Duloxetine (SNRI) and Escitalopram (most selective SSRI) were compared to evaluate the safety in mild tomoderate depressivedisorder. A 6-week, double blind, randomized, parallel-group study in collaboration with Departments of pharmacology andpsychiatry, Era’S Medical College and Hospital, Lucknow (n= 60 patients) on patients suffering fromdepression single episode( F 32.0 or F 32.1 A/T ICD X), recurrent depressive disorder ( F 33.0 or F 33.1 A/T ICD X) was conducted. Scoring onMADRS was kept as primary end point. Subjects were randomly assigned (1:1) into two different groups(Duloxetine 40-60mg/day (flexibly dosed) and to escitalopram 10-20mg/day) i.e. Group A and Group B with the step-up dosing pattern. The primaryefficacy variable was change from baseline at week 6 in MADRS total score and DOTES . A significantly greater proportion ofescitalopram-treated patients completed the 6-week study compared with duloxetine-treated patients. At week 6, Duloxetinetreatment resulted in slightly lesser improvement, more drop outs, and more adverse effects comparedwith escitalopram, howeverthe differences were not clinically significant. These findings suggest that SSRI, Escitalopram is better tolerated and at least aseffective as the SNRI, Duloxetine in the treatment of major depressive disorder with mild to moderate severity.