Introduction: The troubling issues of conventional antidepressants are inadequate disease remission and potential adverse effects. There is a dearth of research findings comparing vilazodone, escitalopram, and vortioxetine. The objective of this analysis is to determinechanges in the Hamilton Depression Rating Scale (HDRS) and Montgomery-Åsberg Depression Rating Scale (MADRS) scoresand the incidence of adverse events at 12 weeks.Methods: This is an exploratory interim analysis of a randomized, three-arm, open-label ongoing study. The participants were randomly assigned in a 1:1:1 ratio to receive either vilazodone (20-40 mg/d), escitalopram (10-20 mg/d), or vortioxetine (5-20 mg/d). Efficacy and safety assessments were done at baseline, four weeks, eight weeks, and 12 weeks.Results: Forty-nine(69%) of the 71 enrolled participants (mean age 43.9±12.2 years; 37 men (52%)) completed the 12-week follow-up. At baseline, the three groups' median HDRS scores were 30.0, 29.5, and 29.0 (p=0.76), respectively, and at 12 weeks, they amounted to 19.5, 19.5, and 18.0 (p=0.18), respectively. At baseline, group-wise median MADRS scores were 36, 36, and 36, respectively (p=0.79); at 12 weeks, they were 24, 24, and 23, respectively (p=0.03). In the post-hoc analysis, the inter-group comparison of the change in HDRS (p = 0.02) and MADRS (p = 0.06) scores from baseline did not reach statistical significance. No participants experienced serious adverse events.Conclusion: In this initial assessment of a continuing study, vortioxetine exhibited a clinically (not statistically) significant drop in HDRS and MADRS scores, compared to vilazodone and escitalopram. The antidepressant effects need to be investigated further.