The authors of Multiple Possible Inaccuracies Cast Doubt on a Recent Report Suggesting Selective Serotonin Reuptake Inhibitors to be Toxic and Ineffective discuss their Open Access article which was published in Acta Neuropsychiatrica. 

Having been used as antidepressants for decades, and currently used by 7-10% of the population in many countries, the selective serotonin reuptake inhibitors (SSRIs) are unusually well-tried drugs. Their antidepressant efficacy has been confirmed in numerous trials, as has their relative safety.

Nevertheless, in recent years, a number of scientific papers questioning the use of these drugs have been published. Apparently fuelled by the enthusiasm of anyone believing that he/she is disclosing a gigantic pharma industry-driven conspiracy, the authors of such papers usually find multiple reasons to denounce them: the SSRIs are thus described as totally ineffective and dependence-producing and marred by serious side effects. Often such alarmist conclusions, though unjustified, are widely disseminated in lay media, thus causing concern by patients.

Illustrating this phenomenon, BMC Psychiatry recently published a systematic review by Jakobsen and co-authors claiming, e.g., that SSRIs increase the risk for serious adverse events. The grim message conveyed by the authors, when feverishly marketing their results in Scandinavian lay-media, has been that no relief, but suicide or death by other means, is what awaits the unfortunate patient treated with an SSRI.

Prompted by the vast media coverage of these sensational conclusions, we deemed it justified to expose this paper to close reading. Given that it is the product of a unit with alleged expertise in evidence-based medicine, the number of methodological inaccuracies, blatant errors and misleading statements revealed by this review surprised us. After having corrected for some of these mistakes, and re-analyzed the data, we found no evidence for the claim that SSRIs enhance the risk for serious adverse events regardless of age but could however confirm what is conventional wisdom, i.e. that they, while being remarkably safe in the non-elderly adult population, may enhance the risk for serious adverse events in the elderly.

With respect to the increased risk for serious adverse events in the elderly taking SSRIs, one should consider that the definition of serious adverse events used by Jakobsen and co-workers (and by us in our re-analysis) comprises not only life-threating events but also quite innocuous phenomena, such as precautionary hospital admittance for an abnormal laboratory value or some other transient low-risk event. Notably, in stark contrast to the way the results were communicated to the public, suicides and deaths appeared numerically less common in those treated with an SSRI.

On the web page of the Copenhagen Trial Unit, where the report by Jakobsen and co-workers has been produced, it is stated that the systematic review represents the highest form of publication in terms of quality of evidence. What this episode illustrates is however that systematic reviews and meta-analyses, when conducted without proper rigour and impartiality, may be grossly misleading. Given that such papers often influence treatment guidelines, and not seldom are cited in lay media, exposing them to critical examination both before and after publication is an important, albeit time-consuming, endeavour.

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