Clinical Efficacy of the 5-HT3 Antagonist Ondansetron in Alcohol Abuse and Dependence

Medications that act on the serotonergic system have been found to be of benefit in the treatment of alcohol‐dependent individuals. In a randomized, placebo‐controlled study, the efficacy of 6 weeks of ondansetron, a 5‐HT3 antagonist (0.25 mg bid or 2.0 mg bid), in the treatment of 71 nonseverely alcohol‐dependent males was tested. The results showed reduction of drinking differences were steadily increasing toward the end of the treatment period approached significance at week 7 in the 0.25 mg group (p= 0.06). Twice as many patients in this group showed >2 standard deviations decrease in drinking compared with the other groups. When patients drinking >10 drinks/drinking day at baseline (n= 11) were excluded from the analysis, significant group differences were found at both treatment and follow‐up, with the lower ondansetron dose producing the greatest reduction from baseline (i.e., 2.8 standard drinks; –35% compared with baseline and –21% compared with placebo; p < 0.02–0.001). Within this group, there was an almost 4‐fold greater number of patients showing a clinically meaningful decrease in drinking. Lower baseline drinking and higher level of education were significant and strong predictors of drinking reduction during treatment. Ondansetron was very well tolerated; hence, further long‐term studies with 5‐HT3 antagonists alone or in combination with other treatment components may offer promise for treatment of alcoholism.