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Declining Differences in Response Rates with Antidepressants versus Placebo: A Modest Proposal for Another Contributing Cause

PRESKORN, SHELDON H. MD

Journal of Psychiatric Practice: May 2013 - Volume 19 - Issue 3 - p 227–233
doi: 10.1097/01.pra.0000430506.37144.d1
COLUMNS: Psychopharmacology

This column discusses declining differences in response rates between sequentially introduced selective serotonin reuptake inhibitors (SSRI) and placebo. Although discussions of this phenomenon in the literature have largely focused on increasing placebo response rates, the author proposes that another factor may be responsible. That factor is an order effect, meaning that response rates have been declining as a function of the number of SSRIs on the market when the next SSRI is in development. The rationale is that the pool of potential clinical trial participants likely to respond to a drug with this mechanism of action (MOA) becomes progressively smaller with the introduction of each new agent with the same MOA, because many patients will already have been treat- ed and responded to an earlier member of the class. This phenomenon is not limited to the SSRIs but generalizes to any class of treatments that shares the same MOA. (Journal of Psychiatric Practice 2013;19:227–233)

SHELDON H. PRESKORN, MD, is Professor, Department of Psychiatry, University of Kansas School of Medicine-Wichita, and Chief Science Officer and Medical Director, Kansas University- Wichita Clinical Trials Unit (KU-W CTU), Wichita, Kansas. He has more than 35 years of drug development research experience at all levels (i.e., preclinical through Phase IV) and has been a principal investigator on over 350 clinical trials—funded by industry, the federal government, or private foundations—including trials of every antidepressant and antipsychotic medication marketed in the United States over a period of 25 years. Dr. Preskorn maintains a website at www.preskorn.com where readers can access previ- ous columns and other publications.

The author acknowledges Frederick J. Ross, MS, and Carroll W. Hughes, PhD, for helpful comments and feedback on this article.

Disclosure statement: Over his career, Dr. Preskorn has worked with over 100 pharmaceutical companies in the United States and throughout the world. Over the past year, Dr. Preskorn has received grants/research support from or has served as a con- sultant, on the advisory board, or on the speakers bureau for the following: Abbott, AssureRx Health, Bristol-Myers Squibb, Cyberonics, Envivo, Johnson & Johnson, Merck, National Insti- tute of Mental Health, Naurex, Novartis, Pfizer, Stanley Medical Research Institute, Sunovion, and Taisho.

© 2013 by Lippincott Williams & Wilkins, Inc.