JOP0010.1177/0269881115581093Journal of PsychopharmacologyCleare et al. 581093research-article2015 BAP Guidelines Evidence-based guidelines for treating depressive disorders with antidepressants: A revision of the 2008 British Association Journal of Psychopharmacology 2015, Vol. 29(5) 459 –525 for Psychopharmacology guidelines © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0269881115581093 jop.sagepub.com Anthony Cleare1, CM Pariante2 and AH Young3 With expert co-authors (in alphabetical order): IM Anderson4, D Christmas5, PJ Cowen6, C Dickens7, IN Ferrier8, J Geddes9, S Gilbody10, PM Haddad11, C Katona12, G Lewis12, A Malizia13, RH McAllister-Williams14, P Ramchandani15, J Scott16, D Taylor17, R Uher18 and the members of the Consensus Meeting19 Endorsed by the British Association for Psychopharmacology Abstract A revision of the 2008 British Association for Psychopharmacology evidence-based guidelines for treating depressive disorders with antidepressants was undertaken in order to incorporate new evidence and to update the recommendations where appropriate. A consensus meeting involving experts in depressive disorders and their management was held in September 2012. Key areas in treating depression were reviewed and the strength of evidence and clinical implications were considered. The guidelines were then revised after extensive feedback from participants and interested parties. A literature review is provided which identifies the quality of evidence upon which the recommendations are made. These guidelines cover the nature and detection of depressive disorders, acute treatment with antidepressant drugs, choice of drug versus alternative treatment, practical issues in prescribing and management, next-step treatment, relapse prevention, treatment of relapse and stopping treatment. Significant changes since the last guidelines were published in 2008 include the availability of new antidepressant treatment options, improved evidence supporting certain augmentation strategies (drug and non-drug), management of potential long-term side effects, updated guidance for prescribing in elderly and adolescent populations and updated guidance for optimal prescribing. Suggestions for future research priorities are also made. Keywords Antidepressants, depression, depressive disorder, treatment, evidence-based guidelines 1 Professor of Psychopharmacology & Affective Disorders, King’s College 11 Consultant Psychiatrist, Cromwell House, Greater Manchester West London, Institute of Psychiatry, Psychology and Neuroscience, Centre Mental Health NHS Foundation Trust, Salford, UK for Affective Disorders, London, UK 12Division of Psychiatry, University College London, London, UK 2 Professor of Biological Psychiatry, King’s College London, Institute 13 Consultant in Neuropsychopharmacology and Neuromodulation, North of Psychiatry, Psychology and Neuroscience, Centre for Affective Bristol NHS Trust, Rosa Burden Centre, Southmead Hospital, Bristol, UK Disorders, London, UK 14 Reader in Clinical Psychopharmacology, Institute of Neuroscience, 3Professor of Psychiatry and Chair of Mood Disorders, King’s College Newcastle University, Royal Victoria Infirmary, Newcastle upon London, Institute of Psychiatry, Psychology and Neuroscience, Centre Tyne, UK for Affective Disorders, London, UK 15Reader in Child and Adolescent Psychiatry, Centre for Mental Health, 4 Professor and Honorary Consultant Psychiatrist, University of Manchester Imperial College London, London, UK Department of Psychiatry, University of Manchester, Manchester, UK 16 Professor of Psychological Medicine, Institute of Neuroscience, 5Consultant Psychiatrist, Advanced Interventions Service, Ninewells Newcastle University, Newcastle upon Tyne, UK Hospital & Medical School, Dundee, UK 17 Professor of Psychopharmacology, King’s College London, London, UK 6 Professor of Psychopharmacology, Psychopharmacology Research 18 Associate Professor, Canada Research Chair in Early Interventions, Unit, Neurosciences Building, University Department of Psychiatry, Dalhousie University, Department of Psychiatry, Halifax, NS, Canada Warneford Hospital, Oxford, UK 19Other members of the consensus meeting: Prof David Baldwin, Prof 7 Professor of Psychological Medicine, University of Exeter Medical Thomas Barnes, Dr David Coghill, Prof Guy Goodwin, Prof Tony Hale, School and Devon Partnership Trust, Exeter, UK Prof Louise Howard, Prof Brian Leonard, Dr Alan Lenox-Smith, Prof 8 Professor of Psychiatry, Honorary Consultant Psychiatrist, School Keith Matthews, Dr Stuart Montgomery, Prof Ian Reid, Prof Barbara J of Neurology, Neurobiology & Psychiatry, Royal Victoria Infirmary, Sahakian, Dr Orla White. Newcastle upon Tyne, UK 9 Head, Department of Psychiatry, University of Oxford, Warneford Corresponding author: Hospital, Oxford, UK Anthony Cleare, King’s College London, Institute of Psychiatry, 10 Director of the Mental Health and Addictions Research Group Psychology and Neuroscience, Centre for Affective Disorders, De (MHARG), The Hull York Medical School, Department of Health Crespigny Park, London SE5 8AF, UK. Sciences, University of York, York, UK Email: [email protected] 460 Journal of Psychopharmacology 29(5) Introduction NNTs may, however, be clinically relevant in the context of more severe and/or treatment-resistant depression. Therefore, the The British Association for Psychopharmacology (BAP) aims to assessment of clinical importance depends on context and needs advance education and research in the science of psychopharma- to be judged in individual situations. In addition, the outcome cology by arranging scientific meetings, fostering research and measures used are ratings of depressive symptoms which only teaching, encouraging publication of research results and provid- capture certain aspects of the clinical condition. A further prob- ing guidance and information to the public and professions on mat- lem is that patients entered into clinical trials are not representa- ters relevant to psychopharmacology. As an important part of this tive of patients seen in routine practice (Zimmerman et al., 2002, process the BAP has published a series of evidence-based guide- 2005). This reminds us that the effect size estimates from RCTs lines for the use of drugs in psychiatric disorders, with the empha- have limitations in their generalisability and their interpretation sis on producing comprehensive but concise and useable guidelines requires caution. Statistical significance is taken as p<0.05; for based on a review of the evidence (see www.bap.org.uk). simplicity and space considerations we do not give 95% confi- This revision of the BAP guidelines for treating depressive dence intervals. disorders with antidepressants (Anderson et al., 2000, 2008) was Categories of evidence for causal relationships and strength undertaken in order to update the guidelines in the light of new of recommendations are provided in Table 1. They have been evidence. As previously, every effort was taken to make recom- developed from Shekelle et al. (1999) and are the same as those mendations explicitly evidence based. used in the 2008 BAP guidelines. Although we have included meta-analytic evidence within the highest category, we acknowl- edge that meta-analyses are only as good as the underlying trials, Methodology which are of variable – and often poor – quality. Large, head-to- A consensus meeting was held under the auspices of the BAP in head RCTs are the ideal basis upon which to form judgements, 2012 involving experts in the field of depression and antidepres- but unfortunately are too often lacking in relation to the key ques- sant treatment, user representatives and medical and scientific tions of interest; there remain extensive gaps in the evidence staff from pharmaceutical companies. Presentations on key areas base. Thus, we have taken the decision to include indirect meta- with an emphasis on systematic reviews and randomised con- analytic comparisons (e.g. network meta-analysis methods) trolled trials (RCTs) were made by each co-author of the guide- where other evidence is lacking, but we acknowledge that these lines, followed by discussion within the whole group about the are less robust than RCTs, or meta-analyses of RCTs, of direct quality of evidence and its implications. Subsequently, the main comparisons. It is also important to note that it is difficult to com- authors revised the previous literature review from 2008 where pare response rates and effect sizes between studies for a large necessary to incorporate significant developments and drafted number of reasons; in particular we are mindful that some meth- revised recommendations and their strength based on the level of odologies (such as the use of waiting list control) will tend to evidence. This was then circulated to all participants, user groups inflate the observed efficacy of some treatment modalities and and other interested parties for feedback which was incorporated cannot be compared directly with the more robust data obtained into the final version of the guidelines. from more rigidly standardised, double-blind placebo-controlled studies. Where relevant we discuss this further in the appropriate sections of the evidence review. There are no generally agreed Identification of relevant evidence categories for non-causal evidence and we have not routinely graded this evidence but, if appropriate, we have done so as out- The breadth of information covered in these guidelines did not