Placebo Response in Studies of Major Depression: Variable, Substantial, and Growing

• Published in: JAMA : the journal of the American Medical Association 2002-04, Vol.287 (14), p.1840-1847
• Main Authors: Walsh, B. Timothy, Seidman, Stuart N, Sysko, Robyn, Gould, Madelyn
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antidepressants; Antidepressive Agents - therapeutic use; Bioethics; Biological and medical sciences; Clinical trial. Drug monitoring; Clinical trials; Control Groups; Depressive Disorder, Major - drug therapy; Drug therapy; Female; General pharmacology; Humans; Male; Medical sciences; Mental depression; Middle Aged; Neuropharmacology; Pharmacology. Drug treatments; Placebo Effect; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Randomized Controlled Trials as Topic; Statistics as Topic
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.287.14.1840

CONTEXT Intense debate persists about the need for placebo-controlled groups in clinical trials of medications for major depressive disorder (MDD). There is continuing interest in the development of new medications, but because effective antidepressants are already available, ethical concerns have been raised about the need for placebo groups in new trials. OBJECTIVE To determine whether the characteristics of placebo control groups in antidepressant trials have changed over time. DATA SOURCES AND STUDY SELECTION We searched MEDLINE and PsychLit for all controlled trials published in English between January 1981 and December 2000 in which adult outpatients with MDD were randomly assigned to receive medication or placebo. Seventy-five trials met our criteria for inclusion. DATA EXTRACTION Data were extracted from the articles by 2 of the authors and discrepancies were resolved via discussion and additional review by a third author. DATA SYNTHESIS The mean (SD) proportion of patients in the placebo group who responded was 29.7% (8.3%) (range, 12.5%-51.8%). Most studies examined more than a single active medication, and, in the active medication group with the greatest response, the mean (SD) proportion of patients responding was 50.1% (9.0%) (range, 31.6%-70.4%). Both the proportion of patients responding to placebo and the proportion responding to medication were significantly positively correlated with the year of publication (for placebo: n = 75; r = 0.45; 95% confidence interval [CI], 0.25-0.61; P