Background: Recent publications have raised questions over the efficacy and clinically relevant effects of antidepressants that have been approved for the treatment of major depression. In this context, the European Commission requested that the European Medicines Agency (EMEA) and its scientific committee (CHMP) issue an opinion on these data under Article 5(3) of Regulation (EC) No 726/2004.
Findings: Results from a recent meta-analysis [Kirsch, I., Deacon, B.J. et al., (2008) Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLoS Med. 5(2), e45.] have questioned the clinical relevance of the use of some antidepressants in treating major depression. This analysis focused only on statistically significant mean differences versus placebo in changes in a rating scale (such as the Hamilton Depression Rating Scale). This, however, would not be an adequate basis for the evaluation of clinical relevance and, from a regulatory perspective, would not be sufficient to grant an antidepressant the approval needed to allow it onto the market. Improvements that are both statistically significant (based on improvements in validated rating scales between baseline and study end) and clinically relevant (based on responder rates) need to be shown in short-term studies. In addition, these short-term results need to be confirmed in a randomised withdrawal study to demonstrate the maintenance of an antidepressant's effects.
Conclusions: The CHMP concluded that the approval of antidepressants for the treatment of patients with major depression is based on data that provide robust and sufficient evidence of clinically meaningful benefits for patients with major depression. Therefore, the CHMP is of the opinion that, as no public health concerns have been identified, no regulatory action is necessary on the basis of Kirsch et al.'s findings.