2026/06/23 by Juliette Allen, Andrew Jones, Gillian W. Shorter +9 · 1 voice
Medicine · #Alcoholism and Thiamine Deficiency #Opioid Use Disorder Treatment #Substance Abuse Treatment and Outcomes
paper · doi:10.1111/dar.70196
openalex publication_date 2026/06/23 · openalex created_date 2026/06/24 · openalex updated_date 2026/07/29
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; I 2 = 95%) and modest for consumption reduction (SMD = 0.23, 95% CI [0.01, 0.45]; 13 studies; I 2 = 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.