Reanalysis of clinical trials conducted on two antidepressants contradicts the claim their benefits lie entirely in a super-placebo effect created by their side effects. The analysis was funded by Swedish government agencies and hospitals, rather than pharmaceutical companies, to try to avoid the conflicts of interest that plague research in this area.
Depression is so widespread that drugs used to treat it, particularly selective serotonin reuptake inhibitors (SSRIs) are among the most profitable in the world, creating incentives for drug companies to exaggerate their effectiveness and understate drawbacks. There is plenty of evidence of SSRIs being prescribed inappropriately – such as for bipolar disorder – and even of trial investigators failing to report harms to teenagers.
Some scientists have gone further, claiming SSRIs don't work at all.
However, when Swedish researchers examined the data from FDA-registered trials for citalopram and paroxetine they found evidence of a real benefit not explained by trial failure. The findings have been published in Molecular Psychiatry.
Undoubtedly the placebo effect provides part of any antidepressants benefit. Giving someone a sugar pill and telling them it is a drug can lead to astonishing improvements, and unsurprisingly that is particularly true for mental conditions. Indeed, simply the experience of having someone acknowledge their suffering, and prescribe a treatment for it, frequently lifts the mood of people with depression.
Yet in order to win approval from regulatory bodies, drugs need to perform noticeably better than placebos.
However, the clinical trials in which candidate drugs are tested against placebos rely on double-blind testing, where neither the patient nor the doctor knows whether they are getting the real pill, or the fake one. What happens, some people have asked, if this blind is broken, because side-effects give the game away?
The theory that SSRI's only work because of an enhanced placebo effect, where trial participants and their doctors know they are getting the real drug because of the side-effects dates, back to at least 1998. It has been raised by multiple psychiatrists since, sometimes followed by high-profile coverage in mainstream media.
Professor Elias Eriksson of the Sahlgrenska Academy tested the theory by accessing the original trial data and excluding all those whose noticeable side-effects revealed they were getting the drugs.
Using 3,344 patients, Eriksson found that even among those who described no side-effects, patients given SSRIs experienced substantially greater improvements in their depression than those who were given the placebo.
Eriksson and his co-authors are concerned that dissemination of the “breaking the blind theory” could be discouraging people who would benefit from SSRIs from taking them.
Although this research was government-funded, Eriksson and one of the three co-authors have received funding and speakers fees from SSRI manufacturers in the past.
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