Effectiveness of Alcohol Use Disorder Pharmacotherapies by Sex: Systematic Review and Meta-Analysis

Allen, J ORCID: 0009-0003-1041-9083, Jones, A ORCID: 0000-0001-5951-889X, Shorter, GW, Montgomery, C ORCID: 0000-0003-2805-5807, Kougiali, Z ORCID: 0000-0001-8840-5579, Bagnall, A, Adshead, C, Smith, J, Burton, S ORCID: 0000-0003-3823-3275, Atkinson, AM ORCID: 0000-0002-9936-6138, Guelen, L and Rose, A ORCID: 0000-0003-3267-7318 (2026) Effectiveness of Alcohol Use Disorder Pharmacotherapies by Sex: Systematic Review and Meta-Analysis. Drug and Alcohol Review, 45 (5). ISSN 0959-5236

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Abstract

Issues: Alcohol use disorder (AUD) shows sex-related differences in prevalence, harm and treatment response. Despite growing interest in sex differences, evidence synthesis evaluating pharmacotherapy effectiveness by sex remains limited. Approach: Web of Science, PubMed, Scopus, PsycINFO and Cochrane were searched twice. Eligible records included RCTs or non-randomised studies of adults with AUD receiving pharmacological interventions (licensed or off-label), and reporting or providing outcomes (binary relapse or continuous alcohol consumption change) by sex. Multi-level random-effects models calculated risk ratios (RR) and standardised mean differences (SMD), with sex as a moderator. Key Findings: Twenty-eight studies (25,041 participants, 25% female) were included. No outcomes were rated low risk of bias; non-RCTs were moderate-to-high quality. Overall treatment effects vs. control were small for abstinence (RR = 0.96, 95% CI [0.52, 1.74]; 4 studies; I² = 95%) and modest for consumption reduction (SMD = 0.23, 95% CI [0.01, 0.45]; 13 studies; I² = 89%); sex did not meaningfully moderate these outcomes (ratio of RR = 1.04, 95% CI [0.87, 1.25]; ΔSMD = 0.05, 95% CI [−0.09, 0.18]). Power was low (median 13.7%), requiring ~6358 participants per group to detect the observed sex difference. Narrative synthesis suggested possible sex differences for naltrexone and baclofen, while highlighting the influence of drug (e.g., tolerability), participant (e.g., drinking motives) and design factors (e.g., recruitment setting) on treatment response. Implications: AUD pharmacotherapies provide modest benefits, with sex differences remaining unclear. Future trials should be adequately powered, report sex-specific outcomes and consider adherence, tolerability and psychosocial moderators. Conclusion: Evidence for sex-specific efficacy remains inconclusive. Patterns for naltrexone and baclofen warrant exploration in large, rigorously designed, sex-stratified trials.

Item Type:	Article
Uncontrolled Keywords:	alcohol-related disorders; meta-analysis; pharmacotherapy; sex characteristics; treatment outcome; Humans; Alcoholism; Naltrexone; Alcohol Deterrents; Treatment Outcome; Sex Factors; Sex Characteristics; Female; Male; alcohol‐related disorders; meta‐analysis; pharmacotherapy; sex characteristics; treatment outcome; Humans; Male; Alcoholism; Alcohol Deterrents; Female; Treatment Outcome; Sex Factors; Naltrexone; Sex Characteristics; 5202 Biological Psychology; 52 Psychology; Comparative Effectiveness Research; Behavioral and Social Science; Women's Health; Clinical Research; Substance Misuse; Clinical Trials and Supportive Activities; Alcoholism, Alcohol Use and Health; Brain Disorders; 6.1 Pharmaceuticals; Mental health; 3 Good Health and Well Being; Humans; Male; Alcoholism; Alcohol Deterrents; Female; Treatment Outcome; Sex Factors; Naltrexone; Sex Characteristics; 11 Medical and Health Sciences; 16 Studies in Human Society; 17 Psychology and Cognitive Sciences; Substance Abuse; 42 Health sciences; 44 Human society; 52 Psychology
Subjects:	B Philosophy. Psychology. Religion > BF Psychology R Medicine > RT Nursing
Divisions:	Nursing and Advanced Practice Psychology (from Sep 2019)
Publisher:	Wiley
Date of acceptance:	9 June 2026
Date of first compliant Open Access:	5 August 2026
Date Deposited:	05 Aug 2026 15:04
Last Modified:	05 Aug 2026 15:04
DOI or ID number:	10.1111/dar.70196
URI:	https://researchonline.ljmu.ac.uk/id/eprint/29109

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