title: Sponsorship, antidepressant dose, and outcome in major depressive disorder: meta-analysis of randomized controlled trials.
abstract: OBJECTIVE
  Differences in dosing may influence results of pharmaceutical industry-sponsored medication trials. This study aims to determine the relationship between sponsorship and antidepressant dosing and efficacy in randomized controlled trials for major depressive disorder.
  
  
  METHODS
  Trials were identified through English-language searches of MEDLINE and PsycINFO (January 1996-June 2010) using specific drug names and classes and depressive disorder or major depression and double blind or double-blind method. Other limitations included human subjects and treatment study designs using the clinical queries option. Other sources were also searched following a strict set of inclusion and exclusion criteria.
  
  
  METHODS
  Randomized controlled trials were included if they examined antidepressant treatment for major depressive disorder, reported mean final medication dosages, acknowledged an association with industry, and included study arms of medications produced by the associated manufacturer and a competitor ("sponsor" and "nonsponsor" arms) (58 trials involving 15,026 patients from 101 citations identified).
  
  
  METHODS
  Data on dosing, efficacy, baseline severity, and adverse events were extracted by 2 of the authors.
  
  
  RESULTS
  Meta-analyses were used to examine dosing and efficacy data. Using consensus guidelines for medication dosing, we determined that sponsor medication was dosed relatively higher than nonsponsor medication, in 37% (22/60) of comparisons as opposed to 5% (3/60) in which the nonsponsor medication was dosed higher (χ²₂ = 25.9, P < .001). Trials in which sponsor drugs were dosed higher than nonsponsor drugs demonstrated higher remission rates for the sponsor drug (OR = 1.28, 95% CI = 1.11-1.47, P < .001). These results were confirmed using regulatory dosing guidelines. There was no significant correlation between dosing or outcome with baseline severity or adverse events.
  
  
  CONCLUSIONS
  Sponsor drugs are dosed higher than nonsponsor drugs in antidepressant randomized controlled trials, and higher dosing is associated with better sponsor drug outcomes in some cases.
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, Canada. mark.sinyor@utoronto.ca
authors.forename: Mark
authors.initials: M
authors.lastname: Sinyor
authors.forename: Ayal
authors.initials: A
authors.lastname: Schaffer
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Smart
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Levitt
authors.forename: Krista L
authors.initials: KL
authors.lastname: Lanctôt
authors.forename: Noam H
authors.initials: NH
authors.lastname: Grysman
mesh_terms: D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004345:Drug Industry / Q000191:economics* / Q000706:statistics & numerical data; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000191:economics* / Q000523:psychology / Q000706:statistics & numerical data; D012109:Research Support as Topic / Q000191:economics* / Q000706:statistics & numerical data
chemical_list: D000928:Antidepressive Agents