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A clinical trial was undertaken to evaluate the Anti depressant efficacy of Newer Antidepressant Mirtazapine in the treatment of major Depression in 39 patients in an O.P.D. setup. In addition to this clinical acceptability and safety profile of Mirtazapine as compared to that of Amitriptyline was also assessed. Mitazapine usually described as Noradrenergic and specific serotonergic Anti depressant (NaSSA). Patients aged 18-65 years who fulfilled the diagnostic criteria for a single or recurrent major Depressive disorder (as defined by DSM IV) for a minimum of 2 weeks were enrolled at our study centre. Patient assessment were conducted at screening, baseline, end of week 1, week 2, week 3, week 4, week 5 & end of week 6 for the efficacy & safety Parameters; HRSD, CGI, Adverse event follow up, BP & Pulse. Three level statistical analysis were performed on all efficacy measures including ANOVA (An Analysis of variance). The result indicates that mirtazapine is effective in the treatment of major depression at the dosages range of 15-45 mg/day and it has efficacy equivalent to that of the standard TCA Amitriptyline, albeit, with a substantially better tolerability profile.