Abstract
Several international guidelines for the acute treatment of moderate to severe unipolar depression recommend a first-line treatment with antidepressants (AD). This is based on the assumption that AD obviously outperform placebo, at least in the case of severe depression. The efficacy of AD for severe depression can only be definitely clarified with individual patient data, but corresponding studies have only been available recently. In this paper, we point out discrepancies between the content of guidelines and the scientific evidence by taking a closer look at the German S3-guidelines for the treatment of depression. Based on recent studies and a systematic review of studies using individual patient data, it turns out that AD are marginally superior to placebo in both moderate and severe depression. The clinical significance of this small drug-placebo-difference is questionable, even in the most severe forms of depression. In addition, the modest efficacy is likely an overestimation of the true efficacy due to systematic method biases. There is no related discussion in the S3-guidelines, despite substantial empirical evidence confirming these biases. In light of recent data and with their underlying biases, the recommendations in the S3-guidelines are in contradiction with the current evidence. The risk-benefit ratio of AD for severe depression may be similar to the one estimated for mild depression and thus could be unfavorable. Downgrading of the related grade of recommendation would be a logical consequence.
Highlights
Guidelines may be crucial for adequate treatment if they systematically and critically evaluate the evidence and infer treatment recommendations in a rational and transparent manner
Efficacy of antidepressants Comparing the evidence in the guideline with current evidence In the S3-guidelines, the efficacy of antidepressants (AD) in the acute treatment of major depression is summarized as follows [3]: To prove a clinically relevant efficacy of acute antidepressant treatment in placebo-controlled trials, a minimum improvement of 50% on established scales is suggested [...] In these kinds of clinical trials with a maximum duration of up to twelve weeks, the response rates mostly range between 50 and 60%, the placebo response rates about 25–35% (p. 67)
The S3-guidelines and other international guidelines do not recommend AD as first-line treatment for mild depression, because: Due to the unfavorable risk-benefit ratio, antidepressants are not generally useful in the initial treatment of mild depressive episodes, since antidepressant medication is hardly superior to a placebo condition (p. 74, citations removed)
Summary
Guidelines may be crucial for adequate treatment if they systematically and critically evaluate the evidence and infer treatment recommendations in a rational and transparent manner. This way, guidelines are an important interface between science and clinical practice. The obvious benefit of guidelines vanishes if the recommendations are misleading, for example because of biases in the synthesis of the evidence [1, 2], or because the evidence in the guidelines is outdated and conflicting with current evidence. Correcting the discrepancies between the content of the guidelines and current evidence
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