Reemergence of Sexual Dysfunction in Patients With Major Depressive Disorder: Double-Blind Comparison of Nefazodone and Sertraline

Background: Several different classes ofantidepressants have been associated with sexual adverse effects.This double-blind, randomized trial compared the effects ofnefazodone and sertraline on reemergence of sexual dysfunction indepressed patients who had experienced sexual dysfunction as aresult of sertraline treatment. Depressive symptoms were alsomonitored.

Method: One hundred five patients with DSM-III-Rmajor depressive episode who were experiencing sexual dysfunctionattributable to sertraline (100 mg/day) were screened for entry.Eligible patients entered a 1-week washout period that wasfollowed by a 7- to 10-day single-blind placebo phase. Patientswithout symptoms of sexual dysfunction at the end of thesingle-blind placebo phase were randomly assigned to receivedouble-blind treatment with either nefazodone (400 mg/day) orsertraline (100 mg/day) for 8 weeks.

Results: Nearly 3 times more sertraline-treatedpatients (76%; 25/33) experienced reemergence of sexualdysfunction (ejaculatory and/or orgasmic difficulty) than didnefazodone-treated patients (26%; 10/39) (p < .001). Inaddition, patients treated with nefazodone were more satisfiedwith their sexual functioning than were patients treated withsertraline. Both treatment groups demonstrated a similar andsustained improvement in depressive symptoms. Both drugs werewell tolerated, and the overall incidence of adverse reactionswas similar for both treatment groups; however, 9sertraline-treated patients (26%) discontinued because of adverseevents compared with 5 nefazodone-treated patients (12%). Of thepatients discontinuing therapy for adverse events, 5 of thesertraline-treated patients did so because of sexual dysfunctionreported as an adverse event, whereas only 1 of thenefazodone-treated patients discontinued therapy secondary tosexual dysfunction.

Conclusion: In this sample of patients withmajor depression who had recovered from sexual dysfunctioninduced by treatment with sertraline, nefazodone treatmentresulted in significantly less reemergence of sexual dysfunctionthan did renewed treatment with sertraline and provided continuedantidepressant activity.