Comment: The quality of evidence is downgraded by study limitations (unclear allocation concealment and blinding in most studies) and by inconsistency (unexplained variability in results).

A Cochrane review ¹ included 24 RCTs with a total of 6915 participants. Compared to placebo, acamprosate was shown to significantly reduce the risk of any drinking (RR 0.86; 95% CI 0.81 to 0.91; 24 trials, n=6172); NNT 9.09 (95% CI 6.66 to 14.28) and to significantly increase the cumulative abstinence duration (mean difference MD 10.94; 95% CI 5.08 to 16.81; 19 trials, n=5224), while secondary outcomes (gamma-glutamyltransferase, heavy drinking) did not reach statistical significance. Diarrhea was the only side effect that was more frequently reported under acamprosate than placebo RD 0.11 (95% 0.09 to 0.13); NNTB 9.09 (95% CI 7.69 to 11.11). Effects of industry-sponsored trials RR 0.88 (95% 0.80 to 0.97) did not significantly differ from those of non-profit funded trials RR 0.88 (95% CI 0.81 to 0.96). In addition, the linear regression test did not indicate a significant risk of publication bias (p = 0.861).

A systematic review and meta-analysis ² assessed the efficacy of acamprosate or naltrexone in reducing lapse/relapse compared to placebo in the treatment of alcohol dependence and treatment discontinuation. 22 RCTs studied acamprosate (n=5236) and 27 RCTs naltrexone (n=4199). The risk of returning to any drinking at 6 months was significantly lower for acamprosate (RR 0.83, 95% CI 0.78 to 0.89). There was little difference in the risk of participants discontinuing treatment for any reason (RR  0.91, 95% CI 0.83 to 1.00) or due to adverse events (RR 1.30, 95% CI 0.96 to 1.75) for the acamprosate compared to placebo groups. For natrexone, the risk of individuals returning to any drinking at approximately 3 months was reduced significantly (RR 0.92, 95% CI  0.86 to 1.00), as was the risk of individuals relapsing to heavy drinking at 3 months (RR  0.85, 95% CI  0.78 to 0.93). There was no significant difference between naltrexone and placebo for the risk of individuals discontinuing treatment for any reason (RR  0.94, 95% CI  0.84 to 1.05), but. risk discontinuing treatment due to adverse events was higher (RR  1.72, 95% CI  1.10 to 2.70).

A meta-analysis ³ of drugs for alcohol use disorders included 122 RCTs and 1 cohort study (total 22,803 participants). The NNT to prevent return to any drinking for acamprosate was 12 (95% CI 8 to 26; risk difference [RD] -0.09; 95% CI -0.14 to -0.04; 27 studies, n = 7519) and was 20 (95% CI 11 to 500; RD -0.05; 95% CI -0.10 to -0.002; 53 studies, n = 9140) for oral naltrexone (50 mg/d). There was no statistically significant difference between acamprosate and naltrexone for return to any drinking or heavy drinking.

A network meta-analysis ⁴ exploring the comparative effectiveness of drugs used for alcohol dependence included 32 RCTs with a total of 6036 patients. Nalmefene (standardized mean difference [SMD] -0.19, 95% CI -0.29, -0.10) and topiramate (SMD -0.77, 95% CI -1.12, -0.42%) showed superiority over placebo on total alcohol consumption. No efficacy was observed for naltrexone or acamprosate. No treatment demonstrated any harm reduction (no study was powered to explore health outcomes).