Gepirone-ER treatment of hypoactive sexual desire disorder (HSDD) associated with depression in women.
ABSTRACT 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.
To study the effect of gepirone-ER on HSDD in women with major depressive disorder (MDD).
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.
Number (%) of patients who no longer met criteria for HSDD (percent resolved).
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).
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.
- [Show abstract] [Hide abstract]
ABSTRACT: Gepirone-extended release (ER) is effective in treating hypoactive sexual desire disorder (HSDD), as measured by the percent of females with HSDD that no longer met criteria for HSDD treatment. Another approach is to determine treatment effect on sexual desire using a recognized rating scale for sexual function. Because gepirone-ER has antidepressant and anxiolytic effects, investigation of these effects on sexual desire is appropriate. The aim of this study was to determine whether gepirone-ER has positive effects on sexual desire as measured by the DeRogatis Inventory of Sexual Function (DISF) in a post hoc analysis of 8- and 24-week studies and if this gepirone effect is independent of its antidepressant or anxiolytic activity. The main outcome measures used for this study were the Hamilton Depression Rating Scale (HAMD-25), change from baseline (CFB), and DISF CFB. Three hundred thirty-four women selected for depressive symptoms, not sexual dysfunction, received gepirone-ER (40-80 mg/day) in a controlled study of atypical depression using the HAMD-25 to measure antidepressant efficacy and a DISF subscale (domain I) to measure sexual cognition/fantasy (desire). After treatment, a 50% reduction from baseline HAMD-25 score identified antidepressant responders. Item 12 of HAMD scale (psychic anxiety) was used to define anxiolytic response scores of 0, 1 as responders, and scores of 2, 3, and 4 as nonresponders. Gepirone-ER had no significant antidepressant or an anxiolytic effect in study 134006; however, DISF results demonstrate that gepirone-ER improves sexual desire in short term (P=0.043) and long term (P=0.006). Both gepirone-ER antidepressant and anxiolytic responders have statistically significant improved sexual desire. Gepirone-ER antidepressant and anxiolytic nonresponders also show statistically significant improvement. In depressed women, gepirone-ER has three mechanisms of action affecting sexual desire: an antidepressant effect, an anxiolytic effect, and a pro-sexual effect. Gepirone-ER improves sexual desire from the 24th to the 50th percentile according to population norms for the DISF.Journal of Sexual Medicine 06/2011; 8(9):2569-81. DOI:10.1111/j.1743-6109.2011.02330.x · 3.15 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Eleven hundred eighty-four depressed women were entered into five short-term (8 weeks) studies of gepirone-extended release (ER) vs. placebo for treatment of major depressive disorder (MDD) (134001, 134002, and 134017), or atypical depressive disorder (ADD) (134004 and 134006). The effect of depression on sexual function was examined prior to treatment. To determine the effect of depression on the prevalence of Diagnostic and Statistical Manual Fourth Edition (DSM-IV) sexual dysfunction diagnoses and the Derogatis Inventory of Sexual Function (DISF) total score and domain scores and to measure the effect of severity of depression. Hamilton Depression Rating Scale (HAMD-17), DSM-IV diagnoses, and DISF total and domain scores. DSM-IV diagnoses--hypoactive sexual desire disorder (HSDD), sexual aversion disorder (SAD), female arousal disorder (FAD), and female orgasmic disorder (FOD)--were made by a trained psychiatrist. The HAMD-17 measured antidepressant efficacy. The DISF or its self-report version measured sexual function. To access the effect of severity of depression, baseline HAMD-17 scores were stratified as mild (<18), moderate (19-22), severe (23-25), or extreme (26-33). All measures were taken at baseline. In this depressed female population, prevalence rates were HSDD 17.7%, SAD 3.4%, FAD 5.8%, and FOD 7.7%. These rates for females are within the reported normal (nondepressed) values. However, DISF scores are one or more standard deviations below population norms for total score. DISF domains are not equally affected: orgasm is most impaired, while sexual desire and sexual arousal are somewhat preserved. Higher HAMD scores result in lower DISF scores (greater sexual dysfunction). In women, depression affects DISF scores more than DSM-IV diagnoses for sexual dysfunction. With increasing severity of depression (increased HAMD scores), sexual dysfunction becomes greater (lower DISF scores). For equal HAMD scores, DISF scores for MDD and ADD are the same.Journal of Sexual Medicine 08/2011; 9(1):231-9. DOI:10.1111/j.1743-6109.2011.02445.x · 3.15 Impact Factor
- Journal of Sexual Medicine 10/2011; 8(10):2954. DOI:10.1111/j.1743-6109.2011.02406.x · 3.15 Impact Factor