Naltrexone, an opioid antagonist, is currently one of the most promising pharmacotherapies for alcohol dependence. In clinical trials, naltrexone has been shown to be more effective than placebo in reducing alcohol consumption and relapse rates. A number of critical questions remain, however, about the optimal strategies for using naltrexone in the treatment of alcohol dependence. The proposed research is designed to achieve four specific aims: (1) to evaluate whether a more intensive psychotherapeutic strategy provided with naltrexone enhances initial treatment outcomes in contrast to a less intensive intervention that may be used with naltrexone in primary care settings; (2) to evaluate whether long term treatment with naltrexone provides additional benefit in preventing relapse, alcohol-related impairments, and alcohol related psychiatric symptoms among those who respond to short term naltrexone treatment; (3) to explore predictors of response to the psychotherapeutic interventions and to naltrexone, including gender, craving, neuropsychological functioning, and severity of alcohol dependence; and (4) to evaluate the safety of long-term naltrexone treatment in an alcohol dependent sample. In order to address the question of treatment intensity, 192 subjects will be randomized to receive naltrexone and either weekly coping skills therapy or advice and clinical management for 10 weeks. The coping skills therapy is a treatment commonly used in specialty alcoholism treatment clinics and is designed to increase the patient's coping strategies in an effort to reduce the probability of relapse. Advice and clinical management is a less intensive treatment that is consistent with primary care treatment. Following completion of this study, two parallel discontinuation studies will be conducted in which treatment responders in each group are then randomized to receive naltrexone or placebo for six months. One study compares the outcomes of subjects maintained on naltrexone versus those on placebo among those initially treated using the advice and clinical management. The second study compares outcomes for naltrexone and placebo maintained subjects who were initially treated with coping skills therapy. Taken together, these studies should provide critical information about psychotherapeutic strategies to provide in conjunction with naltrexone and the optimal length of naltrexone treatment.
