Although Lemogne et al, 2010 suggested that Medial Prefrontal Activity does not change after reduction of depressive symptoms, sensitivity of brain regions involved in self-referential processing to antidepressant is unknown. The main goal here was to assess with fMRI early effects of agomelatine, on self-referential processing in depressed patients.

25 acute depressed patients and 14 healthy controls were scanned before and after 7 days treatment, while performing self-referential processing task using emotional pictures. Patients were randomized to agomelatine 25mg/day (n=13) or placebo (n=12), healthy controls received placebo. Subjects were asked to evaluate pictures according to different conditions: Self (Does the picture relate to you?); General (Is the picture positive or negative?). Depression was assessed with Hamilton Scale.

Depressed patients compared to controls at baseline showed hyperactivity in dorsolateral prefrontal cortex, dorsal anterior cingulate and ventrolateral prefrontal cortex (VLPFC). After 7 days treatment, Agomelatine, compared to placebo, normalized the hyperactivity of VLPFC to healthy volunteers’ level.

Agomelatine targets specific brain structures, namely VLPFC, involved in automatic regulation of emotion during self-referential processing. These changes in brain activity at day 7 could contribute to the early clinical effects of agomelatine, suggesting an early set up of the brain for long term response and remission of depression.