A randomized, double-blind, placebo-controlled trial of long-acting risperidone in cocaine-dependent men

Objective: There is no approved pharmacotherapy for cocaine dependence. Risperidone is an atypical antipsychotic drug with combined dopamine-2/serotonin-2 (D-2/5-HT2) antagonist activity that has been effective in reducing cocaine use in some animal studies. We tested the efficacy of a long-acting, injectable preparation of risperidone on cocaine use in active cocaine users. Method: Thirty-one cocaine-dependent men who met DSM-IV diagnostic criteria for current cocaine dependence entered a 12-week, randomized. double-blind, placebo-controlled trial of intramuscular risperidone, 25 mg every other week. The primary outcome measure was cocaine use as measured by urinary concentration of cocaine metabolites. Secondary outcomes were self-report of cocaine use and craving, depressive symptoms as measured by the Hamilton Rating Scale for Depression (HAM-D), and adverse events. Participants were recruited during a 12-month period from October 2005 to September 2006. Results: Both groups reduced their cocaine use during the study. There were no between-group differences in the primary measure of cocaine use (urinary metabolites [F = 0.7, p = .41]) or on craving measures. Those assigned to risperidone reported significantly worsened depressive symptoms (mean SD HAM-D change scores: +7.4 +/- 8.8 vs. -2.3 +/- 5.8, respectively, F = 7.5, p = .018) and gained significantly more weight (mean weight change: +6.3 +/- 9.4 lb vs. -4.0 +/- 8.9 lb, respectively, F = 4.65, p = .044) than those assigned to placebo. Conclusion: Treatment with long-acting injectable risperidone in active cocaine users was not associated with reduction in cocaine use or craving and was associated with worsening of depressive symptoms and weight gain. Trial Registration: clinicaltrials.gov Identifier: NCT00385801.