Jay D. Amsterdam: The Paroxetine 352 Bipolar Study Ethical Conduct
Janusz Rybakowski’s comment
I would like to add a short comment to the endeavor of my long-lasting friend, Jay Amsterdam, to unmask industry corruption in psychiatric trials. That the participants in this rigamarole are prominent psychiatrists is probably one of the worst aspects of this.
The present story concerns the publication of Nemeroff, Evans, Gyulai et al. (2001) in the American Journal of Psychiatry, comparing imipramine and paroxetine as an add-on to a mood stabilizer in the treatment of bipolar depression. The paper presented the results of a multicenter Paroxetine 352 study carried out in the 1990s of which Jay Amsterdam was a Co-investigator. The results of the study showed that both paroxetine and imipramine were superior to placebo in patients with low (> 0.8 mmol/l) serum lithium levels and that, compared to imipramine, paroxetine resulted in a lower incidence of adverse effects.
Despite recruiting a substantial number of patients for this study, Jay Amsterdam was not listed among the authors and was only recognized in the Acknowledgments as a collaborating investigator. On the other hand, Dr. Laszlo Gyulai, from the University of Pennsylvania, providing a lower number of patients than Jay was among the authors, and, on some stage of the publication, was even considered to be the first author. The authors were also Dwight Evans, the future chairman of the Department of Psychiatry at Penn, and other prominent psychiatrists such as Charles Nemeroff, Gary Sachs and Charles Bowden. Jay Amsterdam became aware that the results of the study were about to be published in April 2001 and in the following two months had an excessive e-mail exchange with Dr. Karl Rickels, the supervisor of Dr. Gyulai. It resulted in Dr. Gyulai’s letter of apology to Dr. Amsterdam which was far from giving him satisfaction. Later, it also turned out that the paper was written by the STI (Scientific Therapeutic Information), hired by SmithKline Beecham, the producer of paroxetine.
Ten years later, Jay Amsterdam produced a complaint of scientific misconduct against Dwight Evans, Laszlo Gyulai, Charles Nemeroff, Gary Sachs and Charles Bowden for allowing their names to a manuscript that was “ghostwritten” by the STI. Additionally, he indicated several flaws of the paper of 2001, which was since this time been widely cited, among others, in the article published in such a prestigious journal as the New England Journal of Medicine (Sachs, Nierenberg, Calabrese et al. 2007). And another 10 years later the extensive documentation of this story is being displayed on the INHN site.
As the President of the Editorial Board of the main Polish psychiatric journal, Psychiatria Polska, I arranged a publication in this journal of the paper titled “Industry-corrupted psychiatric trials” written by Jay Amsterdam and co-authored by Leemon McHenry from the Department of Philosophy, California State University, Northridge, and Jon Jureidini from the University of Adelaide, Australia (Amsterdam, McHenry and Jureidini 2017).
The paper exposes the research misconduct of pharmaceutical industry-sponsored clinical trials via three short case studies of corrupted psychiatric trials that were conducted in the United States such as the SmithKline Beecham Paroxetine Study 329, Forest Laboratory Citalopram Study CIT-MD-18 and, last by not least, SmithKline Beecham Paroxetine Study 352. The common elements that enable the misrepresentation of clinical trial results include ghost-writing for medical journals, the role of key opinion leaders as co-conspirators with the pharmaceutical industry and the complicity of top medical journals in failing to uphold standards of science and peer review are discussed. The authors conclude that the corruption of industry-sponsored clinical trials is one of the major obstacles facing evidence-based medicine. Psychiatria Polska is a journal of international reputation (IF=1.657) and the paper has reached a wide audience.
Amsterdam JD, McHenry LB, Jureidini JN. Industry-corrupted psychiatric trials. Psychiatr Pol 2017;51:993-1008.
Nemeroff CB, Evans DL, Gyulai L, Sachs GS, Bowden CL, Gergel P, Oakes R, Pitts CD. Double-blind, placebo-controlled comparison of imipramine and paroxetine in the treatment of bipolar depression. Am J Psychiatry 2001;158(6):906-12.
Sachs GS, Nierenberg AA, Calabrese JR, Marangell LB, Wisniewski SR, Gyulai L, Friedman ES, Bowden CL, Fossey MD, Ostacher MJ, Ketter TA, Patel J, Hauser P, Rapport D, Martinez JM, Allen MH, Miklowitz DJ, Otto MW, Dennehy EB, Thase MiE . Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med 2007;356:1711-22.
May 12, 2022