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Antidepressants and the placebo response

Published online by Cambridge University Press:  11 April 2011

Irving Kirsch*
University of Hull (United Kingdom)
Address fo correspondence: Professor I. Kirsch, Department of Psychology, University of Hull, Cottingham Road, Hull, HU6 7RX (United Kingdom). E-mail:


Aims – To evaluate new generation antidepressants in relation to the placebo response. Methods – I review meta-analyses in which response to antidepressant medication and response to placebo were calculated. Results – All but one of these meta-analyses included unpublished as well as published trials. Most trials failed to show a significant advantage of SSRIs over inert placebo, and the differences between drug and placebo are not clinically significant for most depressed patients. Documents obtained from the U.S. Food and Drug Administration (FDA) revealed an explicit decision to keep this information from the public and from prescribing physicians. Conclusions – Because they do not incur drug risks, exercise and psychotherapy, which show at benefits at least equal to those of antidepressants, may be a better treatment choice for depressed individuals.

Declaration of Interest: The author has not in the last 2 years received any support, including that from drug companies and honoraria for lectures and consultancies, from interests potentially in conflict with this work.

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Copyright © Cambridge University Press 2010

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Abramson, L.Y., Seligman, M.E.P. & Teasdale, J.D. (1978). Learned helplessness in humans: Critique and reformulation. Journal of Abnormal Psychology 87, 4974.CrossRefGoogle ScholarPubMed
Barbui, C., Furukawa, T.A. & Cipriani, A. (2008). Effectiveness of parox-etine in the treatment of acute major depression in adults: a systematic re-examination of published and unpublished data from randomized trials. Canadian Medical Association Journal 178, 296305.CrossRefGoogle ScholarPubMed
Hollon, S.D., DeRubeis, R.J., Shelton, R.C. & Weiss, B. (2002). The Emperor's New Drugs: Effect Size and Moderation Effects. Prevention and Treatment 5, Jul 2002, Art ID 28.CrossRefGoogle Scholar
Kirsch, I. (1985). Response rxpectancy as a determinant of experience and behavior. American Psychologist 40, 11891202.CrossRefGoogle Scholar
Kirsch, I. (Ed.) (1999). How Expectancies Shape Experience. American Psychological Association: Washington DC.CrossRefGoogle Scholar
Kirsch, I. (2009). The Emperor's New Drugs: Exploding the Antidepressant Myth. The Bodley Head: London.Google Scholar
Kirsch, I., & Sapirstein, G. (1998). Listening to Prozac but hearing placebo: A meta-analysis of antidepressant medication. Prevention and Treatment 1, Jun 1998, ArtID 2a.CrossRefGoogle Scholar
Kirsch, I., Moore, T.J., Scoboria, A. & Nicholls, S.S. (2002). The emperor's new drugs: An analysis of antidepressant medication data submitted to the U.S. Food and Drug Administration. Prevention and Treatment 5, Jul 2002, ArtID 23.Google Scholar
Kirsch, I., Deacon, B.J., Huedo-Medina, T.B., Scoboria, A., Moore, T.J. & Johnson, B.T. (2008). Initial severity and antidepressant benefits: A meta-analysis of data submitted to the Food and Drug Administration. PLoS Medicine 5. Retrieved August 21, 2009, from Scholar
Moerman, D.E. (2002). “The loaves and the fishes”: A comment on “The emperor's new drugs: An analysis of antidepressant medication data submitted to the U.S. Food and Drug Administration”. Prevention and Treatment 5, Jul 2002, ArtID 29.Google Scholar
National Institute for Clinical Excellence (2004). Depression: Management of Depression in Primary and Secondary Care. Clinical practice guideline No. 23 Retrieved August 21, 2009, from Scholar
Philipp, M., Kohnen, R. & Hiller, K.O. (1999). Hypericum extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeks British Medical Journal 319, 15341539.CrossRefGoogle ScholarPubMed
Rabkin, J.G., Markowitz, J.S., Stewart, J.W., McGrath, P.J., Harrison, W., Quitkin, F.M. & Klein, D.F. (1986). How blind is blind? Assessment of patient and doctor medication guesses in a placebo-controlled trial of imipramine and phenelzine. Psychiatry Research 19, 7586.CrossRefGoogle Scholar
Spitzer, E. (2004). Major Pharmaceutical Firm Concealed Drug Information: GlaxoSmithKline Misled Doctors About the Safety of Drug Used to Treat Depression in Children. Press Release: Office of the New York State Attorney General, June 2, 2004. Retrieved August 21, 2009, from Scholar
Teasdale, J.D. (1985). Psychological treatments for depression: How do they work? Behaviour Research and Therapy 23, 157165.CrossRefGoogle ScholarPubMed