title: Benefits from antidepressants: synthesis of 6-week patient-level outcomes from double-blind placebo-controlled randomized trials of fluoxetine and venlafaxine.
abstract: BACKGROUND
  Some meta-analyses suggest that efficacy of antidepressants for major depression is overstated and limited to severe depression.
  
  
  OBJECTIVE
  To determine the short-term efficacy of antidepressants for treating major depressive disorder in youth, adult, and geriatric populations.
  
  
  METHODS
  Reanalysis of all intent-to-treat person-level longitudinal data during the first 6 weeks of treatment of major depressive disorder from 12 adult, 4 geriatric, and 4 youth randomized controlled trials of fluoxetine hydrochloride and 21 adult trials of venlafaxine hydrochloride.
  
  
  METHODS
  All sponsor-conducted randomized controlled trials of fluoxetine and venlafaxine.
  
  
  METHODS
  Children's Depression Rating Scale-Revised scores (youth population), Hamilton Depression Rating Scale scores (adult and geriatric populations), and estimated response and remission rates at 6 weeks were analyzed for 2635 adults, 960 geriatric patients, and 708 youths receiving fluoxetine and for 2421 adults receiving immediate-release venlafaxine and 2461 adults receiving extended-release venlafaxine.
  
  
  RESULTS
  Patients in all age and drug groups had significantly greater improvement relative to control patients receiving placebo. The differential rate of improvement was largest for adults receiving fluoxetine (34.6% greater than those receiving placebo). Youths had the largest treated vs control difference in response rates (24.1%) and remission rates (30.1%), with adult differences generally in the 15.6% (remission) to 21.4% (response) range. Geriatric patients had the smallest drug-placebo differences, an 18.5% greater rate of improvement, 9.9% for response and 6.5% for remission. Immediate-release venlafaxine produced larger effects than extended-release venlafaxine. Baseline severity could not be shown to affect symptom reduction.
  
  
  CONCLUSIONS
  To our knowledge, this is the first research synthesis in this area to use complete longitudinal person-level data from a large set of published and unpublished studies. The results do not support previous findings that antidepressants show little benefit except for severe depression. The antidepressants fluoxetine and venlafaxine are efficacious for major depressive disorder in all age groups, although more so in youths and adults compared with geriatric patients. Baseline severity was not significantly related to degree of treatment advantage over placebo.
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL 60637, USA. rdg@uchicago.edu
authors.forename: Robert D
authors.initials: RD
authors.lastname: Gibbons
authors.forename: Kwan
authors.initials: K
authors.lastname: Hur
authors.forename: C Hendricks
authors.initials: CH
authors.lastname: Brown
authors.forename: John M
authors.initials: JM
authors.lastname: Davis
authors.forename: J John
authors.initials: JJ
authors.lastname: Mann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003511:Cyclohexanols / Q000008:administration & dosage*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D005473:Fluoxetine / Q000008:administration & dosage*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage*; D000069470:Venlafaxine Hydrochloride
chemical_list: D003511:Cyclohexanols; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride