A long criticised study on antidepressant use in adolescents has been flagged with an “expression of concern” by a leading academic journal after the launch of legal action.12
George Murgatroyd III, a lawyer, is suing the publishing giant Elsevier, as well as the American Academy of Child and Adolescent Psychiatry, demanding the retraction of the 24 year old randomised trial.3
Concerns about the widely cited article—including numerous demands for retraction456—have been circulating for almost as long as the paper itself, and the trial, known as Study 329, is regularly referred to as one of the best examples of spin, misreporting, and ghostwriting in industry funded medical research.
In 2012 paroxetine’s manufacturer, GlaxoSmithKline (GSK), was fined a record $3bn (£2.27bn; €2.58bn), in part for illegally promoting paroxetine using the journal article.7 Published by the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP) in 2001, the article declared paroxetine “generally well tolerated and effective” in the treatment of major depression in adolescents—a conclusion the new lawsuit labels “false and deceptive.”
And by selling the article, priced online at $33-$41, Murgatroyd argues that the medical society and its publisher, Elsevier, are committing a “deceptive trade practice” in violation of consumer protection laws in Washington, DC, where the academy is based.
Lawsuits have triggered journals to retract studies in the past, but this may be the first time that a consumer protection law has been invoked.8 Murgatroyd told The BMJ, “I filed the suit because I thought I was going to be treated like those who tried before me. The DC consumer protection statute is the best in the country, and I wanted to try it out, although going after a medical journal was unprecedented.”
Elsevier declined to comment when contacted. The publisher and the American Academy of Child and Adolescent Psychiatry have until mid-November to respond to Murgatroyd’s complaint.
Controversy stretching back decades
Serious questions about how the JAACAP article presented its results emerged shortly after its 2001 publication, particularly about safety data.5 Concerns were raised about suicidal ideation, which the article had categorised under “emotional lability” and reported as unrelated.
There were soon calls for retraction. Suicidality, self-harm, and the withdrawal risks of paroxetine were the subject of a BBC Panorama investigation in 2002,9 and in 2003 the UK’s Medicines and Healthcare Products Regulatory Agency warned of a 1.5-3.2 times higher risk of suicidal behaviour when taking the drug. Other regulators, including the US Food and Drug Administration, subsequently issued similar warnings.10
In 2008, on the basis of internal GSK documents made available during a class action lawsuit, the Australia based child psychiatrist Jon Jureidini and colleagues revealed that the JAACAP article had selectively reported its efficacy results.11
The protocol for Study 329 pre-specified two primary and six secondary endpoints. Paroxetine failed to show superiority over placebo on all eight. However, the JAACAP article presented a new endpoint as “primary” and stated that it “separated statistically from placebo.”
What did the study authors know?
GSK’s aggressive marketing of paroxetine for adolescents concealed the fact that the company long knew of the trial’s “disappointing” results. A confidential October 1998 memo stated that the study results “show that there were no statistically significant differences from placebo on either of the primary efficacy parameters.”12
But it seems from documents identified in the new lawsuit that the paper’s named authors had limited understanding of GSK’s internal evaluations. When the 1998 memo later came to the attention of Martin Keller, now professor emeritus of psychiatry and human behaviour at Brown University and first author of the JAACAP paper, he sent GSK an urgent email. He asked a GSK contact, “If GSK deemed the study negative in 19888 [sic], why did we deem the study positive in 2001?”
Although the authors have defended their article, the first draft of the manuscript was not written by Keller or any of his 21 named coauthors but instead by Sally Laden, a hired medical writer who is credited in a footnote to the article as providing “editorial assistance.” Keller did not respond to a request for comment.
Calls to retract Keller’s article have come from both within and without the academy. But despite the sustained pressure the journal elected not to take any corrective action.6
After GSK’s guilty plea and $3bn settlement with the US Department of Justice in 2012, JAACAP’s then editor in chief, Andrés Martin, wrote to Jureidini, “After a comprehensive and extensive review, the Journal editors found no basis for retraction or other editorial action . . . The inquiry is considered complete.”
Nor did the journal act after a major reanalysis of Study 329, based on tens of thousands of pages of original trial documents and published in The BMJ in 2015, which reported finding “clinically significant increases in harms, including suicidal ideation and behaviour.”13
Martin and the American Academy of Child and Adolescent Psychiatry did not respond to a request seeking comment on the new lawsuit.
Is retraction imminent?
Jureidini sees the new expression of concern as a sign that this time will be different. He told The BMJ that a retraction would carry “huge ramifications for authors and journals and their editors,” but he noted the long timeline. A retraction 10 or 20 years ago, he said, “could have saved lives.” Paroxetine has been a heavily prescribed selective serotonin reuptake inhibitor (SSRI) for children and adolescents despite no major regulator ever approving its use in that population.
Murgatroyd told The BMJ he was confident that he would prevail in getting the JAACAP paper retracted. He has intimate experience with Study 329 from his work as an attorney involved in SSRI litigation, including paroxetine.
In 2006 and 2007 Murgatroyd conducted depositions of Keller and other authors of Study 329 and has extensive access to GSK documents. “Basically, I have the goods,” he said. “GSK and the authors of the Keller article created a monster. JAACAP and Elsevier set it loose on the world. The EOC [expression of concern] wounded the monster, and I am now trying to kill it with retraction.”
GSK did not respond to a request for comment.
Footnotes
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Competing interests: I have read and understood the BMJ Group policy on declaration of interests and declare I am the first author of the RIAT declaration, which was coauthored by David Healy, who is part of the group that included Jureidini and reanalysed Study 329. I served as a formal peer reviewer for the reanalysis manuscript and provided Jureidini’s team with unpaid advice on the RIAT process before the paper was submitted and while it was under review. I am also a graduate of Brown University and a decade ago was an active member of a Cochrane review of neuraminidase inhibitors based in part on clinical study reports provided by GSK for zanamivir. I initiated an inquiry in 2012 that resulted in additional information from clinical study reports of Study 329 and eight other studies being posted on GSK’s website. From 2019 to 2020 the RIAT Support Center (which I lead, based at the University of Maryland) provided a grant to Jureidini to reanalyse the TADS study of antidepressants in adolescents.
