Nalmefene for Alcohol Dependence

Summary

A systematic review and meta-analysis1 included 5 double-blind randomized clinical trials (n=2567) evaluating nalmefene to treat adult alcohol dependence. None of these studies was performed in adults with alcohol dependence who consume more than 60 g of alcohol per day (for men) or more than 40 g per day (for women). Subjects were instructed to take nalmefene or placebo when they believed drinking to be imminent. No RCT compared nalmefene with another medication. Mortality at 6 months (RR 0.39, 95% CI 0.08 to 2.01; 4 trials, n=1892) and 1 year (RR 0.98, 95% CI 0.04 to 23.95) and quality of life at 6 mo (SF-36 physical component summary score: mean difference (MD) 0.85, 95% CI -0.32 to 2.01; SF-36 mental component summary score: MD 1.01, 95% CI -1.33 to 3.34; 3 trials, n=1200) were not different across groups. Differences were encountered for alcohol consumption outcomes such as monthly number of heavy drinking days at 6 mo (MD -1.65, 95% CI -2.41 to -0.89; 5 trials) and at 1 y (MD -1.60, 95% CI -2.85 to -0.35; 1 trial) and total alcohol consumption at 6 mo (SMD -0.20, 95% CI -0.30 to -0.10; 5 trials). There were more withdrawals for nalmefene than for placebo, including more withdrawals for safety reasons at both 6 mo (RR 3.65, 95% CI 2.02 to 6.63; 4 trials) and 1 y (RR 7.01, 95% CI 1.72 to 28.63; 1 trial).

Another network meta-analysis 2 included 32 RCTs with a total of 6036 patients. Nalmefene (standardized mean difference [SMD] -0.19, 95% CI -0.29 to -0.10] and topiramate (SMD -0.77, 95% CI -1.12 to -0.42) showed superiority over placebo on total alcohol consumption. No efficacy was observed for naltrexone or acamprosate. The number of withdrawals for safety reasons increased under nalmefene and naltrexone. No treatment demonstrated any harm reduction (no study was powered to explore health outcomes). Indirect comparisons suggested that topiramate was superior to nalmefene, naltrexone and acamprosate on consumption outcomes, but its safety profile is known to be poor.

A third meta-analysis 3 included 122 RCTs and 1 cohort study (total 22 803 participants). The NNT to prevent return to any drinking for acamprosate was 12 and was 20 for oral naltrexone (50 mg/d). Moderate evidence supports an association with improvement in some consumption outcomes for nalmefene (heavy drinking days per month: WMD, -2.0; 95% CI -3.0 to -1.0; drinks per drinking day: WMD, -1.02; 95% CI -1.77 to -0.28) and topiramate (% heavy drinking days: WMD, -9.0%; 95% CI -15.3% to -2.7%; drinks per drinking day: WMD, -1.0; 95% CI, -1.6 to -0.48). For naltrexone and nalmefene, NNHs for withdrawal from trials due to adverse events were 48 (95% CI 30 to 112) and 12 (95% CI 7 to 50), respectively.

A meta-analysis 4 assessing harms of nalmefene included 15 RCTs. Serious adverse events did not occur more often in the nalmefene group than in the placebo group (Peto Odds Ratio 0.97, 95% CI 0.64 to 1.44; P = 0.86). Withdrawals due to adverse events were significantly more likely to occur with nalmefene compared to placebo (Peto Odds Ratio 3.22, 95% CI 2.46 to 4.22; P<0.001).