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A Meta-Analysis of Early Sustained Response Rates Between Antidepressants and Placebo for the Treatment of Major Depressive Disorder

Papakostas, George I. MD; Perlis, Roy H. MD; Scalia, Margaret J. BA; Petersen, Timothy J. PhD; Fava, Maurizio MD

Journal of Clinical Psychopharmacology: February 2006 - Volume 26 - Issue 1 - p 56-60
doi: 10.1097/
Brief Reports

Context: Pattern analysis suggests that "true" drug response is characterized by clinical improvement that is not subsequently followed by a worsening of symptoms (sustained clinical response). To date, several reports demonstrate that early response rates are equivalent between antidepressant-treated and placebo-treated groups of patients with major depressive disorder, suggesting that patients who demonstrate significant and sustained symptom improvement during the first 2 weeks of treatment are not responding to the antidepressant itself, but to nonspecific, placebo-like factors.

Objective: To compare early sustained response rates between antidepressant- and placebo-treated adults with major depressive disorder.

Data Sources: Medline/Pubmed were searched. No year of publication limits were used.

Study Selection: Randomized, double-blind, placebo-controlled antidepressant trials or pooled reports/meta-analyses of such trials reporting early sustained response rates for major depressive disorder. The decision to include studies in the meta-analysis was performed by 2 reviewers.

Data Extraction: Data were extracted with the use of a precoded form.

Data Synthesis: Analyses were performed on the proportion of patients who achieved a sustained response the first 2 weeks of treatment, as well as the first week of treatment. A random-effects model with fixed drug effects was used to combine the studies and make comparisons of sustained early response rates between antidepressant- and placebo-treated groups. Data from 8 reports involving a total of 7121 major depressive disorder patients (4076 randomized to treatment with an antidepressant and 3045 randomized to placebo) were analyzed. Antidepressant-treated patients were more likely to demonstrate sustained clinical response by 2 weeks (odds ratio 2.06, 95% CI: 1.52-2.8) or 1 week of treatment (odds ratio 1.50, 95% CI: 1.08-2.08) than placebo-treated patients.

Conclusions: The results of the present analysis suggest that "true" drug response can occur the first 2 week as well as the first week of treatment of major depressive disorder with conventional antidepressants.

Depression Clinical and Research Program, Massachusetts General Hospital,Harvard Medical School, Boston, MA.

Received June 16, 2005; accepted after revision October 18, 2005.

Address correspondence and reprint requests to George I. Papakostas, MD, Department of Psychiatry, Depression Clinical and Research Program, Massachusetts General Hospital, 15 Parkman Street, WAC 812, Boston, MA 02114. E-mail:

© 2006 Lippincott Williams & Wilkins, Inc.