Clinical Interventions for Adults with Comorbid Alcohol Use and Depressive Disorders

A Systematic Review and Network Meta-Analysis

by Sean Grant, Gulrez Shah Azhar, Eugeniu Han, Marika Booth, Aneesa Motala, Jody Larkin, Susanne Hempel

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Research Questions

  1. What are the effects of clinical interventions on remission from depression and alcohol use (primary outcomes), depressive symptoms, number of drinks, number of heavy drinking days, withdrawal and craving symptoms, health-related quality of life, functional status, and adverse events in adults with a co-occurring AUD and depressive disorder?
  2. What are the effects of interventions by type of AUD or depressive disorder?
  3. What are the effects of interventions by type of clinical setting?
  4. What are the effects of interventions by type of intervention?
  5. What are the relative rankings of identified interventions, in order of effectiveness on outcomes of interest?

Alcohol use disorders (AUDs) and depressive disorders are prevalent, and a significant number of people are diagnosed with both. Identifying effective treatments for patients with co-occurring AUDs and depressive disorders is important, given the potential severity of symptoms and the negative societal consequences of ineffective treatment. The purpose of this review is to synthesize evidence on the effects and compare the effectiveness of clinical interventions for improving symptoms of adults with co-occurring AUDs and depressive disorders. The review aims to support clinical decisionmaking regarding which interventions to use with patients dually diagnosed with co-occurring AUD and depressive disorders.

Key Findings

Three classes of intervention have sufficient evidence to warrant their consideration for policy and practice recommendations

  • The available evidence suggests potentially actionable benefits at postintervention of cognitive behavioral therapy for depressive symptoms, tricyclic antidepressants for depressive symptoms, and selective serotonin reuptake inhibitors (SSRIs) for total drinking and functional status.
  • SSRIs also have higher risks of adverse events (including serious adverse events).

The authors had very low confidence in most effect estimates, primarily due to sparse networks with limited data

  • The authors identified significant effects for several other comparisons but have very limited confidence to support their consideration for policy and practice recommendations on the basis of evidence on effectiveness.
  • Most bodies of evidence included only indirect evidence or direct evidence from single studies with small sample sizes.
  • Notably, numerous clinical interventions contained in clinical practice guidelines for either depression or alcohol use disorder are missing from the current body of evidence on patients with both disorders.

More pragmatic, preregistered, and well-reported randomized controlled trials are needed, particularly on clinical interventions recommended for patients with either a depressive or alcohol use disorder


  • Committees charged with providing recommendations for health systems and updating clinical practice guidelines should use this report as a source of evidence on the comparative effectiveness of clinical interventions for adults with co-occurring alcohol use and depressive disorders.
  • Researchers, policymakers, funders, and practitioners should establish priorities for evaluating clinical interventions for patients with either a depressive or alcohol use disorder.

Table of Contents

  • Chapter One


  • Chapter Two


  • Chapter Three


  • Chapter Four


  • Appendix A

    Electronic Search Strategies

  • Appendix B

    Eligible Diagnoses

  • Appendix C

    Studies Ongoing or Waiting Assessment

  • Appendix D

    Included Studies

  • Appendix E

    Network Geometry

  • Appendix F

    Sensitivity Analyses

This research was sponsored by the Psychological Health Center of Excellence (PHCoE) and conducted within the Forces and Resources Policy Center of the RAND National Security Research Division (NSRD).

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