A widely-used anti-depressant is “ineffective and unsafe” when it comes to treating children and adolescents, with an increased risk of suicidal behavior in some, according to a fresh analysis of the findings from a controversial drug trial.
The re-analysis – published by the British Medical Journal – contradicts the findings of the original trial, which concluded the drug paroxetine was suitable and safe for young people with severe depression.
“There were clinically significant increases in harms, including suicidal ideation and behaviour”
The original study, published in the American Journal of Child and Adolescent Psychiatry in 2001, was funded by drugs company SmithKline Beecham, now GlaxoSmithKline.
The study – known as Study 329 – was criticised and GlaxoSmithKline went on to be fined a record three billion dollars for fraudulently promoting paroxetine.
It is the first trial to be re-examined under a new scheme to ensure abandoned or misreported studies are published or corrected.
Using previously confidential documents, a team of researchers looked again at the trial, which compared the effectiveness and safety of anti-depressant drugs paroxetine and imipramine with a placebo in treating severely depressed adolescents.
They found both paroxetine and high dose imipramine were no more effective than the placebo, while the increased harm caused by both was clinically significant.
“Paroxetine was ineffective and unsafe in this study,” concluded the researchers, who were led by Professor Jon Jureidini at the University of Adelaide.
“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,” said the study authors in the BMJ.
The findings are likely to re-ignite calls for the original study to be retracted and for further investigations to take place.
“Findings from this team’s analysis appear to be in line with the longstanding view that there is an increased risk of suicidality in paediatric and adolescent patients given antidepressants like paroxetine”
The Restoring Invisible and Abandoned Trials project is part of a growing movement to ensure data from all clinical trials is transparent and available to all.
In a statement, GSK highlighted that it had helped the researchers by providing access to the detailed data from the original trial.
“This reflects our commitment to data transparency – we publish the results of all our studies regardless of whether they are positive or negative,” said a spokesman.
“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 paediatric and adolescent patients given antidepressants like paroxetine,” he said.
“This is widely known and clear warnings have been in place on the product label for more than a decade. As such, we don’t believe this re-analysis affects patient safety,” he added.