Placebo response in studies of major depression: variable, substantial, and growing.
BACKGROUND
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.


METHODS
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.


METHODS
Data were extracted from the articles by 2 of the authors and discrepancies were resolved via discussion and additional review by a third author.


RESULTS
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<.001; for medication: n = 75; r = 0.26; 95% CI, 0.03-0.46; P =.02). The association between year of publication and response rate was more statistically robust for placebo than medication.


CONCLUSIONS
The response to placebo in published trials of antidepressant medication for MDD is highly variable and often substantial and has increased significantly in recent years, as has the response to medication. These observations support the view that the inclusion of a placebo group has major scientific importance in trials of new antidepressant medications and indicate that efforts should continue to minimize the risks of such studies so that they may be conducted in an ethically acceptable manner.
Walsh
B Timothy
BT
Department of Psychiatry, College of Physicians and Surgeons of Columbia University, 1051 Riverside Dr, Unit 98, New York, NY 10032, USA.
Seidman
Stuart N
SN
Sysko
Robyn
R
Gould
Madelyn
M
D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D035061:Control Groups; D003865:Major Depressive Disorder / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015990:Placebo Effect; D016032:Randomized Controlled Trials as Topic; D013223:Statistics as Topic
D000928:Antidepressive Agents