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Vol. 59, No. 4, 2009
Issue release date: August 2009
Neuropsychobiology 2009;59:227–233

Tachyphylaxis after Repeated Antidepressant Drug Exposure in Patients with Recurrent Major Depressive Disorder

Amsterdam J.D. · Williams D. · Michelson D. · Adler L.A. · Dunner D.L. · Nierenberg A.A. · Reimherr F.W. · Schatzberg A.F.
aDepression Research Unit, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pa., bLilly Research Laboratories, Eli Lilly & Company, Indianapolis, Ind., cMerck Research Laboratories, Merck & Company, Rahway, N.J., dDepartment of Psychiatry, New York University, New York, N.Y., eCenter for Anxiety and Depression, Mercer Island, Wash., fDepression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, Boston, Mass., gMood Disorders Clinic, Department of Psychiatry, University of Utah Health Sciences Center, Salt Lake City, Utah, and hDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif., USA

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Objective: The aim of this post hoc analysis was to examine whether tachyphylaxis occurs after repeated courses of antidepressant drug therapy. Method: 276 patients with major depressive disorder (MDD) were treated with sertraline (150–200 mg daily) for 8 weeks. Patients with persistent MDD after sertraline therapy were randomized to continuation therapy with either sertraline plus atomoxetine (n = 72) or sertraline plus placebo (n = 74) for 8 additional weeks. Logistic regression was used to test the hypothesis that an increase in prior antidepressant drug exposure is associated with a reduced responsiveness to sertraline therapy. Results: The number of prior antidepressant drug exposures was negatively associated with response to initial sertraline therapy (odds ratio = 0.81, p = 0.0035). The odds ratio indicates a 19.9% reduced likelihood of response with each prior antidepressant treatment trial. In contrast, the number of prior antidepressant treatment trials was not associated with response to continuation sertraline plus atomoxetine or sertraline plus placebo therapy. Conclusion: This observation supports the hypothesis that tachyphylaxis may develop after repeated antidepressant drug trials.

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.
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