Bad science: Depression - the facts and the fables

... This has been a bad week for the SSRI antidepressants. First there's the stuff you already know: bad data got buried. In a cracking new analysis of the "publication bias" in the literature, a group of academics this week published a paper in the New England Journal of Medicine which listed all the trials on SSRIs that had ever been formally registered with the Food and Drug Administration, and then went to look for the same trials in the academic literature.

Thirty-seven studies were assessed by the FDA as positive and, with one exception, every single one of those positive trials got properly written up and published. Meanwhile, 22 studies that had negative or iffy results were simply not published at all, and 11 were written up and published in a way that described them as having a positive outcome.

... Over the past few decades, we have been subjected to a relentless medicalisation of everyday life by people who want to sell us sciencey solutions. Quacks from the $56bn (£28.26bn) international food supplement industry want you to believe that intelligence needs fish oil, and that obesity is just your body's way of crying out for their chromium pills ("to help balance sugar metabolism").

Similarly, quacks from the $600bn pharma industry sell the idea that depression is caused by low serotonin levels in the brain, and so you need drugs which raise the serotonin levels in your brain: you need SSRI antidepressants, which are "selective serotonin reuptake inhibitors".

...

Meanwhile, in popular culture the depression/serotonin theory is proven and absolute, because it was never about research, or theory, it was about marketing, and journalists who pride themselves on never pushing pills or the hegemony will still blindly push the model until the cows come home. Which brings us on to our second new SSRI study.

Guardian UK

The makers of antidepressants like Prozac and Paxil never published the results of about a third of the drug trials that they conducted to win government approval, misleading doctors and consumers about the drugs’ true effectiveness, a new analysis has found.

In published trials, about 60 percent of people taking the drugs report significant relief from depression, compared with roughly 40 percent of those on placebo pills. But when the less positive, unpublished trials are included, the advantage shrinks: the drugs outperform placebos, but by a modest margin, concludes the new report, which appears Thursday in The New England Journal of Medicine.

Background Evidence-based medicine is valuable to the extent that the evidence base is complete and unbiased. Selective publication of clinical trials — and the outcomes within those trials — can lead to unrealistic estimates of drug effectiveness and alter the apparent risk–benefit ratio.

Methods We obtained reviews from the Food and Drug Administration (FDA) for studies of 12 antidepressant agents involving 12,564 patients. We conducted a systematic literature search to identify matching publications. For trials that were reported in the literature, we compared the published outcomes with the FDA outcomes. We also compared the effect size derived from the published reports with the effect size derived from the entire FDA data set.

Results Among 74 FDA-registered studies, 31%, accounting for 3449 study participants, were not published. Whether and how the studies were published were associated with the study outcome. A total of 37 studies viewed by the FDA as having positive results were published; 1 study viewed as positive was not published. Studies viewed by the FDA as having negative or questionable results were, with 3 exceptions, either not published (22 studies) or published in a way that, in our opinion, conveyed a positive outcome (11 studies). According to the published literature, it appeared that 94% of the trials conducted were positive. By contrast, the FDA analysis showed that 51% were positive. Separate meta-analyses of the FDA and journal data sets showed that the increase in effect size ranged from 11 to 69% for individual drugs and was 32% overall.

Conclusions We cannot determine whether the bias observed resulted from a failure to submit manuscripts on the part of authors and sponsors, from decisions by journal editors and reviewers not to publish, or both. Selective reporting of clinical trial results may have adverse consequences for researchers, study participants, health care professionals, and patients.