The commonly prescribed antidepressant Paxil (paroxetine) is unsafe for teens, according to a new paper that reanalyzed data from a study published 14 years ago. The new paper, published Thursday in The BMJ (formerly British Medical Journal), contradicts the study's original findings that the drug is "generally well tolerated and effective" for treating severe clinical depression in adolescents.
GlaxoSmithKline (GSK), the maker of the drug, funded the original trial, Study 329, which compared the efficacy of paroxetine and imipramine, an antidepressant know to consumers as Tofranil, to a placebo. The study involved 275 adolescents, aged 12 to 18, with major depression. Each took one of the two drugs or a placebo for at least eight weeks. The Journal of the American Academy of Child and Adolescent Psychiatry published the original study in 2001.
A look at the U.S. Food and Drug Administration's initial impression of the trial makes the drug's use by teens even more puzzling. In 2002, a FDA official who reviewed the data said the findings indicated that the trial had failed because the patients in treatment groups didn't experience more significant improvement in their depression symptoms than patients in the placebo group. The authors of the new paper also say that "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."
However, that year physicians wrote some 2 million Paxil prescriptions for children and teens. Eventually, in 2012, the pharmaceutical company was fined $3 billion for fraudulently promoting the drug.
In response, GSK said the paper didn't provide any new information because Paxil, like all other serotonin reuptake inhibitors, includes a black box warning alerting patients of the increased risk for suicide.
The new paper is part of The BMJ's initiative called "Restoring Invisible and Abandoned Trials" (RIAT), which is encouraging the review of already published studies that may require more scrutiny. The journal says the effort is to "ensure doctors and patients have complete and accurate information to make treatment decisions."
The RIAT team's reanalysis concludes that the study "illustrates the necessity of making primary trial data and protocols available to increase the rigor of the evidence base."
Additionally, it has since been found that the original paper wasn't actually written by any of the 22 researchers involved in the study, but instead was assigned to a medical writer by the pharmaceutical company. An accompanying paper in The BMJ argues that the original paper should be retracted. The BMJ says the American Academy of Child and Adolescent Psychiatry as well as the journal editors have yet to issue a response.
Dr. Fiona Godlee, editor-in-chief of The BMJ, said in a press statement that this new paper "shows the extent to which drug regulation is failing us." Godlee says too many studies are funded by companies with a vested financial interest in seeing the drug succeed, rather than independent investors. She argues that it may be time for legislation that requires more transparency, such as having clinical data from studies made accessible to everyone.
The number of retracted scientific medical studies has surged in recent years. It's unclear whether mistakes or biased data analysis have become more prevalent or whether the increase in retractions is a result of scientists more closely scrutinizing study findings for biases and mistakes.
A study published in 2012 in the Proceedings for the National Academy of Sciences analyzed 2,047 medical and life science studies and found that just 21.3 percent of retractions were due to error. A majority, 67.4 percent, were due to misconduct, including fraud, suspected fraud, duplicate publication and plagiarism. The researchers found the number of retractions because of fraud has increased tenfold since 1975.
In an effort to call attention to transparency in science, a number of researchers have set about conducting projects that seek to reproduce the results of published studies. Recently, a group of psychology researchers tried to replicate 100 studies and found that less than half actually held up. Another group of researchers sought to replicate the findings of 53 cancer studies, and only six actually made the cut.
