title: A preliminary randomized, double-blind, placebo-controlled study of the safety and efficacy of ondansetron in the treatment of methamphetamine dependence.
abstract: Methamphetamine dependence is an increasing public health problem in the United States. No efficacious medication for methamphetamine dependence has been developed. As ondansetron, a 5-HT3 receptor antagonist and modulator of cortico-mesolimbic dopamine function, has been shown to reduce some of the rewarding effects of d-amphetamine in animal and human laboratory studies, we decided to test whether it would be superior to placebo at reducing methamphetamine use. In a preliminary, multi-site, randomized, double-blind, 8-wk controlled trial, 150 methamphetamine-dependent men and women received ondansetron (0.25 mg, 1 mg, or 4 mg b.i.d.) or placebo. Participants were assessed on several measures of methamphetamine use including urine methamphetamine level up to three times per week. As a psychosocial adjunct to the medication condition, cognitive behavioural therapy also was administered three times per week. Ondansetron was well tolerated and was less likely than placebo to be associated with serious adverse events. Nevertheless, none of the ondansetron doses was superior to placebo at decreasing any of the measures of methamphetamine use, withdrawal, craving, or clinical severity of methamphetamine dependence. Our preliminary results do not support the utility of ondansetron, at the doses tested, as a treatment for methamphetamine dependence. These findings should be viewed in light of the possibility that a less intensive cognitive behavioural therapy regimen might have yielded more positive results in this initial phase II trial exploring for the efficacy of ondansetron.
authors.affiliation: Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA 22908-0623, USA. bankolejohnson@virginia.edu
authors.forename: Bankole A
authors.initials: BA
authors.lastname: Johnson
authors.forename: Nassima
authors.initials: N
authors.lastname: Ait-Daoud
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Elkashef
authors.forename: Edwina V
authors.initials: EV
authors.lastname: Smith
authors.forename: Roberta
authors.initials: R
authors.lastname: Kahn
authors.forename: Francis
authors.initials: F
authors.lastname: Vocci
authors.forename: Shou-Hua
authors.initials: SH
authors.lastname: Li
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Bloch
mesh_terms: D000293:Adolescent; D000328:Adult; D019969:Amphetamine-Related Disorders / Q000188:drug therapy / Q000523:psychology / Q000628:therapy*; D000697:Central Nervous System Stimulants / Q000652:urine; D015928:Cognitive Behavioral Therapy; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000652:urine; D017294:Ondansetron / Q000009:adverse effects / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D012702:Serotonin Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D015813:Substance Abuse Detection; D016896:Treatment Outcome
chemical_list: D000697:Central Nervous System Stimulants; D012702:Serotonin Antagonists; D008694:Methamphetamine; D017294:Ondansetron