title: Placebo-controlled, antidepressant clinical trials cannot be shortened to less than 4 weeks' duration: a pooled analysis of randomized clinical trials employing a diagnostic odds ratio-based approach.
abstract: OBJECTIVE
  In double-blind, randomized, placebo-controlled clinical trials for major depressive disorder (MDD), the impact of study duration on outcome has not been adequately studied. Our aim was to examine whether placebo-controlled antidepressant trials in MDD could be shortened to less than 4 weeks. In order to accomplish this, we examined the relationship between a "positive" or "negative" finding early on (weeks 1-4), and outcome at end point.
  
  
  METHODS
  MEDLINE/PubMed publication databases were searched for randomized, double-blind, placebo-controlled trials of antidepressants for adults with MDD published between January 1, 1980, and July 1, 2009 (inclusive).
  
  
  METHODS
  One hundred seventy-five articles were found eligible. We obtained required measures during the required time points for 101 articles (57.7%). Final inclusion of articles was determined by consensus among the authors.
  
  
  RESULTS
  One hundred eighty-two drug-placebo comparisons from 104 clinical trials were pooled (29,213 patients). The strength of the relationship between early and end point outcome increased progressively. However, only at week 4 did the diagnostic odds ratio (27.44) indicate strong concordance between early and end point outcome. The specificity of early outcome as a predictor of end point outcome did not vary substantially from visit to visit (0.91-0.92), while the sensitivity increased proportionally with each visit (from 0.17 to 0.72).
  
  
  CONCLUSIONS
  The present analysis suggests that antidepressant clinical trials cannot be shortened to less than 4 weeks' duration, primarily due to the increased risk of erroneously concluding that an effective treatment is ineffective. Four weeks is the minimum adequate length of a trial in order to reliably detect drug versus placebo differences.
authors.affiliation: Depression Clinical and Research Program, Harvard Medical School, Massachusetts General Hospital, 50 Staniford St, Boston, MA 02114, USA. etedeschini@partners.org
authors.forename: Enrico
authors.initials: E
authors.lastname: Tedeschini
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
authors.forename: George I
authors.initials: GI
authors.lastname: Papakostas
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000175:diagnosis* / Q000188:drug therapy*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004311:Double-Blind Method; D023381:Endpoint Determination; D006801:Humans; D016239:MEDLINE / Q000706:statistics & numerical data; D016017:Odds Ratio; D010919:Placebos; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D016032:Randomized Controlled Trials as Topic / Q000379:methods* / Q000706:statistics & numerical data; D012107:Research Design / Q000592:standards; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D010919:Placebos