The efficacy of agomelatine in severe depression has been examined in three positive placebo-controlled studies and in a pooled analysis of the data from the three studies in patients treated with 25-50 mg agomelatine (n=357) and placebo (n=360). Agomelatine was significantly more effective than placebo in a subgroup of patients with severe depression with a severity of 25 or more on the Hamilton Depression Rating Scale 17-item scale in each individual study (P<0.05) and in the pooled analysis (P<0.001). Analysis of the pooled data demonstrated that there was an increase in the magnitude of the agomelatine-placebo difference with increasing severity on the baseline Hamilton Depression Rating Scale. When the population was divided into subgroups using increasing cut-off Hamilton Depression Rating Scale values a significant difference between agomelatine and placebo was observed in each subgroup despite the decreasing numbers of patients with higher severity with a difference of 2.06 rising to 4.45 points on the Hamilton Depression Rating Scale. In conclusion, agomelatine is effective in treating severe depression.