title: A pooled analysis of the efficacy of desvenlafaxine for the treatment of major depressive disorder in perimenopausal and postmenopausal women.
abstract: BACKGROUND
  Few studies in the literature have examined the efficacy of antidepressant drugs in perimenopausal and postmenopausal women. The objective of the current study was to assess the efficacy of desvenlafaxine (administered as desvenlafaxine succinate) separately in perimenopausal and postmenopausal women with major depressive disorder (MDD).
  
  
  METHODS
  Data were pooled from two double-blind, placebo-controlled clinical trials enrolling perimenopausal and postmenopausal women (40-70 years old) diagnosed with MDD. Patients were randomly assigned to receive desvenlafaxine 100 to 200 mg/day or placebo (8 weeks) or desvenlafaxine 50 mg/day or placebo (10 weeks). The primary efficacy end point for each trial was change from baseline in Hamilton Rating Scale for Depression (HAM-D17) total score at week 8. Secondary end points included change from baseline in Sheehan Disability Scale (SDS) and Menopause Rating Scale (MRS) scores. Changes from baseline in continuous variables were analyzed using analysis of covariance with treatment, region, and baseline in the model. All treatment comparisons were carried out separately in perimenopausal or postmenopausal women, in individual studies, and in the pooled population, adjusting for menopausal status and study.
  
  
  RESULTS
  A total of 798 patients were included in the full analysis set (perimenopausal, n=252; postmenopausal, n=546). Desvenlafaxine significantly reduced HAM-D17 total scores versus placebo at week 8 in both perimenopausal (-10.3 vs. -6.5; p<0.001) and postmenopausal women (-10.1 vs. -7.6; p<0.001). Significant improvements in SDS and MRS total scores were also observed for desvenlafaxine versus placebo in perimenopausal (p ≤ 0.024) and postmenopausal women (p ≤ 0.009). A significant treatment by menopausal status interaction was observed for SDS only (p=0.036).
  
  
  CONCLUSIONS
  Desvenlafaxine demonstrated antidepressant efficacy in both perimenopausal and postmenopausal subgroups of women with MDD.
  
  
  CONCLUSIONS
  In September 2011, Pfizer received a Complete Response Letter from the United States Food and Drug Administration on its application for approval to market desvenlafaxine for the treatment of moderate to severe vasomotor symptoms associated with menopause. The Complete Response Letter states that the data included in the application are not sufficient to establish an acceptable risk/benefit profile for the treatment of vasomotor symptoms in the general population of postmenopausal women, and therefore desvenlafaxine is not approved for the treatment of vasomotor symptoms in the United States at this time. This decision does not impact desvenlafaxine's approval for the treatment of MDD in adults.
authors: 1 Department of Psychiatry and Institute for Women's Health, Virginia Commonwealth University , Richmond, Virginia.
authors: Susan G
authors: SG
authors: Kornstein
authors: Anita H
authors: AH
authors: Clayton
authors: Weihang
authors: W
authors: Bao
authors: Christine J
authors: CJ
authors: Guico-Pabia
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D003511:Cyclohexanols / Q000009:adverse effects* / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D000069468:Desvenlafaxine Succinate; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D008593:Menopause / Q000187:drug effects / Q000523:psychology*; D008875:Middle Aged; D017698:Postmenopause / Q000187:drug effects / Q000523:psychology*; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D003511:Cyclohexanols; D000069468:Desvenlafaxine Succinate