Baclofen for alcohol use disorder-a systematic meta-analysis.

Objective: To evaluate the efficacy and tolerability of baclofen vs. placebo for long-term treatment of alcohol use disorder.

Method: Systematic review and meta-analysis following methods of the Cochrane Collaboration Handbook (PROSPERO registration: CRD42017073663). Primary outcome was the random-effects summary estimate of all standardized mean differences (SMDs), as calculated from the primary outcomes of each study.

Results: Fourteen double-blind RCTs (1522 patients) were included. Heterogeneity was substantial for most analyses (I about 75%). Baclofen showed a small, but not statistically significant superiority over placebo: SMD = 0.22 ([95% CI: -0.03; 0.47], P = 0.09). This result was supported by a leave-one-out-analysis, and Orwin's fail-safe N, by predefined secondary analyses (on abstinence rates and amount of drinking), and by a post hoc-analysis of high-dose studies (>80 mg/day). An analysis of low risk of bias studies (SMD = 0.10 [-0.20; 0.41], P = 0.51, I  = 43.3%) found no effect. Exclusion of four studies focusing on patients with comorbidity yielded a small positive effect. Drop-out rates were similar.

Conclusion: Our results question baclofen's utility in the long-term treatment of alcohol use disorder at both normal and high doses. While the confidence intervals indicate that marginally harmful or moderately beneficial effects of baclofen remain a possibility, the most likely effect size is slightly above placebo effects.