This proposal incorporates two studies to assess combined behavioral and pharmacological treatments of alcohol dependence. The preliminary study is designed to examine the effect of acamprosate in combination with a brief intervention (motivational enhancement therapy [MET]) on craving, cue-induced reactivity, and the subjective effects of alcohol following the initiation of drinking behavior compared to placebo-controls receiving only MET. Laboratory-based studies in the US have provided us with evidence that naltrexone decreases cue-induced reactivity and craving, and possibly the rewarding value of alcohol, but similar mechanisms of action for acamprosate have not been explored. The purpose of the preliminary study is to determine whether changes in craving and psychophysiological reactivity mediate the effects of acamprosate on drinking. To this end, subjects will be assigned to the acamprosate or placebo group for 12 weeks. Measures from a laboratory based cue reactivity protocol will be evaluated before and after the medication trial. The second phase of the preliminary study will provide all nonresponders with alternative medications to determine the effects of sequencing interventions. After 12 weeks of treatment, nonresponders to acamprosate or placebo will receive either acamprosate plus placebo, acamprosate plus naltrexone, naltrexone plus placebo, or placebo. This phase will allow us to assess whether a combination of medications offers more benefits than either medication alone in sustaining abstinence and whether sequential treatment for nonresponders is helpful in reducing relapse rates. The primary study (11) is designed to examine the relative effectiveness of two behavioral treatments that vary in intensity (MET and cognitive-behavioral treatment [CBT]) combined with one of the following combinations of medications (acamprosate plus placebo, naltrexone plus placebo, acamprosate plus naltrexone, or placebo plus placebo). Subjects will be recruited for a six month treatment trial followed by a 12 month follow-up period that will provide us with the opportunity to evaluate whether behavioral treatments varying in intensity also vary in their effectiveness in treating alcohol dependence. This study will also permit us to examine whether the combination of two medications known to be effective in reducing drinking has benefits over using each medication alone, and whether there are individual patient characteristics that predict treatment outcome. Finally, the proposed primary study will permit an evaluation of the interaction of the two levels of psychological treatment with the varying combination of medications provided. This will be the first study that provides long-term outcome data on the combination of naltrexone with behavior therapy, the combination of more than one medication with behavior therapy, and the combination of a brief intervention with medication in the treatment of alcohol dependence.
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