychosocial intervention (3) psychological or pharmacological intervention Outcome Primary outcome: resolution of symptoms of PTSD Secondary outcomes: symptoms of depression, anxiety and substance misuse/ social and occupational function/ quality of life/ treatment refusal/ dropout over 12 months/ side-effects/ posttraumatic growth/ physical comorbidity. Additional outcomes for children: attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies are found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies Search Period 1966-10/2011a Language English
a New research question
Two studies were identified which assessed comparisons relating to question 21. A study by Frommberger et al (Frommberger et al 2004) compared paroxetine pharmacotherapy with trauma-focused CBT. A three armed study conducted by van der Kolk et al (van der Kolk et al 2007) included a fluoxetine versus EMDR comparison which will be discussed here (the third arm, pill placebo, will not be considered in this section).
PAROXETINE VERSUS TRAUMA FOCUSED CBT The study by Frommberger et al (2004) compared 12 weeks of paroxetine (10-50mg) with 12 weekly sessions of trauma-focused CBT. The subject numbers were small and the trial was rated as low quality. Data analysis was based only on those who received treatment (not intention-to-treat). In studies comprising both drug and psychological intervention treatment arms individuals are not masked to treatment allocation, and in this study neither were the rating assessors. Further, given the lack of placebo control it is not possible to isolate specific effects. Measures that provide limited evidence favouring CBT are based on self-ratings however these effects were not replicated in the clinician ratings. Due to the high bias risk in the study, the results should be interpreted cautiously.
Table 197 Study profiles for RCTs comparing paroxetine and trauma-focused CBT for adults with PTSD. Reference Risk of bias Population Setting N Outcomes measured (Frommberger et al High PTSD outpatients Outpatient treatment 21 PTSD severity, depression and anxiety 2004) (mostly victims of centre, University of symptoms (clinician and patients rated serious accidents, Freiberg, Germany measures) sexual or non-sexual violence)
426 The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between paroxetine and trauma-focused CBT on reducing the severity of clinician-rated PTSD symptoms at post-treatment (k = 1; n = 16; SMD = 0.09; 95% CI, - 0.89, 1.07).
There is limited evidence favouring trauma-focused CBT over paroxetine on reducing the severity of self-rated PTSD symptoms at post-treatment (k = 1; n = 16; SMD =1.06; 95% CI, -0.01, 2.13).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between paroxetine and trauma-focused CBT on reducing post treatment depression symptoms using clinician measure MADRS at post-treatment (k = 1; n = 16; SMD = -0.37; 95% CI, -1.36, 0.62).
There is limited evidence favouring trauma-focused CBT over paroxetine on reducing self- rated depression symptoms post-treatment using BDI at post-treatment (k = 1; n = 16; SMD = 0.55; 95% CI, -0.46, 1.55).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between paroxetine and trauma-focused CBT on reducing anxiety symptoms using clinician measure HAM-A at post-treatment (k = 1; n = 16; SMD = -0.26; 95% CI, -1.25, 0.72).
Box 187 Evidence statement matrix for paroxetine versus trauma-focused CBT for adults with PTSD Component Rating Description Evidence base D One small pilot study with a high risk of bias.
Consistency NA Only one study
Clinical impact D There is limited evidence favouring trauma-focused CBT over paroxetine for reduction in self-rated PTSD severity and depression symptoms. However, these benefits were not detected in the clinician- rated measures, so could be biased.
Generalisability C The results from this small pilot study on German subjects with PTSD are possibly generalisable to a broader PTSD population but the study is too small to be conclusive.
Applicability B May be applicable to the Australian healthcare system.
FLUOXETINE VERSUS EMDR In a well designed, low bias rated trial van der Kolk et al compared fluoxetine with EMDR therapy. The trial also involved a third arm, pill placebo, however the comparison of fluoxetine and placebo is considered under the Pharmacological Interventions section. Adults with PTSD for this study were recruited through a range of methods and a total of 59 subjects were randomized between the fluoxetine and EMDR arms. In both arms, evaluators were blinded to subject treatment. While subjects were not blinded to EMDR treatment, fluoxetine and pill placebo were administered double blind. Intention to treat analysis was conducted and there were relatively few dropouts (15%) over the treatment phase. Only completers from the treatment phase were included in the 6 month follow up data. Evidence statements are presented for results at post treatment.
427
Table 198 Study profiles for RCTs comparing Fluoxetine and EMDR for adults with PTSD Reference Risk of bias Population Setting N Outcomes measured (van der Kolk et al Low PTSD individuals with Trauma centre and 59 PTSD diagnosis 2007) mixed trauma exposure hospital settings, PTSD severity measure (clinician recruited through media Boston, US measure) (newspaper ads and Depression symptoms (patient rated) internet), and from medical Subjects (%) who were asymptomatic and mental health settings
There is limited evidence favouring EMDR over fluoxetine for the percentage of asymptomatic patients found in each group at post-treatment (k=1; n=59; RR=0.48, 95% CI 0.16 to 1.43).
There is limited evidence that favours EMDR over fluoxetine treatment for the reduction depressive symptoms at post-treatment (k=1; n=59; SMD=0.51, 95% CI 0.00 to 1.03).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between fluoxetine and EMDR therapy for reducing the severity of PTSD symptoms at post-treatment (k-1; n=59; SMD=0.45, 95% CI -0.07 to 0.96).
The evidence is inconclusive and so it is not possible to determine if there is a clinically important difference between fluoxetine and EMDR therapy on reducing the likelihood of having a PTSD diagnosis post-treatment (k-1; n=59; RR=0.97, 95% CI 0.72 to 1.3).
Box 188 Evidence statement matrix for Fluoxetine versus EMDR for adults with PTSD Component Rating Description Evidence base B One level II study with low risk of bias
Consistency NA Only one study
Clinical impact B There is limited evidence to show that the reduction in self-rated depression symptoms and the percentage of asymptomatic subjects are greater when treated with EMDR compared with fluoxetine. Despite a well designed trial, further evidence regarding clinician rated PTSD measures was inconclusive. Generalisability B Subjects for this trial were drawn from a broad PTSD population base and therefore results may be generalisable to the broader PTSD population (non-combat related).
Applicability C The intervention in this US study may be adapted to suit the Australian healthcare context
Summary of evidence Although there is limited evidence based on self-rated measures to support trauma-focused psychological interventions over SSRIs in adults with PTSD, this result should be considered with caution due to the lack of comparison with a placebo control to control for non-specific effects of psychological treatments. Results regarding the comparison of pharmacotherapy compared with psychotherapy when measured by clinician rated scales are inconclusive.
428
Comorbidities
Box 189 Study selection criteria for research question 22
Research Question 22. In the context of PTSD and comorbidity, is sequencing of intervention per diagnosis more effective than simultaneous interventions for both diagnoses? Selection criteria Inclusion criteria Population People with PTSD and comorbidity (eg grief, depression, personality disorder, pain and substance misuse) Intervention Sequenced psychological or pharmacological intervention per diagnosis ie treatment for PTSD and then comorbidity or vice versa Comparator Simultaneous psychological and/or pharmacological interventions for both diagnoses Outcome Primary outcome: resolution of symptoms of PTSD Secondary outcomes: symptoms of depression, anxiety and substance misuse/ social and occupational function/ quality of life/ treatment refusal/ dropout over 12 months/ side-effects/ posttraumatic growth/ physical comorbidity. Additional outcomes for children: attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies are found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies Search Period 8/2005-10/2011 for adultsa, 1966-10/2011 for children and adolescentsc Language English a updated search from 2007 Guidelines bexpanded search period if fewer than two Level II studies are found c New research question
No studies were identified which met the inclusion criteria outlined a prior for research question 22 (see Box 189). Although evidence was identified by the VA/DoD as being potentially relevant to this question, none of the studies had an intervention arm of sequential treatment, and were therefore excluded.
429 Child specific questions
Box 190 Study selection criteria for research questions 23 and 24
Research Question 23. For children with PTSD, does the inclusion of parents / primary care givers in psychological interventions improve outcomes for the child compared with no parent / primary care giver inclusion in the psychological interventions? 24. For children with PTSD, does any psychological intervention that includes parents / primary care givers improve outcomes for the child compared to any other psychological intervention that includes parents / primary care givers? Selection criteria Inclusion criteria Population Children with PTSD Intervention Any psychological intervention that includes parents/ primary care givers Comparator 1. Psychological interventions that do not include parents / primary care givers 2. Any other psychological interventions that includes parents / primary care givers Outcome Primary outcome: resolution of symptoms of PTSD Secondary outcomes: resolution of symptoms of depression, anxiety and substance misuse/ social and occupational function / quality of life / treatment refusal/ dropout over 12 months/ posttraumatic growth/ oppositional defiant disorder / attention deficit disorder/ social anxiety disorder/ physical comorbidity / attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies are found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies Search Period 1966-10/2011a Language English
There were two studies that fulfilled the criteria for Question 23 ((Deblinger et al 1996; King et al 2000), King 2000), and further follow-up results of the Deblinger 1996 study were reported in Deblinger 1999(Deblinger et al 1999). Both these studies used cognitive behavioural therapy to treat children who had been sexually abused. The therapy aimed to target sexually abused children’s PTSD symptoms as well as other behavioural and emotional problems, through treating just the child, or the child and non-offending mother both separately and together. The Deblinger 1996 study randomised children and their non- offending mother to one of four interventions: child-only CBT, mother-only CBT, parent and child CBT and treatment as usual (only parent and child CBT and child-only CBT are considered for this question; the other comparisons are considered in Question 11). The interventions in the King 2000 study were developed based on the interventions in the Deblinger study, and thus the two studies were highly comparable in terms of the intervention. The King study randomised children to child-only CBT, child and parent CBT and waiting list (only child-only CBT and parent and child CBT are considered for this question; the comparison of both of these interventions to waitlist is considered in Question 10).
Table 199 Study profiles for RCTs comparing psychological interventions for children with PTSD that include parents/caregivers with psychological interventions that do not include parents/caregivers Reference Risk of bias Population Setting N Outcomes measured (Deblinger et al 1996; High Children aged 7-13 Clinic within University 100 PTSD Deblinger et al 1999) years who had been medical school, USA Anxiety sexually abused Depression Child behaviour
430 (King et al 2000) Moderate Children aged 5-17 ‘Children’s Support 36 PTSD who had been Centre’, Melbourne Anxiety sexually abused Australia Depression Child behaviour Global functioning
Both of these studies were limited by small sample sizes and did not blind the outcomes assessors to group allocation. Whilst both studies claimed to be randomised, no details about the randomisation procedure were given, and neither study detailed the differences between groups, although both stated that no significant differences on any variables of interest were found between the groups. At post-treatment, loss to follow-up was 22% (8/36) for the King study and 11% (11/100) for the Deblinger study; however the Deblinger study followed participants up for up to 2 years, and loss to follow-up varied over that time period, up to as much as 50% in the community control group. The King study presented intention-to-treat analyses, whilst Deblinger only reported completers.
The evidence is inconclusive and so it is not possible to determine whether there is a clinically important difference between psychological interventions for sexually abused children that include parents and psychological interventions for sexually abused children that do not include parents for reducing the symptoms of PTSD at post-treatment (k=2; n=70; SMD -0.05 95% CI -0.52, 0.42).
431
The evidence is inconclusive and so it is not possible to determine whether there is a clinically importance difference between psychological interventions for sexually abused children that include parents and psychological interventions for sexually abused children that do not include parents for reducing the symptoms of PTSD at 3 months follow-up (k=2; n=64; SMD -0.12 95% CI -0.61, 0.38), at 6 months follow-up (k=1; n=40; SMD 0.26 95% CI -0.37, 0.88), at 1 year follow-up (k=1; n=40; SMD -0.21 95% CI -0.84, 0.41) or at 2 years follow-up (k=1; n=40; SMD -0.14 95% CI -0.77, 0.48).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically importance difference between psychological interventions for sexually abused children that include parents and psychological interventions for sexually abused children that do not include parents for reducing the symptoms of depression at post-treatment (k=2; n=70; SMD -0.04 95% CI -0.50, 0.43).
432
The evidence is inconclusive and so it is not possible to determine whether there is a clinically importance difference between psychological interventions for sexually abused children that include parents and psychological interventions for sexually abused children that do not include parents for reducing the symptoms of depression at 3 months follow-up (k=2; n=64; SMD 0.26 95% CI -0.24, 0.75).
There is limited evidence favouring psychological interventions for sexually abused children that do not include parents over psychological interventions for sexually abused children that do include parents for reducing the symptoms of depression at 6 months follow up (k=1, n=40, SMD 0.57 95% CI -0.06, 1.20), at 1 year follow-up (k=1; n=40; SMD 0.42 95% CI - 0.20, 1.05) or at 2 years follow-up (k=1; n=40; SMD 0.04 95% CI -0.58, 0.66).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically importance difference between psychological interventions for sexually abused children that include parents and psychological interventions for sexually abused children
433 that do not include parents for reducing the symptoms of anxiety at post-treatment (k=2; n=70; SMD 0.36 95% CI -0.11. 0.84).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically importance difference between psychological interventions for sexually abused children that include parents and psychological interventions for sexually abused children that do not include parents for reducing the symptoms of anxiety at 3 months follow-up (k=1; n=24; SMD -0.04 95% CI -0.84, 0.76).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically importance difference between psychological interventions for sexually abused children that include parents and psychological interventions for sexually abused children that do not include parents for reducing externalising behaviour at post treatment (k=2; n=70; SMD -0.33 95% CI -0.81, 0.14).
Figure 24 Children plus parents intervention versus child intervention alone: externalising behaviour, 3 months’ follow-up
434 The evidence is inconclusive and so it is not possible to determine whether there is a clinically importance difference between psychological interventions for sexually abused children that include parents and psychological interventions for sexually abused children that do not include parents for reducing externalising behaviour at 3 months follow-up (k=2; n=62; SMD 0.36 95% CI -0.15, 0.86).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically importance difference between psychological interventions for sexually abused children that include parents and psychological interventions for sexually abused children that do not include parents for reducing externalising behaviour at 6 months follow-up (k=1; n=38; SMD 0.17 95% CI -0.47, 0.81), at 1 year follow-up (k=1; n=38; SMD 0.06 95% CI - 0.57, 0.70) or at 2 years follow-up (k=1; n=38; SMD 0.03 95% CI -0.61, 0.67).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically importance difference between psychological interventions for sexually abused children that include parents and psychological interventions for sexually abused children that do not include parents for reducing internalising behaviour at post-treatment (k=2; n=70; SMD -0.34 95% CI -0.82, 0.13).
The evidence is inconclusive and so it is not possible to determine whether there is a clinically importance difference between psychological interventions for sexually abused children that include parents and psychological interventions for sexually abused children that do not include parents for reducing internalising behaviour at 3 months follow-up (k=1; n=24; SMD -0.48 95% CI -1.29, 0.34).
There is limited evidence favouring psychological interventions for sexually abused children that include parents over psychological interventions for sexually abused children that do not include parents for improving overall psychological, social and school functioning at post- treatment (k=1; n=24; SMD 0.60 95% CI -0.22, 1.42).
There is limited evidence favouring psychological interventions for sexually abused children that include parents over psychological interventions for sexually abused children that do not include parents for improving overall psychological, social and school functioning at 3 months follow-up (k=1; n=24; SMD 0.85 95% CI 0.01, 1.68).
435
Box 191: Evidence statement matrix for RCTs comparing psychological interventions for PTSD that include parents/caregivers with psychological interventions that do not and control for people exposed to trauma Component Rating Description Evidence base C Two small level II studies with a moderate risk of bias
Consistency A Studies consistent in finding no conclusive differences between the treatments
Clinical impact D Both treatments were found to be equally effective on all outcome measures, with the exception of global functioning, which was found to be higher post-treatment and at 3 months’ follow-up with the addition of parental involvement.
Generalisability A One study in Australian setting; results generalisable to Australian population of children who have experienced sexual abuse
Applicability A Evidence directly applicable to Australian healthcare context; one study undertaken in Australia.
Summary of evidence
These studies failed to show an advantage for psychological interventions for sexually abused children that included parents over psychological interventions for sexually abused children that did not include parents for most of the outcomes investigated. The exception was global functioning, where the King study showed some benefit of including parents in treatment.
Question 24
No studies were identified that compared psychological interventions for children with PTSD that included parents with other psychological interventions for children with PTSD that included parents.
436 Glossary
ACPMH Australian Centre for Posttraumatic Mental Health
ASD Acute Stress Disorder
CBT Cognitive Behavioural Therapy
DESNOS Disorders of Extreme Stress Not Otherwise Specified
DSM-IV Diagnostic and Statistical Manual of Mental Disorders - Fourth edition
DSM-IV-TR Diagnostic and Statistical Manual of Mental Disorders - Fourth edition - Text revision
EMDR Eye Movement Desensitisation and Reprocessing
ICD-10 International Classification of Diseases - Version 10
MAOI monoamine oxidase inhibitors
NHMRC National Health and Medical Research Centre
PTSD Posttraumatic Stress Disorder
SSRIs selective serotonin re-uptake inhibitors
437 Appendix A Guideline Working Party Members
Chair Prof Beverley Raphael
Trauma Experts: Prof Richard Bryant (adults) Prof Mark Creamer (adults) A/Prof Grant Devilly (adults) Prof David Forbes (adults) Prof Justin Kenardy (children and adolescents) A/Prof Brett McDermott (children and adolescents) Prof Alexander McFarlane (adults)
Psychosocial Rehabilitation Expert: Dr Lynda Matthews
438 Appendix B Process Report
Search Strategy
Table 200 Bibliographic databases Electronic database Time period
Cochrane Library – including: 1966 – 10/2011 Cochrane Database of Systematic Reviews(CDSR); Database of Abstracts of Reviews of Effects (DARE); the Cochrane Central Register of Controlled Trials (CENTRAL); the Health Technology Assessment Database (HTA); and the NHS Economic Evaluation Database (NHS EED) Cinahl 1982 – 10/2011 Embase 1974 – 10/2011 Pre-Medline and Medline 1966 – 10/2011 PsycInfo 1983 – 10/2011 Dartmouth College Published International Literature on Traumatic Stress (PILOTS) catalogue 1966 – 10/2011 Table 201 Other sources of evidence (January 2005- October 2011) Electronic database Time period
Current Controlled Trials metaRegister http://controlled-trials.com/
Health Technology Assessment international http://www.htai.org
International Network for Agencies for Health Technology http://www.inahta.org/ Assessment
National Library of Medicine Health Services / Technology http://text.nlm.nih.gov/ Assessment Text UK National Research Register Archive (until Sept 2007) http://www.nihr.ac.uk/Pages/NRRArchive.aspx UK Clinical Research Network Study Portfolio ( http://public.ukcrn.org.uk/search/
Google Scholar http://www.scholar.google.com/ Websites of Health Technology Agencies See Appendix A Specialty Websites See Appendix B Hand Searching (Journals from 2004) PTSD Research Quarterly Electronic access Expert Clinicians Any information provided by expert clinicians associated with Working Party this review will be assessed as to whether it meets the inclusion criteria (including In Press articles) Pearling All included articles will have their reference lists searched for additional relevant source material
439
Table 202 Search terms utilised for intervention questions for PTSD and ASD review Area of inquiry Search terms All intervention searches MeSH Stress disorders, Traumatic Text words Post-traumatic stress; posttraumatic stress; ptsd; traumatic neurosis; acute stress disorder*; critical incident stress; combat AND (neuros* OR syndrome); concentration camp syndrome; CPSS; trauma symptom checklist Study design MeSH Clinical trials as topic; random allocation; single-blind method; double-blind method; epidemiologic studies; intervention studies; control groups; cross-over studies; matched-pair analysis; meta-analysis; drug evaluation; cohort studies; case-control studies; intervention studies Publication type Comparative study; clinical trial Text words Clinical trials; cross-over studies; random allocation; randomly assigned; randomi*; single-blind; double- blind; triple-blind; systematic review; cohort study; case-control; before-and-after; epidemiological study; intervention study; control group; cross-over stud*; matched-pair analysis; meta-analysis; drug evaluation Limits English; Human
And Psychological MeSH interventions Psychotherapy; behavior therapy (Questions 1-4, 7-14, 21- Text words 24) Psychotherapy; (cognitive OR behavior OR behaviour OR exposure OR hypnotic OR interpersonal) AND (therapy OR intervention OR treatment); hypnosis; interapy; EMDR; eye movement desensitisation; eye movement desensitization; counsel*; debrief*; psychodynamic; critical incident stress management; cism; traumatic incident reduction; stress inoculation; CBT; IPT; acceptance and commitment therapy; circle of security; child and family traumatic stress intervention; CFTSI; trauma assessment pathway; TAP; hostile environment training; resilience; psychoeducation; emotion focussed therapy; EFT; dialectic behaviour therapy; relaxation; e-therapy; meditation; mindfulness; stress inoculation; art therapy; logo therapy; Pharmacological MeSH intervention Psychopharmacology; drug therapy; benzodiazepines; antidepressive agents; hypnotics and sedatives; (Questions 5-7, 15-16, 21- pharmacotherapy 23) Text words Psychopharmacology; drug therapy; pharmacolog* AND (intervention OR therapy OR treatment); pharmacother*; medication; SSRI*; benzodiazepine*; antidepressant*; hypnotic*; sympatholog*; antipsychotic*; tca; antihypertensives; ketamine; opioids; cannabinoids; alcohol; MDMA; cholinesterase inhibitors; cortisol and agomelatine; cycloserine; monoamine oxidase inhibitors; antiadrenergic; beta- blocker*; St John’s Wort; alternative medicine
440 Psychosocial rehabilitation MeSH (Question 17, 22) Activities of daily living; mental health services; socioenvironmental therapy; rehabilitation, vocational; community mental health services; rehabilitation; self care; self medication Text words (psychosocial OR vocational) AND rehabilitation; self-care; supported housing; family skills; social skills training; case management; activities of daily living; mental health services; socioenvironmental therapy; rehabilitation, vocational; psychiatric rehabilitation; residential; transitional employment; supported employment; peer services and support; community integration; recovery; illness management and recovery; illness self management; medication management; assertive community treatment; intensive case management; ICT; family intervention; family psychoeducation; integrated dual disorders treatment; transitional housing; community mental health; social support; peer support; organisational support Additional restrictions for 1966 – 2004: MeSH Child; infant;adolescent Text words Child*; infant; youth; adolescen* ; teenage*; student* ; juvenile Exercise therapy and MeSH Physical therapies Exercise movement techniques; exercise; swimming; walking; jogging; yoga (Question 18-19) Physical therapy (specialty); Physical therapy modalities; Complementary therapies; Musculoskeletal manipulations; Electroconvulsive therapy Text words Exercise movement techniques, exercise, swimming, walking, jogging, yoga Physical therapy; Physical therapy techniques; Complementary therap*; Musculoskeletal manipulations; massage, acupuncture, acupressure, reiki, transcranial magnetic stimulation, electroconvulsive therapy; tft; thought field therapy; emotional freedom techniques; eft; acupressure; visual kinaesthetic disassociation; be set free fast; diet; Healing Touch; CranioSacral therapy; T’ai Chi; movement-to-music; rhythm; competitive sport* Co-morbidities MeSH (Question 22) Comorbidity; depression; personality disorders; pain; substance-related disorders; phobic disorders; panic disorder; psychosis Text words Comorbid*; traumatic grief; depression; personality disorder*; pain; substance use; phobi*; gad; anxiety; panic; co-occurring; concurrent; SMI; schizophrenia; bipolar disorder; grief; psychotic; substance abuse; alcohol abuse; substance dependence; alcohol dependence Additional restrictions for 1966 – 2004: MeSH Child; infant;adolescent Text words Child*; infant; youth; adolescen* ; teenage*; student* ; juvenile
Study selection
Study selection followed the process outlined in Figure 1. Table 203 provides a breakdown of the study selection process in terms of the number of literature citations or articles retrieved and retained from each phase of the process. Any doubt concerning inclusions at Phase 4 was resolved by group consensus. The criteria for including studies to answer specific research questions are provided below.
441
Figure 25 Study selection process
1. All reference citations from all literature sources were collated into an Endnote X3 database.
2. Duplicate references were removed.
3. Studies were excluded, on the basis of the complete citation information, if it was obvious that they did not meet the inclusion criteria. All other studies were retrieved for full-text assessment.
4. Inclusion criteria were applied independently to the full-text articles by several researchers. Those meeting the criteria formed part of the evidence-base. The remainder provided background information.
5. The reference lists of the included articles were pearled for additional relevant studies, in press articles forwarded by ACPMH, and the Working Party suggested additional articles. These were retrieved and assessed according to phase 4.
6. The evidence-base consisted of articles from phases 4 and 5 that met the inclusion criteria.
442 Table 203 Number of citations initially retrieved and then retained at each phase Phase 1 Phase 3 Phase 4 Phase 5 Phase 6 Psychological 9880 Combined 565 ASD 172 Q1& 2 3 1 0 Q1 1 0 0 Q2 0 Q3&4 63 19 0 Q3 19 17 0 Q4 18 Q7 3 0 Q7 3 Q8&9 18 4 1 Q8 5 0 0 Q9 0 PTSD 378 Q10 77 56 7 Q10 63 Q11 NA 89 1 Q11 90 Q12&13 2 0 Q12 2 0 0 Q13 0 Q14 4 0 Q14 4 Q23&24 3 0 Q23 3 0 0 Q24 0 Pharmacological 4508 ASD Q5&6 163 2 1 Q5 3 0 0 Q6 0 Q7 0 0 Q7 0 PTSD Q15&16 163 42 0 Q15 43 10 0 Q16 10 Psychosocial 5118 PTSD Q17 47 2 0 Q17 2 Physical therapies and 1200 ASD Q18&19 0 0 0 Q18 0 exercise 0 0 Q19 0 PTSD Q18&19 35 3 0 Q18 3 4 0 Q19 4 Combined 12 0 Q20 12 2 0 Q21 2 Comorbidities 8471 PTSD 96 0 0 Q22 0 Total 29177 906 275 10 All 285 NA=number not available due to file corruption
Inclusion criteria
Inclusion Criteria
Criteria for including studies in the updated systematic literature review and clinical practice guidelines document follow.
Studies assessing the benefits of interventions in adults were included if: x PTSD symptoms were measured x the main target of the treatment is ASD or PTSD or preventing the development of these disorders x for questions pertaining to PTSD, at least 70 percent of the participants have PTSD, and the remaining participants have symptoms of PTSD following a traumatic event
443 x for continuous data at least 50 percent of the intent-to-treat sample were assessed at the relevant time point
The inclusion criteria for children and adolescents were the same as for adults, except the inclusion criteria that 70% of participants within a study require PTSD was not applied, as the diagnostic criteria for child and adolescent PTSD is still evolving and relatively undeveloped (National Institute for Clinical Excellence 2005). All studies must include a measure of the child’s PTSD symptoms.
This systematic review included the studies already identified in the previous guidelines review conducted by AHTA for ACPMH, the NICE guidelines and the VA/DoD guidelines, where the research questions were the same.
Box 192 Study selection criteria for research questions 1 and 2
Research Question 1. For people exposed to trauma, does pre-incident preparedness training improve outcomes compared to no intervention? 2. For people exposed to trauma, does any pre-incident preparedness training confer any advantage over other pre-incident preparedness training? Selection criteria Inclusion criteria Population People exposed to trauma (including the sub-group with ASD) Intervention Pre-incident preparedness training, delivered by any method Comparator 1. No training 2. Other pre-incident preparedness training Outcome Primary outcome: symptoms of ASD or PTSD Secondary outcomes: symptoms of depression, anxiety and substance misuse/ social and occupational function / quality of life / treatment refusal/ dropout over 12 months/ side-effects/ posttraumatic growth/ physical comorbidity. Additional outcomes for children: attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials: if fewer than two Level II studies are found, then consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies. Search Period 1966-10/2011 for adults, children and adolescentsa Language English
a New research questions
Box 193 Study selection criteria for research question 3
444 Research Question 3. For people exposed to trauma, do early psychological interventions improve outcomes compared to no intervention? Selection criteria Inclusion criteria Population People exposed to trauma, including the subgroup of patients with ASD Intervention Early psychological intervention (eg debriefing, trauma-focused counselling, education, performed within one month of trauma) Comparator No intervention (eg assessment only) Outcome Primary outcomes: symptoms of ASD and PTSD Secondary outcomes: symptoms of depression, anxiety and substance misuse/ social and occupational function/ quality of life/ treatment refusal/ dropout over 12 months/ posttraumatic growth / physical comorbidity Additional outcomes for children: attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies are found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies. Search Period 8/2005-10/2011 for adultsa; 1966-10/2011 if required 1966-10/2011 for children and adolescentsc Language English a updated search from 2007 Guideline b expanded search period if fewer than two Level II studies are found c New research questions
Box 194 Study selection criteria for research question 4
Research Question 4 For people exposed to trauma, does any early psychological intervention confer any advantage over other early psychological interventions? Selection criteria Inclusion criteria Population People exposed to trauma, including the subgroup of patients with ASD Intervention Early psychological intervention (eg debriefing, trauma-focused counselling, education, performed within one month of trauma) Comparator Other early psychological intervention Outcome Primary outcomes: symptoms of ASD and PTSD Secondary outcomes: symptoms of depression, anxiety and substance misuse/ social and occupational function/ quality of life/ treatment refusal/ dropout over 12 months/ posttraumatic growth / physical comorbidity. Additional outcomes for children: attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies. Search Period 8/2005-10/2011 for adultsa ; possibly 1966-10/2011 if requiredb 1966-10/2011 for children and adolescentsc Language English a Updated search b Expanded search period if fewer than two Level II studies are found c New research questions
445 Box 195 Study selection criteria for research question 5
Research Question 5. For people exposed to trauma, do early pharmacological interventions improve outcomes compared to no intervention? Selection criteria Inclusion criteria Population People exposed to trauma, including the subgroup of patients with ASD Intervention Early pharmacological intervention, (eg imipramine, propranolol, benzodiazepines, other sympatholytics, other antidepressants, anticonvulsants, antipsychotics, chloral hydrate, given within one month of trauma) Comparator No intervention (eg assessment only) Outcome Primary outcomes: symptoms of ASD or PTSD Secondary outcomes: symptoms of depression, anxiety and substance misuse/ social and occupational function/ quality of life/ treatment refusal/ dropout over 12 months/ side effects/ posttraumatic growth/ physical comorbidity. Additional outcomes for children: attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies are found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies. Search Period 8/2005-10/2011 for adultsa ; possibly 1966-10/2011 if requiredb 1966-10/2011 for children and adolescentsc Language English aUpdated search from 2007 Guidelines bExpanded search period if fewer than two Level II studies are found c New research questions
Box 196 Study selection criteria for research question 6
Research Question 6. For people exposed to trauma, does any early pharmacological intervention confer any advantage over other early pharmacological interventions? Selection criteria Inclusion criteria Population People exposed to trauma, including the subgroup of patients with ASD Intervention Early pharmacological intervention (eg imipramine, propranolol, benzodiazepines, other sympatholytics, other antidepressants, anticonvulsants, antipsychotics, chloral hydrate, given within one month of trauma) Comparator Other early pharmacological intervention Outcome Primary outcomes: symptoms of ASD and PTSD Secondary outcomes: symptoms of depression, anxiety and substance misuse/ social and occupational function/ quality of life/ treatment refusal/ dropout over 12 months/ side effects/ posttraumatic growth/ physical comorbidity. Additional outcomes for children: attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies are found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies. Search Period 8/2005-10/2011 for adultsa ; possibly 1966-10/2011 if requiredb 1966-10/2011 for children and adolescentsc Language English aUpdated search from 2007 Guidelines b Expanded search period if fewer than two Level II studies are found c New research questions
446 Box 197 Study selection criteria for research question 7
Research Question 7. For people exposed to trauma, is a single early intervention more effective than multiple early interventions? Selection criteria Inclusion criteria Population People exposed to trauma, including the subgroup of patients with ASD Intervention Single early psychological or pharmacological intervention Comparator Early combined psychological or combined pharmacological interventions (within one month of the traumatic event) or combined psychological and pharmacological interventions (within one month of the traumatic event) Outcome Primary outcomes: symptoms of ASD or PTSD Secondary outcomes: symptoms of depression, anxiety and substance misuse/ social and occupational function/ quality of life/ treatment refusal/ dropout over 12 months/ side-effects/ posttraumatic growth/ physical comorbidity. Additional outcomes for children: attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies are found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies. Search Period 8/2005-10/2011 for adultsa , 1966-10/2011 if requiredb 1966-10/2011 for children and adolescentsc Language English aUpdated search from 2007 Guidelines. b expanded search period if less than two Level II studies are found c New research questions
Box 198 Study selection criteria for research questions 8 and 9
Research Question 8. For children exposed to trauma, does any intervention delivered through school, improve outcomes for the child over no intervention? 9. For children exposed to trauma, does any intervention delivered through school, improve outcomes for the child compared to any other intervention delivered through school? Selection criteria Inclusion criteria Population Children exposed to trauma. Intervention Any intervention delivered through school. Comparator 1. No intervention. 2. Other intervention delivered through school. Outcome Primary outcome: resolution of symptoms of PTSD Secondary outcomes: resolution of symptoms of depression, anxiety and substance misuse/ social and occupational function / quality of life / treatment refusal/ dropout over 12 months/ posttraumatic growth/ oppositional defiant disorder / attention deficit hyperactivity disorder/ social anxiety disorder/ physical comorbidity. Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies are found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies. Search Period 1966-10/2011a Language English a New research questions
447 Box 199 Study selection criteria for research questions 10 and 11
Research Question 10. For people with PTSD do psychological interventions improve outcomes compared to no intervention? 11. For people with PTSD, does any psychological intervention confer any advantage over other psychological interventions? Selection criteria Inclusion criteria Population People with PTSD Intervention Psychological intervention (eg trauma-focused CBT, stress management therapy, EMDR, narrative exposure therapy, supportive counselling, interapy, thought field therapy) Comparator 1. No intervention (eg assessment only) 2. Other psychological intervention Outcome Primary outcome: resolution of symptoms of PTSD Secondary outcomes: symptoms of depression, anxiety and substance misuse/ social and occupational function/ quality of life/ treatment refusal/ dropout over 12 months/ side-effects/ posttraumatic growth/ physical comorbidity Additional outcomes for children: attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies are found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies Search Period 8/2005-10/2011 for adultsa; 1966-10/2011 if requiredb 1966–10/2011 for children and adolescentsc Language English a Updated search from 2007 Guidelines b expanded search period if fewer than two Level II studies are found c New research questions CBT = cognitive behavioural therapy; EMDR = eye movement desensitisation and reprocessing
Box 200 Study selection criteria for research question 12
Research Question 12. For people with PTSD, is individual therapy more effective than group therapy? Selection criteria Inclusion criteria Population People with PTSD Intervention Individual therapy (eg psychodynamic psychotherapy, individual cognitive behavioural therapies, EMDR, narrative exposure therapy, image rehearsal therapy, supportive counselling, hypnosis) Comparator Group therapy (eg supportive therapy, psychoeducation, psychodynamic therapy, group CBT such as anxiety management, stress inoculation, assertiveness training, prolonged exposure, cognitive restructuring) Outcome Primary outcome: resolution of symptoms of PTSD Secondary outcomes: symptoms of depression, anxiety and substance misuse/ social and occupational function/ quality of life/ treatment refusal/ dropout over 12 months/ side-effects/ posttraumatic growth/ physical comorbidity Additional outcomes for children: attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies are found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies Search Period 8/2005-10/2011 for adultsa ; 1966-10/2011 if requiredb 1966–10/2011 for children and adolescentsc Language English a Updated search from 2007 Guidelines b Expanded search period if fewer than two Level II studies are found c New research questions CBT = cognitive behavioural therapy; EMDR = eye movement desensitisation and reprocessing
448
Box 201 Study selection criteria for research question 13
Research Question 13. For people with PTSD, is the combination of individual therapy and group therapy more effective than either alone? Selection criteria Inclusion criteria Population People with PTSD Intervention Individual therapy and group therapy (see Box 116 for examples) Comparator Individual therapy or group therapy (see Box 116 for examples) Outcome Primary outcome: resolution of symptoms of PTSD Secondary outcomes: symptoms of depression, anxiety and substance misuse/ social and occupational function/ quality of life/ treatment refusal/ dropout over 12 months/ side-effects/ posttraumatic growth/ physical comorbidity Additional outcomes for children: attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies are found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies Search Period 8/2005-10/2011 for adultsa ; 1966-10/2011 if requiredb 1966–10/2011 for children and adolescentsc Language English
a Updated search from 2007 Guidelines b Expanded search period if fewer than two Level II studies are found c New research questions
Box 202 Study selection criteria for research question 14
Research Question 14. Are established interventions for PTSD effective when self-delivered or self-delivered with practitioner support compared to practitioner delivered intervention or no intervention? Selection criteria Inclusion criteria Population People with PTSD Intervention Self-delivered psychological intervention with/without face-to-face practitioner support (eg web-based interapy or telephone support) Comparator 1. Practitioner delivered psychological intervention 2. No treatment (eg assessment only) Outcome Primary outcome: resolution of symptoms of PTSD Secondary outcomes: symptoms of depression, anxiety and substance misuse/ social and occupational function/ quality of life/ treatment refusal/ dropout over 12 months/ side-effects/ posttraumatic growth/ physical comorbidity. Additional outcomes for children: attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies are found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies Search Period 8/2005-10/2011 for adultsa ; 1966-10/2011 if requiredb 1966-10/2011 for children and adolescentsc Language English
aupdated search from 2007 Guidelines. b Expanded search period if fewer than two Level II studies are found c New research questions
449 Box 203 Study selection criteria for research questions 15 and 16
Research Question 15. For people with PTSD, do pharmacological interventions improve outcomes compared with placebo? 16. For people with PTSD, does any pharmacological intervention confer any advantage over other pharmacological interventions? Selection criteria Inclusion criteria Population People with PTSD Intervention Pharmacological intervention (eg SSRIs, other second-generation antidepressants, tricyclic antidepressants, monoamine oxidase inhibitors, benzodiazepines, mood stabilisers, anti- convulsants, and some non-benzodiazepine hypnotics and anti-anxiety medications) Comparator 1. Placebo 2. Other pharmacological intervention Outcome Primary outcome: resolution of symptoms of PTSD Secondary outcomes: symptoms of depression, anxiety and substance misuse/ social and occupational function/ quality of life/ treatment refusal/ dropout over 12 months/ side-effects/ posttraumatic growth/ physical comorbidity. Additional outcomes for children: attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies are found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies Search Period 8/2005-10/2011 for adultsa , 1966-10/2011 if requiredb 1996-10/2011 for children and adolescentsc Language English a Updated search from 2007 Guidelines b Expanded search period if fewer than two Level II studies are found c New research questions SSRIs = selective serotonin reuptake inhibitors
Box 204 Study selection criteria for research questions 17 and 18
Research Question 17. For people with PTSD, does psychosocial rehabilitation improve outcomes compared to no intervention? Selection criteria Inclusion criteria Population People with PTSD Intervention Psychosocial rehabilitation (eg teaching self-care and independent living skills techniques, providing supported housing, marital/family skills training, social skills training, vocational rehabilitation and case management) in addition to a psychological intervention or pharmacological intervention Comparator 1. No intervention (e.g. assessment only) Outcome Primary outcome: functional improvement, quality of life Secondary outcomes: symptoms of depression, anxiety and substance misuse/ social and occupational function/ quality of life/ treatment refusal/ dropout over 12 months/ side-effects/ posttraumatic growth/ physical comorbidity. Additional outcomes for children: attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies are found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies Search Period 8/2005-10/2011 for adultsa , 1966-10/2011 if requiredb 1966-10/2011 for children and adolescentsc Language English aUpdated search from 2007 Guidelines. b Expanded search period if fewer than two Level II studies are found cNew research questions
450 Box 205 Study selection criteria for research questions 18 and 19
Research Question 18. For people with ASD or PTSD, do physical interventions or exercise improve outcomes compared to no intervention? 19. For people with ASD or PTSD, do physical interventions or exercise confer an advantage over psychological or pharmacological interventions? Selection criteria Inclusion criteria Population People with ASD or PTSD Intervention (1) Physical therapy (eg electroconvulsive therapy, transcranial magnetic stimulation, massage, acupuncture, acupressure, Healing Touch, CranioSacral therapy) (2) Exercise therapy (eg yoga, T’ai Chi, movement-to-music, rhythm activities, competitive sports, walking, jogging, swimming) Comparator 1. No intervention / placebo 2. Any psychological or pharmacological intervention (eg trauma-focused CBT, stress management therapy, EMDR, narrative exposure therapy, supportive counselling, interapy, SSRIs, other second- generation antidepressants, tricyclic antidepressants, monoamine oxidase inhibitors, benzodiazepines, mood stabilisers, anti-convulsants, and some non-benzodiazepine hypnotics and anti-anxiety medications) Outcome Primary outcome: resolution of symptoms of ASD or PTSD Secondary outcomes: symptoms of depression, anxiety and substance misuse/ social and occupational function/ quality of life/ treatment refusal/ dropout over 12 months/ side-effects/ posttraumatic growth/ physical comorbidity. Additional outcomes for children: attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies are found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies Search Period 8/2005-10/2011 for adultsa , 1966-10/2011 if requiredb 1966-10/2011 for children and adolescentsc Language English aupdated search from 2007 Guidelines bExpanded search period if fewer than two Level II studies are found cNew research questions CBT= cognitive behavioural therapy; EMDR = eye movement desensitisation and reprocessing; SSRIs = selective serotonin reuptake inhibitors
Box 206 Study selection criteria for research question 20
Research Question 20. For people with PTSD, is a single intervention more effective than multiple interventions? Selection criteria Inclusion criteria Population People with PTSD Intervention Single psychological or pharmacological intervention or psychosocial rehabilitation strategy Comparator Combined psychological interventions, combined pharmacological interventions, combined psychosocial interventions, or combined psychological, pharmacological, physical, exercise therapy, or psychosocial interventions Outcome Primary outcome: resolution of symptoms of PTSD Secondary outcomes: symptoms of depression, anxiety and substance misuse/ social and occupational function/ quality of life/ treatment refusal/ dropout over 12 months/ side-effects/ posttraumatic growth/ physical comorbidity. Additional outcomes for children: attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies are found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies Search Period 8/2005-10/2011 for adultsa , 1966-10/2011 if requiredb 1966-10/2011 for children and adolescentsc Language English aUpdated search from 2007 Guidelines. bExpanded search period if fewer than two Level II studies are found
451 c New research questions
Box 207 Study selection criteria for research question 21
Research Question 21. For people with PTSD, is any intervention (pharmacotherapy, psychotherapy or psychosocial rehabilitation) more effective than any other intervention (pharmacotherapy, psychotherapy or psychosocial rehabilitation) Selection criteria Inclusion criteria Population People with PTSD Intervention (1) pharmacological intervention (2) psychological intervention (3) psychosocial rehabilitation intervention Comparator (1) psychological or psychosocial rehabilitation intervention (2) pharmacological or psychosocial intervention (3) psychological or pharmacological intervention Outcome Primary outcome: resolution of symptoms of PTSD Secondary outcomes: symptoms of depression, anxiety and substance misuse/ social and occupational function/ quality of life/ treatment refusal/ dropout over 12 months/ side-effects/ posttraumatic growth/ physical comorbidity. Additional outcomes for children: attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies are found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies Search Period 1966-10/2011a Language English a New research question
Box 208 Study selection criteria for research question 22
Research Question 22. In the context of PTSD and comorbidity, is sequencing of intervention per diagnosis more effective than simultaneous interventions for both diagnoses? Selection criteria Inclusion criteria Population People with PTSD and comorbidity (eg grief, depression, personality disorder, pain and substance misuse) Intervention Sequenced psychological or pharmacological intervention per diagnosis ie treatment for PTSD and then comorbidity or vice versa Comparator Simultaneous psychological and/or pharmacological interventions for both diagnoses Outcome Primary outcome: resolution of symptoms of PTSD Secondary outcomes: symptoms of depression, anxiety and substance misuse/ social and occupational function/ quality of life/ treatment refusal/ dropout over 12 months/ side-effects/ posttraumatic growth/ physical comorbidity. Additional outcomes for children: attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies are found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies Search Period 8/2005-10/2011 for adultsa, 1966-10/2011 if requiredb 1966-10/2011 for children and adolescentsc Language English a updated search from 2007 Guidelines bexpanded search period if fewer than two Level II studies are found c New research question
452
Box 209 Study selection criteria for research questions 23 and 24
Research Question 23. For children with PTSD, does the inclusion of parents / primary care givers in psychological interventions improve outcomes for the child compared with no parent / primary care giver inclusion in the psychological interventions? 24. For children with PTSD, does any psychological intervention that includes parents / primary care givers improve outcomes for the child compared to any other psychological intervention that includes parents / primary care givers? Selection criteria Inclusion criteria Population Children with PTSD Intervention Any psychological intervention that includes parents/ primary care givers Comparator 1. Psychological interventions that do not include parents / primary care givers 2. Any other psychological interventions that includes parents / primary care givers Outcome Primary outcome: resolution of symptoms of PTSD Secondary outcomes: resolution of symptoms of depression, anxiety and substance misuse/ social and occupational function / quality of life / treatment refusal/ dropout over 12 months/ posttraumatic growth/ oppositional defiant disorder / attention deficit disorder/ social anxiety disorder/ physical comorbidity / attention deficit hyperactivity disorder / conduct disorder / oppositional defiant disorder / attachment reactive disorder / social anxiety disorder Study design Systematic reviews of randomised controlled trials, randomised controlled trials; if fewer than two Level II studies are found, consider: pseudo-randomised controlled trials, non-randomised controlled trials, cohort studies, before-and-after controlled studies, case-control studies Search Period 1966-10/2011a Language English
aNew research question
Validity Assessment
All studies identified through the new searches, and those identified through the previous reviews (AHTA, NICE and VA/DoD) will be critically appraised – in terms of internal and external validity - and the statistical and clinical relevance and applicability of results will be determined utilising the NHMRC dimensions of evidence (NHMRC 2000a; NHMRC 2000b) and the recently developed NHMRC interim levels and grades of evidence (see Table 205).
Critical appraisal of the included systematic reviews, randomised trials and where appropriate, other types of studies will occur using the NHMRC quality criteria (NHMRC 2000b; NHMRC 2003).
The NHMRC dimensions of evidence (Table 204) consider three main aspects that are critical to an assessment of evidence: strength of the evidence, size of the effect and relevance of the evidence. The first domain is derived directly from the literature identified as informing a particular intervention. The last two require expert clinical input as part of their determination.
453 Table 204 Evidence dimensions Type of evidence Definition Strength of the evidence Level The study design used, as an indicator of the degree to which bias has been eliminated by design.* Quality The methods used by investigators to minimise bias within a study design. Statistical precision The p-value or, alternatively, the precision of the estimate of the effect. It reflects the degree of certainty about the existence of a true effect. Size of effect The distance of the study estimate from the “null” value and the inclusion of only clinically important effects in the confidence interval. Relevance of evidence The usefulness of the evidence in clinical practice, particularly the appropriateness of the outcome measures used. *See Table 205
Strength of evidence
Three sub-domains (level, quality and statistical precision) are collectively a measure of the strength of the evidence.
Level of evidence The research design of each study included in the systematic review is assessed according to its place in a hierarchy. The hierarchy reflects the effectiveness of the study design to answer a particular research question. Effectiveness is based on the probability that the design of the study has reduced or eliminated the impact of bias on the results. (See page 6 - How to use the evidence: assessment and application of scientific evidence (NHMRC 2000b).)
The NHMRC levels of evidence for questions on interventions, diagnosis, prognosis, aetiology and screening are provided in Table 205 (Merlin et al 2009). For the purposes of this systematic review, level II interventional evidence included studies which were randomised by a variety of means, including block randomisation.
454 Table 205 Designations of levels of evidence* according to type of research question (including tablenotes) (Merlin et al 2009)
Level Intervention 1 Diagnostic accuracy 2 Prognosis Aetiology 3 Screening Intervention
I 4 A systematic review of level II A systematic review of level A systematic review of level II A systematic review of level II A systematic review of level II studies II studies studies studies studies II A randomised controlled trial A study of test accuracy with: an A prospective cohort study7 A prospective cohort study A randomised controlled trial independent, blinded comparison with a valid reference standard,5 among consecutive persons with a defined clinical presentation6 III-1 A pseudorandomised controlled trial A study of test accuracy with: an All or none8 All or none8 A pseudorandomised controlled (i.e. alternate allocation or some independent, blinded trial other method) comparison with a valid (i.e. alternate allocation or some reference standard,5 among other method) non-consecutive persons with a defined clinical presentation6 III-2 A comparative study with A comparison with reference Analysis of prognostic factors A retrospective cohort study A comparative study with concurrent controls: standard that does not meet the amongst persons in a single concurrent controls: ▪ Non-randomised, experimental criteria required for arm of a randomised controlled ▪ Non-randomised, experimental trial trial9 Level II and III-1 evidence trial ▪ Cohort study ▪ Cohort study ▪ Case-control study ▪ Case-control study ▪ Interrupted time series with a control group III-3 A comparative study without Diagnostic case-control study6 A retrospective cohort study A case-control study A comparative study without concurrent controls: concurrent controls: ▪ Historical control study ▪ Historical control study ▪ Two or more single arm study10 ▪ Two or more single arm study ▪ Interrupted time series without a parallel control group IV Case series with either post-test or Study of diagnostic yield (no Case series, or cohort study of A cross-sectional study or case Case series pre-test/post-test outcomes reference standard)11 persons at different stages of series disease
455 Explanatory notes:
1 Definitions of these study designs are provided on pages 7-8 How to use the evidence: assessment and application of scientific evidence (NHMRC 2000b) and in the accompanying Glossary. 2 These levels of evidence apply only to studies of assessing the accuracy of diagnostic or screening tests. To assess the overall effectiveness of a diagnostic test there also needs to be a consideration of the impact of the test on patient management and health outcomes (Medical Services Advisory Committee 2005, Sackett and Haynes 2002). The evidence hierarchy given in the ‘Intervention’ column should be used to assess the impact of a diagnostic test on health outcomes relative to an existing method of diagnosis/comparator test(s). The evidence hierarchy given in the ‘Screening’ column should be used to assess the impact of a screening test on health outcomes relative to no screening or opportunistic screening. 3 If it is possible and/or ethical to determine a causal relationship using experimental evidence, then the ‘Intervention’ hierarchy of evidence should be utilised. If it is only possible and/or ethical to determine a causal relationship using observational evidence (eg. cannot allocate groups to a potential harmful exposure, such as nuclear radiation), then the ‘Aetiology’ hierarchy of evidence should be utilised. 4 A systematic review will only be assigned a level of evidence as high as the studies it contains, excepting where those studies are of level II evidence. Systematic reviews of level II evidence provide more data than the individual studies and any meta-analyses will increase the precision of the overall results, reducing the likelihood that the results are affected by chance. Systematic reviews of lower level evidence present results of likely poor internal validity and thus are rated on the likelihood that the results have been affected by bias, rather than whether the systematic review itself is of good quality. Systematic review quality should be assessed separately. A systematic review should consist of at least two studies. In systematic reviews that include different study designs, the overall level of evidence should relate to each individual outcome/result, as different studies (and study designs) might contribute to each different outcome. 5 The validity of the reference standard should be determined in the context of the disease under review. Criteria for determining the validity of the reference standard should be pre-specified. This can include the choice of the reference standard(s) and its timing in relation to the index test. The validity of the reference standard can be determined through quality appraisal of the study (Whiting et al 2003). 6 Well-designed population based case-control studies (eg. population based screening studies where test accuracy is assessed on all cases, with a random sample of controls) do capture a population with a representative spectrum of disease and thus fulfil the requirements for a valid assembly of patients. However, in some cases the population assembled is not representative of the use of the test in practice. In diagnostic case-control studies a selected sample of patients already known to have the disease are compared with a separate group of normal/healthy people known to be free of the disease. In this situation patients with borderline or mild expressions of the disease, and conditions mimicking the disease are excluded, which can lead to exaggeration of both sensitivity and specificity. This is called spectrum bias or spectrum effect because the spectrum of study participants will not be representative of patients seen in practice (Mulherin and Miller 2002). 7 At study inception the cohort is either non-diseased or all at the same stage of the disease. A randomised controlled trial with persons either non-diseased or at the same stage of the disease in both arms of the trial would also meet the criterion for this level of evidence. 8 All or none of the people with the risk factor(s) experience the outcome; and the data arises from an unselected or representative case series which provides an unbiased representation of the prognostic effect. For example, no smallpox develops in the absence of the specific virus; and clear proof of the causal link has come from the disappearance of small pox after large- scale vaccination. 9 This also includes controlled before-and-after (pre-test/post-test) studies, as well as adjusted indirect comparisons (ie. utilise A vs B and B vs C, to determine A vs C with statistical adjustment for B).
456 10 Comparing single arm studies ie. case series from two studies. This would also include unadjusted indirect comparisons (ie. utilise A vs B and B vs C, to determine A vs C but where there is no statistical adjustment for B). 11 Studies of diagnostic yield provide the yield of diagnosed patients, as determined by an index test, without confirmation of the accuracy of this diagnosis by a reference standard. These may be the only alternative when there is no reliable reference standard. Note A: Assessment of comparative harms/safety should occur according to the hierarchy presented for each of the research questions, with the proviso that this assessment occurs within the context of the topic being assessed. Some harms (and other outcomes) are rare and cannot feasibly be captured within randomised controlled trials, in which case lower levels of evidence may be the only type of evidence that is practically achievable; physical harms and psychological harms may need to be addressed by different study designs; harms from diagnostic testing include the likelihood of false positive and false negative results; harms from screening include the likelihood of false alarm and false reassurance results. Note B: When a level of evidence is attributed in the text of a document, it should also be framed according to its corresponding research question eg. level II intervention evidence; level IV diagnostic evidence; level III-2 prognostic evidence. Note C: Each individual study that is attributed a “level of evidence” should be rigorously appraised using validated or commonly used checklists or appraisal tools to ensure that factors other than study design have not affected the validity of the results.
Source: Hierarchies adapted and modified from: NHMRC 1999; Bandolier 1999; Lijmer et al. 1999; Phillips et al. 2001.
457 Quality of evidence Each study included in the systematic review will be critically appraised for methodological quality. The study is assessed according to the likelihood that bias, confounding and/or chance have influenced the results. Potential confounders include co-morbidities, type of trauma and the duration of the intervention. Treatments other than the target intervention will be recorded where possible and noted when not mentioned.
The NHMRC toolkit How to review the evidence: systematic identification and review of the scientific literature (NHMRC 2000a) has various example checklists that can be used.
The quality of the evidence included in this systematic review was assessed using the following checklists:
Critical Appraisal Checklists
Checklist for appraising the quality of randomised controlled trials
Source: (NHMRC 2000a) Modified for this appraisal to combine sections 3 (blinding) and 4 (blinding not possible), given blinding was not possible for the majority of studies.
1. Method of treatment assignment a. Correct, blinded randomisation method described OR randomised, double- blind method stated AND group similarity documented b. Blinding and randomisation stated but method not described OR suspect technique (eg allocation by drawing from an envelope) c. Randomisation claimed but not described and investigator not blinded d. Randomisation not mentioned
2. Control of selection bias after treatment assignment a. Intention to treat analysis AND <15% loss to follow-up b. Intention to treat analysis AND >15% loss to follow-up c. Analysis by treatment received AND <15% loss to follow-up OR no mention of withdrawals d. Analysis by treatment received AND no mention of withdrawals OR more than 15% withdrawals/loss-to-follow-up/post-randomisation exclusions
3. Blinding a. Blinding of outcome assessor AND patient and care giver b. Blinding of outcome assessor OR patient and care giver c. Blinding not done, but standardised assessment d. Blinding not done, and no standardised assessment, OR not mentioned
458
Based on a consensus of the review team within AHTA and correspondence with the ACPMH, studies were considered to be at a low risk of bias if they scored: 1. a 2. a or b 3. a or b Studies were considered to be at a moderate risk of bias if they scored: 1. a or b or c 2. a or b or c 3. a or b or c
Studies were considered to be at high risk of bias if they scored: 1. d 2. d 3. d
459
Checklist for the critical appraisal of cohort studies 6. Are the main findings of the study clearly described? Simple outcome data (including denominators and Source: Downs & Black, 1998 – adapted by numerators) should be reported for all major AHTA findings so that the reader can check the major Reporting analyses and conclusions (This question does not 1. Is the hypothesis/aim/objective of the study clearly cover statistical tests which are considered below). described? yes 1 yes 1 no 0 no 0 7. Does the study provide estimates of the random 2. Are the main outcomes to be measured clearly variability in the data for the main outcomes? described in the Introduction or Methods section? In non-normally distributed data the inter-quartile If the main outcomes are first mentioned in the range of results should be reported. In normally Results section, the question should be answered distributed data the standard error, standard ‘no’. deviation or confidence intervals should be reported. If the distribution of the data is not yes 1 described, it must be assumed that the estimates no 0 used were appropriate and the question should be answered ‘yes’. 3. Are the characteristics of the patients included in the study clearly described? yes 1 In cohort studies and trials, inclusion and/or no 0 exclusion criteria should be given. 8. Have all important adverse events that may be a yes 1 consequence of the intervention been reported? no 0 This should be answered ‘yes’ if the study demonstrates that there was a comprehensive 4. Are the interventions of interest clearly described? attempt to measure adverse events. Interventions that are to be compared should be Adverse events = maternal and fetal mortality, clearly described. vascular complications (haemorrhage, haematoma, transfusion), osteoporosis, fracture, allergy, heparin- yes 1 induced thrombocytopenia, birth abnormalities.
no 0 yes 1
5. Are the distributions of principal confounders in no 0 each group of subjects to be compared clearly described? 9. Have the characteristics of patients lost to follow-up Confounders = type of thrombophilia, hetero or been described? homozygosity, history of obstetric complications, This should be answered ‘yes’ where there were no age, caesarian section, multiple pregnancy. losses to follow-up or where losses to follow-up were so small that findings would be unaffected by yes 2 their inclusion. This should be answered ‘no’ where a study does not report the number of patients lost partially 1 to follow-up. no 0
yes 1 no 0
10. Have the actual probability values been reported (e.g. 0.035 rather than <0.05) for the main outcomes, except where the probability value is less than 0.001?
yes 1 no 0
460
External validity All the following criteria attempt to address the Internal validity - Bias representativeness of the findings of the study and 14. Was an attempt made to blind study subjects to the whether they may be generalised to the population from intervention they have received? which the study subjects were derived. For studies where the patients would have no way 11. Were the subjects asked to participate in the study of knowing which intervention they received, this representative of the entire population from which should be answered ‘yes’. they were recruited? The study must identify the source population for yes 1 patients and describe how the patients were no 0 selected. Patients would be representative if they unable to determine 0 comprised the entire source population, an unselected sample of consecutive patients, or a 15. Was an attempt made to blind those measuring the random sample. Random sampling is only feasible main outcomes of the intervention? where a list of all members of the relevant population exists. Where a study does not report the yes 1 proportion of the source population from which the no 0 patients are derived, the question should be unable to determine 0 answered as ‘unable to determine’. 16. If any of the results of the study were based on yes 1 “data dredging”, was this made clear? no 0 Any analyses that had not been planned at the unable to determine 0 outset of the study should be clearly indicated. If no retrospective unplanned subgroup analyses were 12. Were those subjects who were prepared to reported, then answer ‘yes’. participate representative of the entire population from which they were recruited? yes 1 The proportion of those asked who agreed should no 0 be stated. Validation that the sample was unable to determine 0 representative would include demonstrating that the distribution of the main confounding factors was the 17. In trials and cohort studies, do the analyses adjust same in the study sample and the source for different lengths of follow-up of patients? population. Where follow-up was the same for all study patients the answer should be ‘yes’. If different lengths of yes 1 follow-up were adjusted for by, for example, survival no 0 analysis the answer should be ‘yes’. Studies where unable to determine 0 differences in follow-up are ignored should be answered ‘no’. 13. Were the staff, places, and facilities where the patients were treated, representative of the yes 1 treatment the majority of patients receive? no 0 For the question to be answered ‘yes’ the study unable to determine 0 should demonstrate that the intervention was representative of that in use in the source 18. Were the statistical tests used to assess the main population. The question should be answered ‘no’ if, outcomes appropriate? for example, the intervention was undertaken in a The statistical techniques used must be appropriate specialist centre unrepresentative of the hospitals to the data. For example non-parametric methods most of the source population would attend. should be used for small sample sizes. Where little statistical analysis has been undertaken but where yes 1 there is no evidence of bias, the question should be no 0 answered ‘yes’. If the distribution of the data unable to determine 0 (normal or not) is not described it must be assumed that the estimates used were appropriate and the question should be answered ‘yes’.
yes 1 no 0 unable to determine 0
461
19. Was compliance with the intervention/s reliable? yes 1 Where there was non-compliance with the allocated no 0 treatment or where there was contamination of one unable to determine 0 group, the question should be answered ‘no’. For studies where the effect of any misclassification was 24. Was the randomised intervention assignment likely to bias any association to the null, the concealed from both patients and health care staff question should be answered ‘yes’. until recruitment was complete and irrevocable? All non-randomised studies should be answered yes 1 ‘no’. If assignment was concealed from patients but no 0 not from staff, it should be answered ‘no’. unable to determine 0 yes 1 20. Were the main outcome measures used accurate no 0 (valid and reliable)? unable to determine 0 For studies where the outcome measures are clearly described, the question should be answered 25. Was there adequate adjustment for confounding in ‘yes’. For studies which refer to other work or that the analyses from which the main findings were demonstrates the outcome measures are accurate, drawn? the question should be answered ‘yes’. This question should be answered ‘no’ for trials if: the main conclusions of the study were based on yes 1 analyses of treatment rather than intention-to-treat; no 0 the distribution of known confounders in the unable to determine 0 different treatment groups was not described; or the distribution of known confounders differed between the treatment groups but was not taken into account Internal validity – Confounding (selection bias) in the analyses. In non-randomised studies if the effect of the main confounders was not investigated 21. Were the patients in different intervention groups or confounding was demonstrated but no (trials and cohort studies) recruited from the same adjustment was made in the final analyses the population? question should be answered as ‘no’. For example, patients for all comparison groups
should be selected from the same hospital. The yes 1 question should be answered ‘unable to determine’ no 0 where there is no information concerning the source of patients included in the study. unable to determine 0
yes 1 26. Were losses of patients to follow-up taken into account? no 0 If the number of patients lost to follow-up are not unable to determine 0 reported, the question should be answered as
‘unable to determine’. If the proportion lost to follow- 22. Were study subjects in different intervention groups up was too small to affect the main findings, the (trials and cohort studies) recruited over the same question should be answered ‘yes’. period of time?
For a study which does not specify the time period yes 1 over which the patients were recruited, the question no 0 should be answered as ‘unable to determine’. unable to determine 0 yes 1 no 0 Subscale Scores unable to determine 0 Reporting = /11 External validity = /3 23. Were study subjects randomised to intervention Bias = /7 groups? Confounding = /6 Studies which state that subjects were randomised should be answered ‘yes’ except where method of randomisation is unknown or would not ensure Total Quality Index Score = /27 random allocation. For example, alternate allocation would score ‘no’ because it is predictable.
462
Checklist for the critical appraisal of systematic reviews
Source: (NHMRC 2000b).
1. Was an adequate search strategy used? 2. Were the inclusion criteria appropriate and applied in an unbiased way? 3. Was a quality assessment of included studies undertaken? 4. Were the characteristics and results of the individual studies appropriately summarised? 5. Were the methods for pooling the data appropriate? 6. Were the sources of heterogeneity explored?
Statistical precision Statistical precision will be determined using standard statistical principles. The primary outcomes of each included study are critically appraised to determine whether the effect is ‘real’ as opposed to being due to chance. Small confidence intervals and p-values give an indication as to the probability that the reported effect is real. (See page 17 - How to use the evidence: assessment and application of scientific evidence (NHMRC 2000b).)
Size of effect For intervention studies it is important to assess whether statistically significant differences are also clinically important. The size of the effect needs to be determined, as well as whether the 95% confidence interval includes only clinically important effects. (See pages 17-23 - How to use the evidence: assessment and application of scientific evidence (NHMRC 2000b).)
Table 206 Checklist for assessing clinical importance of benefit and harm
Ranking Clinical importance of benefit/harm
1 A clinically important benefit for the full range of plausible estimates. The confidence limit closest to the measure of no effect (the ‘null’) rules out a clinically unimportant effect of the intervention.
2 The point estimate of effect is clinically important BUT the confidence interval includes clinically unimportant effects.
3 The confidence interval does not include any clinically important effects.
4 The range of estimates defined by the confidence interval includes clinically important effects BUT the range of estimates defined by the confidence interval is also compatible with no effect, or a harmful effect.
Source: (National Health and Medical Research Council 2000)
463
Relevance of evidence Similarly, the outcome being measured should be appropriate and clinically relevant. Inadequately validated (predictive) surrogate measures of a clinically relevant outcome should be avoided (National Health and Medical Research Council 2000). Checklists assessing the clinical importance and relevance of results from each study will be utilised and are provided in a separate document. This dimension assesses the relevance of the results of each individual study with respect to: a. Outcomes: the appropriateness of the outcomes. Are they relevant to the patient? (See pages 23-27 - How to use the evidence: assessment and application of scientific evidence (NHMRC 2000b).) b. Population: are the outcomes of the study based on a similar population and therefore generalisable or applicable to the population of interest? c. Intervention: are the outcomes of the study a consequence of a similar intervention and therefore generalisable or applicable to the intervention of interest?
Table 207 Checklist for assessing the relevance of outcomes
Ranking Relevance of the evidence
1 Evidence of an effect on patient-relevant clinical outcomes, including benefits and harms, and quality of life and survival.
2 Evidence of an effect on a surrogate outcome that has been shown to be predictive of patient- relevant outcomes for the same intervention.
3 Evidence of an effect on proven surrogate outcomes but for a different intervention.
4 Evidence of an effect on proven surrogate outcomes but for a different intervention and population.
5 Evidence confined to unproven surrogate outcomes.
Source: (National Health and Medical Research Council 2000)
Grading the body of evidence
Once each included study is assessed according to the three dimensions of evidence, a grade of recommendation for the whole body of evidence can be determined.
NHMRC grades of recommendation are provided to assist users of the clinical practice guideline in making clinical judgements and indicate the strength of the recommendation. Grade A and B recommendations are generally based on a body of evidence which can be trusted to guide clinical practice, whereas Grade C and D recommendations must be applied carefully to individual clinical and organisational circumstances and should be followed with care.
464
Table 208 Definition of NHMRC grades of recommendation Grade of recommendation Description A Body of evidence can be trusted to guide practice
B Body of evidence can be trusted to guide practice in most situations Body of evidence provides some support for recommendation(s) but care C should be taken in its application
D Body of evidence is weak and recommendation must be applied with caution
How to assess the body of evidence and formulate recommendations
The NHMRC has developed a process for assessing the body of evidence and formulating recommendations with the aim of assisting guideline developers and ensuring that different guidelines are consistent in their development of evidence- based recommendations.
In the methods/process section of the guidelines document, the following will be reproduced to explain how recommendations should be formulated. The application of a grade to a recommendation is based on an assessment of all the included studies for that recommendation (the ‘body of evidence’). The five components that are considered in judging the body of evidence are: x volume of evidence (which includes the number of studies sorted by their methodological quality and relevance to patients) x consistency of the study results x the potential clinical impact of the proposed recommendation (including the balance of risks and benefits, the relevance of the evidence to the clinical question, the size of the patient population and resource issues) x the generalisability of the body of evidence to the target population for the guideline x the applicability of the body of evidence to the Australian healthcare context.
Each of these components is initially graded according to the matrix in Table 209.
465 Table 209 Body of evidence assessment matrix Component A B C D Excellent Good Satisfactory Poor
Evidence base1 one or more level I one or two level II one or two level III level IV studies, or studies with a low risk studies with a low risk studies with a low risk level I to III of bias or several level of bias or a SR/several of bias, or level I or II studies/SRs with a II studies with a low level III studies with a studies with a high risk of bias risk of bias low risk of bias moderate risk of bias
Consistency2 all studies consistent most studies some inconsistency evidence is consistent and reflecting genuine inconsistent inconsistency may be uncertainty around explained clinical question
Clinical impact very large substantial moderate slight or restricted
Generalisability population/s studied in population/s studied in population/s studied in population/s studied in body of evidence are the body of evidence body of evidence differ body of evidence differ the same as the target are similar to the to target population for to target population population for the target population for guideline but it is and hard to guideline the guideline clinically sensible to judgewhether it is apply this evidence to sensible to generalise target population3 to target population
Applicability directly applicable to applicable to probably applicable to not applicable to Australian healthcare Australian healthcare Australian healthcare Australian healthcare context context with few context with some context caveats caveats SR = systematic review; several = more than two studies 1 Level of evidence determined from the NHMRC evidence hierarchy – Table 3, Part B 2 If there is only one study, rank this component as ‘not applicable’. 3 For example, results in adults that are clinically sensible to apply to children OR psychosocial outcomes for one cancer that may be applicable to patients with another cancer
Applying evidence in real clinical situations is not usually straightforward and thus the body of evidence supporting a recommendation is rarely entirely one grade for all important components. For example, a body of evidence may contain a large number of studies with a low risk of bias that are consistent but may not be directly applicable to the target population or Australian healthcare context or may not be expected to have a very large clinical impact. Alternatively, a body of evidence may only consist of one or two randomised trials with small sample sizes that have a moderate risk of bias but have a very large clinical impact and are directly applicable to the Australian healthcare context and target population. The grading process is designed to allow for this mixture of components while still reflecting the overall strength of the body of evidence supporting a recommendation.
A form for assessing the body of evidence has also been developed to assist with the formulation of the guideline recommendations (See Table 210).
How to use the Assessing the Body of Evidence Form NOTE: The form is intended to be used for each clinical question identified prior to the systematic review of the relevant literature. Prior to completing the form, each individual study relevant to the clinical question is critically appraised and the relevant data synthesised (as per the NHMRC minimum standards). The form is used as the basis of discussion regarding the five key components important in grading the
466 recommendations – volume of evidence, consistency, clinical impact, generalisability, applicability. The process for development of the recommendations is as follows:
1. Grade each of the five components and note any important issues arising in the discussion and grading on the form (See Table 210). 2. Write an evidence statement (page 2 of the form) summarising briefly the assessment of the five separate components. 3. The grades for each of the components and the accompanying descriptor (excellent, good, satisfactory, poor) should be written in the relevant boxes. 4. Determine the overall grade for the body of evidence by summing the individual component grades. REMEMBER: A recommendation cannot be graded A or B unless the volume and consistency of evidence components are both graded either A or B. 5. Formulate a recommendation based on this body of evidence. The recommendation should address the original clinical question and ideally be written as an action statement.
Overall grade of recommendation The overall grade of recommendation reflects the strength of the evidence supporting it. It is based on a summation of the grading of individual components of the body of evidence assessment. A recommendation cannot be graded A or B unless the volume and consistency of evidence components are both graded either A or B.
467 Table 210 NHMRC body of evidence form Key question(s): Evidence table ref:
1. Evidence base (number of studies, level of evidence and risk of bias in the included studies) A One or more level I studies with a low risk of bias or several level II studies with a low risk of bias B One or two Level II studies with a low risk of bias or SR/several Level III studies with a low risk of bias C One or two Level III studies with a low risk of bias or Level I or II studies with a moderate risk of bias D Level IV studies or Level I to III studies/SRs with a high risk of bias 2. Consistency (if only one study was available, rank this component as ‘not applicable’) A All studies consistent B Most studies consistent and inconsistency can be explained C Some inconsistency, reflecting genuine uncertainty around question D Evidence is inconsistent NA Not applicable (one study only) 3. Clinical impact (Indicate in the space below if the study results varied according to some unknown factor (not simply study quality or sample size) and thus the clinical impact of the intervention could not be determined) A Very large B Substantial C Moderate D Slight/Restricted 4. Generalisability (How well does the body of evidence match the population and clinical settings being targeted by the Guideline?) A Evidence directly generalisable to target population B Evidence directly generalisable to target population with some caveats C Evidence not directly generalisable to the target population but could be sensibly applied D Evidence not directly generalisable to target population and hard to judge whether it is sensible to apply 5. Applicability (Is the body of evidence relevant to the Australian healthcare context in terms of health services/delivery of care and cultural factors?) A Evidence directly applicable to Australian healthcare context B Evidence applicable to Australian healthcare context with few caveats C Evidence probably applicable to Australian healthcare context with some caveats
468 D Evidence not applicable to Australian healthcare context Other factors (Indicate here any other factors that you took into account when assessing the evidence base (for example, issues that might cause the group to downgrade or upgrade the recommendation)
EVIDENCE STATEMENT MATRIX Please summarise the development group’s synthesis of the evidence relating to the key question, taking all the above factors into account.
Component Rating Description 1. Evidence base 2. Consistency 3. Clinical impact 4. Generalisability 5. Applicability Evidence statement (Indicate any dissenting opinions)
RECOMMENDATION What recommendation(s) does the guideline development group draw from this evidence? Use action GRADE OF RECOMMENDATION statements where possible.
UNRESOLVED ISSUES If needed, keep note of specific issues that arise when each recommendation is formulated and that require follow-up.
IMPLEMENTATION OF RECOMMENDATION Please indicate yes or no to the following questions. Where the answer is yes please provide explanatory information about this. This information will be used to develop the implementation plan for the guidelines. Will this recommendation result in changes in usual care? YES / NO Are there any resource implications associated with implementing this recommendation? YES / NO Will the implementation of this recommendation require changes in the way care is currently organised? YES / NO Are the guideline development group aware of any barriers to the implementation of this recommendation? YES / NO
469 Appendix C Multidisciplinary Panel Members
Person Position Chair 1 Prof. Beverley Raphael Professor of Psychological Medicine , ANU; Professor Population Mental Health and Disasters, UWS Trauma specialists Executive Director Mental Health Metro South Mental Health Services which includes Centre for Disaster, Trauma, Resilience and Recovery, 2 A/ Prof. David Crompton Advisor to Queensland Health on Adult Mental Health and Disasters 3 Prof. Brian Draper Academic Dept. for Old Age Psychiatry, Prince of Wales Hospital, UNSW 4 Dr Rob Gordon Consultant Psychologist, Victorian Disaster Recovery Plan 5 Dr Chris Lee Director of Clinical Psychology program, Murdoch University 6 Ms Cait McMahon Managing Director of DART Centre for Journalism & Trauma 7 Prof. Helen Milroy Director of the Centre for Aboriginal Medical and Dental Health (CAMDH); Professor of Psychiatry, UWA 8 Dr Shirley Morrissey Deputy Head, School of Psychology, Griffith University, QLD 9 Prof. Louise Newman Director of Developmental Psychiatry, Monash University 10 A/Prof. Reg Nixon School of Psychology, Flinders University 11 Ms Rebecca Reay Psychological Medicine, ANU 12 Ms Michelle Roberts Consultant to The Australian Child & Adolescent Trauma, Loss & Grief Network 13 Prof. Kevin Ronan Professor, Clinical Psychology, Central Queensland University 14 Prof. Derrick Silove Director, Refugee and Asylum Seeker Mental Health Centre, UNSW 15 Dr Kevin Vaughan Senior Lecturer, University of Sydney 16 Dr Duncan Wallace Psychiatrist ADF Centre of Mental Health 17 Mr Richard Weston CEO, Aboriginal and Torres Strait Islander Healing Foundation 18 Ms Carolyn Worth Convenor of Victorian Centres Against Sexual Assault
470 19 Ms Ruth Wraith Disaster Recovery Consultant and Child Psychotherapist Professional colleges/associations Occupational Therapist 20 Ms Ann Drew Occupational Therapy Australia representative
General Practitioner Northern Territory 21 Dr Gerald Goodhand College of Rural and Remote General Practitioners representative Mental Health Nurse Professor of Contemporary Nursing and Director of the Institute for Health and Social Science Research, Central Queensland 22 Prof Brenda Happell University Australian College of Mental Health Nurses representative Psychiatrist Director Veterans Psychiatry Unit, Austin Health Assoc Professor Department of Psychiatry University of Melbourne 23 A/Prof Malcolm Hopwood Australian and New Zealand College of Psychiatrists representative
General Practitioner Medical Educator, University of Melbourne Endorsements Co-ordinator, RACGP 24 Dr Caroline Johnson Royal Australian College of General Practitioners representative
Social Worker Mental Health Professional Officer , AASW 25 Ms Liz Sommerville Australian Association of Social Workers representative
Psychologist Manager Professional Issues, APS 26 Mr David Stokes Australian Psychological Society representative
Social Worker School of Social Work and Human Services, UQ President ACGA 27 Dr Brian Sullivan Australian Counselling & Guidance Association representative
Consumer and carer representatives 28 Ms Cassandra Bertram Nominated by the Mental Health Council of Australia 29 Ms Karene Eggleton Nominated by the Mental Health Council of Australia 30 Ms Larisa Trotter Nominated by the Mental Health Council of Australia Representatives from national organisations who provide support to trauma survivors 31 Mr Andrew Coughlin National Manager of Emergency Services, Red Cross 32 Ms Suzanne Pope Director of Research and Planning, beyondblue
471 Appendix D HTA Internet Sites
AUSTRALIA x Australian Safety and Efficacy Register of New Interventional Procedures – Surgical (ASERNIP-S) http://www.surgeons.org/racs/research-and- audit/asernip-s
x Centre for Clinical Effectiveness, Monash University http://www.southernhealth.org.au/page/Health_Professionals/CCE/
x Centre for Health Economics, Monash University http://www.buseco.monash.edu.au/centres/che/
AUSTRIA x Institute of Technology Assessment / HTA unit http://www.oeaw.ac.at/ita/welcome.htm
CANADA x Agence d’Evaluation des Technologies et des Modes d’Intervention en Santé (AETMIS) http://www.aetmis.gouv.qc.ca/site/home.phtml
x Alberta Heritage Foundation for Medical Research (AHFMR) http://www.ahfmr.ab.ca
x Canadian Agency for Drugs and Technologies in Health (formerly Canadian Coordinating Office for Health Technology Assessment (CCHOTA)) http://www.cadth.ca/en
x Canadian Association for Health Services and Policy Research https://cahspr.ca/
x Centre for Health Economics and Policy Analysis (CHEPA), McMaster University http://www.chepa.org
x Centre for Health Services and Policy Research (CHSPR), University of British Columbia http://www.chspr.ubc.ca
x Health Utilities Index (HUI) http://www.fhs.mcmaster.ca/hug/index.htm
x Institute for Clinical and Evaluative Sciences (ICES) http://www.ices.on.ca
DENMARK x Danish Institute for Health Technology Assessment (DIHTA) http://www.sst.dk/english/dacehta.aspx
x Danish Institute for Health Services Research (DSI) http://dsi.dk/english/
472 FINLAND x FINOHTA http://finohta.stakes.fi/EN/index.htm
FRANCE x Haute Autorité de Santé http://www.has- sante.fr/portail/jcms/c_5443/english?cid=c_5443
GERMANY x German Institute of Medical Documentation and Information (DIMDI) / HTA http://www.dimdi.de/dynamic/en/index.html
THE NETHERLANDS x Health Council of the Netherlands Gezondheidsraad http://www.gezondheidsraad.nl/en
NORWAY x Norwegian Knowledge Centre for the Health Services http://www.kunnskapssenteret.no/Home
SPAIN x Agencia de Evaluación de Tecnologias Sanitarias, Instituto de Salud “Carlos III”I/Health Technology Assessment Agency (AETS) http://www.isciii.es/htdocs/en/investigacion/Agencia_quees.jsp
x Catalan Agency for Health Information, Assessment and Quality http://www.gencat.cat/salut/depsan/units/aatrm/html/en/Du8/index.html
SWEDEN x Swedish Council on Health Technology Assessment (SBU) http://www.sbu.se/en/
x Center for Medical Technology Assessment http://www.imh.liu.se/halso-och- sjukvardsanalys/cmt/?l=en
SWITZERLAND x Swiss Network for Health Technology Assessment (SNHTA) http://www.snhta.ch/
UNITED KINGDOM x National Institute for Health Research Health Technology Assessment Program http://www.hta.ac.uk/
x University of York NHS Centre for Reviews and Dissemination (NHS CRD) http://www.york.ac.uk/inst/crd/
x National Institute for Clinical Excellence (NICE) http://www.nice.org.uk
473 UNITED STATES x Agency for Healthcare Research and Quality (AHRQ) http://www.ahrq.gov/clinic/techix.htm
x U.S. Blue Cross/ Blue Shield Association Technology Evaluation Center (TEC) http://www.bcbs.com/blueresources/tec/
474 Appendix E Specialty Websites x American Psychiatric Association http://www.psych.org/ x Australian Psychological Society http://www.psychology.org.au x Gateway for Post Traumatic Stress Disorder information http://www.ptsdinfo.org/ x International Society for Traumatic Stress Studies http://www.istss.org/ x National Centre for Post Traumatic Stress Disorder (NCPTSD) http://www.ptsd.va.gov/ x The Posttraumatic Stress Disorder (PTSD) Alliance http://www.ptsdalliance.org
475 Appendix F NHMRC Minimum Requirements
Minimum requirements for formulating NHMRC evidence-based guidelines
It is expected that compliance with these minimum requirements will facilitate the approval of guidelines by HAC/NHMRC. These are methodological requirements only – process requirements can be found in the document ‘Procedures and requirements for meeting the 2011 NHMRC standard for clinical practice guidelines’, which can be found at:
http://www.nhmrc.gov.au/guidelines/publications/cp133-and-cp133a
The relevant section of the document, regarding the evidence review, is reproduced below.
Table 211 NHMRC minimum requirements for the evidence review Requirement Documented in : Mandatory: The guideline/development process must meet all the following conditions: C.1 Clinical questions addressed by the guideline are stated in a structured and consistent format Technical report, to define the boundaries of the topic, i.e. by specifying the relevant population, intervention/s (e.g. Guideline treatment/s or diagnostic test/s), comparator/s and outcomes measured.
C.2. Systematic searches for evidence are undertaken and the search strategy is Technical report documented, including the search terms and databases searched.
C.3. The population groups specified in the search strategy include Aboriginal and Torres Strait Technical report Islander peoples and any population subgroups that have been identified (see Requirement B.4 and B.5). C.4. The publication period covered by the searches is stated, and the latest date is within 12 Technical report months of the first day of public consultation and within 20 months of submission of the final draft guideline to NHMRC for approval.
C.5. The inclusion and exclusion criteria used to select studies for appraisal are described. Technical report
C.6. For each clinical question, the developer has provided an evidence table, which summarises Technical report the systematic assessment and critical appraisal of all studies that meet the inclusion criteria (i.e. the body of evidence on which a recommendation will be based). Each evidence table should include information on study design, outcomes, level of evidence, the findings of meta-analysis (if performed) and other relevant information.
C.7 For each clinical question, the developer has provided an evidence statement form, which Technical report documents the synthesis and evaluation of the body of evidence to determine the grade of each recommendation, according to an NHMRC-approved method (NHMRC grades for recommendations10 or GRADE11).
C.8 For each recommendation, the developer has provided an evidence summary, which briefly Guideline states the outcomes of each clinical studies on which the recommendation was based, their level of evidence and reference details.
C.9 A recommended date for future update of the guideline is identified. Guideline
476 Desirable The guideline/development process should meet the following conditions, where applicable: C.3.1 The population groups specified in the search strategy include groups such as culturally Technical report and linguistically diverse communities or other groups for whom specific sociocultural factors (including ethnicity, gender, age, disability, socioeconomic status and location) in treatment or prevention outcomes should be considered.
C.3.2 Search strategies include search terms to identify evidence related to consumers’ Technical report perceptions and experiences. C.3.3 Dependent on the guideline scope, the search strategy is designed to identify evidence for Technical report all relevant alternatives for screening, prevention, diagnosis or treatment of the condition addressed by the guideline, including relevant complementary and alternative medicine approaches.
C.3.4 Search strategies include search terms to identify evidence related to cost effectiveness Technical report and resource implications of practice. C.8.1 If gaps in the evidence are identified during the evidence review, these are described in the Guideline guideline and areas for further research are noted.
477 Appendix G Evidence Tables
Summary table for intervention studies Please note: completed evidence tables and study appraisals are included as separate documents. Source: (NHMRC 2005b) Table 212 Summary table for intervention studies (including explanatory notes)*
STUDY DETAILS Reference [1] Affiliation/source of funds [2]
Study design [3] Level of evidence [4] Location/setting [5]
Intervention [6] Comparator(s) [8]
Sample size [7] Sample size [9] Selection criteria Inclusion criteria –
Exclusion criteria –
Patient characteristics [10] Intervention group – Comparator group(s) –
Length of follow-up [11] Outcome(s) measured [12]
INTERNAL VALIDITY Allocation [13] Comparison of study Blinding [15] Treatment/ Follow-up (ITT) [17] groups [14] measurement bias [16] Overall quality assessment (descriptive) [18]
RESULTS
Outcome [19] Intervention group Control group [21] Measure of Benefits (NNT) [23] [20] effect/effect size [22] 95% CI [25] 95% CI [25] Harms (NNH) [24]
95% CI [25] Clinical importance (1-4) [26] Relevance (1-5) [27]
Any other adverse effects [28]
EXTERNAL VALIDITY
Generalisabilty [29]
Applicability [30]
Comments [31]
478 Explanatory Notes STUDY DETAILS [1] Full reference citation details [2] Details of how the study was funded or other relevant affiliations of the authors (designed to expose potential conflicts of interest, such as drug company funding for the drug being trialed) [3] The study type (eg RCT, case-control study, cohort study), with additional detail where relevant [4] As per the NHMRC levels of evidence, provided at pg-8 of the NHMRC Toolkit publication: How to use the evidence: assessment and application of scientific evidence [5] Country/setting (eg hospital, primary care, hospice) [6] Provide detail on the intervention. This will generally be a therapeutic procedure such as treatment with a pharmaceutical agent, surgery, a dietary supplement, a dietary change or psychotherapy. Some other interventions are less obviously categorised as interventions, such as early detection (screening) and patient educational materials. The key characteristic is that a person or their environment is manipulated in the hope of benefiting that person or reducing harm [7] Number of participants enrolled in the intervention/treatment group [8] The intervention (eg drug, therapy, placebo) used as a comparison in the study. There may be more than one comparator [9] Number of participants enrolled in the comparison/control group(s) [10] Any factors that may confound/influence the results and/or the external validity (see below) of the results (eg age, sex, comorbidities, obesity, existing medications, previous surgery) [11] Length of follow-up of the participants [12] The outcomes studied (list all outcomes in terms of primary and secondary outcomes). Indicate which outcomes are relevant to the review/guidelines inclusion criteria INTERNAL VALIDITY (QUALITY ASSESSMENT) [13] The method used to assign patients to treatment or control groups (eg coin toss, random number table, computer-generated random numbers, sealed envelopes). Also indicate whether the allocation list was concealed (eg computerised random number generation, administered from a central trial office, assigned locally) [14] The results of the group analysis, noting any clinically or statistically significant differences between the groups at study inception [15] Whether the participants, outcome assessors and (if different) investigators were blinded to the group allocation [16] Indicate whether, aside from the experimental treatment, the groups were treated and measured the same [17] The proportion of participants that were followed up and whether all participants were analysed according to the group to which they were initially allocated, regardless of whether or not they dropped out, fully complied with the treatment, or crossed over and received the other treatment (‘intention to treat analysis’ - ITT) [18] Describe your assessment (in words) of the overall quality of the study. Is the study quality good enough that you have confidence in the results? RESULTS [19] The outcome relevant for this entry in the database (Note: more than one table may be required if there are several outcomes relevant to different clinical questions/guidelines) [20] For discontinuous (binary) outcomes, show numbers of patients with the outcome. For continuous outcomes, show means ± standard deviations; or medians and interquartile ranges [21] For discontinuous (binary) outcomes, show numbers of patients with the outcome. For continuous outcomes, show means ± standard deviations; or medians and interquartile ranges. Add number of columns as needed (eg 3-arm trials) [22] Absolute and relative measures of effect eg risk differences (absolute risk reduction or absolute risk increase), mean differences, relative risk, odds ratio [23] A measure of benefit, when the treatment increases the probability of a good event. The number needed to treat to benefit (NNT) = the number of participants who must receive the treatment to create one additional improved outcome in comparison with the control treatment; calculated as 1/absolute benefit increase, rounded up to the next highest whole number [24] A measure of harm, when the treatment increases the risk of specified adverse outcomes of a condition or reduces the probability of a good event. The number needed to treat to harm (NNH) = the number of patients who, if they receive the treatment, would lead to one additional person being harmed compared with patients who receive the control treatment; calculated as 1/absolute risk increase, rounded up to the next highest whole number [25] 95% confidence interval (CI) for all measures, if available, otherwise use P-value [26] Insert the words corresponding to the appropriate rating from the scale provided at pg-23 of the NHMRC Toolkit publication: How to use the evidence: assessment and application of scientific evidence [27] Insert the words corresponding to the appropriate rating from the scale provided at pg-28 of the NHMRC Toolkit publication: How to use the evidence: assessment and application of scientific evidence [28] Information on any adverse events mentioned in the study EXTERNAL VALIDITY [29] Are the patients in the study so different from those being considered for the guideline that the results may not be applicable to them? [30] Will the potential benefits outweigh any potential harms of treatment in the guideline population? [31] Add your overall comments regarding the interpretation or implications of this study
Source: (NHMRC 2005b)
479 Appendix H Publication bias funnel plots
Funnel plots were performed for the primary outcome measures of PTSD diagnosis, and severity of PTSD symptoms (clinician-rated and self-report), where there were more than 3 studies providing these outcomes for a particular comparison, at a particular time point. It should be noted that plots with less than 10 studies do not provide sufficient data to draw any conclusions.
Q3, 4 Early interventions
DEBRIEFING VERSUS CONTROL
480
CBT VERSUS SUPPORTIVE PSYCHOTHERAPY
481
482
483
484 Questions 10 and 11
CBT VERSUS WAITLIST/CONTROL
Given the asymmetry in the above funnel plot, with an absence of smaller studies showing non-significant or small effect sizes, it seems plausible that there is reporting bias.
485
486 CBT VERSUS WAITLIST/CONTROL Intention-to-treat analyses
487
STRESS MANAGEMENT VERSUS WAITLIST
488
489 EMDR VERSUS WAITLIST
Although there are too few studies providing data for the above funnel plot on which to make any strong conclusions, given the skewed data, it is possible that reporting bias exists for this comparison.
490
CBT VERSUS TREATMENT AS USUAL
491
492
493 EMDR VERSUS STRESS MANAGEMENT
494
495 EMDR VERSUS TRAUMA-FOCUSED CBT
496
497 Questions 15 and 16
SERTRALINE VERSUS PLACEBO
498 Appendix I Excluded studies
Reasons for exclusion of studies involving psychological interventions (questions 1-4, 7-14, 20-21, and 23-24)
Incorrect study design
Non-systematic reviews
Bisson, J. I. (2003). 'Single-session early psychological interventions following traumatic events', Clin Psychol Rev, 23 (3), 481-499.
Brewer, M. & Melnyk, B. M. (2007). 'Evidence-based practice. Effective coping/mental health interventions for critically ill adolescents: an evidence review', Pediatric Nursing, 33 (4), 361.
Bryant, RA 2007, 'Early intervention for post-traumatic stress disorder', Early Interv Psychiatry, vol. 1, no. 1, Feb, pp. 19-26.
Bryant, RA 2011, 'Mental disorders and traumatic injury', Depress Anxiety, vol. 28, no. 2, Feb, pp. 99-102.
Cohen, JA, Mannarino, AP, Murray, LK & Igelman, R 2006, 'Psychosocial Interventions for Maltreated and Violence-Exposed Children', Journal of Social Issues, vol. 62, no. 4, pp. 737- 766.
Cohen, JA, Mannarino, AP, Zhitova, AC & Capone, ME 2003, 'Treating child abuse-related posttraumatic stress and comorbid substance abuse in adolescents', Child Abuse Negl, vol. 27, no. 12, Dec, pp. 1345-1365.
Ehlers, A & Clark, D 2003, 'Early psychological interventions for adult survivors of trauma: a review', Biol Psychiatry, vol. 53, no. 9, May 1, pp. 817-826.
Feinstein, D 2010, 'Rapid treatment of ptsd: Why psychological exposure with acupoint tapping may be effective', Psychotherapy, vol. 47, no. 3, pp. 385-402.
Lowenstein, L. B. (1995). 'The resolution scrapbook as an aid in the treatment of traumatized children', Child Welfare, 74 (4), 889-889.
Pai, A. L. & Kazak, A. E. (2006). 'Pediatric medical traumatic stress in pediatric oncology: family systems interventions', Current Opinion in Pediatrics, 18 (5), 558-562
Reviews including studies with non-randomised or pseudorandomised design
Adler-Nevo, G & Manassis, K 2005, 'Psychosocial treatment of pediatric posttraumatic stress disorder: The neglected field of single-incident trauma', Depression and Anxiety, vol. 22, no. 4, pp. 177-189.
499 Adler-Tapia, R & Settle, C 2009, 'Evidence of the efficacy of EMDR with children and adolescents in individual psychotherapy: A review of the research published in peer-reviewed journals', Journal of EMDR Practice and Research, vol. 3, no. 4, pp. 232-247.
Belleville, G, Cousineau, H, Levrier, K, St-Pierre-Delorme, M-È & Marchand, A 2010, 'The impact of cognitive-behavior therapy for anxiety disorders on concomitant sleep disturbances: a meta-analysis', Journal of Anxiety Disorders, vol. 24, no. 4, May, pp. 379- 386.
Chard, KM 1995, 'A meta-analysis of posttraumatic stress disorder treatment outcome studies of sexually victimized women [dissertation]', Indiana University, vol. 124.
Cooper, J, Carty, J & Creamer, M 2005, 'Pharmacotherapy for posttraumatic stress disorder: empirical review and clinical recommendations', Aust N Z J Psychiatry, vol. 39, no. 8, Aug, pp. 674-682.
Harvey, ST & Taylor, JE 2010, 'A meta-analysis of the effects of psychotherapy with sexually abused children and adolescents', Clin Psychol Rev, vol. 30, no. 5, Jul, pp. 517-535.
Harvey, ST & Taylor, JE 2010, ''A meta-analysis of the effects of psychotherapy with sexually abused children and adolescents': Erratum', Clinical Psychology Review, vol. 30, no. 8, pp. 1049-1050.
Peltonen, K & Punamäki, R-L 2010, 'Preventive interventions among children exposed to trauma of armed conflict: a literature review', Aggressive Behavior, vol. 36, no. 2, March/April, pp. 95-116.
Puttre, JJ 2010, 'A meta-analytic review of the treatment outcome literature for traumatized children and adolescents [dissertation]', St. John's University, vol. 120.
Roberts Neil, P., Kitchiner Neil, J. et al (2010). 'Early psychological interventions to treat acute traumatic stress symptoms', Cochrane Database of Systematic Reviews, (3).
Roberts, N. P., Kitchiner, N. J. et al (2009). 'Systematic review and meta-analysis of multiple-session early interventions following traumatic events', Am J Psychiatry, 166 (3), 293-301.
Rolfsnes, E. S. & Idsoe, T. (2011). 'School-based intervention programs for PTSD symptoms: a review and meta-analysis', J Trauma Stress, 24 (2), 155-165.
Sloan, DM, Gallagher, MW, Feinstein, BA, Lee, DJ & Pruneau, GM 2011, 'Efficacy of Telehealth Treatments for Posttraumatic Stress-Related Symptoms: A Meta-Analysis', Cogn Behav Ther, May 1, pp. 1-15.
Taylor, JE & Harvey, ST 2009, 'Effects of psychotherapy with people who have been sexually assaulted: A meta-analysis', Aggression and Violent Behavior, vol. 14, no. 5, pp. 273-285.
500 Studies with non-randomised or pseudorandomised design
Alvarez, J, McLean, C, Harris, AHS, Rosen, CS, Ruzek, JI & Kimerling, R 2011, 'The comparative effectiveness of cognitive processing therapy for male veterans treated in a VHA posttraumatic stress disorder residential rehabilitation program', Journal of Consulting and Clinical Psychology, vol. 79, no. 5, pp. 590-599.
Berger, R. & Gelkopf, M. (2009). 'School-based intervention for the treatment of tsunami- related distress in children: a quasi-randomized controlled trial', Psychother Psychosom, 78 (6), 364-371.
Berger, R., Pat-Horenczyk, R. & Gelkopf, M. (2007). 'School-based intervention for prevention and treatment of elementary-students' terror-related distress in Israel: a quasi- randomized controlled trial', J Trauma Stress, 20 (4), 541-551.
Brinkman, W.P., Vertmetten, E. Van den Steen, M. & Neerincx, M.A (2011) ‘Cognitive engineering of a military multi-model memory restructuring system’, Journal of CyberTherapy and Rehabilitation, 4(1): 83-99.
Devilly, G. J. & Spence, S. H. (1999). 'The relative efficacy and treatment distress of EMDR and a cognitive- behavior trauma treatment protocol in the amelioration of Posttraumatic Stress Disorder', Journal of Anxiety Disorders, 13 (1-2), 131-157.
Difede, J, Cukor, J, Jayasinghe, N, Patt, I, Jedel, S, Spielman, LA, Giosan, C & Hoffman, HG 2007, 'Virtual reality exposure therapy for the treatment of posttraumatic stress disorder following September 11, 2001', Journal of Clinical Psychiatry, vol. 68, no. 11, November, pp. 1639-1647.
Drožđek, B & Bolwerk, N 2010, 'Evaluation of group therapy with traumatized asylum seekers and refugees—The Den Bosch Model', Traumatology, vol. 16, no. 4, pp. 117-127.
Essar, N, Palgi, Y, Saar, R & Ben-Ezra, M 2010, 'Pre-traumatic vaccination intervention: can dissociative symptoms be reduced?', Prehospital & Disaster Medicine, vol. 25, no. 3, pp. 278- 284.
Feeny, NC, Zoellner, LA, Mavissakalian, MR & Roy-Byrne, PP 2009, 'What would you choose? Sertraline or prolonged exposure in community and PTSD treatment seeking women', Depress Anxiety, vol. 26, no. 8, pp. 724-731.
Germain, V, Marchand, A, Bouchard, S, Drouin, MS & Guay, S 2009, 'Effectiveness of cognitive behavioural therapy administered by videoconference for posttraumatic stress disorder', Cogn Behav Ther, vol. 38, no. 1, pp. 42-53.
Gelkopf, M. & Berger, R. (2009). 'A school-based, teacher-mediated prevention program (ERASE-Stress) for reducing terror-related traumatic reactions in Israeli youth: a quasi- randomized controlled trial', J Child Psychol Psychiatry, 50 (8), 962-971.
Goodwin, L, Jones, M, Rona, RJ, Sundin, Wessely, S, Fear, NT In press ‘Prevalence of delayed-onset PTSD in military personnel: is there evidence for this disorder? Results of a prospective UK cohort study’.
501 Gray, M.J., Schorr, Y., Nash, W., Lebowitz, L., Amidon, A., Lansing, A. et al (In press) ‘Adaptive disclosure: an open trial of a novel exposure-based intervention for service members with combat-related psychological stress injuries’ Behavior Therapy
Gros, DF, Yoder, M, Tuerk, PW, Lozano, BE & Acierno, R 2011, 'Exposure therapy for PTSD delivered to veterans via telehealth: predictors of treatment completion and outcome and comparison to treatment delivered in person', Behav Ther, vol. 42, no. 2, Jun, pp. 276- 283.
Gupta, L & Zimmer, C 2008, 'Psychosocial intervention for war-affected children in Sierra Leone', Br J Psychiatry, vol. 192, no. 3, Mar, pp. 212-216.
Hammarberg, M & Silver, SM 1994, 'Outcome of treatment for post-traumatic stress disorder in a primary care unit serving Vietnam veterans', J Trauma Stress, vol. 7, no. 2, Apr, pp. 195- 216.
Jarero, I & Uribe, S. In press ‘The EMDR protocol for recent critical incidents: follow-up report of an application in a human massacre situation’.
Jeffres, MJ 2003, 'The efficacy of EMDR with traumatized children [dissertation]', Fielding Graduate Institute, vol. 264.
Johnson, DR & Lubin, H 2002, 'Effect of brief versus long-term inpatient treatment on homecoming stress in combat-related posttraumatic stress disorder: three-year follow-up', J Nerv Ment Dis, vol. 190, no. 1, Jan, pp. 47-51.
Jotzo, M & Poets, CF 2005, 'Helping parents cope with the trauma of premature birth: an evaluation of a trauma-preventive psychological intervention', Pediatrics, vol. 115, no. 4, Apr, pp. 915-919.
Karam, EG, Fayyad, J, Nasser Karam, A, Cordahi Tabet, C, Melhem, N, Mneimneh, Z & Dimassi, H 2008, 'Effectiveness and specificity of a classroom-based group intervention in children and adolescents exposed to war in Lebanon', World Psychiatry, vol. 7, no. 2, pp. 103-109.
Kataoka, SH, Stein, BD, Jaycox, LH, Wong, M, Escudero, P, Tu, W, Zaragoza, C & Fink, A 2003, 'A school-based mental health program for traumatized latino immigrant children', Journal of the American Academy of Child and Adolescent Psychiatry, vol. 42, no. 3, pp. 311-318.
Khachiyants, N, Ali, R, Kovesdy, CP, Detweiler, JG, Kim, KY & Detweiler, MB 2010, 'Effectiveness of risperidone for the treatment of nightmares in veterans with posttraumatic stress disorder', Journal of Clinical Psychopharmacology, vol. 30, no. 6, pp. 735-737.
LaMontagne, L. L., Hepworth, J. T. et al (1994). 'Psychophysiological Responses of Parents to Pediatric Critical Care Stress', Clinical Nursing Research, 3 (2), 104-118.
Lande, RG, Williams, LB, Francis, JL, Gragnani, C & Morin, ML 2010, 'Efficacy of biofeedback for post-traumatic stress disorder', Complement Ther Med, vol. 18, no. 6, Dec, pp. 256-259.
502 Lerner, JA 2007, 'Internet-based assessment and treatment for posttraumatic stress disorder among motor vehicle accident survivors [dissertation]', State University of New York at Albany, vol. 187.
Manger, TA & Motta, RW 2005, 'The impact of an exercise program on posttraumatic stress disorder, anxiety, and depression', Int J Emerg Ment Health, vol. 7, no. 1, Winter, pp. 49-57.
Marchand, A, Beaulieu-Prevost, D, Guay, S, Bouchard, S, Drouin, MS & Germain, V 2011, 'Relative efficacy of cognitive-behavioral therapy administered by videoconference for posttraumatic stress disorder: A six-month follow-up', Journal of Aggression, Maltreatment and Trauma, vol. 20, no. 3, pp. 304-321.
McClatchey, IS, Vonk, ME & Palardy, G 2009, 'Efficacy of a camp-based intervention for childhood traumatic grief', Research on Social Work Practice, vol. 19, no. 1, January, pp. 19- 30.
Mert, A. & Vermetten, E. (In press) ‘Military motion-based memory desensitization and reprocessing (3MDR): a novel treatment for PTSD – proof of concept’.
Mouthaan, J, Sijbrandij, M, Reitsma, JB, Gersons, BPR, & Olff, M In press ‘Internet-based prevention of posttraumatic stress symptoms in injured trauma patients: design of a randomized controlled trial’ European Journal of Psychotraumatology 2011, 2: 8294
Mouthaan, J, Sijbrandij, M, Reitsma, JB, Goslings, JC, & Olff, M 2011 ‘Trauma tips: an internet based intervention to prevent posttraumatic stress disorder in injured trauma patients’, Journal of Cybertherapy and Rehabilitation, vol. 4, no. 3: 331-340.
Muller, RT & Rosenkranz, SE 2009, 'Attachment and treatment responses among adults in inpatient treatment for posttraumatric stress disorder', Psychotherapy, vol. 46, no. 1, pp. 82- 96.
Neuner, F, Onyut, PL, Ertl, V, Odenwald, M, Schauer, E & Elbert, T 2008, 'Treatment of posttraumatic stress disorder by trained lay counselors in an African refugee settlement: a randomized controlled trial', J Consult Clin Psychol, vol. 76, no. 4, Aug, pp. 686-694.
Oflaz, F, Hatipoglu, S & Aydin, H 2008, 'Effectiveness of psychoeducation intervention on post-traumatic stress disorder and coping styles of earthquake survivors', Journal of Clinical Nursing, vol. 17, no. 5, pp. 677-687.
Palic, S & Elklit, A 2011, 'Psychosocial treatment of posttraumatic stress disorder in adult refugees: a systematic review of prospective treatment outcome studies and a critique', J Affect Disord, vol. 131, no. 1-3, Jun, pp. 8-23.
Resnick, H, Acierno, R, Waldrop, AE, King, L, King, D, Danielson, C, Ruggiero, KJ & Kilpatrick, D 2007, 'Randomized controlled evaluation of an early intervention to prevent post-rape psychopathology', Behav Res Ther, vol. 45, no. 10, Oct, pp. 2432-2447.
Rothbaum, BO, Houry, D, Heekin, M, Leiner, AS, Daugherty, J, Smith, LS & Gerardi, M 2008, 'A pilot study of an exposure-based intervention in the ED designed to prevent
503 posttraumatic stress disorder', American Journal of Emergency Medicine, vol. 26, no. 3, pp. 326-330.
Savedra, M. C. & Highley, B. L. (1988). 'Photography: Is it useful in learning how adolescents view hospitalization?', Journal of Adolescent Health Care, 9 (3), 219-224.
Schaal, S, Elbert, T & Neuner, F 2009, 'Narrative exposure therapy versus interpersonal psychotherapy. A pilot randomized controlled trial with Rwandan genocide orphans', Psychother Psychosom, vol. 78, no. 5, pp. 298-306.
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Servan-Schreiber, D, Schooler, J, Dew, MA, Carter, C & Bartone, P 2006, 'Eye movement desensitization and reprocessing for posttraumatic stress disorder: a pilot blinded, randomized study of stimulation type', Psychother Psychosom, vol. 75, no. 5, pp. 290-297.
Shooshtary, MH, Panaghi, L & Moghadam, JA 2008, 'Outcome of cognitive behavioral therapy in adolescents after natural disaster', J Adolesc Health, vol. 42, no. 5, May, pp. 466- 472.
Stalker, CA, Palmer, SE, Wright, DC & Gebotys, R 2005, 'Specialized inpatient trauma treatment for adults abused as children: a follow-up study', Am J Psychiatry, vol. 162, no. 3, Mar, pp. 552-559.
Thabet, AA, Vostanis, P & Karim, K 2005, 'Group crisis intervention for children during ongoing war conflict', Eur Child Adolesc Psychiatry, vol. 14, no. 5, Aug, pp. 262-269.
Tourigny, M & Hebert, M 2007, 'Comparison of open versus closed group interventions for sexually abused adolescent girls', Violence Vict, vol. 22, no. 3, pp. 334-349.
Tourigny, M, Hébert, M, Daigneault, I & Simoneau, AC 2005, 'Efficacy of a Group Therapy for Sexually Abused Adolescent Girls', Journal of Child Sexual Abuse, vol. 14, no. 4, pp. 71- 93.
Trappler, B & Newville, H 2007, 'Trauma healing via cognitive behavior therapy in chronically hospitalized patients', Psychiatr Q, vol. 78, no. 4, Dec, pp. 317-325.
Turner, SM, Beidel, DC & Frueh, BC 2005, 'Multicomponent behavioral treatment for chronic combat-related posttraumatic stress disorder: Trauma management therapy', Behavior Modification, vol. 29, no. 1, pp. 39-69.
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504 Wolmer, L, Hamiel, D & Laor, N 2011, 'Preventing children's posttraumatic stress after disaster with teacher-based intervention: a controlled study', J Am Acad Child Adolesc Psychiatry, vol. 50, no. 4, Apr, pp. 340-348, 348 e341-342.
Not a study
'Implementing CBT for traumatized children and adolescents after september 11: lessons learned from the Child and Adolescent Trauma Treatments and Services (CATS) Project', 2007, J Clin Child Adolesc Psychol, vol. 36, no. 4, Oct-Dec, pp. 581-592.
'Early treatment for PTSD', 2009, Journal of the National Medical Association, vol. 101, no. 7, p. 742.
Adshead, G 2000, 'Psychological therapies for post-traumatic stress disorder', Br J Psychiatry, vol. 177, Aug, pp. 144-148.
Basoglu, M 2007, 'Treatment for depression symptoms in ugandan adolescent survivors of war and displacement [5]', Journal of the American Medical Association, vol. 298, no. 18, p. 2138.
Berliner, L 2005, 'The results of randomized clinical trials move the field forward', Child Abuse Negl, vol. 29, no. 2, Feb, pp. 103-105.
Beyerstein, BL 2001, 'Fringe psychotherapies: The public at risk', Scientific Review of Alternative Medicine, vol. 5, no. 2, pp. 70-79.
Beyzarov, EP 2000, 'New alliance, new approval put PTSD in the spotlight', Drug Topics, vol. 144, no. 7, pp. 16-19.
Bisson, J 2002, 'Post-traumatic stress disorder', Clin Evid, no. 7, Jun, pp. 913-919.
Bjornstad, GJ, Ramchandani, P, Montgomery, P & Gardner, F 2009, 'Child-focused cognitive behavioural therapy for children who have been physically abused', Cochrane Database of Systematic Reviews, no. 2.
Bloom, BL 2002, 'Brief interventions for anxiety disorders: Clinical outcome studies', Brief Treatment and Crisis Intervention, vol. 2, no. 4, pp. 325-339.
Brinson, T & Treanor, V 1988, 'Alcoholism and post traumatic stress disorder among combat Vietnam veterans', Alcoholism Treatment Quarterly, vol. 5, no. 3-4, pp. 65-82.
Cantor, C 2008, 'DSM-IV cure for post-traumatic stress disorder', Australas Psychiatry, vol. 16, no. 4, Aug, p. 297.
Clark, HW & Power, AK 2005, 'Women, Co-occurring Disorders, and Violence Study: a case for trauma-informed care', J Subst Abuse Treat, vol. 28, no. 2, Mar, pp. 145-146.
Cohen, J, Goodman, RF, Brown, EJ & Mannarino, A 2004, 'Treatment of childhood traumatic grief: contributing to a newly emerging condition in the wake of community trauma', Harv Rev Psychiatry, vol. 12, no. 4, Jul-Aug, pp. 213-216.
505 Cole, EM & Piercy, FP 2007, 'The use of dolls to assist young children with PTSD symptoms', Journal of Family Psychotherapy, vol. 18, no. 2, pp. 83-89.
Ehlers, A, Bisson, J, Clark, DM, Creamer, M, Pilling, S, Richards, D, Schnurr, PP, Turner, S & Yule, W 2010, 'Do all psychological treatments really work the same in posttraumatic stress disorder?', Clin Psychol Rev, vol. 30, no. 2, Mar, pp. 269-276.
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Fernando, GA 2005, 'Interventions for survivors of the tsunami disaster: Report from Sri Lanka', Journal of Traumatic Stress, vol. 18, no. 3, pp. 267-268.
Gardner, F, Bjornstad, GJ, Ramchandani, P, Tao, X & Montgomery, P 2009, 'Family therapy for children who have been physically abused', Cochrane Database of Systematic Reviews, no. 2.
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Voshaar, RCO, Hendriks, GJ, Keijsers, G & Van Balkom, AJ 2009, 'Cognitive behavioural therapy for anxiety disorders in later life', Cochrane Database of Systematic Reviews, no. 1.
Incorrect study population
Abbasnejad, M, Mahani, KN & Zamyad, A 2007, 'Efficacy of "eye movement desensitization and reprocessing" in reducing anxiety and unpleasant feelings due to earthquake experience', Psychological Research, vol. 9, no. 3-4, pp. 104-117.
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506 Anderson, T, Fende Guajardo, J, Luthra, R & Edwards, KM 2010, 'Effects of clinician- assisted emotional disclosure for sexual assault survivors: a pilot study', Journal of Interpersonal Violence, vol. 25, no. 6, June, pp. 1113-1131.
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Benoit, D, Green, D & Arts-Rodas, D 1997, 'Posttraumatic feeding disorders', Journal of the American Academy of Child and Adolescent Psychiatry, vol. 36, no. 5, pp. 577-578.
Bernstein, G. A., Layne, A. E. et al (2005). 'School-Based Interventions for Anxious Children', Journal of the American Academy of Child & Adolescent Psychiatry, 44 (11), 1118-1127.
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Bolton, PA, Bass, JK, Betancourt, TS, Speelman, L, Onyango, GR, Clougherty, KF, Neugebauer, R, Murray, LK & Verdeli, H 2007, 'Interventions for depression symptoms among adolescent survivors of war and displacement in northern Uganda: a randomized
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Chen, YY 2005, 'Written emotional expression and religion: effects on PTSD symptoms', Int J Psychiatry Med, vol. 35, no. 3, pp. 273-286.
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Craske, MG, Stein, MB, Sullivan, G, Sherbourne, C, Bystritsky, A, Rose, RD, Lang, AJ, Welch, S, Campbell-Sills, L, Golinelli, D & Roy-Byrne, P 2011, 'Disorder-specific impact of coordinated anxiety learning and management treatment for anxiety disorders in primary care', Arch Gen Psychiatry, vol. 68, no. 4, Apr, pp. 378-388.
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Cvetek, R 2008, 'EMDR treatment of distressful experiences that fail to meet the criteria for PTSD', Journal of EMDR Practice and Research, vol. 2, no. 1, pp. 2-14.
508 Davis, JL & Wright, DC 2007, 'Randomized clinical trial for treatment of chronic nightmares in trauma-exposed adults', J Trauma Stress, vol. 20, no. 2, Apr, pp. 123-133.
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509 Jouriles, EN, McDonald, R, Rosenfield, D, Stephens, N, Corbitt-Shindler, D & Miller, PC 2009, 'Reducing conduct problems among children exposed to intimate partner violence: a randomized clinical trial examining effects of Project Support', J Consult Clin Psychol, vol. 77, no. 4, Aug, pp. 705-717.
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Analogue
Varker, T & Devilly, G. In press ‘An Analogue Trial of Inoculation / Resilience Training for Emergency Services Personnel: Proof of Concept’
Incorrect intervention Not treatment for PTSD
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No intervention d' Ardenne, P, Ruaro, L, Cestari, L, Fakhoury, W & Priebe, S 2007, 'Does interpreter- mediated CBT with traumatized refugee people work? A comparison of patient outcomes in East London', Behavioural and Cognitive Psychotherapy, vol. 35, no. 3, pp. 293-301.
Intervention for those exposed to trauma, after 1 month
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Early exercise intervention (not in those diagnosed with PTSD)
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Incorrect comparator
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No comparator
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No outcomes data
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Cannot extract data
Berkowitz, S. J., Stover, C. S. & Marans, S. R. (2011). 'The Child and Family Traumatic Stress Intervention: secondary prevention for youth at risk of developing PTSD', J Child Psychol Psychiatry, 52 (6), 676-685. (uncertain how many Pp in each arm)
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Schnurr, P.P. & Lunney, C.A. (In press) Effects of Treatment on Work-Related Quality of Life in Female Veterans and Service Members.
Schreier, H., Ladakakos, C. et al (2005). 'Posttraumatic Stress Symptoms in Children after Mild to Moderate Pediatric Trauma: A Longitudinal Examination of Symptom Prevalence, Correlates, and Parent-Child Symptom Reporting', The Journal of Trauma and Acute Care Surgery, 58 (2), 353-363.
Patient dropout exceeding 50 per cent
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519 Jaycox, LH, Cohen, JA, Mannarino, AP, Walker, DW, Langley, AK, Gegenheimer, KL, Scott, M & Schonlau, M 2010, 'Children's mental health care following Hurricane Katrina: a field trial of trauma-focused psychotherapies', J Trauma Stress, vol. 23, no. 2, Apr, pp. 223- 231.
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Data included in another intervention study or review
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Bisson, JI 2007, 'Eye movement desensitisation and reprocessing reduces PTSD symptoms compared with fluoxetine at six months post-treatment', Evidence Based Mental Health, vol. 10, no. 4, pp. 118-118.
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Griffin, M.G., Resick, P.A. & Galovski, T.E. (In press) ‘Does physiologic response to loud tones change following cognitive behavioural treatment for posttraumatic stress disorder?’
521 Greene, CJ, Morland, LA, Macdonald, A, Frueh, BC, Grubbs, KM & Rosen, CS 2010, 'How does tele-mental health affect group therapy process? Secondary analysis of a noninferiority trial', J Consult Clin Psychol, vol. 78, no. 5, Oct, pp. 746-750.
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522 Lester, K, Artz, C, Resick, PA & Young-Xu, Y 2010, 'Impact of race on early treatment termination and outcomes in posttraumatic stress disorder treatment', Journal of Consulting and Clinical Psychology, vol. 78, no. 4, pp. 480-489.
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523 Roberts, NP, Kitchiner, NJ, Kenardy, J & Bisson, J 2009, 'Multiple session early psychological intervention to prevent and treat post-traumatic stress disorder', Cochrane Database of Systematic Reviews, no. 3.
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Studies predating the year 2005 and included in the NICE review
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525 Brady, K, Pearlstein, T, Asnis, GM, Baker, D, Rothbaum, B, Sikes, CR & Farfel, GM 2000, 'Efficacy and safety of sertraline treatment of posttraumatic stress disorder: A randomized controlled trial', Journal of the American Medical Association, vol. 283, no. 14, pp. 1837- 1844.
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526 Cusack, K & Spates, CR 1999, 'The cognitive dismantling of Eye Movement Desensitization and Reprocessing (EMDR) treatment of Posttraumatic Stress Disorder (PTSD)', J Anxiety Disord, vol. 13, no. 1-2, Jan-Apr, pp. 87-99.
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Edmond, TE 1997, 'Eye movement desensitization and reprocessing: evaluating its effectiveness in reducing trauma symptoms in adult female survivors of childhood sexual abuse [dissertation]', University of Texas at Austin, vol. 254.
Everly, GS, Jr. & Boyle, SH 1999, 'Critical incident stress debriefing (CISD): a meta- analysis', Int J Emerg Ment Health, vol. 1, no. 3, Summer, pp. 165-168. Everly, GS, Boyle, SH & Lating, JM 1999, 'The effectiveness of psychological debriefing with vicarious trauma: a meta-analysis', Stress Medicine, vol. 15, no. 4, October, pp. 229-233.
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527 Falsetti, SA, Erwin, BA, Resnick, HS, Davis, J & Combs-Lane, AM 2003, 'Multiple Channel Exposure Therapy of PTSD: Impact of Treatment on Functioning and Resources', Journal of Cognitive Psychotherapy, vol. 17, no. 2, pp. 133-147.
Fecteau, GW 1999, 'Treatment of posttraumatic stress reactions to traffic accidents [dissertation]', University of New Brunswick, vol. 232.
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Glynn, SM, Eth, S, Randolph, ET, Foy, DW, Urbaitis, M, Boxer, L, Paz, GG, Leong, GB, Firman, G, Salk, JD, Katzman, JW & Crothers, J 1999, 'A test of behavioral family therapy to augment exposure for combat-related posttraumatic stress disorder', J Consult Clin Psychol, vol. 67, no. 2, Apr, pp. 243-251.
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528 Hobbs, M, Mayou, RA, Harrison, B & Worlock, P 1996, 'A randomised controlled trial of psychological debriefing for victims of road traffic accidents', British Medical Journal, vol. 313, no. 7070, 7, pp. 1438-1439.
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Ironson, G, Freud, B, Strauss, JL & Williams, J 2002, 'Comparison for two treatments for traumatic stress: A community-based study of EMDR and prolonged exposure', Journal of Clinical Psychology, vol. 58, no. 1, pp. 113-128.
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529 Largo-Marsh, LK & Spates, CR 2002, 'The effects of writing therapy in comparison to EMD/R on traumatic stress: the relationship between hypnotizability and client expectancy to outcome', Professional Psychology: Research and Practice, vol. 33, no. 6, December, pp. 581- 586.
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Mellman, TA, Bustamante, V, David, D & Fins, AI 2002, 'Hypnotic medication in the aftermath of trauma', Journal of Clinical Psychiatry, vol. 63, no. 12, pp. 1183-1184.
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Morland, LA, Pierce, K & Wong, MY 2004, 'Telemedicine and coping skills groups for Pacific Island veterans with post-traumatic stress disorder: A pilot study', Journal of Telemedicine and Telecare, vol. 10, no. 5, pp. 286-289.
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530 Paunovic, N & Öst, L-G 2001, 'Cognitive-behavior therapy vs exposure therapy in the treatment of PTSD in refugees', Behaviour Research and Therapy, vol. 39, no. 10, October, pp. 1183-1197.
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532 Wallis, DA 2002, 'Reduction of trauma symptoms following group therapy', Aust N Z J Psychiatry, vol. 36, no. 1, Feb, pp. 67-74.
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Not in English
Andre, C, Lelord, F, Legeron, P, Reignier, A & Delattre, A 1997, 'Controlled study of outcome after 6 months to early intervention of bus driver victims of aggression', L'Encephale, vol. 23, no. 1, pp. 65-71.
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533 Reasons for exclusion of studies involving pharmacological interventions (Questions 5-7, 15-16, and 20-21)
Incorrect study design
Non-systematic reviews
Bajor, LA, Ticlea, AN & Osser, DN 2011, 'The psychopharmacology algorithm project at the harvard south shore program: An update on posttraumatic stress disorder', Harvard Review of Psychiatry, vol. 19, no. 5, pp. 240-258.
Berlant, J 2006, 'Topiramate as a Therapy for Chronic Posttraumatic Stress Disorder', Psychiatry, vol. 3, no. 3, pp. 40-44.
Bisson, JI 2010, 'Post-traumatic stress disorder', Clin Evid (Online), vol. 2010.
Bryant, RA 2007, 'Early intervention for post-traumatic stress disorder', Early Interv Psychiatry, vol. 1, no. 1, Feb, pp. 19-26.
Cohen, JA, Mannarino, AP, Zhitova, AC & Capone, ME 2003, 'Treating child abuse-related posttraumatic stress and comorbid substance abuse in adolescents', Child Abuse Negl, vol. 27, no. 12, Dec, pp. 1345-1365.
Cooper, J, Carty, J & Creamer, M 2005, 'Pharmacotherapy for posttraumatic stress disorder: Empirical review and clinical recommendations', Australian and New Zealand Journal of Psychiatry, vol. 39, no. 8, pp. 674-682.
Fava, GA, Ruini, C & Rafanelli, C 2005, 'Sequential treatment of mood and anxiety disorders', Journal of Clinical Psychiatry, vol. 66, no. 11, pp. 1392-1400.
Fletcher, S, Creamer, M & Forbes, D 2010, 'Preventing post traumatic stress disorder: Are drugs the answer?', Australian and New Zealand Journal of Psychiatry, vol. 44, no. 12, pp. 1064-1071.
Gaynard, L., Goldberger, J. & Laidley, L. N. (1991). 'The Use of Stuffed, Body-Outline Dolls With Hospitalized Children and Adolescents', Children's Health Care, 20 (4), 216-224.
Huemer, J, Erhart, F & Steiner, H 2010, 'Posttraumatic stress disorder in children and adolescents: a review of psychopharmacological treatment', Child psychiatry and human development, vol. 41, no. 6, pp. 624-640.
Strawn, JR, Keeshin, BR, DelBello, MP, Geracioti Jr, TD & Putnam, FW 2010, 'Psychopharmacologic treatment of posttraumatic stress disorder in children and adolescents: A review', Journal of Clinical Psychiatry, vol. 71, no. 7, pp. 932-941.
534 Reviews including studies with non-randomised or pseudorandomised design
Adams, E 2010, 'Hyperbaric oxygen therapy for traumatic brain injury (TBI) and post traumatic stress disorder (PTSD)', Boston: VA Technology Assessment Program (VATAP)
Berger, W, Mendlowicz, MV, Marques-Portella, C, Kinrys, G, Fontenelle, LF, Marmar, CR & Figueira, I 2009, 'Pharmacologic alternatives to antidepressants in posttraumatic stress disorder: A systematic review', Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 33, no. 2, pp. 169-180.
Boscarino, JA, Adams, RE & Figley, CR 2005, 'A prospective cohort study of the effectiveness of employer-sponsored crisis interventions after a major disaster', Int J Emerg Ment Health, vol. 7, no. 1, Winter, pp. 9-22.
Boscarino, JA, Adams, RE, Foa, EB & Landrigan, PJ 2006, 'A propensity score analysis of brief worksite crisis interventions after the World Trade Center disaster: implications for intervention and research', Med Care, vol. 44, no. 5, May, pp. 454-462.
Palic, S & Elklit, A 2011, 'Psychosocial treatment of posttraumatic stress disorder in adult refugees: a systematic review of prospective treatment outcome studies and a critique', J Affect Disord, vol. 131, no. 1-3, Jun, pp. 8-23.
Studies with non-randomised or pseudorandomised design
Cohen, LR & Hien, DA 2006, 'Treatment outcomes for women with substance abuse and PTSD who have experienced complex trauma', Psychiatr Serv, vol. 57, no. 1, Jan, pp. 100- 106. de Quervain, DJ 2006, 'Glucocorticoid-induced inhibition of memory retrieval: implications for posttraumatic stress disorder', Ann N Y Acad Sci, vol. 1071, Jul, pp. 216-220. de Quervain, DJ 2008, 'Glucocorticoid-induced reduction of traumatic memories: implications for the treatment of PTSD', Prog Brain Res, vol. 167, pp. 239-247.
Deahl, MP, Srinivasan, M, Jones, N, Thomas, J, Neblett, C & Jolly, A 2000, 'Preventing psychological trauma in soldiers: the role of operational stress training and psychological debriefing', British Journal of Medical Psychology, vol. 73, no. 1, March, pp. 77-85.
Freyth, C., Elsesser, K. et al (2010). 'Effects of additional prolonged exposure to psychoeducation and relaxation in acute stress disorder', J Anxiety Disord, 24 (8), 909-917.
Lande, RG, Williams, LB, Francis, JL, Gragnani, C & Morin, ML 2010, 'Efficacy of biofeedback for post-traumatic stress disorder', Complement Ther Med, vol. 18, no. 6, Dec, pp. 256-259.
Noether, CD, Finkelstein, N, VanDeMark, NR, Savage, A, Reed, BG & Moses, DJ 2005, 'Design strengths and issues of SAMHSA's Women, Co-occurring Disorders, and Violence Study', Psychiatr Serv, vol. 56, no. 10, Oct, pp. 1233-1236.
535 Oflaz, F, Hatipoglu, S & Aydin, H 2008, 'Effectiveness of psychoeducation intervention on post-traumatic stress disorder and coping styles of earthquake survivors', Journal of Clinical Nursing, vol. 17, no. 5, March, pp. 677-687.
Pivac, N & Kozaric-Kovacic, D 2006, 'Pharmacotherapy of treatment-resistant combat- related posttraumatic stress disorder with psychotic features', Croatian Medical Journal, vol. 47, no. 3, pp. 440-451.
Sharpley, JG, Fear, NT, Greenberg, N, Jones, M & Wessely, S 2008, 'Pre-deployment stress briefing: does it have an effect?', Occup Med (Lond), vol. 58, no. 1, Jan, pp. 30-34.
Tcheung, WJ, Robert, R, Rosenberg, L, Rosenberg, M, Villarreal, C, Thomas, C, Holzer Iii, CE & Meyer Iii, WJ 2005, 'Early treatment of acute stress disorder in children with major burn injury', Pediatric Critical Care Medicine, vol. 6, no. 6, pp. 676-681.
Conference abstracts
Fani, N, Ashraf, A, Afzal, N, Jawed, F & Bremner, JD 2010, 'Changes in neural response to trauma-related reminders in patients with posttraumatic stress disorder following paroxetine treatment', Biological Psychiatry, vol. 67, no. 9, p. 207S.
Haimov, I, Blanaro, M, Arnon, Z, Ziv, N, Bloch, B, Reshef, A, Vadas, L & Kremer, I 2010, 'The effects of music and muscle relaxation therapies on sleep quality in individuals with post-traumatic stress disorder', Journal of Sleep Research, vol. 19, p. 364.
Hamner, M, Robert, S, Canive, J & Caleis, L 2009, 'Quetiapine monotherapy in chronic posttraumatic stress disorder: A randomized, double-blind, placebo-controlled trial', Journal of Cancer Education, vol. 24, pp. S591-S592.
Nijdam, MJ & Olff, M 2010, 'Verbal memory deficits in patients with posttraumatic stress disorder with and without major depression', European Neuropsychopharmacology, vol. 20, p. S524.
Tavanti, M, Bossini, L, Calossi, S, Marino, D, Vatti, G, Galli, R, Pieraccini, F & Castrogiovanni, P 2008, 'Sertraline versus Eye Movement Desensitization and Reprocessing (EMDR): Effects on hippocampal volumes and PTSD symptoms', European Neuropsychopharmacology, vol. 18, no. S4, p. S262.
Yatzkar, U & Klein, E 2010, 'Intranasal oxytocin in patients with post traumatic stress disorder: A single dose, pilot double blind crossover study', European Neuropsychopharmacology, vol. 20, p. S84.
Letters
Amital, D, Vishne, T, Roitman, S, Kotler, M & Levine, J 2006, 'Open study of creatine monohydrate in treatment-resistant posttraumatic stress disorder [3]', Journal of Clinical Psychiatry, vol. 67, no. 5, pp. 836-837.
Annitto, W & Mueller, PS 2005, 'Rapid treatment of posttraumatic stress disorder with sibutramine', Epilepsy and Behavior, vol. 7, no. 3, pp. 565-566.
536 Bossini, L, Tavanti, M, Lombardelli, A, Calossi, S, Polizzotto, NR, Galli, R, Vatti, G, Pieraccini, F & Castrogiovanni, P 2007, 'Changes in hippocampal volume in patients with post-traumatic stress disorder after sertraline treatment', J Clin Psychopharmacol, vol. 27, no. 2, Apr, pp. 233-235.
Khachiyants, N, Ali, R, Kovesdy, CP, Detweiler, JG, Kim, KY & Detweiler, MB 2010, 'Effectiveness of risperidone for the treatment of nightmares in veterans with posttraumatic stress disorder', Journal of Clinical Psychopharmacology, vol. 30, no. 6, pp. 735-737.
Mellman, TA, Bustamante, V, David, D & Fins, AI 2002, 'Hypnotic medication in the aftermath of trauma', Journal of Clinical Psychiatry, vol. 63, no. 12, pp. 1183-1184.
Commentaries
Deahl, MP, Srinivasan, M, Jones, N, Neblett, C & Jolly, A 2001, 'Evaluating psychological debriefing: are we measuring the right outcomes?', J Trauma Stress, vol. 14, no. 3, Jul, pp. 527-529.
Krystal, AD & Davidson, JRT 2007, 'The Use of Prazosin for the Treatment of Trauma Nightmares and Sleep Disturbance in Combat Veterans with Post-Traumatic Stress Disorder', Biological Psychiatry, vol. 61, no. 8, pp. 925-927.
Incorrect study population
Studies for which population did not have PTSD
Amaro, H, Dai, J, Arevalo, S, Acevedo, A, Matsumoto, A, Nieves, R & Prado, G 2007, 'Effects of integrated trauma treatment on outcomes in a racially/ethnically diverse sample of women in urban community-based substance abuse treatment', Journal of Urban Health, vol. 84, no. 4, pp. 508-522.
Classen, CC, Palesh, OG, Cavanaugh, CE, Koopman, C, Kaupp, JW, Kraemer, HC, Aggarwal, R & Spiegel, D 2011, 'A comparison of trauma-focused and present-focused group therapy for survivors of childhood sexual abuse: a randomized controlled trial', Psychological Trauma: Theory, Research, Practice, and Policy, vol. 3, no. 1, March, pp. 84-93.
Cohen, JA, Mannarino, AP & Knudsen, K 2005, 'Treating sexually abused children: 1 year follow-up of a randomized controlled trial', Child Abuse Negl, vol. 29, no. 2, Feb, pp. 135- 145.
Cuijpers, P, Van Straten, A & Smit, F 2005, 'Preventing the incidence of new cases of mental disorders: a meta-analytic review', J Nerv Ment Dis, vol. 193, no. 2, Feb, pp. 119-125.
Fallot, RD, McHugo, GJ, Harris, M & Xie, H 2011, 'The trauma recovery and empowerment model: A quasi-experimental effectiveness study', Journal of Dual Diagnosis, vol. 7, no. 1-2, pp. 74-89.
Lewis, CC, Simons, AD, Nguyen, LJ, Murakami, JL, Reid, MW, Silva, SG & March, JS 2010, 'Impact of childhood trauma on treatment outcome in the Treatment for Adolescents
537 with Depression Study (TADS)', J Am Acad Child Adolesc Psychiatry, vol. 49, no. 2, Feb, pp. 132-140.
McWhirter, PT 2011, 'Differential therapeutic outcomes of community-based group interventions for women and children exposed to intimate partner violence', Journal of Interpersonal Violence, vol. 26, no. 12, August, pp. 2457-2482.
Nakamura, Y, Lipschitz, DL, Landward, R, Kuhn, R & West, G 2011, 'Two sessions of sleep-focused mind-body bridging improve self-reported symptoms of sleep and PTSD in veterans: A pilot randomized controlled trial', Journal of Psychosomatic Research, vol. 70, no. 4, pp. 335-345.
Petrakis, IL, Poling, J, Levinson, C, Nich, C, Carroll, K, Ralevski, E & Rounsaville, B 2006, 'Naltrexone and Disulfiram in Patients with Alcohol Dependence and Comorbid Post- Traumatic Stress Disorder', Biological Psychiatry, vol. 60, no. 7, pp. 777-783.
Petrakis, IL, Poling, J, Levinson, C, Nich, C, Carroll, K & Rounsaville, B 2005, 'Naltrexone and disulfiram in patients with alcohol dependence and comorbid psychiatric disorders', Biological Psychiatry, vol. 57, no. 10, pp. 1128-1137.
Possemato, KA, Ouimette, PC & Knowlton, P 2011, 'A brief self-guided telehealth intervention for post-traumatic stress disorder in combat veterans: a pilot study', Journal of Telemedicine and Telecare, Published online, vol. 2.
Price, C 2005, 'Body-oriented therapy in recovery from child sexual abuse: An efficacy study', Alternative Therapies in Health and Medicine, vol. 11, no. 5, pp. 46-57.
Shakibaei, F, Harandi, AA, Gholamrezaei, A, Samoei, R & Salehi, P 2008, 'Hypnotherapy in management of pain and reexperiencing of trauma in burn patients', International Journal of Clinical and Experimental Hypnosis, vol. 56, no. 2, pp. 185-197.
Studies for which insufficient proportion of population had PTSD
Boden, MT, Kimerling, R, Jacobs-Lentz, J, Bowman, D, Weaver, C, Carney, D, Walser, R & Trafton, JA 2011, 'Seeking Safety Treatment for Male Veterans with a Substance Use Disorder and PTSD Symptomatology', Addiction, Sep 16.
Ziegenhorn, AA, Roepke, S, Schommer, NC, Merkl, A, Danker-Hopfe, H, Perschel, FH, Heuser, I, Anghelescu, IG & Lammers, CH 2009, 'Clonidine improves hyperarousal in borderline personality disorder with or without comorbid posttraumatic stress disorder: A randomized, double-blind, placebo-controlled trial', Journal of Clinical Psychopharmacology, vol. 29, no. 2, pp. 170-173.
Incorrect intervention
Observational studies with no intervention
Farrugia, PL, Mills, KL, Barrett, E, Back, SE, Teesson, M, Baker, A, Sannibale, C, Hopwood, S, Rosenfeld, J, Merz, S & Brady, KT 2011, 'Childhood trauma among individuals
538 with co-morbid substance use and post traumatic stress disorder', Ment Health Subst Use, vol. 4, no. 4, Nov, pp. 314-326.
Incorrect outcome
No PTSD-relevant outcomes data
Brunet, A, Orr, SP, Tremblay, J, Robertson, K, Nader, K & Pitman, RK 2008, 'Effect of post- retrieval propranolol on psychophysiologic responding during subsequent script-driven traumatic imagery in post-traumatic stress disorder', J Psychiatr Res, vol. 42, no. 6, May, pp. 503-506.
Hien, DA, Campbell, AN, Killeen, T, Hu, MC, Hansen, C, Jiang, H, Hatch-Maillette, M, Miele, GM, Cohen, LR, Gan, W, Resko, SM, DiBono, M, Wells, EA & Nunes, EV 2010, 'The impact of trauma-focused group therapy upon HIV sexual risk behaviors in the NIDA Clinical Trials Network "Women and trauma" multi-site study', AIDS Behav, vol. 14, no. 2, Apr, pp. 421-430.
Hien, DA, Jiang, H, Campbell, AN, Hu, MC, Miele, GM, Cohen, LR, Brigham, GS, Capstick, C, Kulaga, A, Robinson, J, Suarez-Morales, L & Nunes, EV 2010, 'Do treatment improvements in PTSD severity affect substance use outcomes? A secondary analysis from a randomized clinical trial in NIDA's Clinical Trials Network', Am J Psychiatry, vol. 167, no. 1, Jan, pp. 95-101.
Lurie, I & Levine, SZ 2010, 'Meta-analysis of dropout rates in SSRIs versus placebo in randomized clinical trials of PTSD', Journal of Nervous and Mental Disease, vol. 198, no. 2, pp. 116-124.
Najavits, LM, Gallop, RJ & Weiss, RD 2006, 'Seeking safety therapy for adolescent girls with PTSD and substance use disorder: a randomized controlled trial', J Behav Health Serv Res, vol. 33, no. 4, Oct, pp. 453-463.
Price, CJ, McBride, B, Hyerle, L & Kivlahan, DR 2007, 'Mindful awareness in body-oriented therapy for female veterans with post-traumatic stress disorder taking prescription analgesics for chronic pain: A feasibility study', Alternative Therapies in Health and Medicine, vol. 13, no. 6, pp. 32-40.
Taylor, FB, Lowe, K, Thompson, C, McFall, MM, Peskind, ER, Kanter, ED, Allison, N, Williams, J, Martin, P & Raskind, MA 2006, 'Daytime prazosin reduces psychological distress to trauma specific cues in civilian trauma posttraumatic stress disorder', Biol Psychiatry, vol. 59, no. 7, Apr 1, pp. 577-581.
Cannot extract data
Gidron, Y., Gal, R. et al (2007). 'Interactive Effects of Memory Structuring and Gender in Preventing Posttraumatic Stress Symptoms', The Journal of Nervous and Mental Disease, 195 (2), 179-182
539 Greenberg, N., Langston, V. et al (2010). 'A cluster randomized controlled trial to determine the efficacy of Trauma Risk Management (TRiM) in a military population', Journal of Traumatic Stress, 23 (4), 430-436. Nugent, N. R., Christopher, N. C. et al (2010). 'The efficacy of early propranolol administration at reducing PTSD symptoms in pediatric injury patients: a pilot study', Journal of Traumatic Stress, 23 (2), 282-287. (Individual level data provided in graphical format).
Data included in another intervention study or review
'Divalproex for treating PTSD in conduct-disordered adolescents', 2007, Brown University Child & Adolescent Psychopharmacology Update, vol. 9, no. 12, pp. 3-4.
'Tiagabine not effective for PTSD', 2007, Brown University Psychopharmacology Update, vol. 18, no. 5, pp. 4-4.
Back, SE, Brady, KT, Sonne, SC & Verduin, ML 2006, 'Symptom improvement in co- occurring PTSD and alcohol dependence', Journal of Nervous and Mental Disease, vol. 194, no. 9, pp. 690-696.
Bisson, JI 2005, 'Adding hypnosis to cognitive behavioural therapy may reduce some acute stress disorder symptoms', Evidence Based Mental Health, vol. 8, no. 4, pp. 109-109.
Bisson, JI 2007, 'Eye movement desensitisation and reprocessing reduces PTSD symptoms compared with fluoxetine at six months post-treatment', Evidence Based Mental Health, vol. 10, no. 4, pp. 118-118.
Bolton, P, Murray, L & Bass, J 2009, 'School based intervention improves PTSD symptoms in children affected by political violence', Evidence Based Mental Health, vol. 12, no. 2, pp. 47-47.
Cabral, P, Meyer, HB & Ames, D 2011, 'Effectiveness of yoga therapy as a complementary treatment for major psychiatric disorders: A meta-analysis', Primary Care Companion to the Journal of Clinical Psychiatry, vol. 13, no. 4, p. 7.
Crumlish, N & O'Rourke, K 2010, 'A systematic review of treatments for post-traumatic stress disorder among refugees and asylum-seekers', Journal of Nervous and Mental Disease, vol. 198, no. 4, pp. 237-251.
Ipser, J, Seedat, S & Stein, DJ 2006, 'Pharmacotherapy for post-traumatic stress disorder - A systematic review and meta-analysis', South African Medical Journal, vol. 96, no. 10, pp. 1088-1096.
Ipser, JC & Stein, DJ 2011, 'Evidence-based pharmacotherapy of post-traumatic stress disorder (PTSD)', Int J Neuropsychopharmacol, Jul 29, pp. 1-16.
Mithoefer, MC, Wagner, MT, Mithoefer, AT, Jerome, L & Doblin, R 2011, 'Corrigendum: 'The safety and efficacy of ±3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: The first randomized controlled pilot study'', Journal of Psychopharmacology, vol. 25, no. 6.
540 Noordik, E, van der Klink, JJ, Klingen, EF, Nieuwenhuijsen, K & van Dijk, FJ 2010, 'Exposure-in-vivo containing interventions to improve work functioning of workers with anxiety disorder: a systematic review', BMC public health, vol. 10, p. 598.
Pae, CU, Lim, HK, Peindl, K, Ajwani, N, Serretti, A, Patkar, AA & Lee, C 2008, 'The atypical antipsychotics olanzapine and risperidone in the treatment of posttraumatic stress disorder: A meta-analysis of randomized, double-blind, placebo-controlled clinical trials', International Clinical Psychopharmacology, vol. 23, no. 1, pp. 1-8.
Passarela, CDM, Mendes, DD & De Jesus Mari, J 2010, 'A systematic review to study the efficacy of cognitive behavioral therapy for sexually abused children and adolescents with posttraumatic stress disorder', Revista de Psiquiatria Clinica, vol. 37, no. 2, pp. 63-73.
Sijbrandij, M 2010, 'Review: multiple session early psychological interventions after trauma do not prevent PTSD', Evidence Based Mental Health, vol. 13, no. 1, pp. 29-29.
Stewart, CL & Wrobel, TA 2009, 'Evaluation of the efficacy of pharmacotherapy and psychotherapy in treatment of combat-related post-traumatic stress disorder: a meta-analytic review of outcome studies', Military medicine, vol. 174, no. 5, pp. 460-469.
Stiffler, CL 2006, 'PTSD symptom reductions following seeking safety and relapse prevention treatments', 66 thesis, ProQuest Information & Learning.
Stovall-McClough, C 2004, 'Trauma focused cognitive behavioural therapy reduces PTSD more effectively than child centred therapy in children who have been sexually abused', Evidence Based Mental Health, vol. 7, no. 4, pp. 113-113.
Taylor, JE & Harvey, ST 2009, 'Effects of psychotherapy with people who have been sexually assaulted: A meta-analysis', Aggression and Violent Behavior, vol. 14, no. 5, pp. 273-285.
Wethington, HR, Hahn, RA, Fuqua-Whitley, DS, Sipe, TA, Crosby, AE, Johnson, RL, Liberman, AM, Moscicki, E, Price, LN, Tuma, FK, Kalra, G & Chattopadhyay, SK 2008, 'The Effectiveness of Interventions to Reduce Psychological Harm from Traumatic Events Among Children and Adolescents. A Systematic Review', American Journal of Preventive Medicine, vol. 35, no. 3, pp. 287-313.
Xu, JJ, Chan, MJ & Yang, YC 2011, 'Fluoxetine as a treatment for post-traumatic stress disorder', Neurosciences, vol. 16, no. 3, pp. 257-262.
Studies for which full text was unavailable/unobtainable within time constraints
Davis, LL, Ward, C, Rasmusson, A, Newell, JM, Frazier, E & Southwick, SM 2008, 'A placebo-controlled trial of guanfacine for the treatment of posttraumatic stress disorder in veterans', review of only first two pages available- seeing if we can get whole thing, Psychopharmacol Bull, vol. 41, no. 1, pp. 8-18.
Gaiton, LR 2005, 'Investigation of therapeutic alliance in a treatment study with substance- abusing women with PTSD', 65 thesis, ProQuest Information & Learning.
541
542 Reasons for exclusion of studies involving psychosocial rehabilitation (questions 17, 20 and 21)
Incorrect intervention (psychotherapy rather than psychosocial rehabilitation)
Carbonell, D. M. & Parteleno-Barehmi, C. (1999). 'Psychodrama groups for girls coping with trauma', International Journal of Group Psychotherapy, 49 (3), 285-306.
Celano, M, Hazzard, A, Webb, C & McCall, C 1996, 'Treatment of traumagenic beliefs among sexually abused girls and their mothers: an evaluation study', Journal of abnormal child psychology, no. 1, pp. 1-17
Cloitre, M, Koenen, KC, Cohen, LR & Han, H 2002, 'Skills training in affective and interpersonal regulation followed by exposure: A phase-based treatment for PTSD related to childhood abuse', Journal of Consulting and Clinical Psychology, vol. 70, no. 5, pp. 1067- 1074.
Silverman, WK, Ortiz, CD, Viswesvaran, C, Burns, BJ, Kolko, DJ, Putnam, FW & Amaya- Jackson, L 2008, 'Evidence-based psychosocial treatments for children and adolescents exposed to traumatic events (Structured abstract)', Journal of Clinical Child and Adolescent Psychology, no. 1, pp. 156-183
Tol, WA, Komproe, IH, Jordans, MJ, Gross, AL, Susanty, D, Macy, RD & de Jong, JT 2010, 'Mediators and moderators of a psychosocial intervention for children affected by political violence', Journal of Consulting and Clinical Psychology, no. 6, pp. 818-828
Tol, W. A., Komproe, I. H. et al (2008). 'School-based mental health intervention for children affected by political violence in Indonesia: a cluster randomized trial', JAMA, 300 (6), 655- 662.
Incorrect population (not PTSD)
Andersson, A. L., Dahlback, L. O. & Bunketorp, O. (2005). 'Psychosocial aspects of road traffic trauma--benefits of an early intervention?', Injury, 36 (8), 917-926.
Fantuzzo, J. W., Sutton-Smith, B. et al (1996). 'Community-based resilient peer treatment of withdrawn maltreated preschool children', Journal of Consulting and Clinical Psychology, 64 (6), 1377-1386.
Riosa, P. B., McArthur, B. A. & Preyde, M. (2011). 'Effectiveness of psychosocial intervention for children and adolescents with comorbid problems: A systematic review', Child and Adolescent Mental Health, 16 (4), 177-185.
Stecker, T., Fortney, J. C. & Sherbourne, C. D. (2011). 'An intervention to increase mental health treatment engagement among OIF Veterans: a pilot trial', Military Medicine, 176 (6), 613-619.
543 Taussig, H. N. & Culhane, S. E. (2010). 'Impact of a mentoring and skills group program on mental health outcomes for maltreated children in foster care', Archives of Pediatrics and Adolescent Medicine, 164 (8), 739-746.
Williams, M. & Thompson, S. (2011). 'The Use of Community-Based Interventions in Reducing Morbidity from the Psychological Impact of Conflict-Related Trauma Among Refugee Populations: A Systematic Review of the Literature', Journal of Immigrant & Minority Health, 13 (4), 780-794.
Winzelberg, AJ, Classen, C, Alpers, GW, Roberts, H, Koopman, C, Adams, RE, Ernst, H, Dev, P & Taylor, CB 2003, 'Evaluation of an internet support group for women with primary breast cancer', Cancer, no. 5, pp. 1164-1173
Zatzick, D., Roy-Byrne, P. et al (2004). 'A Randomized Effectiveness Trial of Stepped Collaborative Care for Acutely Injured Trauma Survivors', Archives of General Psychiatry, 61 (5), 498-506.
Incorrect study design
Studies with non-randomised or pseudorandomised design
Becker, S. M. (2009). 'Psychosocial care for women survivors of the tsunami disaster in India', Am J Public Health, 99 (4), 654-658.
Berger, R. & Gelkopf, M. (2009). 'School-based intervention for the treatment of tsunami- related distress in children: A quasi-randomized controlled trial', Psychotherapy and Psychosomatics, 78 (6), 364-371.
Bolton, P., Murray, L. & Bass, J. (2009). 'School based intervention improves PTSD symptoms in children affected by political violence', Evidence Based Mental Health, 12 (2), 47-47.
Boscarino, J. A., Adams, R. E. & Figley, C. R. (2005). 'A prospective cohort study of the effectiveness of employer-sponsored crisis inerventions after a major disaster', International Journal of Emergency Mental Health, 7 (1), 9-22.
Brewin, C. R., Scragg, P. et al (2008). 'Promoting mental health following the london bombings: A screen and treat approach', Journal of Traumatic Stress, 21 (1), 3-8.
Cacciatore, J. (2007). 'Effects of support groups on post traumatic stress responses in women experiencing stillbirth', Omega: Journal of Death and Dying, 55 (1), 71-90.
Carr, A. (2004). 'Interventions for post-traumatic stress disorder in children and adolescents', Pediatr Rehabil, 7 (4), 231-244.
Chudakov, B., Cohen, H. et al (2008). 'A naturalistic prospective open study of the effects of adjunctive therapy of sexual dysfunction in chronic PTSD patients', Israel Journal of Psychiatry and Related Sciences, 45 (1), 26-32.
544 Fallot, R. D., McHugo, G. J. et al (2011). 'The trauma recovery and empowerment model: A quasi-experimental effectiveness study', Journal of Dual Diagnosis, 7 (1-2), 74-89.
Gelkopf, M. & Berger, R. (2009). 'A school-based, teacher-mediated prevention program (ERASE-Stress) for reducing terror-related traumatic reactions in Israeli youth: a quasi- randomized controlled trial', Journal of child psychology and psychiatry, and allied disciplines, 50 (8), 962-971.
Hardin, S. B., Weinrich, S. et al (2002). 'Effects of a long-term psychosocial nursing intervention on adolescents exposed to catastrophic stress', Issues in Mental Health Nursing, 23 (6), 537-551.
Hasanovi, M., Srabovi, S., Rasidovi, Sehovi, Hasanbasi, E., Husanovi, J., Hodzi & R. 2009, 'Psychosocial assistance to students with posttraumatic stress disorder in primary and secondary schools in post-war Bosnia Herzegovina', Psychiatria Danubina, no. 4, pp. 463- 473
Helfrich, C. A., Peters, C. Y. & Chan, D. V. (2011). 'Trauma Symptoms of Individuals with Mental Illness at Risk for Homelessness Participating in a Life Skills Intervention', Occupational Therapy International, 18 (3), 115-123.
Hyatt, J. M. (2010). 'Pharmacist-directed PTSD medication management clinic at the VAWNY healthcare system', Journal of Pharmacy Practice, 23 (2), 149.
Jordans, M. J. D., Tol, W. A. et al (2009). 'Systematic review of evidence and treatment approaches: Psychosocial and mental health care for children in war', Child and Adolescent Mental Health, 14 (1), 2-14.
Kasprow, W. J. & Rosenheck, R. A. (2007). 'Outcomes of critical time intervention case management of homeless veterans after psychiatric hospitalization', Psychiatric Services, 58 (7), 929-935.
Kazdin, A. (2002). 'A school based psychosocial intervention was effective in children with persistent post-disaster trauma symptoms', Evidence Based Mental Health, 5 (3), 76-76.
Last, B. F., Grootenhuis, M. A. & Eiser, C. (2005). 'International comparison of contributions to psychosocial research on survivors of childhood cancer: Past and future considerations', Journal of Pediatric Psychology, 30 (1), 99-113.
Lekskes, J., van Hooren, S. & de Beus, J. (2007). 'Appraisal of psychosocial interventions in Liberia', Intervention: International Journal of Mental Health, Psychosocial Work & Counselling in Areas of Armed Conflict, 5 (1), 18-26.
Rosen, C. S., DiLandro, C. et al (2006). 'Telephone monitoring and support for veterans with chronic posttraumatic stress disorder: a pilot study', Community Mental Health Journal, 42 (5), 501-508.
Wolmer, L., Laor, N. et al (2005). 'Teacher-mediated intervention after disaster: A controlled three-year follow-up of children's functioning', Journal of Child Psychology and Psychiatry and Allied Disciplines, 46 (11), 1161-1168.
545 Yehua, R. (2003). 'Skills training plus exposure therapy may reduce post traumatic stress in women who experienced childhood abuse', Evidence Based Mental Health, 6 (2), 50-50.
Data could not be extracted
Chemtob, C. M., Nakashima, J. P. & Hamada, R. S. (2002). 'Psychosocial intervention for postdisaster trauma symptoms in elementary school children: a controlled community field study', Arch Pediatr Adolesc Med, 156 (3), 211-216.
Dunn, NJ, Rehm, LP, Schillaci, J, Souchek, J, Mehta, P, Ashton, CM, Yanasak, E & Hamilton, JD 2007, 'A randomized trial of self-management and psychoeducational group therapies for comorbid chronic posttraumatic stress disorder and depressive disorder', Journal of Traumatic Stress, no. 3, pp. 221-237
Duplicate information (SRs where primary studies are already included)
Palic, S. & Elklit, A. (2011). 'Psychosocial treatment of posttraumatic stress disorder in adult refugees: A systematic review of prospective treatment outcome studies and a critique', Journal of Affective Disorders, 131 (1-3), 8-23.
Tol, W. A., Barbui, C. et al (2011). 'Mental health and psychosocial support in humanitarian settings: linking practice and research', The Lancet.
546 Reasons for exclusion of studies involving co-morbidities (question 22)
Incorrect study design Adamou, M, Puchalska, S, Plummer, W & Hale, AS 2007, 'Valproate in the treatment of PTSD: systematic review and meta analysis', Curr Med Res Opin, vol. 23, no. 6, Jun, pp. 1285-1291.
Amital, D, Vishne, T, Roitman, S, Kotler, M & Levine, J 2006, 'Open study of creatine monohydrate in treatment-resistant posttraumatic stress disorder [3]', Journal of Clinical Psychiatry, vol. 67, no. 5, pp. 836-837.
Back, SE 2010, 'Toward an improved model of treating co-occurring PTSD and substance use disorders', Am J Psychiatry, vol. 167, no. 1, Jan, pp. 11-13.
Berger, W, Mendlowicz, MV, Marques-Portella, C, Kinrys, G, Fontenelle, LF, Marmar, CR & Figueira, I 2009, 'Pharmacologic alternatives to antidepressants in posttraumatic stress disorder: a systematic review', Prog Neuropsychopharmacol Biol Psychiatry, vol. 33, no. 2, Mar 17, pp. 169-180.
Bohus, M, Priebe, K, Dyer, A & Steil, R 2009, 'Dialectical behavioral therapy for patients with borderline features and posttraumatic stress disorder after childhood sexual abuse (DBT- P)', European Psychiatry, vol. 24, p. S91.
Bossini, L, Fagiolini, A, Valdagno, M, Polizzotto, NR & Castrogiovanni, P 2007, 'Sexual disorders in subjects treated for mood and anxiety diseases [8]', Journal of Clinical Psychopharmacology, vol. 27, no. 3, pp. 310-312.
Bossini, L, Tavanti, M, Lombardelli, A, Calossi, S, Polizzotto, NR, Galli, R, Vatti, G, Pieraccini, F & Castrogiovanni, P 2007, 'Changes in hippocampal volume in patients with post-traumatic stress disorder after sertraline treatment [17]', Journal of Clinical Psychopharmacology, vol. 27, no. 2, pp. 233-235.
Cantor, C 2008, 'DSM-IV cure for post-traumatic stress disorder', Australas Psychiatry, vol. 16, no. 4, Aug, p. 297.
Clark, HW & Power, AK 2005, 'Women, Co-occurring Disorders, and Violence Study: a case for trauma-informed care', J Subst Abuse Treat, vol. 28, no. 2, Mar, pp. 145-146.
Cohen, JA, Mannarino, AP, Zhitova, AC & Capone, ME 2003, 'Treating child abuse-related posttraumatic stress and comorbid substance abuse in adolescents', Child Abuse and Neglect, vol. 27, no. 12, pp. 1345-1365.
Deacon, BJ & Abramowitz, JS 2004, 'Cognitive and behavioral treatments for anxiety disorders: a review of meta-analytic findings', J Clin Psychol, vol. 60, no. 4, Apr, pp. 429- 441.
Fonagy, P, Roth, A & Higgitt, A 2005, 'Psychodynamic psychotherapies: Evidence-based practice and clinical wisdom', Bulletin of the Menninger Clinic, vol. 69, no. 1, pp. 1-58.
547 Hoffman, EJ & Mathew, SJ 2008, 'Anxiety disorders: A comprehensive review of pharmacotherapies', Mount Sinai Journal of Medicine, vol. 75, no. 3, pp. 248-262.
Kellner, M, Muhtz, C & Wiedemann, K 2010, 'Primary add-on of ziprasidone in sertraline treatment of posttraumatic stress disorder: Lessons from a stopped trial?', Journal of Clinical Psychopharmacology, vol. 30, no. 4, pp. 471-473.
Khachiyants, N, Ali, R, Kovesdy, CP, Detweiler, JG, Kim, KY & Detweiler, MB 2010, 'Effectiveness of risperidone for the treatment of nightmares in veterans with posttraumatic stress disorder', Journal of Clinical Psychopharmacology, vol. 30, no. 6, pp. 735-737.
Kösters, M, Burlingame, GM, Nachtigall, C & Strauss, B 2006, 'A meta-analytic review of the effectiveness of inpatient group psychotherapy', Group Dynamics: Theory, Research, and Practice, vol. 10, no. 2, pp. 146-163.
Mancini, M, Perna, G, Rossi, A & Petralia, A 2010, 'Use of duloxetine in patients with an anxiety disorder, or with comorbid anxiety and major depressive disorder: A review of the literature', Expert Opinion on Pharmacotherapy, vol. 11, no. 7, pp. 1167-1181.
McCloskey, LA & Southwick, K 1996, 'Psychosocial problems in refugee children exposed to war', Pediatrics, vol. 97, no. 3, pp. 394-397.
Mimica, N, Uzun, S, Folneoovic-Smalc, V, Markan-Sosic, V & Ljubin, T 2001, 'Sertraline: A novel antidepressant with broad treatment spectrum', Periodicum Biologorum, vol. 103, no. 4, pp. 301-308.
Mula, M, Pini, S & Cassano, GB 2007, 'The role of anticonvulsant drugs in anxiety disorders: A critical review of the evidence', Journal of Clinical Psychopharmacology, vol. 27, no. 3, pp. 263-272.
Munoz-Solomando, A, Kendall, T & Whittington, CJ 2008, 'Cognitive behavioural therapy for children and adolescents', Current Opinion in Psychiatry, vol. 21, no. 4, pp. 332-337.
Raboni, MR, Tufik, S & Suchecki, D 2006, 'Treatment of PTSD by eye movement desensitization reprocessing (EMDR) improves sleep quality, quality of life, and perception of stress', Ann N Y Acad Sci, vol. 1071, Jul, pp. 508-513.
Silverman, JJ 1986, 'Post-traumatic stress disorder', Adv Psychosom Med, vol. 16, pp. 115- 140.
Stamatakos, M & Campo, JV 2010, 'Psychopharmacologic treatment of traumatized youth', Current Opinion in Pediatrics, vol. 22, no. 5, pp. 599-604.
Thuile, J, Even, C & Rouillon, F 2009, 'Long-term outcome of anxiety disorders: A review of double-blind studies', Current Opinion in Psychiatry, vol. 22, no. 1, pp. 84-89.
Tiet, QQ & Mausbach, B 2007, 'Treatments for patients with dual diagnosis: A review', Alcoholism: Clinical and Experimental Research, vol. 31, no. 4, pp. 513-536.
548 Townsend, E, Walker, D, Sargeant, S, Stocker, O, Vostanis, P, Sithole, J & Hawton, K 2008, 'Interventions for mood and anxiety disorders, and self harm in young offenders', Cochrane Database of Systematic Reviews, no. 2.
Verdeli, H, Mufson, L, Lee, L & Keith, JA 2006, 'Review of evidence-based psychotherapies for pediatric mood and anxiety disorders', Current Psychiatry Reviews, vol. 2, no. 3, pp. 395- 421.
Vitzthum, K, Mache, S, Joachim, R, Quarcoo, D & Groneberg, DA 2009, 'Psychotrauma and effective treatment of post-traumatic stress disorder in soldiers and peacekeepers', Journal of Occupational Medicine and Toxicology, vol. 4, no. 1.
Voshaar, RCO, Hendriks, GJ, Keijsers, G & Van Balkom, AJ 2009, 'Cognitive behavioural therapy for anxiety disorders in later life', Cochrane Database of Systematic Reviews, no. 1.
Wurz, A & Sungur, MZ 2009, 'Combining cognitive behavioural therapy and pharmacotherapy in the treatment of anxiety disorders: True gains or false hopes?', Klinik Psikofarmakoloji Bulteni, vol. 19, no. 4, pp. 436-447.
Incorrect population Adler, AB, Litz, BT, Castro, CA, Suvak, M, Thomas, JL, Burrell, L, McGurk, D, Wright, KM & Bliese, PD 2008, 'A group randomized trial of critical incident stress debriefing provided to U.S. peacekeepers', J Trauma Stress, vol. 21, no. 3, Jun, pp. 253-263.
Fava, GA, Ruini, C & Rafanelli, C 2005, 'Sequential treatment of mood and anxiety disorders', Journal of Clinical Psychiatry, vol. 66, no. 11, pp. 1392-1400.
In-Albon, T & Schneider, S 2007, 'Psychotherapy of childhood anxiety disorders: A meta- analysis', Psychother Psychosom, vol. 76, no. 1, pp. 15-24.
Lowry, F, Wachter, K & Worcester, S 2008, 'Meta-analysis supports gabapentin/new antidepressants', Oncology Report, no. FALL, p. 104.
Parslow, R, Purcell, R, Garner, B & Hetrick, SE 2008, 'Combined pharmacotherapy and psychological therapies for post traumatic stress disorder (PTSD)', Cochrane Database of Systematic Reviews, no. 3.
Postel, MG, De Haan, HA & De Jong, CAJ 2008, 'E-therapy for mental health problems: A systematic review', Telemedicine and e-Health, vol. 14, no. 7, pp. 707-714.
Reinblatt, SP & Riddle, MA 2007, 'The pharmacological management of childhood anxiety disorders: A review', Psychopharmacology, vol. 191, no. 1, pp. 67-86.
Silverman, WK, Ortiz, CD, Viswesvaran, C, Burns, BJ, Kolko, DJ, Putnam, FW & Amaya- Jackson, L 2008, 'Evidence-based psychosocial treatments for children and adolescents exposed to traumatic events', Journal of Clinical Child and Adolescent Psychology, no. 1, pp. 156-183
549 Incorrect intervention Belleville, G, Cousineau, H, Levrier, K, St-Pierre-Delorme, M-È & Marchand, A 2010, 'The impact of cognitive-behavior therapy for anxiety disorders on concomitant sleep disturbances: a meta-analysis', Journal of Anxiety Disorders, vol. 24, no. 4, May, pp. 379- 386.
Bisson, J & Andrew, M 2005, 'Psychological treatment of post-traumatic stress disorder (PTSD)', Cochrane Database Syst Rev, no. 2, p. CD003388.
Bisson, JI, Ehlers, A, Matthews, R, Pilling, S, Richards, D & Turner, S 2007, 'Psychological treatments for chronic post-traumatic stress disorder: systematic review and meta-analysis', British Journal of Psychiatry, no. 2, pp. 97-104
Boden, MT, Kimerling, R, Jacobs-Lentz, J, Bowman, D, Weaver, C, Carney, D, Walser, R & Trafton, JA 2011, 'Seeking Safety Treatment for Male Veterans with a Substance Use Disorder and PTSD Symptomatology', Addiction, Sep 16.
Bradley, R, Greene, J, Russ, E, Dutra, L & Westen, D 2005, 'A multidimensional meta- analysis of psychotherapy for PTSD', American Journal of Psychiatry, vol. 162, no. 2, pp. 214-227.
Butler, AC, Chapman, JE, Forman, EM & Beck, AT 2006, 'The empirical status of cognitive- behavioral therapy: A review of meta-analyses', Clinical Psychology Review, vol. 26, no. 1, pp. 17-31.
Clarke, SB, Rizvi, SL & Resick, PA 2008, 'Borderline Personality Characteristics and Treatment Outcome in Cognitive-Behavioral Treatments for PTSD in Female Rape Victims', Behavior Therapy, vol. 39, no. 1, pp. 72-78.
Durham, RC, Chambers, JA, Power, KG, Sharp, DM, Macdonald, RR, Major, KA, Dow, MG & Gumley, AI 2005, 'Long-term outcome of cognitive behaviour therapy clinical trials in central Scotland', Health Technol Assess, vol. 9, no. 42, Nov, pp. 1-174.
Foa, EB & Williams, MT 2010, 'Methodology of a randomized double-blind clinical trial for comorbid posttraumatic stress disorder and alcohol dependence', Mental Health and Substance Use: Dual Diagnosis, vol. 3, no. 2, pp. 131-147.
Jordans, MJD, Tol, WA, Komproe, IH & De Jong, JVTM 2009, 'Systematic review of evidence and treatment approaches: Psychosocial and mental health care for children in war', Child and Adolescent Mental Health, vol. 14, no. 1, pp. 2-14.
Kowalik, J, Weller, J, Venter, J & Drachman, D 2011, 'Cognitive behavioral therapy for the treatment of pediatric posttraumatic stress disorder: a review and meta-analysis', J Behav Ther Exp Psychiatry, vol. 42, no. 3, Sep, pp. 405-413.
Macdonald, GM, Higgins, JP & Ramchandani, P 2006, 'Cognitive-behavioural interventions for children who have been sexually abused', Cochrane Database Syst Rev, no. 4, p. CD001930.
550 Meads, C, Lyons, A & Carroll, D 2003, 'The impact of the emotional disclosure intervention on physical and psychological health - a systematic review', Birmingham: West Midlands Health Technology Assessment Collaboration
Meyerbröker, K & Emmelkamp, PMG 2010, 'Virtual reality exposure therapy in anxiety disorders: a systematic review of porcess-and-outcome studies', Depression and Anxiety, vol. 27, no. 10, October, pp. 933-944.
Mooney, P, Oakley, J, Ferriter, M & Travers, R 2004, 'Sertraline as a treatment for PTSD: a systematic review and meta-analysis', Irish Journal of Psychological Medicine, no. 3, pp. 100-103
Palic, S & Elklit, A 2011, 'Psychosocial treatment of posttraumatic stress disorder in adult refugees: A systematic review of prospective treatment outcome studies and a critique', Journal of Affective Disorders, vol. 131, no. 1-3, pp. 8-23.
Parsons, TD & Rizzo, AA 2008, 'Affective outcomes of virtual reality exposure therapy for anxiety and specific phobias: a meta-analysis', Journal of Behavior Therapy and Experimental Psychiatry, vol. 39, no. 3, September, pp. 250-261.
Ponniah, K & Hollon, SD 2009, 'Empirically supported psychological treatments for adult acute stress disorder and posttraumatic stress disorder: a review', Depression and Anxiety, no. 12, pp. 1086-1109
Provencher, MD, Hawke, LD & Thienot, E 2010, 'Psychotherapies for comorbid anxiety in bipolar spectrum disorders', Journal of Affective Disorders, Published online, vol. 18.
Rakofsky, JJ & Dunlop, BW 2011, 'Treating nonspecific anxiety and anxiety disorders in patients with bipolar disorder: A review', Journal of Clinical Psychiatry, vol. 72, no. 1, pp. 81-90.
Riosa, PB, McArthur, BA & Preyde, M 2011, 'Effectiveness of psychosocial intervention for children and adolescents with comorbid problems: A systematic review', Child and Adolescent Mental Health, vol. 16, no. 4, pp. 177-185.
Roberts, NP, Kitchiner, NJ, Kenardy, J & Bisson, JI 2009, 'Systematic review and meta- analysis of multiple-session early interventions following traumatic events ', American Journal of Psychiatry, no. 3, pp. 293-301
—— 2010, 'Early psychological interventions to treat acute traumatic stress symptoms', Cochrane database of systematic reviews (Online), vol. 3, p. CD007944.
Roshanaei-Moghaddam, B, Pauly, MC, Atkins, DC, Baldwin, SA, Stein, MB & Roy-Byrne, PP 2011, 'Relative effects of CBT and pharmacotherapy in depression versus anxiety: is medication somewhat better for depression, and CBT somewhat better for anxiety?', Depression and Anxiety, vol. 28, no. 7, July, pp. 560-567.
Seidler, GH & Wagner, FE 2006, 'Comparing the efficacy of EMDR and trauma-focused cognitive-behavioral therapy in the treatment of PTSD: a meta-analytic study', Psychological Medicine, no. 11, pp. 1515-1522
551 Shepherd, J, Stein, K & Milne, R 2000, 'Eye movement desentitization and reprocessing in the treatment of post-traumatic stress disorder: a review of an emerging therapy’, Psychological Medicine, no. 4, pp. 863-871
Sherman, JJ 1998, 'Effects of psychotherapeutic treatments for PTSD: A meta-analysis of controlled clinical trials', Journal of Traumatic Stress, vol. 11, no. 3, pp. 413-435.
Stein Dan, J, Ipser Jonathan, C & Seedat, S 2006, 'Pharmacotherapy for post traumatic stress disorder (PTSD)', Cochrane Database of Systematic Reviews, no. 1, DOI 10.1002/14651858.CD002795.
Stein, DJ, Ipser, J & McAnda, N 2009, 'Pharmacotherapy of posttraumatic stress disorder: a review of meta-analyses and treatment guidelines', CNS Spectr, vol. 14, no. 1 Suppl 1, Jan, pp. 25-31.
Stein, DJ, Ipser, JC & Seedat, S 2006, 'Pharmacotherapy for post traumatic stress disorder (PTSD)', Cochrane database of systematic reviews (Online), no. 1, p. CD002795.
Stewart, RE & Chambless, DL 2009, 'Cognitive-Behavioral Therapy for Adult Anxiety Disorders in Clinical Practice: A Meta-Analysis of Effectiveness Studies', Journal of Consulting and Clinical Psychology, vol. 77, no. 4, pp. 595-606.
Townsend, E, Walker, DM, Sargeant, S, Vostanis, P, Hawton, K, Stocker, O & Sithole, J 2010, 'Systematic review and meta-analysis of interventions relevant for young offenders with mood disorders, anxiety disorders, or self-harm', Journal of Adolescence, no. 1, pp. 9-20
Vulink, NCC, Figee, M & Denys, D 2011, 'Review of atypical antipsychotics in anxiety', European Neuropsychopharmacology, vol. 21, no. 6, pp. 429-449.
Wethington, HR, Hahn, RA, Fuqua-Whitley, DS, Sipe, TA, Crosby, AE, Johnson, RL, Liberman, AM, Moscicki, E, Price, LN, Tuma, FK, Kalra, G & Chattopadhyay, SK 2008, 'The Effectiveness of Interventions to Reduce Psychological Harm from Traumatic Events Among Children and Adolescents. A Systematic Review', American Journal of Preventive Medicine, vol. 35, no. 3, pp. 287-313.
No outcomes data United States Department of Veterans Affairs. Health Services, R & Development, S 2009, 'The assessment and treatment of individuals with history of traumatic brain injury and post- traumatic stress disorder: a systematic review of the evidence', Washington: Department of Veterans Affairs, August, vol. 72.
Van Etten, ML & Taylor, S 1998, 'Comparative efficacy of treatments for post-traumatic stress disorder: a meta-analysis', Clinical Psychology and Psychotherapy, pp. 126-144
Zlotnick, C 1997, 'Posttraumatic stress disorder (PTSD), PTSD comorbidity, and childhood abuse among incarcerated women', Journal of Nervous and Mental Disease, vol. 185, no. 12, pp. 761-763.
Incorrect comparator
552 Ito, H, Kudo, Y, Kabeshima, Y, Nobushima, S & Komine, K 1968, 'Double-blind controlled trial of lucidril (meclofenoxate) in the post-traumatic syndrome, especially dizziness', Folia psychiatrica et neurologica japonica, vol. 22, no. 1, pp. 23-42.
Kaplan, Z, Amir, M, Swartz, M & Levine, J 1996, 'Inositol treatment of post-traumatic stress disorder', Anxiety, no. 1, pp. 51-52
Stewart, CL & Wrobel, TA 2009, 'Evaluation of the efficacy of pharmacotherapy and psychotherapy in treatment of combat-related post-traumatic stress disorder: a meta-analytic review of outcome studies', Military medicine, vol. 174, no. 5, pp. 460-469.
Xu, JJ, Chan, MJ & Yang, YC 2011, 'Fluoxetine as a treatment for post-traumatic stress disorder', Neurosciences, vol. 16, no. 3, pp. 257-262.
Unpublished data Auringer, ML 2011, 'Clinical efficacy of a brief hypnotic intervention for hyperarousal symptoms in sexual trauma', 71 thesis, ProQuest Information & Learning, psyh
Viers, RL 2011, 'Comparative analysis of depression and anxiety in adult survivors of child sexual abuse with and without early intervention', 72 thesis, ProQuest Information & Learning, psyh
Not in English Hebebrand, J & Schulte-Markwort, M 2009, 'Post traumatic stress disorder and dissociation', Zeitschrift f?r Kinder- und Jugendpsychiatrie und Psychotherapie, vol. 37, no. 4, p. 327.
Khozhenko, EV 2008, 'Pain syndrome and neuroendocrine disorders in posttraumatic stress disorder', Voenno-meditsinski? zhurnal, vol. 329, no. 4, pp. 30-34.
Kraft, S, Schepker, R, Goldbeck, L & Fegert, JM 2006, 'Treatment of posttraumatic stress disorder in children and adolescents - A review of treatment outcome studies', Nervenheilkunde, vol. 25, no. 9, pp. 709-716.
Millet, B 2007, 'Use of ISRS (serotonin uptake inhibitor) and IRSNA (serotonin noradrenaline reuptake inhibitor) in anxiety-depression', Encephale, vol. 33, no. 4 C3, pp. S699-S700.
Olivares Rodríguez, J, Sánchez Meca, J & Alcázar, AIR 1999, 'Eficacia de las intervenciones conductuales en problemas de ansiedad en España', Psicología Conductual Revista Internacional de Psicología Clínica de la Salud, vol. 7, no. 2, pp. 283-300.
Vauth, R & Bottlender, R 2007, '[Post-traumatic stress disorder in schizophrenia]', Psychiatr Prax, vol. 34, no. 2, Mar, pp. 55-57.
Duplicated data McCleery, JM 2001, 'Review: SSRIs and tricyclic antidepressants increase response rates in post-traumatic stress disorder in the short term', Evidence Based Mental Health, vol. 4, no. 2, pp. 54-54.
553 Reasons for exclusion of studies involving exercise and physical therapies (questions 7, 18-21)
Outside search period for adults Guerin, JJ 1993, 'The use of sport and exercise training for adult women psychotherapy clients with post-traumatic stress disorder [dissertation]', Temple University, vol. 173.
Kessler, RA 2002, 'The differential impact of thought field therapy as a treatment modality for male perpetrators of domestic violence diagnosed with posttraumatic stress disorder [dissertation]', Walden University, vol. 105.
Ragsdale, KG, Cox, RD, Finn, P & Eisler, RM 1996, 'Effectiveness of short-term specialized inpatient treatment for war-related posttraumatic stress disorder: a role for adventure-based counseling and psychodrama', J Trauma Stress, vol. 9, no. 2, Apr, pp. 269-283.
Rosenberg, PB, Mehndiratta, RB, Mehndiratta, YP, Wamer, A, Rosse, RB & Balish, M 2002, 'Repetitive transcranial magnetic stimulation treatment of comorbid posttraumatic stress disorder and major depression', Journal of Neuropsychiatry and Clinical Neurosciences, vol. 14, no. 3, pp. 270-276.
Silver, SM, Brooks, A & Obenchain, J 1995, 'Treatment of Vietnam War veterans with PTSD: a comparison of eye movement desensitization and reprocessing, biofeedback, and relaxation training', J Trauma Stress, vol. 8, no. 2, Apr, pp. 337-342.
Watson, CG, Tuorila, JR, Vickers, KS, Gearhart, LP & Mendez, CM 1997, 'The efficacies of three relaxation regimens in the treatment of PTSD in Vietnam war veterans', Journal of Clinical Psychology, vol. 53, no. 8, pp. 917-923.
Zwanzger, P, Fallgatter, AJ, Zavorotnyy, M & Padberg, F 2009, 'Anxiolytic effects of transcranial magnetic stimulation-an alternative treatment option in anxiety disorders?', Journal of Neural Transmission, vol. 116, no. 6, pp. 767-775.
Incorrect population (adults without minimum 70% PTSD) Cusack, K & Spates, CR 1999, 'The cognitive dismantling of Eye Movement Desensitization and Reprocessing (EMDR) treatment of Posttraumatic Stress Disorder (PTSD)', J Anxiety Disord, vol. 13, no. 1-2, Jan-Apr, pp. 87-99.
Jorm, AF, Christensen, H, Griffiths, KM, Parslow, RA, Rodgers, B & Blewitt, KA 2004, 'Effectiveness of complementary and self-help treatments for anxiety disorders', Medical Journal of Australia, vol. 181, no. 7, 4, pp. S29-S46.
Nakamura, Y, Lipschitz, DL, Landward, R, Kuhn, R & West, G 2011, 'Two sessions of sleep-focused mind-body bridging improve self-reported symptoms of sleep and PTSD in veterans: A pilot randomized controlled trial', Journal of Psychosomatic Research, vol. 70, no. 4, pp. 335-345.
Price, C 2005, 'Body-oriented therapy in recovery from child sexual abuse: an efficacy study', Alternative Therapies in Health & Medicine, vol. 11, no. 5, pp. 46-57.
554
Telles, S, Singh, N, Joshi, M & Balkrishna, A 2010, 'Post traumatic stress symptoms and heart rate variability in Bihar flood survivors following yoga: a randomized controlled study', BMC Psychiatry, vol. 10, p. 18.
Incorrect intervention/no intervention LeardMann, CA, Kelton, ML, Smith, B, Littman, AJ, Boyko, EJ, Wells, TS, Smith, TC & Millennium Cohort Study, T 2011, 'Prospectively assessed posttraumatic stress disorder and associated physical activity', Public Health Reports, vol. 126, no. 3, May-June, pp. 371-383.
Systematic review with uncontrolled studies Paes, F, Machado, S, Arias-Carrion, O, Velasques, B, Teixeira, S, Budde, H, Cagy, M, Piedade, R, Ribeiro, P, Huston, JP, Sack, AT & Nardi, AE 2011, 'The value of repetitive transcranial magnetic stimulation (rTMS) for the treatment of anxiety disorders: An integrative review', CNS and Neurological Disorders - Drug Targets, vol. 10, no. 5, pp. 610- 620.
Incorrect study design Descilo, T, Vedamurtachar, A, Gerbarg, PL, Nagaraja, D, Gangadhar, BN, Damodaran, B, Adelson, B, Braslow, LH, Marcus, S & Brown, RP 2010, 'Effects of a yoga breath intervention alone and in combination with an exposure therapy for post-traumatic stress disorder and depression in survivors of the 2004 South-East Asia tsunami', Acta Psychiatr Scand, vol. 121, no. 4, Apr, pp. 289-300.
Dietrich, AM, Baranowsky, AB, Devich-Navarro, M, Gentry, JE, Harris, CJ & Figley, CR 2000, 'A review of alternative approaches to the treatment of post traumatic sequelae', Traumatology, vol. 6, no. 4, December, pp. 251-271.
George, MS, Padberg, F, Schlaepfer, TE, O'Reardon, JP, Fitzgerald, PB & Nahas, ZH 2009, 'Controversy: repetitive transcranial magnetic stimulation or transcranial direct current stimulation shows efficacy in treating psychiatric diseases (depression, mania, schizophrenia, obsessive-complusive disorder, panic, posttraumatic stress disorder)', Brain Stimulation, vol. 2, no. 1, January, pp. 14-21.
Haimov, I, Blanaro, M, Arnon, Z, Ziv, N, Bloch, B, Reshef, A, Vadas, L & Kremer, I 2010, 'The effects of music and muscle relaxation therapies on sleep quality in individuals with post-traumatic stress disorder', Journal of Sleep Research, vol. 19, p. 364.
Lande, RG, Williams, LB, Francis, JL, Gragnani, C & Morin, ML 2010, 'Efficacy of biofeedback for post-traumatic stress disorder', Complementary Therapies in Medicine, vol. 18, no. 6, pp. 256-259.
Piltch, C & Menard, MB 2007, 'Serenity now: research shows that massage can be healing for your clients that suffer from post-traumatic stress disorder', Massage Therapy Journal, vol. 46, no. 4, pp. 159-165.
Cannot extract data Boggio, PS, Rocha, M, Oliveira, MO, Fecteau, S, Cohen, RB, Campanha, C, Ferreira-Santos, E, Meleiro, A, Corchs, F, Zaghi, S, Pascual-Leone, A & Fregni, F 2010, 'Noninvasive brain stimulation with high-frequency and low-intensity repetitive transcranial magnetic
555 stimulation treatment for posttraumatic stress disorder', Journal of Clinical Psychiatry, vol. 71, no. 8, pp. 992-999.
Colosetti, SD & Thyer, BA 2000, 'The relative effectiveness of EMDR versus relaxation training with battered women prisoners', Behav Modif, vol. 24, no. 5, Oct, pp. 719-739.
Haimov, I, Blanaru, M, Yehezkeli, E, Shorkin, R, Vadas, L, Arnon, Z, N, Z & Bloch, B 2010, 'The effects of music and muscle relaxation therapies on sleep quality and emotional measures in PTSD patients', Isr J Psychiatry Relat Sci, vol. 46, no. 1, Spring, p. 37.
Kraft, K & Telles, S 2010, 'Yoga practice may be useful after post-traumatic stress', Focus on Alternative and Complementary Therapies, vol. 15, no. 3, pp. 255-256.
López-lbor Aliño, JJ, López-Ibor, M-I & Pastrana Jiménez, JI 2008, 'Transcranial magnetic stimulation', Current Opinion in Psychiatry, vol. 21, no. 6, November, pp. 640–644.
Osuch, EA, Benson, BE, Luckenbaugh, DA, Geraci, M, Post, RM & McCann, U 2009, 'Repetitive TMS combined with exposure therapy for PTSD: A preliminary study', Journal of Anxiety Disorders, vol. 23, no. 1, pp. 54-59.
Technical include (SRs which have found no relevant RCTs)
Lawrence, S, De Silva, MJ & Henley, R 2010, 'Sports and games for post-traumatic stress disorder (PTSD)', Cochrane Database of Systematic Reviews, vol. 2010, no. 1, p. Article CD007171. da Silva, TL, Ravindran, LN & Ravindran, AV 2009, 'Yoga in the treatment of mood and anxiety disorders: A review', Asian Journal of Psychiatry, vol. 2, no. 1, pp. 6-16.
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578 Appendix 4: Public consultation
The Draft Guidelines for the Treatment of ASD and PTSD were made available for public consultation between November 30 2012 and January 11 2013. Members of the public were advised of the public consultation through an advertisement placed in the Australian newspaper on November 30. The content of the advertisement was as follows:
Draft Guidelines: The Australian Guidelines for the Treatment of Acute Stress Disorder (ASD) and Posttraumatic Stress Disorder (PTSD) Proposed for submission to the NHMRC for approval under section 14A of the National Health and Medical Research Council Act 1992. The Australian Centre for Posttraumatic Mental Health (ACPMH) has prepared draft guidelines on the treatment of ASD and PTSD. You are invited to make a submission to ACPMH on the draft guidelines.
How to make a submission A copy of the draft guidelines can be viewed and downloaded here: http://www.acpmh.unimelb.edu.au/resources/resources-guidelines.html To make your submission, please down load a submission form at the above web address or contact us for a submission form at: x email: [email protected] x Address: ACPMH Level 1, 340 Albert Street East Melbourne 3002 x Telephone: (03) 9936 5100 x Fax: (03) 9936 5199
You may make a submission in writing or as a recorded audio format. (Electronic submissions are preferred). Please include your name and an address or telephone number at which you can be contacted.
Closing date Your submission must be received at the above address by the 11th of January 2013.
579 In addition, the following government departments, organisations and individuals were notified directly of the public consultation and invited to make a submission.
Government agencies x Australian Government Department of Families, Housing, Community Services, and Indigenous Affairs x Australian Government Department of Health and Ageing x Medical Services Advisory Committee x Medicare Benefits Schedule Pharmaceutical Benefits Advisory Committee x Therapeutic Goods Administration x All state and territory health departments
Professional colleges/associations x Australian Association of Social Workers x Australian Psychological Society x Occupational Therapy Australia x Royal Australian College of General Practitioners x Royal Australian and New Zealand College of Psychiatrists
Members of the Health Economic Advisory Panel x Mr Richard Bartlett (First Assistant Secretary Medical Benefits Division, Department of Health and Ageing) x Associate Professor Jan Coles (Department of General Practice, Monash University) x Professor Mark Creamer (Clinical Psychologist) x Ms Judy Daniel (First Assistant Secretary Health and Community, Department of Veterans Affairs)
580 x Mr David Davies (Representing the State Health Departments) x Associate Professor Brett MecDermott (Child Psychiatrist) x Mr James McKenzie (Director Health Services, ComCare) x Mr David Morton (Director Genearl Mental Health, Psychology & Rehabilitation, Department of Defence)
Members of the Multidisciplinary Panel x Professor Beverley Raphael, Psychiatrist (Population Mental Health and Disasters, Disaster Response and Resilience Research Group, University of Western Sydney) x Professor Brian Draper, Psychogeriatrician (Assistant Director, Academic Department for Old Age Psychiatry, University of New South Wales) x Dr Rob Gordon, Clinical Psychologist (Clinical and Consulting Psychologist) x Dr Chris Lee, Clinical Psychologist (Senior Lecturer, School of Psychology and Exercise Science, Murdoch University) x Ms Cait McMahon, Psychologist (Director, DART Centre for Journalism and Trauma) x Professor Helen Milroy, Psychiatrist (Director, Centre for Aboriginal Medical and Dental Health, University of Western Australia) x Associate Professor Shirley Morrissey, Clinical and Health Psychologist (Deputy Head, School of Psychology, Griffith University)
581 x Professor Louise Newman, Psychiatrist (Director, Centre for Developmental Psychiatry and Psychology, Monash University) x Associate Professor Reginald Nixon, Clinical Psychologist (Director, Clinical Psychology Program, Flinders University) x Ms Rebecca Reay, Research Officer (Academic Unit of Psychological Medicine, Australian National University) x Professor Kevin Ronan, Clinical Psychologist (Chair, Clinical Psychology, Central Queensland University) x Professor Derrick Silove, Psychiatrist (Director, Psychiatry Research and Teaching Unit, University of New South Wales) x Dr Kevin Vaughan, Psychiatrist (Clinical Senior Lecturer, Sydney Medical School, University of Sydney) x Mr Richard Weston, Chief Executive Officer (Healing Foundation) x Ms Carolyn Worth, Social Worker (Convenor, Victorian Centres Against Sexual Assault) x Ms Ruth Wraith, OAM (Child trauma psychotherapist) x Professor Malcolm Hopwood (Chair, Victorian Branch, Australian and New Zealand College of Psychiatrists) x Ms Elizabeth Sommerville (Mental Health Professional Officer, Australian Association of Social Workers) x Ms Michelle Roberts (Psychologist, Australian Child and Adolescent Trauma, Loss and Grief Network) x Professor Brenda Happell (Member, Board of Directors, Australian College of Mental Health Nurses) x Ms Roslyn Isles (President, Australian Guidance and Counselling Association)
582 x Ms Lesley Fraser (Secretary, Australian Guidance and Counselling Association) x Mr David Stokes (Executive Manager, Professional Practice, Australian Psychological Society) x Dr Gerald Goodhand (College of Rural and Remote General Practitioners) x Ms Ann Drew (Occupational Therapy Australia) x Dr Caroline Johnson (Fellow, Royal Australian College of General Practitioners) x Ms Cassandra Bertram (Consumer representative) x Ms Karene Eggleton (Consumer representative) x Ms Larisa Trotter (Consumer representative) x Mr Andrew Coghlan (National Manager, Emergency Services, Australian Red Cross) x Ms Suzanne Pope (Director, Research and Planning, beyondblue) x Dr Duncan Wallace (Psychiatrist, Australian Defence Force Centre for Mental Health)
Submissions were invited using a standard pro forma, available for download from the ACPMH website.
Four submissions were received, one from the RANZCP and three from individuals. These submissions are presented in full below, along with the Guideline developer’s response and, where relevant, resulting changes to the Guideline. Note that identifying information on the individual submissions has been removed.
583 Public Consultation Submission Comments and Guideline Developer’s Response Change to Guideline Developer’s Submission Comments Guideline Yes/No response Ref of new section Submission from the Royal Australian and New Zealand College of Psychiatrists Early psychological interventions for adults exposed to a potentially traumatic event GPP1 ‘screening for GPP1 is on pages 7 This practice point relates to symptoms psychological causes’ and 40. that could be from a wide has been added to GPP1. range of psychological conditions, and could be misinterpreted as suggesting that PTSD is the main psychological condition to consider in the presence of such symptoms. The RANZCP recommends consideration of inclusion of a qualifier – for example, it is recommended that the primary care practitioner consider screening for psychological causes, including asking whether the person has experienced a traumatic event and describe some examples of such events. Sequencing comorbidities CP6 The term ‘integrated’ CP6 is on pages 17 RANZPC agrees with the need for has been added and the and 159. simultaneous treatment generally, term ‘simultaneously’ however the term for this is “integrated has been removed from treatment” rather than CP6. simultaneous. There is an extensive “dual diagnosis” literature that refers to integrated treatment – where treatment interventions for all the co-morbid clinical disorders are brought together into the one CP8 is on pages 17 consistent treatment plan. The College and 159. proposes that the term The phrase ‘clinicians “simultaneous” be replaced with should be aware that “integrated”. PTSD symptoms may CP8 worsen due to acute In the context of treating the SU problem substance withdrawal or before the PTSD, the loss of substance use as clinician should also be aware that patients a coping mechanism’ report that their PTSD has been added to CP8. symptoms increase or are exacerbated by the reduction of substance use – this may represent
584 worsening symptoms due to acute substance withdrawal or may result from the loss of the person’s coping mechanism for PTSD symptoms – emphasising the need to advise on strategies for managing PTSD symptoms even when not actively treating the PTSD. General comments: While extremely thorough, the length of Noted. A brief No change the document means it is not easy to practitioner and engage with. In order for guidelines to be consumer guide will be clinically useful, they should be succinct. developed after the It would be preferable for the ACPMH to publication of these develop a brief version of the guidelines, Guidelines. focussed on the recommendations and good practice points, and/or a version for patients/ public (similar to some NICE products) There appears to be an absence of any A paragraph on Motivation for discussion or recommendations about how ‘motivation for change’ change is included to manage the impact of the individual’s has been added to in Chapter 2, page motivation for change; or ‘stage of change’ Chapter 2. 54. (see Murphy, R.T., et al., Development of a group treatment for enhancing motivation to change PTSD symptoms. Cognitive and Behavioral Practice, 2002. 9(4): p. 308- 316.). This issue would appear particularly Further specific mention Motivation for important with regards to older people, of this issue in the older change is included where the stage of change a person is at people section was not in Chapter 2, page may be very significant in determining considered necessary 54. how or how assertively to intervene. A related matter to the above point is how A paragraph Terminal illness is to appropriately intervene in the presence commenting on included in Chapter of terminal illness. This is discussed well ‘terminal illness’ was 2, page 52. in Feldman, D.B., Posttraumatic stress added to Chapter 2. disorder at the end of life: Extant research and proposed psychosocial treatment approach. Palliative & Supportive Care. 9(04): p. 407-418. The 3-stage approach in this may be applicable more generally to older people, depending not just on their physical state, but also their Stage of Change. It would be worthwhile to refer to the A bullet point to this 2nd bullet point ability to take constructive action in the effect was added to page added to Chapter 7, presence of dementia. A relevant reference 227 in Chapter 7. page 227. for this is Cook, J.M. and C. O’Donnell, Assessment and Psychological Treatment
585 of Posttraumatic Stress Disorder in Older Adults. Journal of Geriatric Psychiatry and Neurology, 2005. 18(2): p. 61-71. Individual submission Early psychological interventions for adults exposed to a potentially traumatic These comments were No change. event noted however the RR4: suggestion is beyond the Given the range of ANS based responses to scope of the guidelines. trauma (such as increased or decreased arousal, digestive disorders, muscular tension, insomnia, heart rate and respiration changes) and the effects of physical and exercise based interventions upon these individual processes that would be shown by a review of the existing literature, I suggest including the affects of physical and exercise based interventions upon the neurophysiological responses to trauma as part of the recommendation for future research into early interventions. Reviewing research into body based interventions affecting ANS symptoms commonly experienced after trauma (even if not focused upon specific ASD and PTSD outcome measures) may assist towards the goal stated on p 56 that “future research should focus on furthering our understanding of what mechanisms are involved in the development and maintenance of PTSD and by extension, what mechanism need to be targeted in treatment” Exercise and physical therapies GPP66 and lack of RR in relation to A research The research physical therapies, P 147: recommendation in recommendation Trauma inherently incorporates regards to physical was added as RR10. neurophysiological responses including exercise has been added. All existing RRs symptoms of Autonomic Nervous System from 10 onwards dys-regulation such as heart rate, blood moved up by one pressure, digestion, sleep, arousal, number (i.e. 10 breathing, energy levels and physical became 11). tension changes. Given your statement on p 56 that “future research should focus on furthering our understanding of what mechanisms are involved in the development and maintenance of PTSD and by extension, what mechanism need to be targeted in treatment” and your GPP
586 recommendation to advise regular aerobic exercise in managing their symptoms and that exercise may assist in the management of sleep disturbance and somatic symptoms that are common accompaniments of PTSD, I request you consider a specific research recommendation into physical and exercise based interventions as part of future research for the following reasons:
x A brief review of existing literature would show a substantial evidence base for the effects of physical and body based interventions upon individual neurophysiological responses that may be a part of the ANS dys-regulation symptoms after trauma. (The inclusion criteria for this review for research only measuring outcomes against ASD and PTSD criteria inadvertently excludes more body based research that tends to assess the effects of physical and exercise interventions upon individual neurophysiological outcomes) x The use of treatment approaches incorporating body-based interventions (such as EMDR) has already shown promising results with the incorporation of the body and it’s movement providing an additional entry point for the treatment of ASD and PTS. x A review of the literature would show a substantial evidence base that exercise is just as effective as any other treatment for mild to moderate depression (although this review has only included studies into ASD and PTSD and not depression following trauma.) x The US Military has already instigated a number of recovery centres that incorporate body based interventions such as yoga along with existing cognitive behavioural approaches in their treatment of PTSD with “promising” results. x Research showing
587 neurophysiological trauma responses as a phylogenetically ordered mobilisation then immobilisation continuum (Dr Stephen Porges’s - Poly-vagal theory) suggests physical discharge of arousal states from the body may be an important aspect of the re- regulation of the ANS that can potentially be supported or enhanced to compliment existing treatment approaches As an example of potentially relevant research showing the benefits of body based interventions not included in this guideline review (probably as it was not assessing against global ASD and PTSD criteria,) was research conducted by the US Military Centre for Excellence for Psychological Health and Traumatic Brain Injury into 13 mind body skills for re- regulating the ANS as part of their research into PTSD. The review was conduced from ‘a systems perspective on health and resilience seeking to establish good functioning and balance across all body symptoms through integration of beneficial health and mind- body practices, ” recognising that “integrative mind-body practices have also been gaining increased attention in the military as potential augmentative treatment strategies in a number of conditions, including post traumatic stress disorder and chronic pain.’ The review categorised the techniques into three domains of 1) breath exercises, 2) body based tension modulation exercises and 3) mindfulness, meditation and guided imagery techniques and found “the results of this review suggest that integrative practices designed to regulate the ANS and improve mood, stress regulation and arousal are promising” The results of the Centre for Excellence review lead to a further study by the Saumueli Institute involving 5000 US Marines pre and post deployment that investigated 4 of these specific body-mind processes to assist with down-regulating
588 the ANS, although the results are classified and have not yet been released. These US Centre for Excellence studies are an example of the way including research only measuring outcomes according to global ASD and PTSD outcomes may inadvertently bias the recommendations for future research towards existing ‘psychological interventions’ (that have a longer research history based around ASD and PTSD outcomes) and away from the evidence base for physical and exercise based interventions to address specific aspects of the neurophysiological responses to trauma. Given your recognition of aerobic exercise as a GPP for it’s obvious clinical relevance to ASD and PTSD treatment, along with the statement future research should focus upon the underlying mechanisms of ASD and PTSD, I am hopeful you will consider making a specific research recommendation into physical and exercise based interventions upon the neurophysiological responses to trauma as part of these guidelines. General comments: Thank you for the chance to comment on These comments were The research these guidelines. While obviously my noted. Thank you. recommendation comments will only be focused upon what A research was added as RR10 I see as areas of improvement or recommendation has expansion, I acknowledge these guidelines been added in relation to as a resource and guide for people working exercise. The guidelines with stress and trauma and the extensive have not included work you have all put into them. recommendations The primary motivation for my comments relating to underlying is to ensure these guidelines do not mechanisms. inadvertently bias future research away from physical and exercise based interventions that may offer a significant opportunity to expand our current understanding and treatment focus by incorporating the underlying dys- regulation of neuro-physiological systems as part of a complete bio-psycho-social model of trauma. An example of the way the body has traditionally been ‘overlooked’ in relation to trauma and it’s treatment is the way involuntary (neurogenic) tremors have
589 been routinely categorised as a symptom of ASD/PTSD (and a range of other mental health disorders) yet without any research into the neurophysiological reason for their frequency or their potential benefits as a self-regulatory mechanism of the human organism itself. There is a significant opportunity for these guidelines to expand and direct future research to include the neuro-physiology of the body (and physical and exercise based interventions to assist ANS re-regulation) in the hope of discovering additional points of entry and treatment influence with the potential to compliment existing treatment approaches. Given the likely influence of these guidelines in directing funding and support for future research initiatives, your inclusion of exercise as a GPP, and the guidelines’ directive to focus upon the underlying mechanisms of ASD and PTSD, I request you consider including a specific recommendation for future research to investigate both the neurophysiological responses to stress and trauma and the range of physical and exercise based interventions that may potentially affect them. Individual submission General comments: Yes, the limitations of No change In the introduction is there a clear the guidelines are statement that the Guidelines only address addressed in Chapter 1, ASD and PTSD as defined in DSM and do Scope of Guidelines, not address other reactions and page 21. psychopathology including the management and treatment of them along with co-morbidity? General comments: ASD in DSM-5 is No change Where do the Guidelines stand in relation addressed in Chapter 2, to ASD in DSM V? Acute Stress Disorder, page 30. General comments: This information is No change Also will the introduction discuss the included in Chapter 1, limited amount of quality research into Scope of the Guidelines, ASD and PTSD management and and in each of the treatment at this stage, particularly in ‘Summary of Literature’ relation to children and adolescents? sections following the research questions.
590 General comments: Yes, this will occur No change In the final format will Recommendations during the design phase and the different levels of GPs etc be prior to printing the colour coded for clarity and quick Guidelines. referencing? General comments: Yes, Appendix 3 No change Will an appendix include a list of the includes a list of research reviewed and indicate that which included and excluded has been cited? studies along with reasons for exclusion Individual submission General comments The overall content of the document is NHMRC guidelines No change very comprehensive. However, I question specify what whether it is appropriate to include this information needs to be depth and breadth of information in the included in the body of main body of the Guidelines as it possibly the Guidelines. renders them too long. However a brief I would prefer to see a brief and more practitioner and approachable set of guidelines with extra consumer guide will be material (rationale, research methods etc) developed after the in the appendices. publication of these Guidelines
591 Appendix 5: DSM-5 Criteria for PTSD
Updated May-11-2012
Note: The following criteria apply to adults, adolescents, and children older than six. There is a Pre-school Subtype for children age six and younger (see below).
Criterion A. Exposure to actual or threatened a) death, b) serious injury, or c) sexual violation, in one or more of the following ways:
1. Directly experiencing the traumatic event(s)
2. Witnessing, in person, the traumatic event(s) as they occurred to others
3. Learning that the traumatic event(s) occurred to a close family member or close friend; cases of actual or threatened death must have been violent or accidental
4. Experiencing repeated or extreme exposure to aversive details of the traumatic event(s) (e.g., first responders collecting human remains; police officers repeatedly exposed to details of child abuse); this does not apply to exposure through electronic media, television, movies, or pictures, unless this exposure is work-related.
Criterion B. Presence of one or more of the following intrusion symptoms associated with the traumatic event(s), beginning after the traumatic event(s) occurred:
1. Spontaneous or cued recurrent, involuntary, and intrusive distressing memories of the traumatic event(s) (Note: In children, repetitive play may occur in which themes or aspects of the traumatic event(s) are expressed.)
2. Recurrent distressing dreams in which the content or affect of the dream is related to the event(s) (Note: In children, there may be frightening dreams without recognizable content.)
3. Dissociative reactions (e.g., flashbacks) in which the individual feels or acts as if the traumatic event(s) are recurring (such reactions may occur on a continuum, with the most extreme expression being a complete loss of awareness of present surroundings. (Note: In children, trauma-specific reenactment may occur in play.)
4. Intense or prolonged psychological distress at exposure to internal or external cues that symbolize or resemble an aspect of the traumatic event(s)
5. Marked physiological reactions to reminders of the traumatic event(s)
592 Criterion C. Persistent avoidance of stimuli associated with the traumatic event(s), beginning after the traumatic event(s) occurred, as evidenced by avoidance or efforts to avoid one or more of the following:
1. Distressing memories, thoughts, or feelings about or closely associated with the traumatic event(s)
2. External reminders (i.e., people, places, conversations, activities, objects, situations) that arouse distressing memories, thoughts, or feelings about, or that are closely associated with, the traumatic event(s)
Criterion D. Negative alterations in cognitions and mood associated with the traumatic event(s), beginning or worsening after the traumatic event(s) occurred), as evidenced by two or more of the following:
1. Inability to remember an important aspect of the traumatic event(s) (typically due to dissociative amnesia that is not due to head injury, alcohol, or drugs)
2. Persistent and exaggerated negative beliefs or expectations about oneself, others, or the world (e.g., “I am bad,” “No one can be trusted,” "The world is completely dangerous"). (Alternatively, this might be expressed as, e.g., “I’ve lost my soul forever,” or “My whole nervous system is permanently ruined”).
3. Persistent, distorted blame of self or others about the cause or consequences of the traumatic event(s)
4. Persistent negative emotional state (e.g., fear, horror, anger, guilt, or shame)
5. Markedly diminished interest or participation in significant activities
6. Feelings of detachment or estrangement from others
7. Persistent inability to experience positive emotions (e.g., unable to have loving feelings, psychic numbing)
Criterion E. Marked alterations in arousal and reactivity associated with the traumatic event(s), beginning or worsening after the traumatic event(s) occurred, as evidenced by two or more of the following:
1. Irritable or aggressive behavior
2. Reckless or self-destructive behavior
3. Hypervigilance
4. Exaggerated startle response
5. Problems with concentration
6. Sleep disturbance (e.g., difficulty falling or staying asleep or restless sleep)
593 Criterion F. Duration of the disturbance (Criteria B, C, D, and E) is more than 1 month.
Criterion G. The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.
Criterion H. The disturbance is not attributed to the direct physiological effects of a substance (e.g., medication, drugs, or alcohol) or another medical condition (e.g. traumatic brain injury).
Specify if:
With Delayed Expression: if the diagnostic threshold is not exceeded until at least 6 months after the event (although the onset and expression of some symptoms may be immediate).
Subtype: Posttraumatic Stress Disorder in Preschool Children
Criterion A. In children (less than age 6 years), exposure to one or more of the following events: death or threatened death, actual or threatened serious injury, or actual or threatened sexual violation, in one or more of the following ways:
1. directly experiencing the event(s)
2. witnessing, in person, the event(s) as they occurred to others, especially primary caregivers (Note: Witnessing does not include events that are witnessed only in electronic media, television, movies or pictures.)
3. learning that the traumatic event(s) occurred to a parent or caregiving figure;
Criterion B. Presence of one or more intrusion symptoms associated with the traumatic event(s) , beginning after the traumatic event(s) occurred:
1. spontaneous or cued recurrent, involuntary, and intrusive distressing memories of the traumatic event(s) (Note: spontaneous and intrusive memories may not necessarily appear distressing and may be expressed as play reenactment.)
2. recurrent distressing dreams in which the content and/or affect of the dream is related to the traumatic event(s) (Note: it may not be possible to ascertain that the frightening content is related to the traumatic event.)
3. dissociative reactions in which the child feels or acts as if the traumatic event(s) were recurring, (such reactions may occur on a continuum with the most extreme expression being a complete loss of awareness of present surroundings). Such trauma-specific re-enactment may occur in play.
4. intense or prolonged psychological distress at exposure to internal or external cues that symbolize or resemble an aspect of the traumatic event(s)
5. marked physiological reactions to reminders of the traumatic event(s)
594 One item from criterion C or D below:
Criterion C. Persistent avoidance of stimuli associated with the traumatic event, beginning after the traumatic event occurred, as evidenced by avoidance or efforts to avoid:
1. activities, places, or physical reminders that arouse recollections of the traumatic event
2. people, conversations, or interpersonal situations that arouse recollections of the traumatic event.
Criterion D. Negative alterations in cognitions and mood associated with the traumatic event, beginning or worsening after the traumatic event occurred, as evidenced by one or more of the following:
1. markedly diminished interest or participation in significant activities, including constriction of play
2. socially withdrawn behavior
3. persistent reduction in expression of positive emotions
Criterion E. Alterations in arousal and reactivity associated with the traumatic event, beginning or worsening after the traumatic event occurred, as evidenced by two or more of the following:
1. irritable, angry, or aggressive behavior, including extreme temper tantrums
2. hypervigilance
3. exaggerated startle response
4. problems with concentration
5. sleep disturbance (e.g., difficulty falling or staying asleep or restless sleep)
Criterion F. Duration of the disturbance (Criteria B, C, D and E) is more than 1 month.
Criterion G. The disturbance causes clinically significant distress or impairment in relationships with parents, siblings, peers, or other caregivers or with school behavior.
Criterion H. The disturbance is not attributable to another medical condition.
Note: An individual can be diagnosed with both the Preschool and Dissociative Subtypes if criteria for both are met.
Subtype: Posttraumatic Stress Disorder – With Prominent Dissociative (Depersonalization/Derealization) Symptoms
595 The individual meets the diagnostic criteria for PTSD and in addition experiences persistent or recurrent symptoms of A1, A2, or both:
A1. Depersonalization: Experiences of feeling detached from, and as if one is an outside observer of, one’s mental processes or body (e.g., feeling as though one is in a dream, sense of unreality of self or body, or time moving slowly.
A2. Derealization: Experiences of unreality of one’s surroundings (e.g., world around the person is experienced as unreal, dreamlike, distant, or distorted)
B. The disturbance is not due to the direct physiological effects of a substance (e.g., blackouts, or behavior during alcohol intoxication), or another medical condition (e.g., complex partial seizures).
Note: The Dissociative and Preschool Subtypes are not mutually exclusive.
596