This work may not be copied, distributed, displayed, published, reproduced, transmitted, modified, posted, sold, licensed, or used for commercial purposes. By downloading this file, you are agreeing to the publisher’s Terms & Conditions.

Article

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 ([email protected]).

Volume: 71

Quick Links: Assessment Methods , Research Methods Statistics

Continue Reading…

Subscribe to read the entire article

$40.00

Buy this Article as a PDF