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Title Substance misuse in young people in Ireland - a focus on benzodiazepines

Author(s) Murphy, Kevin D. Publication date 2014 Original citation Murphy, K. 2014. Substance misuse in young people in Ireland - a focus on benzodiazepines. PhD Thesis, University College Cork.

Type of publication Doctoral thesis Rights © 2014, Kevin Murphy. http://creativecommons.org/licenses/by-nc-nd/3.0/

Embargo information No embargo required

Item downloaded http://hdl.handle.net/10468/1903 from Downloaded on 2021-10-07T17:21:14Z

Substance Misuse in Young People in Ireland - A Focus on Benzodiazepines

Kevin Murphy BPharm (Hons) MPSI

A thesis submitted to the National University of Ireland, Cork for the degree of Doctor of Philosophy in the School of Pharmacy

June 2014

Head of School

Prof. Stephen Byrne

Supervisors

Prof. Stephen Byrne

Dr. Laura Sahm

Dr. Suzanne McCarthy

Overview of Contents

Declaration ...... ii

Table of Contents ...... iii

Table of Figures ...... viii

Table of Tables ...... ix

Table of Equations ...... x

Table of Abbreviations ...... xi

Publications...... xi

Thesis Abstract ...... xvi

Acknowledgements ...... xxi

Chapter 1 - Thesis Introduction ...... 1

Chapter 2 - Substance use in young persons in Ireland, a systematic review30

Chapter 3 - Benzodiazepine prescribing guideline adherence and misuse potential in Irish minors ...... 68

Chapter 4 - Use of addiction treatment services by Irish youth: does place of residence matter? ...... 94

Chapter 5 - Benzodiazepine use amongst young attendees of an Irish substance treatment centre ...... 108

Chapter 6 - “You Don’t Feel” – The Experience Of Youth Benzodiazepine Misuse ...... 125

Chapter 7 -“They’re too good” - Health-care worker views on youth benzodiazepine misuse ...... 169

Chapter 8 - Thesis Discussion ...... 204

Chapter 9 - References ...... 218

Appendices ...... 242

i

Declaration

I declare that this thesis has not been previously submitted for a degree at this, or any other university. It is entirely my own work, apart from due acknowledgement. The library may lend or copy this thesis upon request.

Signed:______Date:______

ii

Table of Contents

Table of Contents ...... iii

Table of Figures ...... vi

Table of Tables ...... vii

Table of Equations ...... viii

Table of Abbreviations ...... ix

Publications...... xi

Thesis Abstract ...... xvi

Introduction ...... xvi

Methods ...... xvi

Results ...... xviii

Conclusion ...... xx

Acknowledgements ...... xxi

1. Thesis Introduction ...... 1

1.1 Drugs Policy in Ireland ...... 2

1.2 Defining addiction and dependence ...... 7

1.3 Diagnosing dependence ...... 9

1.4 Psychological dependence ...... 13

1.5 Physiology of psychological dependence ...... 16

1.6 Physical dependence ...... 20

1.7 Mechanisms of action of misused substances ...... 23

1.8 Summary ...... 29

2. Substance use in young persons in Ireland, a systematic review ...... 30

2.1 Introduction ...... 31

2.2 Methods ...... 34

2.3 Results...... 39 iii

2.4 Discussion ...... 60

3. Benzodiazepine prescribing guideline adherence and misuse potential in Irish minors ...... 68

3.1 Introduction ...... 69

3.2 Methods ...... 71

3.3 Results...... 77

3.4 Discussion ...... 87

4. Use of addiction treatment services by Irish youth: does place of residence matter? ...... 94

4.1 Introduction ...... 95

4.2 Methods ...... 98

4.3 Results...... 101

4.4 Discussion ...... 105

5. Benzodiazepine use amongst young attendees of an Irish substance treatment centre ...... 108

5.1 Introduction ...... 109

5.2 Methods ...... 112

5.3 Results...... 113

5.4 Discussion ...... 120

6. “You Don’t Feel” – The Experience Of Youth Benzodiazepine Misuse125

6.1 Introduction ...... 126

6.2 Method ...... 128

6.3 Results...... 133

6.4 Discussion ...... 159

7. “They’re too good” - Health-care worker views on youth benzodiazepine misuse ...... 169

7.1 Introduction ...... 170

7.2 Method ...... 171

iv

7.3 Results...... 175

7.4 Discussion ...... 194

8. Thesis Discussion ...... 204

8.1 Discussion ...... 205

8.2 Limitations ...... 215

8.3 Future Work ...... 216

9. References ...... 218

10. Appendices ...... 242

10.1 Appendix I - Controlled drugs schedules in Ireland ...... 243

10.2 Appendix II - Draft Misuse of Drugs (Amendment) Regulations, 2013...... 255

10.3 Appendix III – Substance use in young persons in Ireland ...... 268

10.4 Appendix IV – MINORS rating of reviewed studies ...... 279

10.5 Appendix V – Ethical approval for study in Chapter 3 ...... 281

10.6 Appendix VI – Ethical approval for studies in Chapter 4 and 5 ... 283

10.7 Appendix VII – Sample National Drug Treatment Reporting System form...... 285

10.8 Appendix VIII – Sample Initial Assessment form ...... 287

10.9 Appendix IX – Ethics approval for Chapter 6 research ...... 295

10.10 Appendix X – Information sheet and consent form for Chapter 6 research ...... 299

10.11 Appendix XI – Ethical approval for Chapter 7 research ...... 302

10.12 Appendix XII – Information sheet and consent form for Chapter 7 research ...... 306

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Table of Figures

Figure 1.1. Schematic diagram of the human brain that highlights some of the main brain areas and neurotransmitter pathways implicated in reward processes ...... 17 Figure 1.2. Action of selected dependence-forming substances in the mesolimbic system ...... 18 Figure 1.3. GABA receptors in the mesolimbic dopaminergic systems involved in addiction ...... 26 Figure 2.1. Adapted from the PRISMA flow diagram ...... 40 Figure 3.1.Benzodiazepine consumption in selected European countries between 2009 and 2012 ...... 79 Figure 3.2. Benzodiazepine prescribing between 2009 and 2012 by age ..... 82 Figure 5.1. Number of service-user forms filled out by year ...... 114

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Table of Tables

Table 1.1. ICD-10 diagnostic criteria for substance dependence ...... 10 Table 1.2. DSM-IV-TR diagnostic criteria for substance dependence ...... 11 Table 1.3. DSM-IV-TR diagnostic criteria for substance abuse...... 12 Table 2.1. Summary of study characteristics ...... 37 Table 2.2. Summary of smoking prevalence rates ...... 42 Table 2.3. Summary of alcohol prevalence rates ...... 49 Table 2.4. Summary of prevalence rates ...... 54 Table 2.5. Summary of benzodiazepine prevalence rates ...... 59 Table 3.1. Background statistics of patients issued benzodiazepines between 2009 and 2012 ...... 80 Table 3.2. Benzodiazepine prescribing between 2009 and 2012 ...... 81 Table 3.3. Compliance to benzodiazepine guideline 1 ...... 84 Table 3.4. Compliance to benzodiazepine guideline 2 ...... 85 Table 3.5. Compliance to benzodiazepine guideline 3 ...... 86 Table 4.1. Comparison of demographics between urban and rural service- users ...... 102 Table 4.2. Comparison of substance use between urban and rural service- users ...... 104 Table 5.1. Breakdown of referrals of service users by source of referral .... 114 Table 5.2. Service-users who have ever used a substance ...... 115 Table 5.3. Comparison of service-user characteristics of regular and non- regular benzodiazepine users ...... 116 Table 5.4. Comparison of physical and behavioural symptoms experienced by benzodiazepine users ...... 118 Table 6.1. Street names for benzodiazepines ...... 133 Table 6.2. Themes and categories discussed in interviews ...... 134 Table 7.1. Themes and categories discussed in interviews ...... 176

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Table of Equations

Equation 3.1. DDD/1,000/day calculation ...... 76

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Table of Abbreviations

AIDS Acquired Immune Deficiency Syndrome CBT Cognitive Behavioural Therapy CINAHL Cumulative Index to Nursing and Allied Health Literature COREQ Consolidated criteria for reporting qualitative research CREC Cork Ethics Research Committee CSO Central Statistics Office DA Dopamine DAT Dopamine Active Transporter DDD Defined Daily Dose DPS Drug Payment Scheme Diagnostic and Statistical Manual of Mental Disorders 4, Text DSM-IV-TR Revision EMCDDA European Monitoring Centre for Drugs and Drug Addiction ERIC Education Resources Information Centre ESPAD European School Survey Project on Alcohol and Other Drugs EU European Union GABA gamma-aminobutyric acid GMS General Medical Services GP General Practitioner HII Health Intelligence Ireland HRB Health Research Board HSE Health Service Executive ICD International Classification of Diseases IQR Interquartile Range JLO Juvenile Liaison Officer LSD Lysergic Acid LTI Long Term Illness MDMA methylenedioxymethamphetamine MeSH Medical Subject Headings MINORS Methodological Index of Non-Randomised Studies

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MOR Mu Opioid Receptors MTS Matt Talbot Services NAc Nucleus Accumbens NACD National Advisory Council on Drugs NDTRS National Drug Treatment Reporting System NHS National Health Service NICE National Institute of Clinical Excellence NMDA N-methyl-D-aspartate PCRS Primary Care Reimbursement Service PFC Prefrontal Cortex PKC Protein Kinase C Preferred Reporting Items for Systematic Reviews and Meta- PRISMA analyses RCT Randomised Control Trial SAMSHA Substance Abuse and Mental Health Services Administration SD Standard Deviation SPC Summary of Product Characteristics SPHE Social Personal and Health Education SUDS Substance Use Disorder Syndrome THC Tetrahydrocannabinol UNICEF United Nations Children's Fund USA United States of America VTA Ventral Tegmental Area WHO World Health Organisation World Health Organisation - Anatomical Therapeutic Chemical WHO-ATC Classification System YC Youth Counsellor

x

Publications

Peer-reviewed publications

. Murphy KD, McCarthy S, Byrne S, Lambert S, Sahm L.

Benzodiazepine use amongst young attendees of an Irish substance

treatment centre. Journal of Addiction Medicine. 2014;In Press.

. Murphy KD, Byrne S, Sahm L, Lambert S, McCarthy S. Use of

addiction treatment services by Irish youth: does place of residence

matter? Rural and Remote Health. 2014;In Press.

. Parsons C, McCorry N, Murphy K, Byrne S, O'Sullivan D,

O'Mahony D, Passmore P, Patterson S, Hughes C. Assessment of

factors that influence physician decision making regarding medication

use in patients with dementia at the end of life. International Journal of

Geriatric Psychiatry. 2013;29(3):281-90.

. Murphy K, Sahm L, McCarthy S, Lambert S, Byrne S.

Substance use in young persons in Ireland, a systematic review.

Addictive Behaviors. 2013;38(8):2392-401.

. O'Sullivan DP, O'Mahony D, Parsons C, Hughes C, Murphy K,

Patterson S, Byrne S. A prevalence study of potentially inappropriate

prescribing in irish long-term care residents. Drugs Aging. 2013

Jan;30(1):39-49.

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Peer-reviewed published abstracts

. Murphy K, Sahm L, Lambert S, Byrne S. A survey of service-

users attending Matt Talbot Services (MTS) during 2009 and their use

of alcohol. International Journal of Clinical Pharmacy. 2012;34(1):231.

. Murphy KD, Sahm L, Lambert S, Byrne S. A descriptive

analysis of service-users attending an outpatient treatment centre

during 2009/2010. International Journal of Pharmacy Practice.

2012;20(S1):19-20.

Published reports

. Parsons C, McCorry N, Hughes C, Passmore P, Patterson S,

Olver A, Kennedy G, Megraw V, Byrne S, O' Mahony D, O' Sullivan D,

Murphy K, Hickey M, Collins U. Assessment of factors which influence

physician decision-making regarding medication use in patients with

dementia at the end of life. Dublin/Belfast: Centre for Ageing

Research and Development in Ireland, 2012.

Presentations and Posters

. School of Pharmacy Scientific Conference, University College

Cork

School of Pharmacy, University College Cork, Cork, 27th September

2013

Poster: Adolescent benzodiazepine use and its health effects

Murphy, K., Byrne, S., McCarthy, S., Sahm, L., Lambert, S.

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. Association for Children and Adolescent Mental Health

Research Day 2013

St James’s Hospital, Dublin, 17th May 2013

Poster: Adolescent benzodiazepine use and its health effects

Murphy, K., Byrne, S., McCarthy, S., Sahm, L., Lambert, S.

. European Society of Clinical Pharmacy 2012

Hotel Fira Palace, Barcelona, Spain, 28th-31st October 2012

Poster: Substance Use in Young Persons in Ireland, a Systematic

Review

Murphy, K., Sahm, L., Lambert, S., Byrne, S.

Poster: Analysis of service-users attending Matt Talbot Services

(MTS) from 2007-2010

Murphy, K., Sahm, L., Lambert, S., Byrne, S.

. Health Services Research & Pharmacy Practice 2012

School of Pharmacy, University College Cork, Cork, 24th April 2012

Presentation: A descriptive analysis of service-users attending an outpatient treatment centre during 2009/2010

Murphy, K., Sahm, L., Lambert, S., Byrne, S.

xiii

. All-Ireland Schools of Pharmacy 2012

School of Pharmacy, University College Cork, Cork, 2nd April 2012

Presentation: A descriptive analysis of service-users attending an outpatient treatment centre during 2007-2010

Murphy, K., Sahm, L., Lambert, S., Byrne, S.

Poster: A survey of service-users attending Matt Talbot Services during 2009 and their use of alcohol

Murphy, K., Sahm, L., Lambert, S., Byrne, S.

. European Society of Clinical Pharmacy 2011

Dublin, Ireland, 19th -21st October 2011

Poster: A survey of service-users attending Matt Talbot Services during 2009 and their use of alcohol

Murphy, K., Sahm, L., Lambert, S., Byrne, S.

. Postgraduate Annual Presentation 2011

School of Pharmacy, University College Cork, Cork, 15th September

2011

xiv

Presentation: The Evaluation of Substance Use in Adolescents in

Cork

Murphy, K., Sahm, L., Lambert, S., Byrne, S.

Postgraduate Taught Module Credits Awarded

. PG6024 - Qualitative Research Inquiry

Credit weighting: 5

Award date: 10th December 2013

. ST6013 - Statistics and Data Analysis for Postgraduate

Research Students, awarded Credit weighting: 10

Award date: 7th October 2013

. PG6003 - Teaching and Learning for Graduate Students

Credit weighting: 5

Award date: 5th March 2012

. PG6001 - Scientific Training for Enhanced Postgraduate Study

Credit weighting: 5

Award date: 29th February 2012

. PG6009 - Graduate Information Literacy Skills

Credit weighting: 5

Award date: 20th June 2011

xv

Thesis Abstract

Introduction Substance misuse in Ireland has a long history. Alcohol was recognised as the main concern, but it was not until the 1960s that other dependence- forming substances have been recognised as problematic in Ireland. Since then, the number of misused substances has risen sharply to include novel synthetic compounds and prescription-only medicines. Many attempts have been made to reduce the misuse of these substances: restricting growth and manufacture of substances, criminalising possession, increasing prescribing requirements, and using treatment centres to assist those who wish to stop misusing. Despite enormous expense and effort, substance misuse is still a problem. The mechanism by which these substances excite the brain’s natural reward pathways means it can be difficult for misusers to stop desiring the effects of the substances. Much has been discovered about how misused substances create their dependence-forming effect, but there is still much unsolved in such a complex area.

Methods A systematic review was undertaken on the prevalence of substance misuse amongst young people in Ireland between 2000 and 2012 to create a context in which later research among substance misusers can be compared, and to put benzodiazepine misuse in the context of other misused substances.

xvi

Data from national reimbursement claims were analysed to examine trends in: (i) the prescribing of benzodiazepines nationally and internationally and

(ii) the prescribing of benzodiazepines to patients younger than 18 years between 2009 and 2012, to monitor adherence to benzodiazepine prescribing guidelines and to highlight areas in prescribing where the potential for misuse could be decreased.

The differences between urban and rural attendees of a substance misuse treatment centre in Cork were compared to examine whether there were differences in substance misuse between the groups. This was followed by a comparison of regular and non-regular benzodiazepine misusers from the substance misuse treatment centre and their self-reported misuse-related symptoms.

The next stage involved qualitative research using semi-structured interviews with young people who had misused benzodiazepines in their adolescence.

This approach was used to describe the experiences and causes of youth benzodiazepine misuse in Cork and to guide future interventions to reduce misuse. This approach was also utilised for interviews conducted with youth counsellors (YCs) and general practitioners (GPs). As substance misuse in adolescence can lead to damaged brain development, which may result in a lack of insight into their behaviours, it was important to gain this information from those who have worked with young benzodiazepine misusers.

xvii

Results The systematic review returned 18 articles that matched the inclusion criteria for the study. The review showed that tobacco, alcohol and cannabis use levels in Ireland have reduced in the period between 2000 and 2012. Lifetime tobacco use reported at the beginning of the review period ranged from approximately 61-67%, and decreased to 43-48% at the end of the study period. Lifetime alcohol levels similarly decreased from 71-92% at the beginning of the review period to 58-81%. Lifetime cannabis misuse decreased from 29-39% to approximately 18%. Lifetime benzodiazepine misuse was the only parameter which did not decrease over the study period. Research conducted into the comparison of Irish prescribing data relative to European counterparts found that Ireland had the fourth highest level of benzodiazepine prescribing among those countries surveyed between 2009 and 2012. However Irish prescribing did decrease by 16% over this time. Approximately 15% of Irish people aged 17 and under were prescribed benzodiazepines for greater than four weeks, whilst approximately 40% were prescribed hypnotics, both in contravention of the

Good Practice Guideline for Clinicians.

Data comparing urban and rural treatment centre attendees showed that a greater percentage of rural service-users were employed (p = 0.015), more urban service-users were unemployed (p = 0.015), while there were similar levels of students from urban and rural areas. A greater proportion of urban service-users had taken multiple substances in their lifetime (73.7% vs.

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52.2%, p = 0.001) and continued to use multiple substances regularly (49.3% vs. 31.3%, p = 0.003) compared with their rural counterparts. The study comparing regular and non-regular benzodiazepine usage showed that benzodiazepines had ever been used by 51.0% treatment centre attendees, and of these, 55.8% were regular benzodiazepine users. The mean age of first use was 14.9 ± 1.4 years.