A CONTROLLED TRIAL OF ONDANSETRON, A 5-HT3 ANTAGONIST, IN BENZODIAZEPINE DISCONTINUATION

Serotonin is implicated in the etiology of anxiety disorders and in th e anxiolytic actions of benzodiazepines. Preclinical studies with 5-HT 3 receptor antagonists, including ondansetron, show they have anxiolyt ic properties and that ondansetron suppresses withdrawal anxiety after abrupt discontinuation of chronic benzodiazepine treatment, We evalua ted the efficacy of ondansetron as an adjunctive medication in the dis continuation of benzodiazepines in long-term users, One hundred eight patients who had used alprazolam or lorazepam regularly for > 3 months entered, and 97 completed a randomized double-blind discontinuation t reatment program during which they received either ondansetron 2 mg tw ice daily or placebo and flexibly tapered their benzodiazepine over a B-week period. There were no significant differences between the patie nts who had entered and completed treatment. Three weeks postmedicatio n, 63% of the patients discontinued use of benzodiazepine. The percent age of reduction of benzodiazepine daily dosage at all time points in the treatment trial was similar for the ondansetron and placebo groups , Ondansetron had no significant effects on severity of withdrawal sym ptoms or levels of anxiety, High placebo response may have prevented d etection of an ondansetron effect. At 1 year follow-up, 68% of patient s reported that they stopped using benzodiazepine. Patient characteris tics were more important than ondansetron in tapered benzodiazepine di scontinuation.