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© 2005 American Academy of Neurology
Placebo response in clinical trials of depression and its implications for research on chronic neuropathic painFrom the Departments of Anesthesiology (Drs. Dworkin and Katz) and Neurology (Dr. Dworkin), University of Rochester School of Medicine and Dentistry, Rochester, NY; the Department of Psychology, State University of New York College at Geneseo (Dr. Katz), Geneseo, NY; and the Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles (Dr. Gitlin), Los Angeles, CA. Address correspondence and reprint requests to Dr. Robert H. Dworkin, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Box 604, Rochester, NY, 14642; e-mail: robert_dworkin{at}urmc.rochester.edu This article reviews studies of the placebo response in antidepressant clinical trials, describes methods that have been attempted to decrease it, and discusses implications of the placebo response in depression for research on treatments for neuropathic pain. Literature reviews and research studies examining the placebo response in clinical trials of treatments for depression were reviewed. Existing data suggest that the placebo response in antidepressant clinical trials is substantial and that a high placebo response in a clinical trial is associated with a reduced likelihood of demonstrating the statistical superiority of antidepressant treatment vs. placebo. Attempts to decrease the placebo response in antidepressant clinical trials have generally not been effective. In addition, there is little evidence that decreasing the placebo response rate makes it more likely that superiority of active vs. placebo treatment will be demonstrated. Analyses of neuropathic pain clinical trial databases should be conducted to examine factors associated with trial outcomes. Aspects of neuropathic pain clinical trials that require further consideration or investigation include the following: (a) exclusion of patients with mild pain severity; (b) exclusion of patients with short episode duration; (c) maximizing reliability, validity, and responsiveness of outcome measures; (d) minimizing extraneous contact with investigative staff and other sources of nonspecific therapeutic effects; (e) trial duration; (f) minimizing the number of treatment groups; (g) flexible vs. fixed dose designs; (h) strategies for identifying patients and accelerating enrollment; (i) identification of run-in periods that reduce the placebo response rate; and (j) registration of clinical trials and publication of negative studies.
Publication of this supplement was supported in part by an educational grant from Pfizer Inc to the Office of Professional Education, University of Rochester School of Medicine and Dentistry. Disclosure: RHD has received research support, consulting fees, and lecture honoraria in the past year from Abbott Laboratories, Cephalon, Eli Lilly & Co., Endo Pharmaceuticals, EpiCept Corporation, NeurogesX, Novartis Pharmaceuticals, Organon, Ortho-McNeil Pharmaceutical, Pfizer, Ranbaxy Corporation, UCB Pharma, Wyeth, and Yamanouchi Europe. MJG has received lecture honoraria in the past year from Bristol-Myers Squibb, Cephalon, GlaxoSmithKline, and Pfizer. JK has disclosed no financial relationships.
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