This column addresses two important clinical trial issues in psychiatry. Placebo is frequently misrepresented by the media as representing nothing. In fact, placebo represents everythingexceptthe investigational treatment. That is an important distinction. The second is the concept of the drug-specific response/remission rate. While manufacturers frequently cite the overall response/remission rate observed in the group treated with their drug in their clinical trials, that is not the true rate specifically attributable to the drug. Instead, it represents the combined rate due to both the drug and the non-drug (or “placebo”) therapeutic aspects of the trial. To determine the drug-specific response/remission rate, the placebo response/remission rate must be subtracted from the overall response/remission rate observed in the drug treated group. That is because the drug treated group receives both the therapeutic benefit of the drug and all of the nondrug therapeutic benefit of the trial (i.e., the “placebo” condition). Viewed from this perspective, only about one out of four patients with major depression responds specifically to either selective serotonin or serotonin-norepinephrine reuptake inhibitors. These principles are important if one is to put the recent controversy about the effectiveness of modern antidepressant treatment into perspective. The critical issue is not how good the drugs are but rather how serious our diseases are. When evaluating the current antidepressants, the principal issue is not how many patients with major depression they treat but instead how well they treat the patients they do treat. The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study has clearly documented that approximately 40% of patients with major depression do not respond to existing antidepressants. That finding is consistent with the concept that there are likely many forms of depressive illness, only a fraction of which are responsive to drugs that work via effects on biogenic amines.(Journal of Psychiatric Practice2011;17:420–424)
Professor, Department of Psychiatry, University of Kansas School of Medicine-Wichita, and Chief Science Officer and Medical Direc tor, Kansas University-Wichita Clinical Trials Unit (KU-W CTU), Wichita, Kansas. He has more than 30 years of drug development research experience at all levels (i.e., preclinical through Phase IV) and has been a principal investigator on over 300 clinical trials including every antidepressant marketed in the United States over the last 25 years. Dr. Preskorn maintains a website at <http://www.preskorn.com> where readers can access previous columns and other publications.
Adapted from Preskorn SH. “A dangerous idea.” Journal of Practi cal Psychiatry and Behavioral Health 1996;2:231–4.
Disclosure statement: Dr. Preskorn, as chief science officer of the KU-Wichita Clinical Trials Unit and, in many cases, as principal investigator, has received grants/research support from or has served as a consultant for, on the advisory board, or on the speakers bureau for the following entities: Abbott, Allergan, Biovail, Boehringer Ingelheim, Bristol-Myers-Squibb, Eisai, Eli Lilly, Evotec, Ipsen, Johnson & Johnson, Labopharma, Link Medicine, Merck, NovaDel Pharma, Orexigen, Prexa, Psylin, Pfizer, Sunovion, Takeda, and Targacept.