title: Does differential drop-out explain the influence of study design on antidepressant response? A meta-analysis.
abstract: BACKGROUND
  Response to antidepressants is higher in active comparator relative to placebo-controlled clinical trials. Increased patient expectancy in comparator trials has been hypothesized to explain this finding, but previous analyses have not accounted for the increased drop-out observed in placebo-controlled trials.
  
  
  METHODS
  A systematic literature review was conducted to identify published antidepressant clinical trials reporting data on intent-to-treat (ITT) as well as completer patient populations. The influence of participant drop-out on observed antidepressant response was investigated by comparing the ITT and completer data sets in separate multilevel meta-analyses of antidepressant response in placebo-controlled and comparator trials.
  
  
  RESULTS
  18 placebo-controlled and 18 active comparator studies were available for analysis. Using the intent-to-treat data, the odds of responding to medication in comparator trials were 1.9 times the odds in placebo-controlled trials (95% CI=1.3-2.7, p=0.001). The same pattern was obtained among study completers, in whom the odds of responding to antidepressant medication were 1.9 times higher in comparator as opposed to placebo-controlled study designs (95% CI=1.2-3.0, p=0.009).
  
  
  CONCLUSIONS
  Publication bias, the use of trial-level summary data, and unreported clinical or demographic differences between the ITT and completer patient populations may have influenced the study results.
  
  
  CONCLUSIONS
  Increased drop-out in placebo-controlled vs. active comparator studies of antidepressant medications does not appear to explain the difference in response rates between these study types. Rather, increased patient expectancy resulting from the certainty of receiving active medication in comparator trials may lead to improved response rates.
authors.affiliation: Columbia University College of Physicians and Surgeons, New York State Psychiatric Institute, United States. brr8@columbia.edu
authors.forename: Bret R
authors.initials: BR
authors.lastname: Rutherford
authors.forename: Joel R
authors.initials: JR
authors.lastname: Sneed
authors.forename: Steven P
authors.initials: SP
authors.lastname: Roose
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use*; D018849:Controlled Clinical Trials as Topic / Q000379:methods*; D003863:Depression / Q000188:drug therapy*; D003866:Depressive Disorder / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D010342:Patient Acceptance of Health Care; D010352:Patient Dropouts; D010919:Placebos; D012107:Research Design
chemical_list: D000928:Antidepressive Agents; D010919:Placebos