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Evidence summaries

Nalmefene for Alcohol Dependence

Nalmefene appears to be effective in reducing alcohol consumption taken before alcohol drinking for alcohol dependence compared with placebo. Level of evidence: "B"

Comment: The quality of evidence is downgraded by study limitations.

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).

Clinical comments

Note

Date of latest search: 2020-11-23

    References

    • Palpacuer C, Laviolle B, Boussageon R et al. Risks and Benefits of Nalmefene in the Treatment of Adult Alcohol Dependence: A Systematic Literature Review and Meta-Analysis of Published and Unpublished Double-Blind Randomized Controlled Trials. PLoS Med 2015;12(12):e1001924. [PubMed]
    • 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.[PubMed]
    • 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. [PubMed]
    • Johansen KGV, Tarp S, Astrup A et al. Harms associated with taking nalmefene for substance use and impulse control disorders: A systematic review and meta-analysis of randomised controlled trials. PLoS One 2017;12(8):e0183821. [PubMed]

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