OBJECTIVE: The primary objective of this study was to evaluate the safety and 
tolerability of the investigational drug vortioxetine (Lu AA21004) in the 
long-term treatment of patients with major depressive disorder.
METHODS: Patients entered this 52-week, open-label extension study after 
completing an 8-week lead-in study. Safety and tolerability were evaluated at 
regular intervals on the basis of spontaneously reported adverse events (AEs), 
clinical safety laboratory tests, vital signs, ECG and physical examination. 
Effectiveness of treatment was assessed using the Montgomery-Åsberg Depression 
Rating Scale (MADRS) total score.
RESULTS: A total of 535 patients were treated and 61.3% (n = 328) completed the 
study, resulting in 393 patient years of exposure to vortioxetine. AEs reported 
by ≥10% of patients were nausea, headache, and nasopharyngitis. Taken together, 
six patients had eight AEs related to sexual dysfunction. There were no 
clinically significant safety findings with respect to mean changes of vital 
signs, weight, ECG parameters, or clinical laboratory values. Patients entered 
the extension study with a mean MADRS total score of 13.5 ± 8.7. The mean MADRS 
total score decreased (improved) by approximately 8 points to 5.5 ± 6.0 at Week 
52 (OC). By the end of the study, the proportion of responders had increased 
from 63% to 94% (OC), as had the proportion in remission (MADRS ≤10), increasing 
from 42% to 83% (OC). Patients in remission (n = 226) at the start of this study 
had a relapse rate (MADRS ≥22) of 9.7%.
CONCLUSIONS: As with all open-label studies, the conclusions that can be drawn 
are limited by the lack of a placebo control, making it difficult to assess 
causality of any changes in outcome measures. However, on the basis of these 
findings, vortioxetine (2.5, 5, 10 mg/day) demonstrated a favourable safety and 
tolerability profile and maintained effectiveness over 12 months of treatment.
TRIAL REGISTRATION: This study has the ClinicalTrials.gov identifier: 
NCT00694304.