title: An integrated analysis of the efficacy of desvenlafaxine compared with placebo in patients with major depressive disorder.
abstract: BACKGROUND
  To assess the efficacy of desvenlafaxine (administered as desvenlafaxine succinate) in outpatients with major depressive disorder.
  
  
  METHODS
  A meta-analysis of individual patient data was performed on the complete set of registration trials (nine randomized, double-blind, placebo-controlled 8-week studies) of desvenlafaxine. Patients received fixed (50, 100, 200, or 400 mg/day; n=1,342) or flexible doses (100-400 mg/day; n=463) of desvenlafaxine or placebo (n=1,108). The primary efficacy variable was the 17-item Hamilton Rating Scale for Depression (HAM-D(17)); the primary intent to treat analyses used the last-observation-carried-forward method.
  
  
  RESULTS
  Significantly greater improvement with desvenlafaxine versus placebo on the HAM-D(17) total score was observed for the full data set (difference in adjusted means: -1.9; P<.001), each fixed-dose group (all P<.001), and the flexible-dose group (P=.024). Overall rates of HAM-D1(17) response (> or =150% decrease from baseline score: 53% vs 41%) and remission (HAM-D(17) < or =7: 32% vs 23%) were significantly greater for desvenlafaxine versus placebo (all P<.001). Discontinuation rates due to adverse events increased with dose (4% to 18%; placebo: 3%).
  
  
  CONCLUSIONS
  Desvenlafaxine demonstrated short-term efficacy for treating major depressive disorder across the range of doses studied. No evidence of greater efficacy was observed with doses >50 mg/day; a strong dose-response effect on tolerability was observed.
authors.affiliation: Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. thase@mail.med.upenn.edu
authors.forename: Michael E
authors.initials: ME
authors.lastname: Thase
authors.forename: Susan G
authors.initials: SG
authors.lastname: Kornstein
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Germain
authors.forename: Qin
authors.initials: Q
authors.lastname: Jiang
authors.forename: Christine
authors.initials: C
authors.lastname: Guico-Pabia
authors.forename: Philip T
authors.initials: PT
authors.lastname: Ninan
mesh_terms: D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003511:Cyclohexanols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D016032:Randomized Controlled Trials as Topic; D000069470:Venlafaxine Hydrochloride
chemical_list: D018687:Antidepressive Agents, Second-Generation; D003511:Cyclohexanols; D000069470:Venlafaxine Hydrochloride