Neurology -- Correspondence for Ettinger, 67 (11) 1916-1925

Correspondence published:

Psychotropic effects of antiepileptic drugs: Laura S. Boylan (15 July 2007)

Reply from the Author: Alan B. Ettinger, M.D. (15 July 2007)

Psychotropic effects of antiepileptic drugs 15 July 2007

Laura S. Boylan,
New York University School of Medicine
462 First Avenue H7W11, New York, NY
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Re: Psychotropic effects of antiepileptic drugs

laura.boylan{at}med.nyu.edu Laura S. Boylan

I read the recent article by Dr. Ettinger with interest. [1] The acknowledgements and disclosures accompanying a recent review article on “Psychotropic effects of antiepileptic drugs” are puzzling. The article is “Funded through an unrestricted educational grant from GlaxoSmithKline” yet states “Disclosure: The authors report no conflict of interest.” I ask the editors to clarify both this apparent contradiction and the journal’s policy on industry sponsorship of review articles.
Dr. Ettinger reports that “only a few clinical trials have evaluated the mood-modifying effects of AEDs in patients with epilepsy” [1]; however, there is substantial data about adverse psychiatric events available from the pivotal randomized controlled trials of AEDs for seizure control in epilepsy. For example, depression was noted as an adverse event more often than in placebo and in more than 2% of patients in the pivotal trials for felbamate, gabapentin, lamotrigine, levetiracetam, tiagabine, topiramate and zonisamide.[2] However, phenytoin, an older, less expensive generic medication, is cited as having a probable association with depressive symptomatology without citation of evidence.
The choice of phenytoin is ironic given the excitement in the Nixon era over the antidepressant properties of phenytoin. [3]
References
1. Ettinger AB. Psychotropic effects of antiepileptic drugs. Neurology 2006;67(11):1916-1925.
2. Boylan LS, Devinsky O, Barry JJ, Ketter TA. Psychiatric uses of antiepileptic treatments. Epilepsy Behav 2002;3(5S):54-59.
3. New York Times. Shangri-La In a Bottle?; A Wall Street Lion's Campaign to Promote A 'Miracle Drug'. Barry Meier. October 24, 2000.
Disclosure: The author reports no conflicts of interest.
Editor’s note: Dr. Ettinger acknowledged above the Disclosure statement for the article that his work is funded through an unrestricted educational grant (a grant allowing scholarly activities to be pursued without influence by the granting agency). At the time of publication, the statement fulfilled the journal’s criteria for disclosure. Neurology® now requires authors of all submitted manuscripts to disclose all funding activities within the Disclosure statement so that readers have the opportunity to review all Neurology® content for potential bias.

Reply from the Author 15 July 2007

Alan B. Ettinger, M.D.,
North Shore-LIJ Comprehensive Epilepsy Centers
New Hyde Park, NY
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Re: Reply from the Author

AEttinge{at}lij.edu Alan B. Ettinger, M.D.

I read Dr. Boylan’s comments with interest. This writer’s emphasis on pivotal antiepileptic drug trials for information about psychotropic effects misses essential points about the nature of this literature. Pivotal trials are not designed to study psychotropic effects. At best, they include various mood scales and misrepresent psychotropic effects.
My review clearly provided references showing that allusions to phenytoin’s potential effect on mood should be interpreted with caution given that most of that information is based upon “older, review article-based literature”. Asserting that phenytoin has antidepressant properties and referencing unjustified excitement about it in the Nixon era is inappropriate for a scholarly, data-driven review.
Contrary to this letter’s implication, there was no conflict of interest in the generation of my review article. Based on this line of thinking, any drug studies developed by pharmaceutical companies including pivotal trials should be excluded from publication. Unrestricted educational grants are specifically designed to allow scholarly activities to be undertaken without any influence upon the conduct of the activity by the granting agency.
My review encompassed all antiepileptic drugs and summarized positive and negative psychotropic properties based upon methodologically sound studies. This article underwent a rigorous peer review process. IMPRINT Science received instructions from me on assembling the voluminous references required to formulate this comprehensive article and assisted in formatting tables. Neither IMPRINT Science nor the sponsor performed a revision of the manuscript. I received no compensation for writing this article and I strictly adhered to the conflict of interest guidelines of Neurology.
Disclosure: The author reports no conflicts of interest.The article to which this correspondence refers was funded through an unrestricted educational grant from GlaxoSmithKline.