title: Antidepressant treatment history and drug-placebo separation in a placebo-controlled trial in major depressive disorder.
abstract: BACKGROUND
  A history of antidepressant treatment may predispose subjects toward placebo nonresponse in randomized controlled trials (RCTs) in major depressive disorder (MDD).
  
  
  OBJECTIVE
  The objective of this study is to examine self-reported prior antidepressant treatment and response in relationship to clinical outcome in an 8-week randomized trial of reuptake inhibitor antidepressant medication (MED) versus placebo (PBO) administered along with limited supportive care.
  
  
  METHODS
  Chi-square and MMRM analyses examined MED vs. PBO outcomes in antidepressant-naïve vs. antidepressant-experienced subjects. Linear regression models examined treatment history along with covariates as predictors of clinical improvement.
  
  
  RESULTS
  Among completers (n = 56), there was no significant difference in response rate between MED (53.3 %) and PBO (42.3 %) (χ (2) = 0.33, p = 0.28, 1-tailed). The antidepressant-experienced subgroup (n = 37), however, showed a significantly greater response rate to MED (52.4 %) than PBO (25.0 %) (χ (2) = 2.82, p = 0.047, 1-tailed). The full intent-to-treat (ITT) sample (n = 69) did not show a significant difference between MED and PBO group improvement over time, but in the treatment-experienced subgroup (n = 46), MED showed significantly greater improvement than PBO (coefficient = .39, SE = .23, p = .045, 1-tailed). A history of prior antidepressant treatment predicted poorer overall response independent of pretreatment symptom severity, number or length of previous episodes, subject expectations, or family history of MDD.
  
  
  CONCLUSIONS
  Treatment history appears to constitute a factor that is distinct from other commonly studied illness characteristics or expectancy measures, and that impacts overall response as well as drug-placebo separation in RCTs.
authors: Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, University of California Los Angeles, 760 Westwood Plaza, Rm. 57-455, Los Angeles, CA, 90024-1759, USA, amhunter@ucla.edu.
authors: Aimee M
authors: AM
authors: Hunter
authors: Ian A
authors: IA
authors: Cook
authors: Molly
authors: M
authors: Tartter
authors: Simi K
authors: SK
authors: Sharma
authors: Gregory D
authors: GD
authors: Disse
authors: Andrew F
authors: AF
authors: Leuchter
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000175:diagnosis* / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D057566:Self Report / Q000592:standards*
chemical_list: D000928:Antidepressive Agents