A Placebo-Controlled, Crossover Trial of Granisetron in SRI-Induced Sexual Dysfunction

Background: Sexual side effects are commonlyassociated with serotonin reuptake inhibitor (SRI) therapy. Themechanism underlying SRI-induced sexual dysfunction has beenhypothesized to be mediated by direct serotonergic effects.Evidence from open-label reports suggests that cyproheptadine,nefazodone, mirtazapine, and mianserin, which block one or moreserotonin receptors, may reverse sexual side effects. The currentstudy was a prospective, randomized, crossover trial comparinggranisetron, a serotonin-3 antagonist, with placebo inoutpatients who developed sexual dysfunction during SRItreatment.

Method: Thirty-one outpatients who werecurrently experiencing sexual dysfunction associated with SRIswere randomly assigned to double-blind treatment with granisetron(1-1.5 mg) or placebo for use 1 to 2 hours prior to sexualactivity. Patients rated sexual symptoms after each trial usingthe Sexual Side Effect Scale (SSES). After 4 trials of themedication, patients crossed over to the other treatment for 4more trials.

Results: Twenty patients received at least 1dose of placebo and granisetron. Analysis by repeated-measuresanalysis of variance showed no significant effects of granisetronrelative to placebo. Significant improvement between baseline andtreatment-phase SSES scores was observed for both granisetron (p= .0004) and placebo (p = .0081). The study medication wasgenerally well tolerated.

Conclusion: The results of this study do notsupport the efficacy of granisetron (1-2 mg) in the treatment ofSRI-associated sexual side effects. A significant placeboresponse may be associated with the treatment of SRI-inducedsexual dysfunction.