Agomelatine efficacy and acceptability revisited: systematic review and meta-analysis of published and unpublished randomised trialsby Markus Koesters, Giuseppe Guaiana, Andrea Cipriani, Thomas Becker, and Corrado BarbuiThe British Journal of Psychiatry. 2013 203:179-18.
Background: Agomelatine is a novel antidepressant drug with narrative, non-systematic reviews making claims of efficacy.Aims: The present study systematically reviewed published and unpublished evidence of the acute and long-term efficacy and acceptability of agomelatine compared with placebo in the treatment of major depression.Method: Randomised controlled trials comparing agomelatine with placebo in the treatment of unipolar major depression were systematically reviewed. Primary outcomes were (a) Hamilton Rating Scale for Depression (HRSD) score at the end of treatment (short-term studies) and (b) number of relapses (long-term studies).Results: Meta-analyses included 10 acute-phase and 3 relapse prevention studies. Seven of the included studies were unpublished. Acute treatment with agomelatine was associated with a statistically significant superiority over placebo of –1.51 HRSD points (99% CI –2.29 to –0.73, nine studies). Data extracted from three relapse prevention studies failed to show significant effects of agomelatine over placebo (relative risk 0.78, 99% CI 0.41–1.48). Secondary efficacy analyses showed a significant advantage of agomelatine over placebo in terms of response (with no effect for remission). None of the negative trials were published and conflicting results between published and unpublished studies were observed.Conclusions: We found evidence suggesting that a clinically important difference between agomelatine and placebo in patients with unipolar major depression is unlikely. There was evidence of substantial publication bias.
Problems with current methods for approving new drugs
In Europe new drugs are approved or rejected on the basis of the results of studies carried out by the manufacturer and submitted to the EMA. We note that decisions are taken on the basis of the results of individual studies with no role for aggregating efficacy data using meta-analytic techniques. We argue, however, that pooling studies would have some beneficial consequences for the review process by increasing statistical power and by contributing to the detection of between-study heterogeneity.