Bicyclic Antidepressants - Controversy

Controversy

• Ghost writing of studies for industry-sponsored drug trials is common. Of all 44 trial which was approved between 1994 and 1995 by the ethics committees of Copenhagen and Frederiksberg in Denmark, up to 91%, that is 40 of the 44 trials, has some form of ghostwriting, and for the most part, the ghost was a statistician. Cases relating to gabapentin, paroxetine, sertraline, fenfluramine/phentermine (fen-phen) are well documented, while many others, relating to olanzapine, quetiapine,remain under seal by the courts.
• Publication bias. Trials for which results were unfavourable were less likely to be published. Published data suggest a favourable risk-benefit profile for some SSRIs; however, addition of unpublished data indicates that risks could outweigh benefits of these drug to treat depression in children and young people. Of 90 drugs approved by the FDA between 1998 and 2000,the trials which did not show statistically significant results were 34% less likely to have been published, on the other hand, positive results are often published more than once. Based on Healy's examination of the data produced from the Cochrane study of Olanzapine for schizophrenia, the four initial trials of Zyprexa gave rise to 234 publications, most of which were ghost written.
• Lack of access to raw data, data suppression, misrepresentation, and manipulation has eroded value of trial results. Demands on access to data has been met by resistance on the part of industry.
• Questionable efficacy for most SSRIs was brought to light when a meta-analysis by UK, US and Canadian researchers, published in 2008, surveyed all pharmaceutical-company-sponsored drug trials on the six most widely prescribed new-generation antidepressants submitted for approval to the FDA between 1987 and 1999. The results showed that the difference in efficacy between antidepressants and placebo was minimal, but that it increased from virtually no difference at moderate levels of initial depression to a relatively small difference for patients with very severe depression. The difference reached conventional criteria for clinical significance for patients at the upper end of the very severely depressed category, due to a reduction in the efficacy of placebo. The study received widespread media coverage in some countries, but was met with criticism from the professional community.

Eli Lilly and Company responded by highlighting that the study did not take into account more recent studies on its product, Prozac, and that it was proud of the difference Prozac has made to millions of people. GlaxoSmithKline warned that this one study should not be used to cause unnecessary alarm and concern for patients. Wyeth pointed out that the data were good enough for FDA approval of the drugs. Two leading UK psychiatrists/pharmacologists, with financial and professional links to pharmaceutical companies, argued that short-term approval trials are not very suitable for evaluating effectiveness, that the unpublished trials are of poorer quality, that the meta-analysis authors came from a "psychology background" rather than drug testing background, and that the media and "elements of the medico/scientific community" have "a down on antidepressants" and that the media does not appreciate the seriousness of depression and blames and stigmatizes sufferers in a manner rooted in medieval religious attitudes.