Patients with major depressive disorder often experience relapse after 
responding to treatment; therefore, maintenance therapy with antidepressants is 
recommended for maintaining response or remission. This multicenter, open-label, 
flexible-dose, 52-week extension study evaluated the long-term safety, 
tolerability, and maintenance of efficacy in study participants who had 
completed one of two randomized, double-blind, placebo-controlled, 8-week 
dose-ranging vortioxetine trials in study participants with major depressive 
disorder. At the open-label baseline, all study participants were switched to 
vortioxetine 5 mg/day for the first week, with subsequent dose adjustments from 
2.5 to 10 mg/day on the basis of response and tolerability. Treatment with 
vortioxetine for 52 weeks was well tolerated, with no new safety signals 
identified. Among the 834 evaluable study participants, treatment-emergent 
adverse events were reported in 70.6%, with the most common in the combined (all 
doses) population of nausea (15.2%), headache (12.4%), nasopharyngitis (9.8%), 
diarrhea (7.2%), and dizziness (6.8%). The rate of adverse events related to 
sexual dysfunction was low and weight gain was minimal. Laboratory values, vital 
signs, ECGs, physical examinations, and Columbia-Suicide Severity Rating Scale 
results showed no trends of clinical concern. The change in the severity of 
depressive and anxiety symptoms was maintained throughout the study as reflected 
by a 24-item Hamilton Depression Scale total score of 8.2 at week 52 (from 17.6 
at open-label baseline) in the observed case data set.