title: Influence of sex and menopausal status on response, remission, and recurrence in patients with recurrent major depressive disorder treated with venlafaxine extended release or fluoxetine: analysis of data from the PREVENT study.
abstract: OBJECTIVE
  To evaluate the effects of sex and menopausal status on acute-, continuation-, and maintenance-phase treatment outcomes in patients with recurrent major depressive disorder (MDD).
  
  
  METHODS
  This was a secondary analysis of data from the Prevention of Recurrent Episodes of Depression With Venlafaxine for Two Years (PREVENT) trial, a multiphase, multicenter, double-blind study in which adult outpatients with recurrent MDD (by DSM-IV criteria) were randomly assigned to 10 weeks of acute-phase venlafaxine extended release (ER) (75-300 mg/d) or fluoxetine (20-60 mg/d). Patients achieving response or remission had 6 months of continuation-phase treatment. Responding or remitting patients in the venlafaxine ER group were randomly assigned to venlafaxine ER or placebo for 2 consecutive 12-month maintenance phases; fluoxetine-treated patients continued receiving fluoxetine. The outcome measures for this analysis were acute- and continuation-phase response and remission rates (as measured by the 17-item Hamilton Depression Rating Scale) and time to depression recurrence in the maintenance phases according to sex and menopausal status at baseline.
  
  
  RESULTS
  The intent-to-treat population comprised 781 patients in the venlafaxine ER group (65% women) and 266 patients in the fluoxetine group (61% women); 64% of all women were premenopausal, and 25% were postmenopausal (5% perimenopausal; not analyzed). At acute-phase end, remission rates in the venlafaxine ER vs fluoxetine groups were 44% vs 47% in men, 51% vs 52% in women, 50% vs 52% in premenopausal women, and 52% vs 55% in postmenopausal women. At continuation-phase end, remission rates in the venlafaxine ER vs fluoxetine groups were 71% vs 74% in men, 72% vs 67% in women, 72% vs 69% in premenopausal women and 71% vs 63% in postmenopausal women. Response rates were consistent with these findings. Based on a Cox proportional hazards model, sex was not a significant predictor of recurrence during the first or second maintenance phase (hazard ratio [HR] = 1.233; P = .3712 and HR = 1.103; P = .8075, respectively), and neither was menopausal status at acute-phase baseline (HR = 0.941; P = .8234 and HR = 0.531; P = .2065, respectively).
  
  
  CONCLUSIONS
  In this study of patients with recurrent MDD, treatment outcomes with venlafaxine ER and fluoxetine did not differ on the basis of sex or menopausal status. Our confidence in these findings is limited by the lack of a placebo arm during the acute and continuation phases and by the small sample sizes for subgroup analyses in the maintenance phases.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT00046020.
authors.affiliation: Department of Psychiatry and Obstetrics/Gynecology, Executive Director, Institute for Women's Health, PO Box 980319, Richmond, VA 23298 skornste@vcu.edu.
authors.forename: Susan G
authors.initials: SG
authors.lastname: Kornstein
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Pedersen
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Holland
authors.forename: Charles B
authors.initials: CB
authors.lastname: Nemeroff
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Rothschild
authors.forename: Michael E
authors.initials: ME
authors.lastname: Thase
authors.forename: Madhukar H
authors.initials: MH
authors.lastname: Trivedi
authors.forename: Philip T
authors.initials: PT
authors.lastname: Ninan
authors.forename: Martin B
authors.initials: MB
authors.lastname: Keller
mesh_terms: D000328:Adult; D003511:Cyclohexanols / Q000008:administration & dosage / Q000494:pharmacology*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000494:pharmacology; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008593:Menopause / Q000187:drug effects*; D008875:Middle Aged; D010919:Placebos; D016016:Proportional Hazards Models; D012008:Recurrence; D012074:Remission Induction; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D012737:Sex Factors; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride
chemical_list: D003511:Cyclohexanols; D003692:Delayed-Action Preparations; D005473:Fluoxetine; D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride