Gepirone-er treatment of hypoactive sexual desire disorder (HSDD) associated with depression in women

Introduction. There is currently no Food and Drug Administration (FDA)-approved treatment for hypoactive sexual desire disorder (HSDD). FDA approval of products utilizing testosterone has been delayed due to possible safety concerns. Flibanserin, a 5-HT_1A agonist, 5-HT₂ antagonist, and gepirone-ER, a 5-HT_1A agonist, have been shown to have activity in treatment of HSDD. However, more recently, the FDA issued a non-approval letter for flibanserin. Aim. To study the effect of gepirone-ER on HSDD in women with major depressive disorder (MDD). Methods. At baseline and post-treatment visits, a trained psychiatrist made diagnoses of HSDD based on Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria. Subjects meeting criteria for HSDD were followed to observe the effect of gepirone-ER (20-80mg/day), comparator antidepressants (fluoxetine, 20-40mg/day or paroxetine, 10-40mg/day), or placebo in reversing DSM-IV diagnosis. A subpopulation of women with Hamilton Depression Rating Scale (HAMD-17) entry scores of 18 or less was evaluated. Adverse events (AEs) of sexual dysfunction were also collected. Main Outcome Measure. Number (%) of patients who no longer met criteria for HSDD (percent resolved). Results. Eight hundred seventy-five women (18-64 years of age, average 38 years old, ∼80% premenopausal) entered three studies; 668 (72.5%) completed. Only 161 (18.4%) met DSM-IV criteria for HSDD. Cumulatively, 63% of gepirone-ER-treated patients reversed their diagnosis of HSDD compared to 40% of placebo-treated patients at end point (8 weeks) (P=0.007). Selective serotonin reuptake inhibitor-treated patients were not different from placebo. Significant results for gepirone-ER occurred by week 2 (P=0.0001). Patients who were mildly depressed (HAMD scores of 18 or less) also improved at week 2 (P=0.01) and week 8 (P=0.07). Sexual dysfunction AEs were significantly less in gepirone-ER-treated patients than placebo (P=0.013). Conclusions. Gepirone-ER may have efficacy in the treatment of HSDD among depressed and possibly nondepressed women. Efficacy occurs by week 2, and does not seem to be purely an antidepressant effect.