A 2003 paper may have left out potentially “significant” data on the long-term side-effects of an antipsychotic drug used in children, according to a former head of the U.S. Food and Drug Administration.

As reported by the Toronto Star, David Kessler is alleging that Janssen, the maker of Risperdal (and owned by Johnson & Johnson), omitted data about the risks of the drug: In particular, that boys who use it over a long period may be at risk of growing breasts.

There’s anecdotal evidence of the side effect. One family claimed the drug had caused their son to grow a pair of 46 DD-sized breasts in a lawsuit against Johnson & Johnson, reported the Wall Street Journal in February. They won, to the tune of $2.5 million. The suit is apparently just one of 1,200 like it.

The abstract of the paper, “Prolactin levels during long-term risperidone treatment in children and adolescents,” published in The Journal of Clinical Psychiatry, suggests that levels of a key hormone aren’t a problem in the long term:

With long-term risperidone treatment in children and adolescents, serum prolactin levels tended to rise and peak within the first 1 to 2 months and then steadily decline to values within or very close to the normal range by 3 to 5 months.

But the published article — since cited 78 times, according to Thomson Scientific’s Web of Knowledge — allegedly left out something “flagged as ‘significant'” from an earlier draft, as the Star reports:

The medical article was singled out in recent U.S. lawsuits against Janssen [a company under the J&J umbrella] as an alleged example of drug company influence on doctors and published research. A court exhibit shows a draft of the study describing an association with certain side-effects — a finding that a Janssen employee internally flagged as “significant.” This information is not in the published version of the article. “My name is on an article in which there is some data that has been left out. That, to me, crosses a line,” [Denis] Daneman, pediatrician-in-chief at the Hospital for Sick Children [in Toronto], told the Star. For now, we don’t know what those data are. Neither does Robert Findling, the first author of the paper and a psychiatrist for kids and teens at Johns Hopkins. He provided this statement, via the Johns Hopkins Medicine communications office:

At the time of manuscript submission, I was confident in the accuracy of the information provided and in the interpretation of the study results. However, in light of ongoing scrutiny of Risperdal, I became concerned about the questions raised and if there are errors. I am committed to determining what they may be and to correcting them. Due to the proprietary nature of the study, access to the data needs to be authorized by Janssen, a subsidiary of Johnson & Johnson. I reached out to them to request a complete set of the data so that a comprehensive review of the findings, including a reanalysis of all data by an independent biostatistician, can be conducted. That independent review is currently under way. Based on the findings, we will decide whether the paper warrants full retraction, a partial correction or whether the original findings stand.

A spokesperson for Janssen told us that the omitted data weren’t significant:

…all results of the analysis that were clinically meaningful in addressing the research question were included in the published paper as is customary in scientific studies.

This article isn’t the only one under scrutiny, according to a report by Kessler mentioned by the Star:

The report, filed in U.S. court, said Janssen “controlled and influenced” more than 40 manuscripts, including the one co-authored by Daneman. Kessler called the company’s alleged promotion of the drug for unapproved use in vulnerable children “deeply troubling.”

A Janssen spokesperson told the Star:

We do not agree with Dr. Kessler’s opinions expressed in his report.

A current version of the side effect literature for the Risperdal notes the problems with the hormone prolactin, in the short term:

RISPERDAL® has been shown to elevate prolactin levels in children and adolescents as well as in adults [see Warnings and Precautions (5.6)]. The company also notes that abnormal breast enlargement occurs in a small number of cases: In clinical trials in 1885 children and adolescents…gynecomastia was reported in 2.3% of RISPERDAL®-treated patients. It doesn’t provide insight into what happens over the course of years, though: The long-term effects of ­RISPERDAL® on growth and sexual maturation have not been fully evaluated in children and adolescents. We asked a Janssen spokesperson for more details about these clinical trials of breast growth: …the data were derived from both short-term placebo-controlled trials and longer-term uncontrolled studies in pediatric patients (ages 5 to 17 years) with schizophrenia, bipolar disorder, autistic disorder or other psychiatric disorders. The short-term studies were 3-8 weeks, and the long-term, open-label studies were generally a year in duration. J&J’s Janssen previously made an appearance on this blog in 2012, for corrections to a paper it produced on an antidepressant. As we noted: …the authors, headed by Pascal Bonaventure, made two mistakes, originally noted by U.K.-based blogger NeuroSkeptic: In the abstract that noted that the treatment with the drug was “statistically significant” compared with a placebo (it wasn’t) and the group mistakenly refers to citalopram (Celexa) as a positive depression drug control when they really meant escitalopram (Lexapro). Like Retraction Watch? Consider supporting our growth. You can also follow us on Twitter, like us on Facebook, add us to your RSS reader, and sign up on our homepage for an email every time there’s a new post. Click here to review our Comments Policy.

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