A preliminary randomized, double-blind, placebo-controlled study of the safety and efficacy of ondansetron in the treatment of cocaine dependence.
Prior studies have demonstrated inefficacy among dopamine receptor antagonists for treating cocaine dependence. An alternative approach would be to investigate the ability of indirect inhibitors of cortico-mesolimbic dopamine release, such as the 5-HT(3) receptor antagonist ondansetron, to reduce cocaine's reinforcing effects. We hypothesized that ondansetron might be more efficacious than placebo at reducing cocaine intake and promoting abstinence in cocaine-dependent individuals. In a pilot randomized, double-blind, 10-week controlled trial, 63 treatment-seeking, cocaine-dependent men and women received ondansetron (0.25 mg, 1.0 mg, or 4.0 mg twice daily) or placebo. Up to three times per week, participants were assessed on several measures of cocaine use, including urine benzoylecgonine. Cognitive behavioral therapy was administered weekly. Ondansetron was well tolerated, causing no serious adverse events. The ondansetron 4.0 mg group had the lowest dropout rate among all treatment groups and a greater rate of improvement in percentage of participants with a cocaine-free week compared with the placebo group (p = 0.02), whereas the ondansetron 1.0 mg group had a lower rate of improvement in percentage of weekly mean non-use days than did placebo recipients (p = 0.04). These results suggest the possibility of a non-linear dose-response function, with evidence supporting efficacy for the 4.0 mg group.
Johnson
Bankole A
BA
Department of Psychiatric Medicine, University of Virginia, P.O. Box 800623, Charlottesville, VA 22908-0623, USA. bankolejohnson@virginia.edu
Roache
John D
JD
Ait-Daoud
Nassima
N
Javors
Martin A
MA
Harrison
Joseph M
JM
Elkashef
Ahmed
A
Mojsiak
Jurij
J
Li
Shou-Hua
SH
Bloch
Daniel A
DA
D000328:Adult; D019970:Cocaine-Related Disorders / Q000534:rehabilitation* / Q000628:therapy; D015928:Cognitive Behavioral Therapy / Q000379:methods*; D003131:Combined Modality Therapy; D003710:Demography; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D017294:Ondansetron / Q000009:adverse effects* / Q000627:therapeutic use; D012702:Serotonin Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome
D012702:Serotonin Antagonists; D017294:Ondansetron