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Research Article

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

  • Irving Kirsch mail,

    To whom correspondence should be addressed. E-mail: i.kirsch@hull.ac.uk

    Affiliation: Department of Psychology, University of Hull, Hull, United Kingdom

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  • Brett J Deacon,

    Affiliation: University of Wyoming, Laramie, Wyoming, United States of America

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  • Tania B Huedo-Medina,

    Affiliation: Center for Health, Intervention, and Prevention, University of Connecticut, Storrs, Connecticut, United States of America

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  • Alan Scoboria,

    Affiliation: Department of Psychology, University of Windsor, Windsor, Ontario, Canada

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  • Thomas J Moore,

    Affiliation: Institute for Safe Medication Practices, Huntingdon Valley, Pennsylvania, United States of America

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  • Blair T Johnson

    Affiliation: Center for Health, Intervention, and Prevention, University of Connecticut, Storrs, Connecticut, United States of America

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  • Published: February 26, 2008
  • DOI: 10.1371/journal.pmed.0050045

Reader Comments (48)

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The depressing news for antidepressants.

Posted by plosmedicine on 31 Mar 2009 at 00:21 GMT

Author: Tomi Gomory
Position: Associate Professor
Institution: College of Social Work, Florida State University
E-mail: tgomory@fsu.edu
Submitted Date: February 26, 2008
Published Date: February 27, 2008
This comment was originally posted as a “Reader Response” on the publication date indicated above. All Reader Responses are now available as comments.

I read with interest Kirsch et al. regarding the near identical clinical impact of inactive placebo and antidepressants on those diagnosed with DSM defined unipolar major depressive disorder.

The further finding of the somewhat diminished effect of placebo ( that is inactive placebo) on the extremely depressed, together with the finding of no change in drug effect along the continuum of all the depressed in the analysis raises the possibility that when you are extremely depressed (unhappy) your psychological machinery including the ability to believe that you are getting effective treatment via "inactive" placebo (one with no physiological stimulation) is compromised. That is, your hopeful expectation of improvement without some physiological cue (taking an inactive placebo pill) is harder to maintain in an extremely hopeless state. I think it would be very interesting to see how active placebo (one that provides physiological stimulation but has no impact on the targeted problem) would effect this? These results suggest that since inactive placebos are used by the FDA for their trials we may be underestimating the true placebo effect.

In addition, I was surprised to read in the editors' summary included in the article that "Depression is a serious medical illness caused by imbalances in the brain chemicals that regulate mood." This I believe is a hypothetical assertion that requires proof not yet achieved. For example, the DSM disorders as articulated by those who are responsible for these constructs, the American Psychiatric Association, in their publication that explains why yet another version must be forth coming shortly, "A research agenda for DSM-V" (2002), state very clearly that "In the more than 30 years since the introduction of the Feighner criteria ... which ... led to the DSM-III, the goal of validating these syndromes and discovering common etiologies has remained elusive. Despite many proposed candidates, not one laboratory marker has been found to be specific in identifying any of the DSM-defined syndromes... All these limitations ... suggest that research ... focused on ... the DSM-defined syndromes may never be successful in uncovering their underlying etiologies" (Introduction pp. xviii-xix).

That is, at present we are not even sure that these syndromes exist (are reliable and valid) although surely unhappiness (a continuum of depressive mood) does. So a distinguished journal like yours should be more careful in its presentation of what we actually know scientifically.

In fact you previously published at least one article arguing the deep problem with claiming that chemical imbalances are the cause of depression by Lacasse and Leo (2005).

Finally, the finding of the present article that placebo appears to be as clinically effective as antidepressants makes it rather strange to claim that in depression what is being "corrected" is a chemical imbalance and this is being done by way of a chemically inactive pill.

References:
Kupfer, D.J., First, M.B., & Regier, D.A. (2002). A research agenda for DSM-V. Washington, D.C.: American Psychiatric Association.

Lacasse J.R., Leo J. (2005). Serotonin and Depression: A Disconnect between the Advertisements and the Scientific Literature. PLoS Med 2(12): e392 doi:10.1371/journal.pmed.0020392

No competing interests declared.