Critical Article on the Efficacy of Psychiatric Medication

There is a seminal article in this month’s British Journal of Psychiatry by Leucht, Hierl, Kissling, Dold, and Davis.  The authors did some heavy lifting in the analysis of 6175 Medline abstracts and 1830 Cochrane reviews to eventually compare 94 meta-analyses of 48 drugs in 20 medical diseases and 33 meta-analyses of 16 drugs in 8 psychiatric disorders.  The authors have produced a graphic comparing the Standard mean difference of effect sizes between the general medicine drugs and the psychiatric drugs.  It is apparent from that graphic that the psychiatric drugs are well within the range of efficacies of the general medical drugs.

This is an outstanding study that merits reading on several levels.  The authors have used state of the art approaches to meta-analysis following suggested conventions.  They provide the summary of the studies reviewed and actual details of their calculations in the accompanying tables. (the document including references and PRISMA diagrams is 59 pages long.)  They have a comparison of standard criticisms of psychiatric drugs and illustrate how the criticisms are not fair and the toxicity considerations are often greater in the general medicine drugs than the psychiatric drugs. 

This paper should be read by all psychiatrists since it is an excellent illustration of an approach to large scale data analysis using modern statistical techniques.  It is a good example of the application of the discussion by Ghaemi of hypothesis testing statistics versus effect estimation.  The authors also have an awareness of the limitations of statistics that the detractors of psychiatric care seem to lack.  Their statements are qualified but they provide the appropriate context for decision making about these medications and the implication is that decision matrix is clearly squarely in the realm of other medical treatments in medicine.

From the standpoint of the media and the associated politics it will also be interesting to see if this article gets coverage relative to the articles that have been extremely critical of psychiatric drugs.  I can say that I have provided the link to the article by Davis, et al on the issue of antidepressant effectiveness to several journalists including the New York Times and it was ignored.  The press clearly only wants to tell the story against antidepressants and psychiatric medications.

Never let it be said that any aspect of psychiatric treatment gets objective coverage in the press.  That problem and the lack of investigation of that problem is so glaring at this point that the press lacks credibility in any discussion of psychiatric treatment.

George Dawson, MD

Leucht S, Hierl S, Kissling W, Dold M, Davis JM. Putting the efficacy of psychiatric and general medicine medication into perspective:review of meta-analyses. Br J Psychiatry. 2012 Feb;200:97-106. PubMed PMID: 22297588

S. Nassir Ghaemi (2009) A Clinician’s Guide to Statistics and Epidemiology in Mental Health: Measuring Truth and Uncertainty.  Cambridge University Press, New York.

Davis JM, Giakas WJ, Qu J, Prasad P, Leucht S. Should we treat depression with drugs or psychological interventions? A reply to Ioannidis. Philos Ethics Humanit Med. 2011 May 10;6:8.

Seemuller F, Moller HJ, Dittmann S, Musil R. Is the efficacy of psychopharmacological drugs comparable to the efficacy of general medicine medication? BMC Med. 2012 Feb 15;10(1):17. Free full text commentary on the main article from another journal    -      download the pdf.

Antidepressants - the limited analysis of a polarized argument

The current President John Oldham and President-elect Jeffrey Lieberman of the American Psychiatric Association came out with this press release today on a 60 Minutes episode characterizing antidepressants as no better than placebo.  They describe this characterization as “irresponsible and dangerous reporting” and “a message that could potentially cause suffering and harm to patients with mood disorders.”

It is good to see the APA finally taking a stand on this issue.  Antidepressants and the psychiatrists who prescribe them have been taking a pounding in the popular press for years.  The main proponent here was also featured in a Newsweek headline story two years ago.  This is a prototypical example of how the media and special interest groups can distort science and facts and politicize the discussion that must be nuanced.  The problem is that you have to know something and be fairly free of bias to participate in a nuanced discussion.  Like most issues pertaining to psychiatry, the issue is always polarized and poorly discussed in the media.

I got involved in this issue as a managing editor of an Internet journal and I solicited a paper from a world renowned epidemiologist to get his current view on antidepressant meta-analyses. In order to present the entire argument I also solicited response from a world renowned psychopharmacologist with broad expertise in this field. Both articles are available online for free and I think if they are both read in total they represent the most accurate picture of antidepressant response.  Both references are listed at the bottom of this page.

Rather than get into the specific details at this point I will say that it was extremely difficult to find a anyone willing to provide a rebuttal to the to the original article by Ioannidis, but anyone who reads that paper by Davis, et al and who follows the antidepressant literature will have a greater appreciation of the effectiveness of these medications.  I hope to post some information on the statistical analysis as well.  At some level people tend to view statistics as a hard mathematical science and there is plenty of room for interpretation.  The use of meta-analysis is a common approach to these problems and a detailed look at the shortcomings of meta-analysis are seldom discussed.  That might explain why one meta-analysis shows minimal effects and another shows that there might be some antidepressants with unique effectiveness (see Cipriani, et al)

A final dimension that is critical in the analysis of any source is potential conflicts of interest.  The only conflict of interest that is typically discussed is the financial interests of authors and pharmaceutical companies in producing positive trials.  That ignores the fact that many of these trials have been very public failures and that post trial surveillance limits the use of some of these compounds.  There are other conflicts of interest to consider when an author is selling a viewpoint and can potentially profit from it – either financially or politically.

The APA could provide a valuable service here in making the documents from the FDA and the EMA widely available for public discussion and analysis.

George Dawson, MD

 “60 Minutes” Segment on Antidepressants "Irresponsible and Dangerous" – APA New release Febrary 22, 2012.

Ioannidis JP. Effectiveness of antidepressants: an evidence myth constructed

from a thousand randomized trials? Philos Ethics Humanit Med. 2008 May 27;3:14.

Davis JM, Giakas WJ, Qu J, Prasad P, Leucht S. Should we treat depression with drugs or psychological interventions? A reply to Ioannidis. Philos Ethics Humanit Med. 2011 May 10;6:8.

Cipriani A, Furukawa TA, Salanti G, Geddes JR, et al.  Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis.  The Lancet - 28 February 2009 ( Vol. 373, Issue 9665, Pages 746-758 )