A double-blind, placebo-controlled study of oral nalmefene for alcohol dependence

Nalmefene is a newer opioid antagonist that is structurally similar to naltrexone but with a number of potential pharmacological advantages for the treatment of alcohol dependence, including no dose-dependent association with toxic effects to the liver, greater oral bioavailability, longer duration of antagonist action, and more competitive binding with opioid receptor subtypes that are thought to reinforce drinking.

A double-blind, placebo-controlled trial was conducted to evaluate the safety and efficacy of 2 doses of oral nalmefene for alcohol dependence. The 105 outpatient volunteers were abstinent for a mean of 2 weeks prior to random assignment to the placebo or 20- or 80-mg/d dose nalmefene groups for 12 weeks. Cognitive behavioral therapy was provided weekly during treatment. Self-reported drinking or abstinence was confirmed by determinations of breath alcohol concentration and by collateral informant reports.

Outcomes did not differ between the 20- and 80-mg dose nalmefene groups. Significantly fewer patients treated with nalmefene than patients given placebo relapsed to heavy drinking through 12 weeks of treatment (P<.02), with a significant treatment effect at the first weekly study visit (P<.02). The odds ratio of relapsing to heavy drinking was 2.4 times greater with placebo compared with nalmefene (95% confidence interval, 1.05-5.59). Patients treated with nalmefene also had fewer subsequent relapses (P<.03) than patients given placebo.

Treatment with nalmefene was effective in preventing relapse to heavy drinking relative to placebo in alcohol-dependent outpatients and was accompanied by acceptable side effects.