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). Nefazodone (RR = 2.11; 95% CI, 1.42–3.13), aripiprazole (RR = 1.97; 95% CI, 1.36–2.88), carbamazepine (RR = 1.85; 95% CI, 1.03–3.32), and nalmefene (RR = 1.17; 95% CI, 1.01–1.35) were associated with the most dropouts. Baclofen (RR = 0.83; 95% CI, 0.70–0.97) and pregabalin (RR = 0.63; 95% CI, 0.43–0.94) caused fewer dropouts than placebo. Nalmefene (RR = 3.26; 95% CI, 2.34–4.55), fluvoxamine (RR = 3.08; 95% CI, 1.59–5.94), and topiramate (RR=2.18; 95% CI, 1.36–3.51) caused more dropouts from adverse events over placebo. Gamma-hydroxy-butyrate (RR = 1.90; 95% CI, 1.03–3.53), baclofen (RR = 1.80; 95% CI, 1.39–2.34), disulfiram (RR = 1.71; 95% CI, 1.39–2.10), gabapentin (RR = 1.66; 95% CI, 1.04–2.67), acamprosate (RR = 1.33; 95% CI, 1.15–1.54), and oral naltrexone (RR = 1.15; 95% CI, 1.01–1.32) improved total abstinence over placebo (Fig. 3C). For reduced heavy drinking, disulfiram (RR = 0.19; 95% CI, 0.10–0.35), baclofen (RR = 0.72; 95% CI, 0.57–0.91), acamprosate (RR = 0.78; 95% CI, 0.70–0.86), and oral naltrexone (RR = 0.81; 95% CI, 0.73–0.90) were efficacious against placebo. 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.