OBJECTIVES: To asses the efficacy of agomelatine, a melatonin MT1 / MT2 agonist and 5-HT2B / 5-HT2C antagonist, when compared with placebo and SSRIs. METHODS: An extensive trials search was conducted on electronic databases, clinical trials registries, and EMA reports. We extracted data for depression severity (mean differences or related statistics) on the primary comparisons of 1) agomelatine 25 mg/day versus placebo, and 2) agomelatine 25 mg/day versus any SSRI. We calculated Hedges’ g effect size for each trial and combined them by the inverse variance method assuming a random effects model. Two meta-analyses were conducted: one with the results of published and unpublished trials and the other only with results of published trials. RESULTS: Ten trials (5 unpublished) gave data on the efficacy of agomelatine versus placebo. Overall, the results were homogeneous (I2 = 9.2%), and showed agomelatine was better than placebo for reducing the severity of depression at 8 weeks (g = -0.18; 95% CI = -0.25 to -0.10; p <0.0001). However when the analysis was restricted to published trials the effect size was 45% overestimated (g = -0.26; 95% CI = -0.36 to-0.15; p <0.0001; I2 = 3.4%). 7 trials (4 unpublished) gave data on the comparison of agomelatine versus any SSRI. There was no difference in efficacy with all trials combined (g = 0.01; 95% CI = -0.16 to 0.18; p = 0.87), but agomelatine significantly outperformed SSRIs in the subset of published trials (g = -0.17; 95% CI = -0.29 to -0.05; p = 0.0052). CONCLUSIONS: When combining all available data agomelatine presents a small to moderate efficacy as antidepressant with similar effect sizes to those reported for SSRIs. Previous reports pointing to better results of agomelatine as compared with SSRIs are the result of selective publication bias.