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March 2002

National Depressive and Manic-Depressive Association Consensus Statement on the Use of Placebo in Clinical Trials of Mood Disorders

Author Affiliations

From the National Institute of Mental Health, Bethesda, Md (Drs Charney, Miller, Post, Rosenstein, and Rubinow); Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Ga (Dr Nemeroff); National Depressive and Manic-Depressive Association, Chicago, Ill (Mss Lewis and Grabowski and Dr Reynolds); Scientific Therapeutics Information, Inc, Springfield, NJ (Ms Laden); Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY (Dr Gorman); Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY (Dr Laska); Department of Psychiatry, Albert Einstein College of Medicine, New York (Dr Borenstein); Department of Psychiatry, University of Texas Health Sciences Center at San Antonio (Dr Bowden); Division of Bioethics (Dr Caplan) and Department of Psychiatry(Dr Evans), University of Pennsylvania, Philadelphia; Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas (Drs Emslie and Rush); Department of Psychiatry, Washington University at St Louis, St Louis, Mo(Dr Geller); Applied Logic Associates, Inc, Houston, Tex (Dr Herson); Department of Psychiatry, University of Wisconsin Medical School, Madison (Dr Kalin); Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, Ohio (Dr Keck); Department of Psychology, University of Connecticut, Storrs(Dr Kirsch); Duke University Medical Center, Durham, NC (Dr Krishnan); University of Pittsburgh Medical School, Pittsburgh, Pa (Drs Kupfer and Ryan); Yale University School of Medicine, New Haven, Conn (Dr Makuch); Department of Psychiatry, New York–Presbyterian Hospital, New York (Dr Pardes); Department of Psychiatry, University of New Mexico, Albuquerque (Dr Roberts); Department of Psychiatry, Harvard Medical School, Boston, Mass (Drs Rosenbaum and Sachs); Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif (Dr Schatzberg); and The Child and Adolescent Bipolar Foundation, Palo Alto, Calif (Ms Solomon).

Arch Gen Psychiatry. 2002;59(3):262-270. doi:10.1001/archpsyc.59.3.262

A consensus conference on the use of placebo in mood disorder studies consisted of expert presentations on bioethics, biostatistics, unipolar depression, and bipolar disorder. Work groups considered evidence and presented statements to the group. Although it was not possible to write a document for which there was complete agreement on all issues, the final document incorporated input from all authors. There was consensus that placebo has a definite role in mood disorder studies. Findings of equivalence between a new drug and standard treatment in active control studies is not evidence of efficacy unless the new drug is also significantly more effective than placebo. Add-on studies in which patients are randomized to standard therapy plus the investigational drug or standard therapy plus placebo are especially indicated for high-risk patients. Mood disorders in elderly and pediatric patients are understudied, and properly designed trials are urgently needed. Research is needed on the ethical conduct of studies to limit risks of medication-free intervals and facilitate poststudy treatment. Patients must fully understand the risks and lack of individualized treatment involved in research.

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