We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Review |

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

B. Timothy Walsh, MD; Stuart N. Seidman, MD; Robyn Sysko, BA; Madelyn Gould, PhD
JAMA. 2002;287(14):1840-1847. doi:10.1001/jama.287.14.1840.
Text Size: A A A
Published online

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<.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.

Figures in this Article

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?


Figure. Proportion of Patients Assigned to Placebo, Tricyclic Antidepressants (TCAs), and Selective Serotonin Reuptake Inhibitors (SSRIs) Who Showed a 50% or Greater Improvement in Hamilton Rating Scale For Depression Score by Year of Publication
Graphic Jump Location
For studies that did not provide data on response using this criterion, an estimated proportion was calculated based on the proportion of patients rated moderately or markedly improved on the Clinical Global Impression (see "Results" section). The lines are the best-fit straight lines describing the relationship between proportion of patients responding and year of publication for placebo (r = 0.45, n = 75, P<.001), TCAs (r = 0.29, n = 43, P = .06), and SSRIs (r = 0.47, n = 33, P = .006).



Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.


Some tools below are only available to our subscribers or users with an online account.

643 Citations

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

See Also...
Articles Related By Topic
Related Collections
PubMed Articles

The Rational Clinical Examination: Evidence-Based Clinical Diagnosis
Evidence to Support the Update

The Rational Clinical Examination: Evidence-Based Clinical Diagnosis
Evidence Summary and Review 2