In major depressive disorder (MDD) neurocognitive functions are impaired. In addition to melatonergic properties of agomelatine, via 5-HT2C antagonism it increases extracellular noradrenaline and dopamine in frontal cortex and may improve the neurocognitive functions of patients with MDD.

To investigate the extent of neurocognitive improvement and efficacy of agomelatine and fluoxetine in patients with MDD.

Agomelatine 25 mg/day (n: 24) and fluoxetine 20 mg/day (n: 24) were administered to drug-naive unipolar, non-psychotic, non-suicidal MDD patients according to DSM-IV. Evaluations were performed just before the treatment and at the sixth week of treatment via administering Hamilton Depression Rating Scale, Rey Auditory Verbal Learning Test, Controlled Oral Word Association Test (COWAT), Digit Span Test (DST), Trail Making Test (TMT-A/B), Stroop Test and Wisconsin Card Sorting Test.

Both agomelatine and fluoxetine was found to be efficacious for the treatment of MDD (P < 0.05 for both). Further there was no difference between the antidepressant efficacy of two drugs. Both of the drugs improved measured neurocognitive functions (P < 0.05), except scores of DST (P > 0.05) and only fluoxetine improved significantly scores of COWAT (P < 0.05). Only in terms of TMT-B there was significant difference between groups and agomelatine was superior to fluoxetine (P < 0.05).

Agomelatine and fluoxetine were efficacious in treatment of MDD. Furthermore both of the drugs improved cognitive functions in patients with MDD. Superiority of agomelatine in improvement of executive functioning (TMT-B) is important and therefore it could be an appropriate choice for MDD patients who have pronounced executive disturbances.

The authors have not supplied their declaration of competing interest.