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Early Career Psychiatrists

Placebo-Controlled, Antidepressant Clinical Trials Cannot Be Shortened to Less Than 4 Weeks’ Duration: A Pooled Analysis of Randomized Clinical Trials Employing a Diagnostic Odds Ratio-Based Approach

Enrico Tedeschini, MD; Maurizio Fava, MD; and George I. Papakostas, MD

Published: November 2, 2010

Article Abstract

Objective: In double-blind, randomized, placebo-controlled clinical trials for major depressive disorder (MDD), the impact of study duration on outcome has not been adequately studied. Our aim was to examine whether placebo-controlled antidepressant trials in MDD could be shortened to less than 4 weeks. In order to accomplish this, we examined the relationship between a "positive" or "negative" finding early on (weeks 1-4), and outcome at end point.

Data Sources: MEDLINE/PubMed publication databases were searched for randomized, double-blind, placebo-controlled trials of antidepressants for adults with MDD published between January 1, 1980, and July 1, 2009 (inclusive).

Data Selection: One hundred seventy-five articles were found eligible. We obtained required measures during the required time points for 101 articles (57.7%). Final inclusion of articles was determined by consensus among the authors.

Data Synthesis: One hundred eighty-two drug-placebo comparisons from 104 clinical trials were pooled (29,213 patients). The strength of the relationship between early and end point outcome increased progressively. However, only at week 4 did the diagnostic odds ratio (27.44) indicate strong concordance between early and end point outcome. The specificity of early outcome as a predictor of end point outcome did not vary substantially from visit to visit (0.91-0.92), while the sensitivity increased proportionally with each visit (from 0.17 to 0.72).

Conclusions: The present analysis suggests that antidepressant clinical trials cannot be shortened to less than 4 weeks’ duration, primarily due to the increased risk of erroneously concluding that an effective treatment is ineffective. Four weeks is the minimum adequate length of a trial in order to reliably detect drug versus placebo differences.

J Clin Psychiatry

Submitted: September 28, 2009; accepted January 14, 2010.

Online ahead of print: November 2, 2010 (doi:10.4088/JCP.09m05725blu).

Corresponding author: Enrico Tedeschini, MD, Depression Clinical and Research Program, Massachusetts General Hospital, 50 Staniford St, Boston, MA 02114 (etedeschini@partners.org).

Volume: 71

Quick Links: Assessment Methods , Research Methods Statistics

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