The Emperor's New Drugs
First edition, 2009
|Subject||The efficacy of antidepressants|
|Publisher||The Bodley Head|
The Emperor's New Drugs – Exploding the Antidepressant Myth is a 2009 book by Irving Kirsch, arguing that the chemical imbalance theory of depression is wrong and that antidepressants have little or no direct effect on depression but, because of their common serious side-effects, they are powerful active placebos.
Kirsch is Associate Director of the Program in Placebo Studies and a lecturer in medicine at the Harvard Medical School and Beth Israel Deaconess Medical Center, and professor emeritus of psychology at the Universities of Hull and Plymouth in the United Kingdom, and the University of Connecticut in the United States. His research interests include placebo effects, antidepressants, expectancy, and hypnosis. He is the originator of response expectancy theory.
While analyzing antidepressant trials as part of his research into the placebo effect, Kirsch realised that drug companies do not publish all of their disappointing antidepressant trial results, but most decisions about the efficacy of an antidepressant are based only on published results. Using the Freedom of Information Act, he and his colleagues acquired from the US Food and Drug Administration the unpublished trial results for six antidepressants. When the results from both published and unpublished studies were averaged, the researchers concluded that the drugs produced a small but clinically meaningless improvement in mood compared with an inert placebo (sugar pill). (Some researchers have questioned the statistical basis of this study suggesting that it underestimates the effect size of antidepressants and other studies have reached a range of supporting and conflicting conclusions).
To determine whether their averaging of results was hiding a meaningful benefit to more-severely depressed patients by combining their results with those of moderately and mildly depressed patients, he and his colleagues undertook another study, this time of the four new-generation antidepressants for which all (published and unpublished) trial data were available, and concluded that the difference between drug and placebo effect was greater for more-severely depressed patients, and that this difference was clinically meaningful (but still relatively small) only at the upper end of the very severely depressed category. They attributed this difference to very seriously depressed patients being less responsive to the inert placebo.
Kirsch also addresses the conclusions of the a 2004 study, that if one antidepressant doesn't work on a patient, another should be tried in its place, and then another, until hopefully one will be found to be effective. The 2004 study found that although only 37% of patients were helped by the first antidepressant tried, 67% had found some relief by the time they had tried the fourth. Kirsch cites a 1957 study in which volunteers were given a drug that induces nausea and one to treat nausea. If the anti-nausea drug failed to prevent nausea, they were given another. If that failed, another was tried; and so on. All volunteers experienced complete relief from nausea by the sixth treatment, yet every treatment was a placebo. He concludes that the results of the 2004 antidepressant study are also likely due to the placebo effect.
Since the chemical-imbalance theory of depression is based on the efficacy of antidepressants, Kirsch concludes, "It now seems beyond question that the traditional account of depression as a chemical imbalance in the brain is simply wrong."
Reception and impact
The European Psychiatric Association published a position paper in 2012 that described Kirsch's argument as "misleading". The organization argues that
- The mathematical treatment of the data was flawed and underestimates the efficacy of antidepressants;
- The analysis incorrectly focuses on mean differences between groups and ignores important subgroup effects;
- The size effect cutoff of 0.50 is arbitrary and not demonstrated to be clinically meaningful;
- That efficacy measured by the 15-20% difference between placebo and active antidepressant treatment in rate of remission corresponds to moderate to strong efficacy in evidence-based medicine analyses, and
- Kirsch's analysis disregards the results of double-blind, placebo controlled maintenance studies that show highly statistical effects on the rate of relapse for those treated with antidepressants relative to those receiving placebo
Marcia Angell's review of The Emperor's New Drugs welcomes Kirsch's work as a long overdue application of the scientific method to a field lacking rigorous scientific analysis, stating "Kirsch is a faithful proponent of the scientific method, and his voice therefore brings a welcome objectivity to a subject often swayed by anecdotes, emotions, or, as we will see, self-interest."
Psychiatrist Daniel Carlat called the book "an important book, with the reservation that Kirsch’s selective use of data gives him the appearance of an anti-antidepressant partisan." He states that Irving's conclusions are "provocative but unconvincing", noting that many drugs such as benzodiazepines have been tested for antidepressant activity and found inactive. Carlat argues that if antidepressants were acting purely via a placebo effect, any benzodiazepines and other drugs would show activity as well.
In a 2012 episode of CBS's 60 Minutes featuring Kirsch and his book, host Lesley Stahl said, "The medical community is at war – battling over the scientific research and writings of a psychologist named Irving Kirsch ... Kirsch and his studies have triggered a furious counterattack, mainly from psychiatrists."
After the program's airing, Jeffrey Lieberman, the American Psychiatric Association's president elect at the time, said, "Dr. Kirsch is mistaken and confused, and he's ideologically biased in his thinking. He is conducting an analysis and interpreting the data to support his ideologically biased perspective. What he is concluding is inaccurate, and what he is communicating is misleading to people and potentially harmful to those who really suffer from depression and would be expected to benefit from antidepressant medication. To say that antidepressants are no better than placebo is just plain wrong." 
There have been two English-language editions of the book – one in the UK, one in the US – and it has been translated into Japanese, French, Italian, Turkish, and Polish.
- Irving Kirsch (13 October 2009). The Emperor's New Drugs: Exploding the Antidepressant Myth. Random House. pp. 5–6. ISBN 978-1-4090-8635-2.
- "Our team". Program in Placebo Studies & Therapeutic Encounter (PiPS).
- "Irving Kirsch". University of Plymouth, School of Psychology.
- "Irving Kirsch". University of Connecticut, Dept. Psychology. Archived from the original on 2010-06-24.
- Michael R. Nash; Amanda J. Barnier (19 January 2012). The Oxford Handbook of Hypnosis: Theory, Research, and Practice. Oxford University Press. p. 121. ISBN 978-0-19-162583-1.
- Fran Lowry (20 March 2012). "APA Blasts 60 Minutes Program on Antidepressants". Retrieved 22 February 2014.
- Kirsch, Irving; Moore, Thomas J.; Scoboria, Alan; Nicholls, Sarah S (Jul 2002). "The emperor's new drugs: An analysis of antidepressant medication data submitted to the U.S. Food and Drug Administration". Prevention & Treatment. 5 (1). doi:10.1037/1522-37184.108.40.2063a.
- Horder J, Matthews P, Waldmann R (June 2010). "Placebo, Prozac and PLoS: significant lessons for psychopharmacology". Journal of Psychopharmacology (Oxford, England). 25 (10): 1277–88. doi:10.1177/0269881110372544. hdl:2108/54719. PMID 20571143.
- Fountoulakis KN, Möller HJ (August 2010). "Efficacy of antidepressants: a re-analysis and re-interpretation of the Kirsch data". The International Journal of Neuropsychopharmacology. 14 (3): 405–412. doi:10.1017/S1461145710000957. PMID 20800012.
- Gibbons RD, Hur K, Brown CH, Davis JM, Mann JJ (June 2012). "Benefits from antidepressants: synthesis of 6-week patient-level outcomes from double-blind placebo-controlled randomized trials of fluoxetine and venlafaxine". Archives of General Psychiatry. 69 (6): 572–9. doi:10.1001/archgenpsychiatry.2011.2044. PMC 3371295. PMID 22393205.
- Fournier JC, DeRubeis RJ, Hollon SD, et al. (January 2010). "Antidepressant drug effects and depression severity: a patient-level meta-analysis". JAMA. 303 (1): 47–53. doi:10.1001/jama.2009.1943. PMC 3712503. PMID 20051569.
- Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, Johnson BT (February 2008). "Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration". PLoS Med. 5 (2): e45. doi:10.1371/journal.pmed.0050045. PMC 2253608. PMID 18303940.
- Rush AJ, Fava M, Wisniewski SR, et al. (February 2004). "Sequenced treatment alternatives to relieve depression (STAR*D): rationale and design". Control Clin Trials. 25 (1): 119–42. doi:10.1016/s0197-2456(03)00112-0. PMID 15061154.
- Irving Kirsch (13 October 2009). The Emperor's New Drugs: Exploding the Antidepressant Myth. Random House. p. 59. ISBN 978-1-4090-8635-2.
- Menand, Louis (1 March 2010). "Head Case: Can Psychiatry Be a Science?". The New Yorker.
- Irving Kirsch (13 October 2009). The Emperor's New Drugs: Exploding the Antidepressant Myth. Random House. p. 80. ISBN 978-1-4090-8635-2.
- Möller HJ, Bitter I, Bobes J, Fountoulakis K, Höschl C, Kasper S (2012). "Position statement of the European Psychiatric Association (EPA) on the value of antidepressants in the treatment of unipolar depression". Eur. Psychiatry. 27 (2): 114–28. doi:10.1016/j.eurpsy.2011.08.002. PMID 22119161.
- Angell, Marcia (23 June 2011). "The Epidemic of Mental Illness: Why?". New York Review of Books.
- Carlat, D. (2010). "Book Review: The Emperor's New Drugs: Exploding the Antidepressant Myth. Irving Kirsch Basic Books; 2010". CMAJ. 182 (18): E873. doi:10.1503/cmaj.100772. PMC 3001545.
- "Treating Depression: Is there a Placebo Effect?". CBS, 60 Minutes. 19 February 2012. Retrieved 20 February 2014.
- Lay press:
- David Small (2009) Times Higher Education Supplement "The Pills Work if You're a Believer"
- Sharon Begley (2010) Newsweek "The Depressing News About Antidepressants"
- Louis Menand (2010) The New Yorker "Head Case: Can Psychiatry be a Science?"
- James Le Fanu (2010) Literary Review "Prozac Blues" Archived 2014-02-27 at the Wayback Machine
- Carlin Flora (2010) Discover Psychologist Says Antidepressants Are Just Fancy Placebos
- Marcia Angell (2011) New York Review of Books "The Epidemic of Mental Illness: Why?"
- Peter Kramer (2011) The New York Times Sunday Review "In Defense of Antidepressants"
- Scientific press:
- Liz Else (2009) New Scientist "Review: The Emperor's New Drugs and Doctoring the Mind"
- Neil Richardson (2010) British Journal of Clinical Pharmacy "Book review" Archived 2016-03-04 at the Wayback Machine
- Robert Whitaker (2010) Psychology Today "Mad in America"
- Nicole Brenan (2010) Scientific American "MIND Reviews: The Emperor's New Drugs"
- Robert Whitaker (2011) American Journal of Psychology "The Emperor's Turn to Blush"
- Melvyn A. Gravitz (2011) American Journal of Clinical Hypnosis "Book reviews"
- "Hull academic shortlisted for Mind Book of the Year Award". University of Hull. 2010. Retrieved 20 February 2014.
- Kirsch, I. (2009): The Emperor’s New Drugs: Exploding the Antidepressant Myth. London: The Bodley Head.
- US edition (2010): The Emperor’s New Drugs: Exploding the Antidepressant Myth. New York: Basic Books.
- Japanese edition (2010): アービング・カーシュ (Irving Kirsch) 抗うつ薬は本当に効くのか (Do antidepressant drugs really work?) Translated by石黒千秋 (Chiaki Ishiguro). Tokyo, X-Knowledge Inc.
- French edition: (2010): Antidepresseurs: Le grand mensonge (Antidepressants: The big lie). Translated by Axelle Demoulin. Paris, Music and Entertainments Books.
- Polish edition (2011): Nowe leki cesarza: Demaskowanie mitu antydepresantów. Translated by Zbigniew Dziedzic. Krakow: Wydawnictwo Literackie.
- Turkish edition (2011): Antidepresan efsanesinin sonu: Çiplak kral’in yeni ilaci. Translated by Dilek Onuk. Istanbul, Kuraldişi.
- Italian edition (2012): I farmaci antidepressivi: Il crollo di un mito. Translated by Patrizia Rustichelli Stirgwolt. Milan: Techniche Nuove.
- 2nd French edition (2013): Dépression: Le mensonge des antidépresseurs…et les vraies pistes de guérison. Translated by Axelle Demoulin. Donnemarie-Dontilly: Mosaïque-Santé