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

Background: Nalmefene is a newer opioid antagonist that is structurally sim ilar to naltrexone but with a number of potential pharmacological advantage s for the treatment of alcohol dependence, including no dose-dependent asso ciation with toxic effects to the liver, greater oral bioavailability, long er duration of antagonist action, and more competitive binding with opioid receptor subtypes that are thought to reinforce drinking. Methods: A double-blind, placebo-controlled trial was conducted to evaluate the safety and efficacy of 2 doses of oral nalmefene for alcohol dependenc e. 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 group s for 12 weeks. Cognitive behavioral therapy was provided weekly during tre atment. Self-reported drinking or abstinence was confirmed by determination s of breath alcohol concentration and by collateral informant reports. Results: Outcomes did not differ between the 20- and 80-mg dose nalmefene g roups. Significantly fewer patients treated with nalmefene than patients gi ven 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 wi th placebo compared with nalmefene (95% confidence interval, 1.05-5.59). Pa tients treated with nalmefene also had fewer subsequent relapses (P<.03) th an patients given placebo. Conclusions: Treatment with nalmefene was effective in preventing relapse t o heavy drinking relative to placebo in alcohol-dependent outpatients and w as accompanied by acceptable side effects.