A placebo-controlled, crossover trial of granisetron in SRI-induced sexualdysfunction

Background: Sexual side effects are commonly associated with serotonin reup take inhibitor (SRI) therapy. The mechanism underlying SRI-induced sexual d ysfunction has been hypothesized to be mediated by direct serotonergic effe cts.. Evidence from open-label reports suggests that cyproheptadine, nefazo done, mirtazapine, and mianserin, which block one or more serotonin recepto rs, may reverse sexual side effects. The current study was a prospective, r andomized, crossover trial comparing granisetron, a scrotonin-3 antagonist, with placebo in outpatients who developed sexual dysfunction during SRI tr eatment. Method: Thirty-one outpatients who were currently experiencing sexual dysfu nction associated with SRIs were randomly assigned to double-blind treatmen t with granisetron (1-1.5 mg) or placebo for use 1 to 2 hours prior to sexu al activity. Patients rated sexual symptoms after each trial using the Sexu al Side Effect Scale (SSES). After 4 trials of the medication, patients cro ssed over to the other treatment for 3 more trials. Results: Twenty patients received at least 1 dose of placebo and granisetro n. Analysis by repeated-mensures analysis of variance showed no significant effects of granisetron relative to placebo. Significant improvement betwee n baseline and treatment-phase SSES scores was observed for both granisetro n (p =.0004) and placebo (p =.0081). The study medication was generally wel l tolerated. Conclusion: The results of this study do not support the efficacy of granis etron (1-2 mg) in the treatment of SRI-associated sexual side effects. A si gnificant placebo response may be associated with the treatment of SRI-indu ced sexual dysfunction.