title: Gepirone-ER treatment of hypoactive sexual desire disorder (HSDD) associated with depression in women.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Fabre-Kramer Pharmaceuticals, Houston, TX, USA. lfabre@fabrekramer.com
authors.forename: Louis F
authors.initials: LF
authors.lastname: Fabre
authors.forename: Candace S
authors.initials: CS
authors.lastname: Brown
authors.forename: Louis C
authors.initials: LC
authors.lastname: Smith
authors.forename: Leonard R
authors.initials: LR
authors.lastname: Derogatis
mesh_terms: D000293:Adolescent; D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000150:complications / Q000523:psychology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007989:Libido / Q000187:drug effects; D008875:Middle Aged; D011743:Pyrimidines / Q000627:therapeutic use*; D020018:Sexual Dysfunctions, Psychological / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D011743:Pyrimidines; C039979:gepirone