With permission from
by: Jennifer Lea Reynolds
September 29, 2015
In 2001, a study was published that had many people singing the praises of an adolescent antidepressant chemically known as Paroxetine. Since then, it’s been sold in the UK as Seroxat and in the US as Paxil. That study, which was published in the Journal of the American Academy of Child & Adolescent Psychiatry, concluded that “Paroxetine is generally well tolerated and effective for major depression in adolescents.”
In the years following that study, serious problems emerged that raised questions about just how well-tolerated and effective Paroxetine really is. Numerous stories came to light about the possibility of the drug actually worsening depression instead of improving it in those aged 18 or younger. Other stories came out that seemed to show associations between the drug and suicidal tendencies. How could this come from a drug designed to lift mood? In response, labeling for the drug began carrying warnings about a possible suicide risk. Nevertheless, GlaxoSmithKline (GSK) stood by Paroxetine, holding tight to the positive findings from the aforementioned 2001 study.
Previously published information about adolescent antidepressant reanalyzed, findings are shocking
However, GSK and others who think it’s a good idea to cling to studies published nearly 15 years ago are (hopefully) wising up thanks to a recent study published in the journal BMJ. In a shocking look that sheds light on the importance of questioning heralded studies and the intentions of drug companies, the study found that basically everything in the initial Paroxetine study was essentially false. In a nutshell, experts said that just the opposite of what was reported in 2001 was true.
The article that blew the lid off the previous study is titled “Restoring Study 329: efficacy and harms of Paroxetine and imipramine in treatment of major depression in adolescence.” Its aim was to “reanalyse SmithKline Beecham’s [subsequently GSK] Study 329” to determine its efficacy and safety in adolescents with unipolar major depression.
The eye-opening results were noted as follows:
The efficacy of Paroxetine and imipramine was not statistically or clinically significantly different from placebo for any prespecified primary or secondary efficacy outcome. There were clinically significant increases in harms, including suicidal ideation and behaviour and other serious adverse events in the Paroxetine group and cardiovascular problems in the imipramine group.
Suicidal behaviors ignored, health events brushed aside
It was found that information in the initial study was not properly reported, including the amount of suicidal behaviors that were overlooked. As if that weren’t disturbing enough, the paper notes that the drug’s effects were often masked or inappropriately grouped and that reported events weren’t transcribed from clinical records to larger databases. Events were ignored, coding was altered in order to diminish the severity of situations, and people were restricted regarding the level of detail in which they could report the adverse effects they were experiencing.
Additionally, the latest study suggests that engaging in reanalysis efforts on a more regular basis is essential. Instead of turning to older studies and taking them for truth year after year, it’s necessary to revisit methods and analyses and take new, post-study knowledge into consideration. More importantly, it is vital that information that is found to be incorrect is retracted and not sitting out there for medical professionals to continually reference. Studies should be revisited, methods should be more carefully assessed, and the regulation industry should come under closer scrutiny in light of this discovery.
Reanalysis stresses importance of questioning older studies that are still applauded and the need to retract outdated or false information
The recent finding stresses the need to address older studies that are still referred to today:
Access to primary data from trials has important implications for both clinical practice and research, including that published conclusions about efficacy and safety should not be read as authoritative. The reanalysis of Study 329 illustrates the necessity of making primary trial data and protocols available to increase the rigour of the evidence base.
Furthermore, those responding to this discovery say that the right people should step up to the plate to admit ill-intentioned work and then take steps to address the situation. One such person is BMJ associate editor Peter Doshi. He says the reanalysis “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.”
“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.”