EVALUATION OF THE EFFICACY OF COMBINATION THERAPY OF AGOMELATINE, DULOXETINE AND SERTRALINE IN THE MANAGEMENT OF STRESS INDUCED DEPRESSION

There is unmet need in the treatment of stress induced depression on suggesting requirement of new therapeutic agent. A combination therapy of antidepressants sertraline (5 mg/kg), duloxetine (10 mg/kg) and agomelatine (8 mg/kg) are used in different combinations of doses by intra-peritoneal route. Swiss albino mice were used as an animal model for stress-induced depression; mice were divided into eight groups. Depression was induced through forced swim test, tail suspension test and sucrose preference test (chronic mild stress model). Efficacy of combination therapy was analyzed in specific regions of mice brain associated with depression (hippocampus, cerebral cortices and the whole brain) through brain monoamine estimation by HPLC (High- performance liquid chromatography) with fluorescence detector. Three drug combination [Agomelatine (2.67 mg/kg) plus duloxetine (3.33 mg/kg) plus sertraline (1.67 mg/kg)] showed antidepressant activity in in-vivo animal model testing parameters (decrease in immobility period, increase in swimming count and climbing count and increase sucrose consumption) than other treated group. In the same group, improvement in brain monoamine profile was observed illustrating antidepressant activity (increasing dopamine, serotonin and norepinephrine level in hippocampi, cerebral cortex and whole brain). These findings could be further probed with the aim of understanding the interaction between agomelatine plus duloxetine plus sertraline as a future endeavour.