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Vol. 78, No. 3, 2009
Issue release date: April 2009
Section title: Regular Article
Psychother Psychosom 2009;78:172–181
(DOI:10.1159/000209348)

Does Study Design Influence Outcome?

The Effects of Placebo Control and Treatment Duration in Antidepressant Trials

Rutherford B.R. · Sneed J.R. · Roose S.P.
Department of Psychiatry, Columbia University and the New York State Psychiatric Institute, New York, N.Y., USA

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Article / Publication Details

First-Page Preview
Abstract of Regular Article

Received: 3/27/2008
Published online: 3/24/2009

Number of Print Pages: 10
Number of Figures: 1
Number of Tables: 4

ISSN: 0033-3190 (Print)
eISSN: 1423-0348 (Online)

For additional information: http://www.karger.com/PPS

Abstract

Background: Clinicians and researchers synthesize data from randomized controlled trials (RCTs) of antidepressants to make conclusions about the efficacy of medications for depression. All treatments include nonspecific factors in addition to the specific effects of drugs, and study design may influence patient outcomes via nonspecific factors. This study investigated whether placebo control and treatment duration affect the outcome in antidepressant RCTs. Methods: Medline and the Cochrane Database were searched to identify RCTs of antidepressants for major depression approved by the Food and Drug Administration. Included studies enrolled outpatient participants aged 18–65, lasted 6–12 weeks, compared an antidepressant to placebo or another antidepressant and were published in English after 1985. Excluded trials enrolled inpatients, pregnant women and subjects with psychosis or mania. Mixed-effects logistic regression models including study type (placebo-controlled or comparator) and study duration (6, 8 or 12 weeks) as fixed effects determined whether these factors affected response and remission rates. Results: In the 90 trials analyzed, the odds of depression response (OR = 1.79, 95% CI = 1.45–2.17, p < 0.001) and remission (OR 1.53, 95% CI = 1.11–2.11, p < 0.001) were significantly higher in comparator relative to placebo-controlled trials. Trials lasting 8 (OR = 1.37, CI = 1.14–1.64, p = 0.001) and 12 (OR = 1.52, CI = 1.12–2.07, p = 0.008) weeks had significantly greater response rates than 6-week trials without differing themselves. Conclusions: Response and remission rates to antidepressants are significantly affected by study type and duration. Clinicians and researchers must consider the study design when interpreting and designing RCTs of antidepressant medications.


Article / Publication Details

First-Page Preview
Abstract of Regular Article

Received: 3/27/2008
Published online: 3/24/2009

Number of Print Pages: 10
Number of Figures: 1
Number of Tables: 4

ISSN: 0033-3190 (Print)
eISSN: 1423-0348 (Online)

For additional information: http://www.karger.com/PPS


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

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    External Resources

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  122. Khan A, Leventhal R, Khan S, Brown WA: Severity of depression and response to antidepressants and placebo: an analysis of the Food and Drug Administration Database. J Clin Psychopharmacol 2002;22:40–45.