Acamprosate for alcohol dependence
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).
1. Rösner S, Hackl-Herrwerth A, Leucht S et al. Acamprosate for alcohol dependence. Cochrane Database Syst Rev 2010;(9):CD004332. [PMID:20824837]
2. Donoghue K, Elzerbi C, Saunders R et al. The efficacy of acamprosate and naltrexone in the treatment of alcohol dependence, Europe versus the rest of the world: a meta-analysis. Addiction 2015;110(6):920-30. [PMID:25664494]
3. Jonas DE, Amick HR, Feltner C et al. Pharmacotherapy for adults with alcohol use disorders in outpatient settings: a systematic review and meta-analysis. JAMA 2014;311(18):1889-900. [PMID:24825644]
4. Palpacuer C, Duprez R, Huneau A et al. Pharmacologically controlled drinking in the treatment of alcohol dependence or alcohol use disorders: a systematic review with direct and network meta-analyses on nalmefene, naltrexone, acamprosate, baclofen and topiramate. Addiction 2018;113(2):220-237. [PMID:28940866]
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