Drug study review spots new risks
Fourteen years ago, GlaxoSmithKline published a study claiming the antidepressant paroxetine was safe and effective for teenagers, but now researchers say the opposite is true.
A major reanalysis published in the BMJ includes tens of thousands of pages of original trial documents from GlaxoSmithKline’s infamous Study 329.
The new paper concludes that the antidepressant paroxetine (originally marketed in Australia by GlaxoSmithKline under the brand name Aropax) is neither safe nor effective in adolescents with depression.
This conclusion, drawn by independent researchers, is in direct contrast to that of the trial’s original journal publication in 2001, which had proclaimed paroxetine “generally well tolerated and effective.”
The review has reignited calls for retraction of the original study, putting additional pressure on academic and professional institutions to publicly address the many allegations of wrongdoing.
Questions have been circulating since the 2001 study came out, amid the so-called antidepressant wars of the early 2000s.
At this time, the makers of Paxil and similar drugs started using labels announcing the potential suicide risk for children, adolescents and young adults.
In the years since the study first purported the low risk of deadly sideffects associated with Paxil, thousands of people under the effect of or withdrawing from Paxil and other psychiatric drugs have committed violent acts, including suicide, experts say.
“This paper is alarming, but its existence is a good thing,” said Brian Nosek, a professor of psychology at the University of Virginia, who was not involved in either the original study or the reanalysis.
“It signals that the community is waking up, checking its work and doing what science is supposed to do — self-correct.”
The review is part of the restoring invisible and abandoned trials (RIAT) initiative, a movement across the research world to create a new level of transparency in scientific work.
The original research, led by Dr Martin Keller of Brown University, tracked depression levels in three groups of about 90 adolescents each over eight weeks.
One group took Paxil, one was on placebo pills and one taking imipramine, an older generic drug for depression.
The Paxil group did no better than the other groups according to the study’s measure of depression, but it rated higher on other, “secondary” measures, like another scale of mood problems, the authors say.
But these days, researchers consider secondary measures about as good as circumstantial evidence – it can be meaningful but is barely comparable the strength of primary measures.
Critics surfaced as soon as the study it was published in the Journal of the American Academy of Child and Adolescent Psychiatry.
They argued that the report was not at all convincing, and played down serious side effects.
It has now been formally reviewed by a team including Australian experts.
“We felt that bad prescribing decisions were being made on the basis of the way in which the study was reported,” Adelaide University researcher Professor Jon Jureidini told the ABC this week.
Dr Jureidini led the international review team.
“The study claimed to show that paroxetine, an anti-depressant, was effective and safe for young people and in fact, it's the opposite.”
The team found that the drug had twice the level of severe adverse effects across, and four times the number of psychiatric adverse events than suggested in the primary research.
“Eleven patients experienced suicidal behaviour or self-harm out of less than 100 in the paroxetine group compared to just one in the placebo group,” he said.
The reviewers have emphatically warned that their study should not cause people currently prescribed paroxetine to stop taking their medication, and urges them to refer any questions to their doctor.
The authors of the original study have emphatically denied the findings of the new review.
They have issued a statement disputing the reassessment of their work, saying they incorporated secondary measures before knowing which patients were taking paroxetine and which were not — not afterward, as the new analysis claims.
“In summary, to describe our trial as ‘misreported’ is pejorative and wrong,” they conclude.
For many, the push to review and re-evaluate long-relied-upon studies like this reflects a new era in scientific publishing.
It is hoped that the shifting culture will open the way for journals to post multiple interpretations of the same experiment, giving scientists and potential patients an even more rounded and objective view than before.