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Results of oral therapy for alcohol dependence have been inconsistent, in part because of poor medication adherence. A newly approved, extended-release intramuscular formulation of naltrexone (XR-NTX) may have advantages over oral formulations in terms of adherence. One randomized, double-blind, placebo-controlled trial demonstrated that treatment with XR-NTX significantly decreased the number of heavy-drinking days compared with placebo treatment among patients who had a current DSM-IV diagnosis of alcohol dependence. Another trial, of a different investigational longacting intramuscular formulation of naltrexone (poly [DL-] lactide polymer; DL-NTX), found that time to first drinking day was significantly greater among alcohol-dependent (DSM-IV) subjects using DL-NTX than among those using placebo. Time to first drinking day and cumulative abstinent days were significantly greater among alcohol dependent (DSM-IV) subjects using DL-NTX than among those using placebo. However, the primary outcome measure, cumulative non-heavy drinking days, was not significantly different between the DL-NTX and the placebo groups. Treatment with long-acting intramuscular formulations of naltrexone is generally well tolerated. Nausea, headache, injection-site reactions, and fatigue are the most common adverse events.