Pharmacotherapies for Adults With Alcohol Use Disorders: A Systematic Review and Network Meta-analysis.

BACKGROUND: We aimed to determine medications' comparative efficacy and safety for adults with alcohol use disorders. METHODS: We searched eleven electronic data sources for randomized clinical trials with at least 4 weeks of treatment reporting on alcohol consumption (total abstinence and reduced heavy drinking), dropouts, and dropouts due to adverse events. We conducted network meta-analyses using random-effects, frequentist models, and calculated summary rate ratios (RRs) with 95% confidence intervals (CIs). RESULTS: We included 156 trials (N = 27,334). For total abstinence, gamma-hydroxy-butyrate (RR = 1.96; 95% CI, 1.06-3.63), baclofen (RR = 1.93; 95% CI, 1.47-2.52), disulfiram (RR = 1.77; 95% CI, 1.38-2.27), naltrexone extended-release (RR = 1.64; 95% CI, 1.02-2.64), topiramate (RR = 1.41; 95% CI, 1.07-1.87), acamprosate (RR = 1.33; 95% CI, 1.16-1.54), and oral naltrexone (RR = 1.19; 95% CI, 1.04-1.36) improved total abstinence over placebo. For reduced heavy drinking, disulfiram (RR = 0.19; 95% CI, 0.10-0.34), acamprosate (RR = 0.78; 95% CI, 0.71-0.85), and oral naltrexone (RR = 0.81; 95% CI, 0.73-0.89) were efficacious against placebo. Among medications used off-label, moderate evidence supports baclofen for reducing heavy drinking (RR = 0.57; 95% CI, 0.44-0.73) and improving abstinence (RR = 1.93; 95% CI, 1.47-2.52). Disulfiram (RR = 2.45; 95% CI, 1.02-5.88) and oral naltrexone (RR = 1.47; 95% CI, 1.01-2.14) caused more dropouts from adverse events over placebo, whereas risk was not significantly increased for acamprosate. CONCLUSIONS: The current meta-analyses provide evidence that several medications for AUDs are effective and safe and encourage the expanded use of these medications in the clinical setting. Our review found that acamprosate (2-3 g/d), disulfiram (250-500 mg/d), baclofen (30 mg/d), and oral naltrexone (50 mg/d) had the best evidence for improving abstinence and heavy drinking for patients with AUD. PROSPERO: CRD42020208946.