A few years ago, a neighbor, having just switched antidepressant drugs, walked into his daughter’s room, exchanged a few words and then walked into the bathroom and blew his brains out. At the time, according to news agencies, there had been a rise in suicides among individuals taking anti-depressants, particularly in the population that was switching their prescription. My neighbor became one of those statistics.
I do not remember whether my neighbor had been on Paxil (Paroxetine) or had just switched to Paroxetine. However, the British Journal of Medicine recently published a re-analysis of Paroxetine. Unfortunately, the corrected analysis showed that Paroxetine indeed increases risks of suicide in young people and adolescents.
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.
Conclusions Neither paroxetine nor high dose imipramine showed efficacy for major depression in adolescents, and there was an increase in harms with both drugs.1
A study funded by SmithKline Beecham (SKB; subsequently GlaxoSmithKline, GSK), the British multi-national pharmaceutical company that produced Paxil, had been done in 2001 that claimed no association between Paxil and suicide.
A group of international researchers concerned by the amount of selective reporting of outcomes found in research papers created an initiative called “restoring invisible and abandoned trials” (RIAT). Doing their own research into publishing undisclosed outcomes or correct misleading publications, the initiative has been actively seeking and correcting publications that fit this profile. Their findings dispute the claims made by GSK regarding Paxil.
According to the British Journal of Medicine (BJM)
We acknowledge the work of the original investigators. This double blinded randomised controlled trial to evaluate the efficacy and safety of paroxetine and imipramine compared with placebo for adolescents diagnosed with major depression was reported in the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP) in 2001, with Martin Keller as the primary author.2
According to BJM
The RIAT researchers identified Study 329 [study done on Paroxetine] as an example of a misreported trial in need of restoration. The article by Keller and colleagues, which was largely ghostwritten,3 claimed efficacy and safety for paroxetine that was at odds with the data.4 This is problematic because the article has been influential in the literature supporting the use of antidepressants in adolescents.
Martha Rosenberg, an award-winning investigative public health reporter, found that the 22 doctors and researchers listed as authors in the original research paper
were not authors at all and that the research was actually written by a medical communication company (MCC) that GSK hired. Such ghostwriting is disturbingly common in establishing drug safety.
“You did a superb job with this,” wrote the paper’s first “author,” Brown University’s Martin Keller to Sally Laden, a ghostwriter working for the MCC Scientific Therapeutics Information. “It is excellent. Enclosed are rather minor changes from me. In 2006, Keller, former Brown Professor Emeritus of Psychiatry, acknowledged that GSK had given him tens of thousands of dollars during and after the time the study was conducted.
When RIAT approached GSK in 2013 asking whether they would produce a corrected paper on the side effects of paroxetine, GSK
did not signal any intent to publish a corrected version of any of its trials. In later correspondence, GSK stated that the study by Keller and colleagues “accurately reflects the honestly-held views of the clinical investigator authors” and that GSK did ‘not agree that the article is false, fraudulent or misleading.’
Research studies are not cheap to perform. Thus, many pharmaceutical studies are based on how much money the potential drug can produce rather than on the efficacy of the drug. We live in times when money speaks much more loudly than services or health [please check the many articles in this blog that I have written on the abuses expressed by pharmaceutical companies].
Although there are governmental bodies in place that have been created to protect consumers, often these bodies turn a blind eye. In fact, the health industry presently is one of the largest profit bearing industries and when there is a lot of money involved, much gets overlooked. Obviously not all drugs produced have fraudulent studies or focus their studies on the monetary benefits rather than the health benefits of a drug. But there are too many drugs being allowed on the market that have not been sufficiently researched.
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.
Pharmaceutical companies have to take more responsibility than small print warnings scrolling across the bottom of the Television screen as idyllic scenes with a soothing voice-over laud the benefits of a drug. They also need to reflect on the potential impropriety of buying doctors a huge lunch in order to have their ear regarding the latest and greatest drug they are marketing. On the other hand, doctors need to take more time to do their own research before prescribing a drug and consumers need to be more vigilant in the doctor’s office.
copyright Yvonne Behrens 2015