July 17, 1998 WASHINGTON - They are widely prescribed, their effectiveness has been highly praised and many people consider them to be nothing less than life-savers. But is the effectiveness of drugs used to treat depression a product of their chemistry or the patients' psychological reaction to them? The authors of a meta-analysis of 19 drug studies involving 2,318 patients conclude that it may be the latter: three-quarters of the beneficial effect of anti-depressant medications, they contend, can be ascribed to the placebo effect - the patient's belief and expectation that the pill they are taking will make them better. Furthermore, the authors say, the remaining 25 percent of the positive effect of anti-depressants may be attributable to the fact that the drugs have side effects, which inert pills do not. The article, "Listening to Prozac but Hearing Placebo: A Meta-Analysis of Antidepressant Medication" appears in the premiere issue of APA's new online journal Prevention & Treatment, followed by commentaries from other psychologists and a psychiatrist, and a response from the lead author.
The authors, psychologists Irving Kirsch, Ph.D., of the University of Connecticut, and Guy Sapirstein, Ph.D., of Westwood Lodge Hospital in Needham, MA, pooled and analyzed the data from 19 randomized, placebo-controlled studies assessing the efficacy of various medications in treating depression, including some studies that involved drugs not considered anti-depressants. Looking across all 19 studies, the authors calculated the extent to which the beneficial effects of the various drugs could be attributed to the drugs themselves and the degree of positive effects that could be attributed to the placebo effect.
They concluded that 75 percent of the response to the drugs was a placebo response and that, at most, 25 percent might be a true drug effect. "This does not mean that only 25 percent of patients are likely to respond to the pharmacological properties of the drug. Rather, it means that for a typical patient, 75 percent of the benefit obtained from the active drug would also have been obtained from an inactive placebo," the authors say. And it is possible, they say, that the remaining benefit came not from anything the drugs did to fight depression specifically, but from an enhancement of the placebo effect caused by the fact that those who received medication (rather than a dummy pill) could tell by the side effects that they had taken something.
This result was seen in all the studies in the meta-analysis, including those involving drugs not considered to be anti-depressants, but which were as effective as anti-depressants in treating depression.
As the editors of Treatment & Prevention point out in an editor's note accompanying this article, this is a controversial conclusion. The all-electronic format of the journal made it possible to obtain rapid responses to the article and to publish some of those responses along with it.
The most lengthy and vociferous response ("Listening to Meta-Analysis but Hearing Bias") came from Donald F. Klein, MD, of Columbia University who criticizes the authors' choice of studies to analyze as "a miniscule group of unrepresentative, inconsistently and erroneously selected articles arbitrarily analyzed by an obscure, misleading effect size." Dr. Klein found fault with almost every aspect of the article, including the fact that it is a meta-analysis, pointing to a recent study that compared meta-analyses with large clinical trials and concluded that the meta-analyses "would have led to rejection of a useful treatment in four out of 12 cases." (In his response to the commentaries Dr. Kirsch addresses Dr. Klein's complaints under the heading "Klein's Laundry List.")
Another critic of the article is psychologist Robyn M. Dawes, Ph.D., of Carnegie Mellon University who argues that the authors' logic is seriously flawed and their methodology oversimplified. "Science (like art and life)," he says, "is not that easy."
Psychologist Larry E. Beutler, Ph.D., of the University of California, Santa Barbara is more supportive. In his commentary ("Prozac and Placebo: There's a Pony in There Somewhere") he notes that "the poor showing of antidepressants, both in this and other meta-analytic studies of these drugs, raise an interesting question about why and how public enthusiasm and faith is maintained in these treatments. This is a research question whose importance may even exceed that of the specific effects of the drugs themselves."
Article: "'Listening to Prozac but Hearing Placebo: A Meta-Analysis of Antidepressant Medication," by Irving Kirsch, Ph.D., University of Connecticut, Storrs, CT and Guy Sapirstein, Ph.D., Westwood Lodge Hospital, Needham, MA, in the Treatment and Prevention, Vol. 1, Article 00002a.
(Full text available at http://journals.apa.org/prevention/volume1/pre0010002a.html or by contacting the APA Public Affairs Office.)
Treatment & Prevention is a peer-reviewed, archival, scholarly electronic journal and is part of the regular APA journals program. Articles that appear in it will be available online indefinitely (although they will be posted on the APA website for two years). Journalists can access the journal through the APA website (http://www.apa.org) and can register to be notified of new postings.
The American Psychological Association (APA), in Washington, DC, is the largest scientific and professional organization representing psychology in the United States and is the world's largest association of psychologists. APA's membership includes more than 155,000 researchers, educators, clinicians, consultants and students. Through its divisions in 50 subfields of psychology and affiliations with 59 state, territorial and Canadian provincial associations, APA works to advance psychology as a science, as a profession and as a means of promoting human welfare.
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