A perfect storm seems to be gathering over GlaxoSmithKline and research it funded to determine whether its antidepressant drug Paxil was effective in treating depression.
In March of this year, Australian researchers published an article in the International Journal of Risk and Safety in Medicine on one particular study of Paxil, known as study 329, that purported to show that the drug was more effective than a sugar pill or placebo in treating depression in adolescents. After re-examining raw data from the study, obtained from GlaxoSmithKline under subpoena, the IJRSM researchers instead concluded the data showed that Paxil was no more effective than placebo on all eight of the study’s pre-specified clinical outcome measures. They also found that after the study blind was broken, the researchers added a number of new outcome measures in order to show a statistically significant difference between Paxil and placebo. In other words, as the IJRSM paper concludes, the authors of study 329 manipulated the data. Shortly after this finding was published, Dr. David Egilman, a clinical associate professor at Brown University, filed an ethics complaint against Dr. Martin Keller, the principal investigator of study 329 and chief of psychiatry at Brown. Egilman says Brown’s provost wrote him a letter in May saying that the university reviewed the allegations against Keller, but declined to say what, if any, action it was taking against its long-time psychiatry head.
Likewise, in my book Side Effects: A Prosecutor, a Whistleblower and a Bestselling Antidepressant on Trial, due out Tuesday, I also reveal new information showing that Keller and his co-authors misrepresented data in study 329. In essence, Keller et al miscoded several teenagers as being noncompliant when in fact they were in fact suicidal, thus further skewing the results of this controversial study. Furthermore, as I show in my book, at the very same time Keller was touting study 329 as a positive finding for Paxil (even though the actual data showed the opposite), GlaxoSmithKline was paying him thousands of dollars in personal consulting income.
Finally, just last week, Senator Chuck Grassley (D-Iowa) released a report by Joseph Glenmullen, a Harvard psychiatry instructor, alleging that Glaxo researchers misrepresented data in an earlier study comparing the effectiveness of Paxil and placebo in treating depression in adults. In this 1989 clinical trial, which was used to gain FDA approval for Paxil, Glaxo counted as suicides in the placebo arm of the study, deaths that had actually occurred during the wash-out period of the study. The suicides, thus, occurred before the official start of the study and should not have been counted as placebo suicides, Glenmullen's report contends. Glenmullen prepared his analysis for a law firm who is suing GlaxoSmithKline, and he concludes that the wash-out suicides were included in the study to make Paxil look safer and more effective than it really was, according to The Wall Street Journal. The Journal quoted Glenmullen as saying, “Glaxo was aware of this risk and hid it.”
Taken together, all of this new evidence indicates that the real risk of suicidality from Paxil was far greater than its risk for patients on placebo. As Glenmullen notes in the Journal article, if the FDA had had the correct information back in 1991, when the agency first examined suicidal risks of the SSRI antidepressants, it might have issued warnings about these drugs then. Instead, the FDA didn’t require black box warnings about the suicidal effects of these drugs until 2004. And that raises the haunting question: How many young people’s lives were lost to suicide in the intervening 13 years?