New study says antidepressant not safe for adolescents

The new paper is published today in The BMJ.

Under a new initiative to publish corrections to misreported trials, the prestigious medical journal The BMJ (formerly known as the British Medical Journal) has published a study showing that the popular antidepressant paroxetine is neither safe nor effective for adolescents with depression. Jureidini cites a 2013 international researcher consortium known as “restoring invisible and abandoned trials” (RIAT) that says any research that has not been disclosed to the public should be made available, and that all misleading, or incorrect information should be revised.

Dr Fiona Godlee, editor of the BMJ, said the review of Study 329 meant an “iconic and infamous paper has now been brought to book”.

The original manuscript was not written by any of the 22 named authors, he points out, but by a writer from the drugs company.

Yet, through all of this controversy – and despite numerous calls that original study be retracted – the authors of Study 329, as well as the journal that published it, stood by their findings.

This re-examination was possible due to the release of previously confidential documents, and a new team of researchers took a hard look at the way the trial was conducted.

Millions of young people were prescribed a common anti-depressant on the basis of a notorious medical trial that actually showed the drug was neither safe nor effective in children and adolescents, a major review has confirmed. Their trial is the first to be re-analyzed under the new policy that seeks to correct any misreported studies.

The US Food and Drug Administration in 2002 said that the trial should be considered a failure because the depressed youth taking paroxetine didn’t do better compared to those taking the placebo. Moreover, both had caused increased harm measured in the teenager’s response, so much so that it became clinically significant. In 2003, the FDA began requiring a “black box” warning label describing a risk of suicidal thoughts for Paxil and other selective serotonin reuptake inhibitor antidepressants. “With every medication you need to think about the risk and the benefit”, he said.

“SNF allows us to get a really clear picture into the similarities and differences between patients”, says Dr. Anna Goldenberg, Scientist in Genetics &Genome Biology at SickKids and Assistant Professor in the Department of Computer Science at the University of Toronto, whose lab developed this novel approach. “Although concerns about patient confidentiality and “commercial in confidence” issues are important, the reanalysis of Study 329 illustrates the necessity of making primary trial data available to increase the rigour of evidence-based research”, he says.

“Importantly, the findings from this team’s analysis appear to be in line with the longstanding view that there is an increased risk of suicidality in pediatric and adolescent patients given antidepressants like paroxetine”, the company said in its statement. “As such, we don’t believe this re-analysis affects patient safety”, he added.

Responding to the BMJ study a GSK spokesperson said: “We were able to help this team to carry out their reanalysis by providing access to the detailed data from the original trial”.

“Regulatory research authorities should mandate that all data and protocols are accessible”, Jureidini said.