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Irving Kirsch, placebos and antidepressants

Posted by doxogenic boy on October 18, 2013, at 8:23:17

I have now seen the news report on 60 Minutes about Irving Kirsch and his claims that antidepressants work via the placebo effect: http://www.youtube.com/watch?v=Zihdr36WVi4

babbler20 mentioned it in this message: http://www.dr-bob.org/babble/20130930/msgs/1052163.html

http://www.cbsnews.com/8301-18560_162-57380893/treating-depression-is-there-a-placebo-effect/

Irving Kirsch has said this about placebo and antidepressants repeatedly since 1998, but what do psychiatrists say about his claims today? I will be happy for any response about this theme.

I have made this review of the debate that Irving Kirsch initiated:

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http://web.archive.org/web/19980715085305/http://journals.apa.org/prevention/volume1/pre0010002a.html

Listening to Prozac but Hearing Placebo:
A Meta-Analysis of Antidepressant Medication

Irving Kirsch, Ph.D.
University of Connecticut, Storrs, CT

Guy Sapirstein, Ph.D.
Westwood Lodge Hospital, Needham, MA

ABSTRACT
Mean effect sizes for changes in depression were calculated for 2,318 patients who had been randomly assigned to either antidepressant medication or placebo in 19 double-blind clinical trials. As a proportion of the drug response, the placebo response was constant across different types of medication (75%), and the correlation between placebo effect and drug effect was .90. These data indicate that virtually all of the variation in drug effect size was due to the placebo characteristics of the studies. The effect size for active medications that are not regarded to be antidepressants was as large as that for those classified as antidepressants, and in both cases, the inactive placebos produced improvement that was 75% of the effect of the active drug. These data raise the possibility that the apparent drug effect (25% of the drug response) is actually an active placebo effect. Examination of prepost effect sizes among depressed individuals assigned to no-treatment or wait-list control groups suggest that approximately one quarter of the drug response is due to the administration of an active medication, one half is a placebo effect, and the remaining quarter is due to other nonspecific factors.

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http://web.archive.org/web/19980715085313/http://journals.apa.org/prevention/volume1/pre0010003c.html

Prozac and Placebo: There's a Pony in There Somewhere
Larry E. Beutler
University of California

ABSTRACT.
Kirsch and Sapirstein (1998) have provided a provocative analysis of placebo contributions to antidepressant effects. They distinguish among response to treatment, treatment effect, placebo response, and placebo effect. In each case, response defines the total amount of change associated with the implementation of a treatment or placebo, whereas effect defines that portion of the response that can be attributed to the medication or placebo. They suggest, and I have been persuaded to concur that the field has inappropriately ignored the overshadowing role of the relative size of placebo and treatment effects in its rush to acclaim the effectiveness of antidepressants. They suggest that the inclusion of a proportional measure that describes the relative amount of change that is distributed to active treatment effects and placebo response will help balance presentations on the effects of treatments. The results have even broader and more important implications than those acknowledged by the authors, extending to prescription practices, how depression is conceptualized within a diagnostic perspective, and to the concept of treatment-induced deterioration effects. Collectively, however, 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.

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http://web.archive.org/web/19980715085319/http://journals.apa.org/prevention/volume1/pre0010004c.html


Comment on Listening to Prozac but Hearing Placebo: A Meta-Analysis of Antidepressant Medication
Listening to Prozac and Hearing Noise: Commentary on Kirsch and Sapirstein's "Listening to Prozac but Hearing Placebo"

Lynn P. Rehm, Ph.D.
Department of Psychology, University of Houston

ABSTRACT
It is agrued that the strong correlation between placebo and antidepressant medication outcomes is most likely due to sample differences, which are unlikely to be seen in no treatment versus psychotherapy comparisons. Both sample differences and procedure differences are loud noise factors that mitigate against detecting differences in the differences between effects.

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http://web.archive.org/web/19980715085327/http://journals.apa.org/prevention/volume1/pre0010005c.html


Comment on Listening to Prozac but Hearing Placebo: A Meta-Analysis of Antidepressant Medication
Commentary on Kirsch and Saperstein

Robyn M. Dawes
Carnegie Mellon University

ABSTRACT
The simple posttreatment minus pretreatment difference in an outcome variable for a treatment group or for a placebo group does not define either a treatment effect or a placebo effect, even for groups randomly constructed. Such differences must be compared with the difference obtained from a (randomly selected) no-treatment group in order to evaluate the effect of treatment or placebo. People change anyway, especially after being in a state that would lead them to seek treatment (a regression effect), and how they would change in the absence of anything at all must be compared with how they change given treatment or placebo. Effect involves a comparative judgment, not just a prepost one. And even when a legitimate effect is found for a placebo, it often (almost always?) makes little sense to talk of a proportion of a treatment effect as being accounted for by a placebo effect. The logic of Kirsch and Sapirstein (1998) is thus seriously flawed. Science (like art and life) is not that easy.

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http://web.archive.org/web/19980715085334/http://journals.apa.org/prevention/volume1/pre0010006c.html


Comment on Listening to Prozac but Hearing Placebo: A Meta-Analysis of Antidepressant Medication
Listening to Meta-Analysis but Hearing Bias

Donald F. Klein, M.D.
Department of Psychiatry, Columbia University,
Department of Therapeutics, College of Physicians and Surgeons, and the New York State Psychiatric Institute

ABSTRACT
Kirsch and Sapirstein (1998) present a meta-analysis of 19 studies, attempting to define the relationship of placebo to antidepressant drug effect. They conclude that the substantial majority of drug effect is due to placebo effect and the rest is either measurement error or active placebo effect. The article is criticized because it derives from a miniscule group of unrepresentative, inconsistently and erroneously selected articles arbitrarily analyzed by an obscure, misleading effect size. Further, numerous problems with the meta-analytic approach, in general, and Kirsch and Sapirstein's use of it, in particular, go undiscussed. The attempt to further segment the placebo response, by reference to psychotherapy trials incorporating waiting lists, is confounded by disparate samples, despite Kirsch and Sapirstein's claim of similarity. The failure of peer review and the opportunity provided by an electronic journal for rapid discussion is emphasized.

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http://web.archive.org/web/19980715085341/http://journals.apa.org/prevention/volume1/pre0010007r.html

Rejoinder to comments on Listening to Prozac but Hearing Placebo: A Meta-Analysis of Antidepressant Medication
Reducing Noise and Hearing Placebo More Clearly

Irving Kirsch
University of Connecticut

ABSTRACT
In addition to responding directly to the issues raised by the commentators, I compare the Kirsch and Sapirstein (1998) data to those of two other meta-analyses (Joffe et al., 1996; Walach & Maidhof, in press) of antidepressant medication. The three meta-analyses used different inclusion criteria and different methods of calculating effect sizes. One is confined to long-term effects of treatment and another to acute effects. One is based on number of patients clinically improved and the others on standardized change scores. In addition, one included data allowing for calculation of response rates based on intent-to-treat criteria. Despite differences in study characteristics and methods of analysis, all revealed that the a large proportion of the response to medication was duplicated by placebo, and all revealed exceptionally high correlations between the placebo response and the drug response. These data reveal that the findings we reported are reliable and generalizable, and they indicate a pressing need for new methodologies in clinical trials.

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http://web.archive.org/web/19990203204020/http://journals.apa.org/prevention/volume1/pre0010008r.html


Further Commentary on Listening to Prozac but Hearing Placebo: A Meta-Analysis of Antidepressant Medication
Reply to Kirsch's Rejoinder Regarding Antidepressant Meta-Analysis

Donald F. Klein, M.D.
Department of Psychiatry, Columbia University, College of Physicians and Surgeons
Department of Therapeutics, New York State Psychiatric Institute

ABSTRACT
Kirsch attempts to rebut the critiques of his article by ignoring relevant criticism and citing further irrelevant and inaccurately cited meta-analyses. The irrelevance of the within effect size used by Kirsch to the proportion of patients specifically benefitted in a clinical trial is discussed.

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http://web.archive.org/web/19990203230022/http://journals.apa.org/prevention/volume1/pre0010009r.html


Further Commentary on Listening to Prozac but Hearing Placebo: A Meta-Analysis of Antidepressant Medication
On the Importance of Reading Carefully: A Response to Klein

Irving Kirsch, Ph.D.
University of Connecticut, Storrs, CT

ABSTRACT
Errors, misrepresentations, and distortions in Klein's (1998b) second commentary are corrected. Klein's contention that the between-study differences are due to the type of medication being studied is contradicted by the data. Also, Klein has misrepresented our meta-analytic procedures and the data from studies in that meta-analysis. Contrary to his assertion, all but one of the methods we used to calculate effect sizes were indeed standard meta-analytic practices. The one meta-analytic unconventional method we used corrects for baseline differences but otherwise is mathematically equivalent to the standard method. Contrary to Klein's assertion, Kiev and Okerson (1979) did not reported significant posttreatment superiority of antidepressant medication, and in any case, the significance of posttreatment superiority is irrelevant to the calculation of prepost effect sizes.

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http://web.archive.org/web/19990203005111/http://journals.apa.org/prevention/volume1/com0010001a.html

Additional Reader Comments on

Listening to Prozac but Hearing Placebo: A Meta-Analysis of Antidepressant Medication

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http://alphachoices.com/repository/assets/pdf/EmperorsNewDrugs.pdf

The Emperor's New Drugs: An Analysis of
Antidepressant Medication Data Submitted
to the U.S. Food and Drug Administration
Irving Kirsch
University of Connecticut
Thomas J. Moore
The George Washington University School of Public Health and Health Services
Alan Scoboria and Sarah S. Nicholls
University of Connecticut
ABSTRACT
This article reports an analysis of the efficacy data submitted to the U.S. Food
and Drug Administration for approval of the 6 most widely prescribed
antidepressants approved between 1987 and 1999. Approximately 80% of the
response to medication was duplicated in placebo control groups, and the mean
difference between drug and placebo was approximately 2 points on the 17-item
(50-point) and 21-item (62-point) Hamilton Depression Scale. Improvement at
the highest doses of medication was not different from improvement at the
lowest doses. The proportion of the drug response duplicated by placebo was
significantly greater with observed cases (OC) data than with last observation
carried forward (LOCF) data. If drug and placebo effects are additive, the
pharmacological effects of antidepressants are clinically negligible. If they are not additive, alternative experimental designs are needed for the evaluation of antidepressants.
Keywords: drug efficacy, placebo, meta-analysis, depression

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http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0050045

Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration

Irving Kirsch, Brett J Deacon, Tania B Huedo-Medina, Alan Scoboria, Thomas J Moore, Blair T Johnson

Abstract
[...]
Conclusions

Drugplacebo differences in antidepressant efficacy increase as a function of baseline severity, but are relatively small even for severely depressed patients. The relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely depressed patients, rather than to increased responsiveness to medication.

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Irving Kirsch has written a book about antidepressants and placebo. Have any of you read it, what do you think about the book, and what do psychiatrists say?
http://www.amazon.com/The-Emperors-New-Drugs-Antidepressant/dp/0465022006/ref=sr_1_1?ie=UTF8&qid=1381761757&sr=8-1&keywords=irving+kirsch

I don't think that the effects I have had of antidepressants indicate that they are placebos.

What do you think about this debate and Kirsch's claims?

- doxogenic


Earlier TRD/anxiety
300 mg tianeptine, 6 X 50 mg successfully since Oct 2009
20 mcg liothyronine
40 mg escitalopram
100 mg trimipramine
50 mg agomelatine
600 mg quetiapine


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poster:doxogenic boy thread:1052457
URL: http://www.dr-bob.org/babble/20130930/msgs/1052457.html