A randomized clinical trial of disulfiram at higher doses for the treatment of cocaine use disorder among methadone-stabilized patients.

PURPOSE/BACKGROUND: Previously, disulfiram less than 250 mg/day increased cocaine use relative to placebo whereas disulfiram at 250 mg/day did not differ from placebo among methadone-stabilized individuals with dual cocaine and opioid dependence, suggesting disulfiram at higher doses needed to be tested. This study determined tolerability and efficacy of disulfiram at higher doses (250-500 mg/day).

METHODS/PROCEDURES: In a 14-wk, double blind, placebo-controlled clinical trial, 53 participants with cocaine and opioid dependence were enrolled, inducted onto methadone (weeks 1-2), randomized to receive placebo or disulfiram (250, 375 or 500 mg/day) during weeks 3-14, and provided weekly 1-h individual cognitive behavior therapy throughout. Thrice-weekly urine samples were tested for the presence of cocaine metabolite. Weekly vital signs and monthly mood assessments were obtained.

RESULTS/FINDINGS: Disulfiram groups generally did not differ on subject characteristics or retention. Cocaine-positive urine samples showed a significant increase over time in the placebo group (p = 0.04), with the placebo slope being significantly greater than horizontal. Cocaine-positive urine samples decreased over time in the disulfiram 250 mg (p = 0.014) and 375 mg (p = 0.015), but not 500 mg (p = 0.11), groups relative to placebo, although slopes of these medication groups did not differ significantly from horizontal (p > 0.15). No clinically significant differences across groups with respect to vital signs or mood ratings occurred.

IMPLICATIONS/CONCLUSIONS: Although preliminary due to the small sample size, disulfiram at 250-375 mg/day may be ineffective in reducing cocaine use and have limited efficacy to prevent increases in cocaine use among methadone-stabilized patients with dual cocaine and opioid dependence.