Naltrexone depot for treatment of alcohol dependence: A multicenter, randomized, placebo-controlled clinical trial

Background: Studies of the efficacy of naltrexone for alcohol dependence have yielded variable findings, which may be due, in part, to variation in compliance with oral naltrexone. Efforts to improve naltrexone compliance have included the development of injectable, long-acting depot formulations. Methods: We conducted a multicenter trial in 315 subjects who were randomly assigned to receive an intramuscular injection of a depot formulation containing naltrexone (n = 158) or a placebo formulation (n = 157) monthly for 3 months. All patients received five sessions of manual-guided motivational enhancement therapy during the 12 weeks of the study. The outcomes of interest were based on self-reported alcohol use and gamma-glutamyl transpeptidase level. Missing data or data from subjects who discontinued the study were conservatively treated as heavy-drinking days. Results: Groups were comparable on pretreatment demographic and clinical measures. The medication was well tolerated; 73.7% of subjects received all injections. The time to the first heavy-drinking day, the percentage of subjects with no heavy drinking throughout the study, and gamma-glutamyl transpeptidase levels favored the naltrexone depot, although the effects did not reach statistical significance. There was a significant advantage for naltrexone depot treatment on the time to the first drinking day. Naltrexone depot subjects also had significantly fewer drinking days during treatment and a significantly greater abstinence rate than the placebo group (18% vs. 10%). Conclusions: This is the first multicenter study of a depot formulation of naltrexone for the treatment of alcohol dependence. Using a conservative intent-to-treat analysis, the study showed an advantage for the active medication. Further research with this formulation is warranted.