title: Placebo response and antidepressant clinical trial outcome.
abstract: Placebo response magnitude is suspected to affect the outcome of antidepressant clinical trials. To evaluate this, 52 randomized, double-blind, placebo-controlled clinical trials obtained from the FDA were examined to correlate placebo response magnitude with trial outcome. The magnitude of symptom reduction, percentage mean change from baseline in the Hamilton Depression Rating Scale (HAM-D), was assessed for patients assigned to placebo or an antidepressant. Correlation coefficients between symptom reduction with placebo and antidepressants and between symptom reduction with placebo and magnitude of advantage of antidepressants over placebo were assessed. A statistically significant positive correlation was seen between placebo and antidepressant response magnitude (r =.40, p <.001) and between placebo response magnitude and the advantage of antidepressants over placebo (r = -.592, p <.0001). Only 21.1% of antidepressant treatment arms in trials with high placebo response (>30% mean change from baseline) showed statistical superiority over placebo compared with 74.2% in trials with a low placebo response (< or =30). Response magnitude varies and has an important effect on antidepressant clinical trials, illustrating the need for a placebo arm to determine if the trial was sensitive to treatment differences and highlighting the dangers of cross-study comparisons.
authors.affiliation: Northwest Clinical Research Center, 1900 116th Avenue NE #112, Bellevue, Washington 98004, USA.
authors.forename: Arif
authors.initials: A
authors.lastname: Khan
authors.forename: Michael
authors.initials: M
authors.lastname: Detke
authors.forename: Shirin R F
authors.initials: SR
authors.lastname: Khan
authors.forename: Craig
authors.initials: C
authors.lastname: Mallinckrodt
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D017277:Drug Approval / Q000706:statistics & numerical data; D015507:Drugs, Investigational / Q000627:therapeutic use; D006801:Humans; D015990:Placebo Effect; D010919:Placebos / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration / Q000706:statistics & numerical data
chemical_list: D000928:Antidepressive Agents; D015507:Drugs, Investigational; D010919:Placebos