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-HT(2) 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 (20-80 mg/day), comparator antidepressants (fluoxetine, 20-40 mg/day or paroxetine, 10-40 mg/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.
RCT Entities:
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-HT(2) 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 (20-80 mg/day), comparator antidepressants (fluoxetine, 20-40 mg/day or paroxetine, 10-40 mg/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.