Disulfiram

The use of disulfiram in the treatment of cocaine dependence was first introduced in patients who also were abusing alcohol. Disulfiram was thought to reduce a patient's exposure to alcohol, which could have a positive effect on cocaine exposure. Recent studies examining other medication options for treating cocaine dependency found that disulfiram was an effective treatment even in patients who were not abusing alcohol. This study and others suggest that disulfiram may change the subjective and physiologic response to cocaine, but this treatment has not been studied in the general population of patients dependent on cocaine. Carroll and colleagues evaluated the effectiveness of disulfiram therapy in cocaine-dependent patients. In addition, they evaluated the effectiveness of cognitive-behavior therapy and interpersonal psychotherapy in reducing cocaine use.

The trial was a randomized, placebo-controlled, double-masked study of four treatment strategies. These strategies were disulfiram plus cognitive-behavior therapy, disulfiram plus interpersonal psychotherapy, placebo plus cognitive-behavior therapy, and placebo plus interpersonal psychotherapy. The participants attended a community-based outpatient sub-stance abuse program and met the established criteria for current cocaine dependence. Participants received active medication, disulfiram in a dosage of 250 mg per day, or identical placebo capsules. Participants were advised to avoid alcohol during the study. Follow-up for medication compliance occurred weekly, and adverse events were recorded during this time.Cognitive-behavior therapy and inter-personal psychotherapy were based on an established 12-week program modified for cocaine users. The primary outcome measure was self-reported frequency of cocaine use and urine toxicology results.

There were 121 participants in the study. Medication compliance was 76 percent by self-reporting and 72 percent by laboratory analysis. Participants who received disulfiram were significantly less likely to have a relapse than those taking the placebo. Those in the cognitive-behavior therapy sessions were significantly less likely to have a relapse than participants in the interpersonal psychotherapy sessions. There was no significant difference when the interaction of medication and psychotherapy were compared. Participants who were not alcohol-dependent at the beginning of the study or who abstained from alcohol during the study had a greater benefit from disulfiram and cognitive-behavior therapy. The adverse events in the disulfiram group were not significantly different than those in the placebo group. Those who drank alcohol or used cocaine also reported no more adverse events in the disulfiram group than in the placebo group.

The authors conclude that disulfiram and cognitive-behavior therapy are effective treatment options for patients who are cocaine dependent. They add that disulfiram appears to have a direct effect on cocaine use independent of the patient's alcohol use.

Carroll KM, et al. Efficacy of disulfiram and cognitive behavior therapy in cocaine-dependent outpatients. A randomized placebo-controlled trial. Arch Gen Psychiatry March 2004;61:264-72.

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