Treatment interventions to maintain abstinence from alcohol in primary care: Systematic review and network meta-analysis

Hung-yuan Cheng; Luke A Mcguinness; Roy G Elbers; Georgina J Macarthur; Abigail Taylor; Alexandra Mcaleenan; Sarah Dawson; José A López-lópez; Julian P T Higgins; Sean Cowlishaw; Anne Lingford-hughes; Matthew Hickman; David Kessler

doi:10.1136/bmj.m3934

Treatment interventions to maintain abstinence from alcohol in primary care: Systematic review and network meta-analysis

Hung-yuan Cheng, Luke A Mcguinness, Roy G Elbers, Georgina J Macarthur, Abigail Taylor, Alexandra Mcaleenan, Sarah Dawson, José A López-lópez, Julian P T Higgins, Sean Cowlishaw, Anne Lingford-hughes, Matthew Hickman, David Kessler^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

16 Citations (Scopus)

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Abstract

Objective
To determine the most effective interventions in recently detoxified, alcohol dependent patients for implementation in primary care.

Design
Systematic review and network meta-analysis.

Data sources
Medline, Embase, PsycINFO, Cochrane CENTRAL, ClinicalTrials.gov, and the World Health Organization’s International Clinical Trials Registry Platform.

Study selection
Randomised controlled trials comparing two or more interventions that could be used in primary care. The population was patients with alcohol dependency diagnosed by standardised clinical tools and who became detoxified within four weeks.

Data extraction
Outcomes of interest were continuous abstinence from alcohol (effectiveness) and all cause dropouts (as a proxy for acceptability) at least 12 weeks after start of intervention.

Results
64 trials (43 interventions) were included. The median probability of abstinence across placebo arms was 25%. Compared with placebo, the only intervention associated with increased probability of abstinence and moderate certainty evidence was acamprosate (odds ratio 1.86, 95% confidence interval 1.49 to 2.33, corresponding to an absolute probability of 38%). Of the 62 included trials that reported all cause dropouts, interventions associated with a reduced number of dropouts compared with placebo (probability 50%) and moderate certainty of evidence were acamprosate (0.73, 0.62 to 0.86; 42%), naltrexone (0.70, 0.50 to 0.98; 41%), and acamprosate-naltrexone (0.30, 0.13 to 0.67; 17%). Acamprosate was the only intervention associated with moderate confidence in the evidence of effectiveness and acceptability up to 12 months. It is uncertain whether other interventions can help maintain abstinence and reduce dropouts because of low confidence in the evidence.

Conclusions
Evidence is lacking for benefit from interventions that could be implemented in primary care settings for alcohol abstinence, other than for acamprosate. More evidence from high quality randomised controlled trials is needed, as are strategies using combined interventions (combinations of drug interventions or drug and psychosocial interventions) to improve treatment of alcohol dependency in primary care.

Original language	English
Article number	m3934
Number of pages	13
Journal	BMJ
Volume	371
DOIs	https://doi.org/10.1136/bmj.m3934 https://doi.org/10.1136/bmj.m3934
Publication status	Published - 25 Nov 2020

Bibliographical note

Funding Information:
4National Institute for Health Research Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and University of Bristol, Bristol, UK 5Department of Psychiatry, University of Melbourne, Melbourne, Victoria, Australia 6Faculty of Medicine, Department of Brain Sciences, Imperial College London, London, UK 7National Institute for Health Research School for Primary Care Research, University of Bristol, Bristol, UK We thank the study authors who provided data and extra information for this review, including the Project MATCH executive committee for providing the Project MATCH public dataset for the secondary analysis. The authors acknowledge that the reported results are, in whole or in part, based on analyses of the Project MATCH Public Data Set. These data were collected as part of a multisite clinical trial of alcoholism treatments supported by a series of grants from the National Institute on Alcohol Abuse and Alcoholism and made available to the authors by the Project MATCH Research Group. This article has not been reviewed or endorsed by the Project MATCH Research Group and does not necessarily represent the opinions of its members, who are not responsible for the contents.

Funding Information:
Funding: This review was funded primarily by the School for Primary Care Research, National Institute for Health Research (NIHR SPCR; ref 286). JPTH and MH are NIHR senior investigators. JPTH, MH, and DK are supported by NIHR Bristol Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol. JPTH is supported by the NIHR Applied Research Collaboration West (ARC West) at University Hospitals Bristol and Weston NHS Foundation Trust. JPTH and MH are supported by the NIHR Health Research Health Protection Research Unit (HPRU) HPRU in Evaluation of Interventions at University of Bristol. LAM is supported by a NIHR doctoral research fellowship (DRF-2018-11-ST2-048). GJM was supported by an NIHR postdoctoral fellowship award (PDF-2013-06-026). This report is independent research supported by the NIHR (postdoctoral fellowship, PDF-2013-06-026). The views expressed in this article are those of the authors and do not necessarily represent those of the UK National Health Service or NIHR. The conduct of the review, writing of the paper, and decision to submit for publication were independent of all research funders. The funders had no role in considering the study design or in the collection, analysis, and interpretation of data, writing of the report, or decision to submit the article for publication. Competing interests: All authors have completed the ICMJE uniform disclosure from at www.icmje.org/coi_disclosure.pdf and declare: support from the School for Primary Care Research, National Institute for Health Research for the submitted work; HC, AM, JPTH, and LAM report grants from the National Institute for Health Research (NIHR) School for Primary Care Research during the conduct of the study, LAM reports grants from NIHR doctoral research fellowship during the conduct of the study, ALH reports grants from GSK and Lundbeck and personal fees from Silence Therapeutics during the conduct of the study, JLL reports grants from Economic and Social Research Council outside the submitted work, MH reports personal fess and others from MSD, Gilead, and Abbvie outside the submitted work, ALH reports personal fees from Janssen-Cilag, Pfizer, Sanofi-Aventis, Lundbeck, and others from Opiant and Lightlak (unpaid consultancy) outside the submitted work; ALH led the British Association for Psychopharmacology’s guidelines: Evidence based guidelines for the pharmacological management of substance misuse, addiction, and co-morbidity: recommendations from the British Association for Psychopharmacology. J Psychopharmacol 18(3):293-335; and updated in 2012: Evidence-based guidelines for the pharmacological management of substance misuse, addiction and comorbidity: recommendations from BAP. J Psychopharmacol 26(7):899-952. The original guidelines received support from Archimedes Pharma, Lundbeck, Pfizer, Schering. ALH was a member of the National Institute for Health and Care Excellence clinical guideline group: Alcohol-use disorders: diagnosis, assessment and management of harmful drinking and alcohol dependence. A NICE Clinical guideline (CG115) 2011.

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© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.

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Cheng, H., Mcguinness, L. A., Elbers, R. G., Macarthur, G. J., Taylor, A., Mcaleenan, A., Dawson, S., López-lópez, J. A., Higgins, J. P. T., Cowlishaw, S., Lingford-hughes, A., Hickman, M., & Kessler, D. (2020). Treatment interventions to maintain abstinence from alcohol in primary care: Systematic review and network meta-analysis. BMJ, 371, [m3934]. https://doi.org/10.1136/bmj.m3934, https://doi.org/10.1136/bmj.m3934

@article{53bb4d9344d545e2ab04313e80a8f620,

title = "Treatment interventions to maintain abstinence from alcohol in primary care: Systematic review and network meta-analysis",

abstract = "Objective To determine the most effective interventions in recently detoxified, alcohol dependent patients for implementation in primary care.Design Systematic review and network meta-analysis.Data sources Medline, Embase, PsycINFO, Cochrane CENTRAL, ClinicalTrials.gov, and the World Health Organization{\textquoteright}s International Clinical Trials Registry Platform.Study selection Randomised controlled trials comparing two or more interventions that could be used in primary care. The population was patients with alcohol dependency diagnosed by standardised clinical tools and who became detoxified within four weeks.Data extraction Outcomes of interest were continuous abstinence from alcohol (effectiveness) and all cause dropouts (as a proxy for acceptability) at least 12 weeks after start of intervention.Results 64 trials (43 interventions) were included. The median probability of abstinence across placebo arms was 25%. Compared with placebo, the only intervention associated with increased probability of abstinence and moderate certainty evidence was acamprosate (odds ratio 1.86, 95% confidence interval 1.49 to 2.33, corresponding to an absolute probability of 38%). Of the 62 included trials that reported all cause dropouts, interventions associated with a reduced number of dropouts compared with placebo (probability 50%) and moderate certainty of evidence were acamprosate (0.73, 0.62 to 0.86; 42%), naltrexone (0.70, 0.50 to 0.98; 41%), and acamprosate-naltrexone (0.30, 0.13 to 0.67; 17%). Acamprosate was the only intervention associated with moderate confidence in the evidence of effectiveness and acceptability up to 12 months. It is uncertain whether other interventions can help maintain abstinence and reduce dropouts because of low confidence in the evidence.Conclusions Evidence is lacking for benefit from interventions that could be implemented in primary care settings for alcohol abstinence, other than for acamprosate. More evidence from high quality randomised controlled trials is needed, as are strategies using combined interventions (combinations of drug interventions or drug and psychosocial interventions) to improve treatment of alcohol dependency in primary care.",

author = "Hung-yuan Cheng and Mcguinness, {Luke A} and Elbers, {Roy G} and Macarthur, {Georgina J} and Abigail Taylor and Alexandra Mcaleenan and Sarah Dawson and L{\'o}pez-l{\'o}pez, {Jos{\'e} A} and Higgins, {Julian P T} and Sean Cowlishaw and Anne Lingford-hughes and Matthew Hickman and David Kessler",

note = "Funding Information: 4National Institute for Health Research Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and University of Bristol, Bristol, UK 5Department of Psychiatry, University of Melbourne, Melbourne, Victoria, Australia 6Faculty of Medicine, Department of Brain Sciences, Imperial College London, London, UK 7National Institute for Health Research School for Primary Care Research, University of Bristol, Bristol, UK We thank the study authors who provided data and extra information for this review, including the Project MATCH executive committee for providing the Project MATCH public dataset for the secondary analysis. The authors acknowledge that the reported results are, in whole or in part, based on analyses of the Project MATCH Public Data Set. These data were collected as part of a multisite clinical trial of alcoholism treatments supported by a series of grants from the National Institute on Alcohol Abuse and Alcoholism and made available to the authors by the Project MATCH Research Group. This article has not been reviewed or endorsed by the Project MATCH Research Group and does not necessarily represent the opinions of its members, who are not responsible for the contents. Funding Information: Funding: This review was funded primarily by the School for Primary Care Research, National Institute for Health Research (NIHR SPCR; ref 286). JPTH and MH are NIHR senior investigators. JPTH, MH, and DK are supported by NIHR Bristol Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol. JPTH is supported by the NIHR Applied Research Collaboration West (ARC West) at University Hospitals Bristol and Weston NHS Foundation Trust. JPTH and MH are supported by the NIHR Health Research Health Protection Research Unit (HPRU) HPRU in Evaluation of Interventions at University of Bristol. LAM is supported by a NIHR doctoral research fellowship (DRF-2018-11-ST2-048). GJM was supported by an NIHR postdoctoral fellowship award (PDF-2013-06-026). This report is independent research supported by the NIHR (postdoctoral fellowship, PDF-2013-06-026). The views expressed in this article are those of the authors and do not necessarily represent those of the UK National Health Service or NIHR. The conduct of the review, writing of the paper, and decision to submit for publication were independent of all research funders. The funders had no role in considering the study design or in the collection, analysis, and interpretation of data, writing of the report, or decision to submit the article for publication. Competing interests: All authors have completed the ICMJE uniform disclosure from at www.icmje.org/coi_disclosure.pdf and declare: support from the School for Primary Care Research, National Institute for Health Research for the submitted work; HC, AM, JPTH, and LAM report grants from the National Institute for Health Research (NIHR) School for Primary Care Research during the conduct of the study, LAM reports grants from NIHR doctoral research fellowship during the conduct of the study, ALH reports grants from GSK and Lundbeck and personal fees from Silence Therapeutics during the conduct of the study, JLL reports grants from Economic and Social Research Council outside the submitted work, MH reports personal fess and others from MSD, Gilead, and Abbvie outside the submitted work, ALH reports personal fees from Janssen-Cilag, Pfizer, Sanofi-Aventis, Lundbeck, and others from Opiant and Lightlak (unpaid consultancy) outside the submitted work; ALH led the British Association for Psychopharmacology{\textquoteright}s guidelines: Evidence based guidelines for the pharmacological management of substance misuse, addiction, and co-morbidity: recommendations from the British Association for Psychopharmacology. J Psychopharmacol 18(3):293-335; and updated in 2012: Evidence-based guidelines for the pharmacological management of substance misuse, addiction and comorbidity: recommendations from BAP. J Psychopharmacol 26(7):899-952. The original guidelines received support from Archimedes Pharma, Lundbeck, Pfizer, Schering. ALH was a member of the National Institute for Health and Care Excellence clinical guideline group: Alcohol-use disorders: diagnosis, assessment and management of harmful drinking and alcohol dependence. A NICE Clinical guideline (CG115) 2011. Publisher Copyright: {\textcopyright} Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.",

year = "2020",

month = nov,

day = "25",

doi = "10.1136/bmj.m3934",

language = "English",

volume = "371",

journal = "BMJ",

issn = "0959-8138",

publisher = "BMJ Publishing Group",

}

Cheng, H, Mcguinness, LA, Elbers, RG, Macarthur, GJ, Taylor, A, Mcaleenan, A, Dawson, S , López-lópez, JA , Higgins, JPT, Cowlishaw, S, Lingford-hughes, A, Hickman, M & Kessler, D 2020, 'Treatment interventions to maintain abstinence from alcohol in primary care: Systematic review and network meta-analysis', BMJ, vol. 371, m3934. https://doi.org/10.1136/bmj.m3934, https://doi.org/10.1136/bmj.m3934

TY - JOUR

T1 - Treatment interventions to maintain abstinence from alcohol in primary care

T2 - Systematic review and network meta-analysis

AU - Cheng, Hung-yuan

AU - Mcguinness, Luke A

AU - Elbers, Roy G

AU - Macarthur, Georgina J

AU - Taylor, Abigail

AU - Mcaleenan, Alexandra

AU - Dawson, Sarah

AU - López-lópez, José A

AU - Higgins, Julian P T

AU - Cowlishaw, Sean

AU - Lingford-hughes, Anne

AU - Hickman, Matthew

AU - Kessler, David

N1 - Funding Information: 4National Institute for Health Research Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and University of Bristol, Bristol, UK 5Department of Psychiatry, University of Melbourne, Melbourne, Victoria, Australia 6Faculty of Medicine, Department of Brain Sciences, Imperial College London, London, UK 7National Institute for Health Research School for Primary Care Research, University of Bristol, Bristol, UK We thank the study authors who provided data and extra information for this review, including the Project MATCH executive committee for providing the Project MATCH public dataset for the secondary analysis. The authors acknowledge that the reported results are, in whole or in part, based on analyses of the Project MATCH Public Data Set. These data were collected as part of a multisite clinical trial of alcoholism treatments supported by a series of grants from the National Institute on Alcohol Abuse and Alcoholism and made available to the authors by the Project MATCH Research Group. This article has not been reviewed or endorsed by the Project MATCH Research Group and does not necessarily represent the opinions of its members, who are not responsible for the contents. Funding Information: Funding: This review was funded primarily by the School for Primary Care Research, National Institute for Health Research (NIHR SPCR; ref 286). JPTH and MH are NIHR senior investigators. JPTH, MH, and DK are supported by NIHR Bristol Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol. JPTH is supported by the NIHR Applied Research Collaboration West (ARC West) at University Hospitals Bristol and Weston NHS Foundation Trust. JPTH and MH are supported by the NIHR Health Research Health Protection Research Unit (HPRU) HPRU in Evaluation of Interventions at University of Bristol. LAM is supported by a NIHR doctoral research fellowship (DRF-2018-11-ST2-048). GJM was supported by an NIHR postdoctoral fellowship award (PDF-2013-06-026). This report is independent research supported by the NIHR (postdoctoral fellowship, PDF-2013-06-026). The views expressed in this article are those of the authors and do not necessarily represent those of the UK National Health Service or NIHR. The conduct of the review, writing of the paper, and decision to submit for publication were independent of all research funders. The funders had no role in considering the study design or in the collection, analysis, and interpretation of data, writing of the report, or decision to submit the article for publication. Competing interests: All authors have completed the ICMJE uniform disclosure from at www.icmje.org/coi_disclosure.pdf and declare: support from the School for Primary Care Research, National Institute for Health Research for the submitted work; HC, AM, JPTH, and LAM report grants from the National Institute for Health Research (NIHR) School for Primary Care Research during the conduct of the study, LAM reports grants from NIHR doctoral research fellowship during the conduct of the study, ALH reports grants from GSK and Lundbeck and personal fees from Silence Therapeutics during the conduct of the study, JLL reports grants from Economic and Social Research Council outside the submitted work, MH reports personal fess and others from MSD, Gilead, and Abbvie outside the submitted work, ALH reports personal fees from Janssen-Cilag, Pfizer, Sanofi-Aventis, Lundbeck, and others from Opiant and Lightlak (unpaid consultancy) outside the submitted work; ALH led the British Association for Psychopharmacology’s guidelines: Evidence based guidelines for the pharmacological management of substance misuse, addiction, and co-morbidity: recommendations from the British Association for Psychopharmacology. J Psychopharmacol 18(3):293-335; and updated in 2012: Evidence-based guidelines for the pharmacological management of substance misuse, addiction and comorbidity: recommendations from BAP. J Psychopharmacol 26(7):899-952. The original guidelines received support from Archimedes Pharma, Lundbeck, Pfizer, Schering. ALH was a member of the National Institute for Health and Care Excellence clinical guideline group: Alcohol-use disorders: diagnosis, assessment and management of harmful drinking and alcohol dependence. A NICE Clinical guideline (CG115) 2011. Publisher Copyright: © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.

PY - 2020/11/25

Y1 - 2020/11/25

N2 - Objective To determine the most effective interventions in recently detoxified, alcohol dependent patients for implementation in primary care.Design Systematic review and network meta-analysis.Data sources Medline, Embase, PsycINFO, Cochrane CENTRAL, ClinicalTrials.gov, and the World Health Organization’s International Clinical Trials Registry Platform.Study selection Randomised controlled trials comparing two or more interventions that could be used in primary care. The population was patients with alcohol dependency diagnosed by standardised clinical tools and who became detoxified within four weeks.Data extraction Outcomes of interest were continuous abstinence from alcohol (effectiveness) and all cause dropouts (as a proxy for acceptability) at least 12 weeks after start of intervention.Results 64 trials (43 interventions) were included. The median probability of abstinence across placebo arms was 25%. Compared with placebo, the only intervention associated with increased probability of abstinence and moderate certainty evidence was acamprosate (odds ratio 1.86, 95% confidence interval 1.49 to 2.33, corresponding to an absolute probability of 38%). Of the 62 included trials that reported all cause dropouts, interventions associated with a reduced number of dropouts compared with placebo (probability 50%) and moderate certainty of evidence were acamprosate (0.73, 0.62 to 0.86; 42%), naltrexone (0.70, 0.50 to 0.98; 41%), and acamprosate-naltrexone (0.30, 0.13 to 0.67; 17%). Acamprosate was the only intervention associated with moderate confidence in the evidence of effectiveness and acceptability up to 12 months. It is uncertain whether other interventions can help maintain abstinence and reduce dropouts because of low confidence in the evidence.Conclusions Evidence is lacking for benefit from interventions that could be implemented in primary care settings for alcohol abstinence, other than for acamprosate. More evidence from high quality randomised controlled trials is needed, as are strategies using combined interventions (combinations of drug interventions or drug and psychosocial interventions) to improve treatment of alcohol dependency in primary care.

AB - Objective To determine the most effective interventions in recently detoxified, alcohol dependent patients for implementation in primary care.Design Systematic review and network meta-analysis.Data sources Medline, Embase, PsycINFO, Cochrane CENTRAL, ClinicalTrials.gov, and the World Health Organization’s International Clinical Trials Registry Platform.Study selection Randomised controlled trials comparing two or more interventions that could be used in primary care. The population was patients with alcohol dependency diagnosed by standardised clinical tools and who became detoxified within four weeks.Data extraction Outcomes of interest were continuous abstinence from alcohol (effectiveness) and all cause dropouts (as a proxy for acceptability) at least 12 weeks after start of intervention.Results 64 trials (43 interventions) were included. The median probability of abstinence across placebo arms was 25%. Compared with placebo, the only intervention associated with increased probability of abstinence and moderate certainty evidence was acamprosate (odds ratio 1.86, 95% confidence interval 1.49 to 2.33, corresponding to an absolute probability of 38%). Of the 62 included trials that reported all cause dropouts, interventions associated with a reduced number of dropouts compared with placebo (probability 50%) and moderate certainty of evidence were acamprosate (0.73, 0.62 to 0.86; 42%), naltrexone (0.70, 0.50 to 0.98; 41%), and acamprosate-naltrexone (0.30, 0.13 to 0.67; 17%). Acamprosate was the only intervention associated with moderate confidence in the evidence of effectiveness and acceptability up to 12 months. It is uncertain whether other interventions can help maintain abstinence and reduce dropouts because of low confidence in the evidence.Conclusions Evidence is lacking for benefit from interventions that could be implemented in primary care settings for alcohol abstinence, other than for acamprosate. More evidence from high quality randomised controlled trials is needed, as are strategies using combined interventions (combinations of drug interventions or drug and psychosocial interventions) to improve treatment of alcohol dependency in primary care.

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U2 - 10.1136/bmj.m3934

DO - 10.1136/bmj.m3934

M3 - Article (Academic Journal)

C2 - 33239318

VL - 371

JO - BMJ

JF - BMJ

SN - 0959-8138

M1 - m3934

ER -

Treatment interventions to maintain abstinence from alcohol in primary care: Systematic review and network meta-analysis

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Treatment interventions to maintain abstinence from alcohol in primary care: Systematic review and network meta-analysis

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