Vortioxetine (Lu AA21004) is a multi-modal antidepressant in clinical 
development for the treatment of major depressive disorder (MDD). The current 
study evaluated the efficacy and tolerability of 5 mg vortioxetine compared to 
placebo after 6 wk of treatment in adults with MDD in an out-patient setting. 
Adults aged 18-75 yr, with a diagnosis of MDD and a baseline Montgomery-Asberg 
Depression Rating Scale (MADRS) total score ≥30, were randomized to receive 
either 5 mg vortioxetine or placebo over 6 wk, followed by a 2-wk 
medication-free discontinuation period. The primary efficacy measure was change 
from baseline in Hamilton Rating Scale for Depression (HAMD)-24 total score at 
week 6 compared to placebo. Additional measures included response and remission 
rates, Clinical Global Impression Scale - Improvement scores, HAMD-24 total 
score in subjects with baseline Hamilton Anxiety Scale (HAMA) >19 and MADRS-S 
total score. Adverse events (AEs) were assessed throughout the study. A total of 
600 adults were randomized. There were no significant differences in efficacy 
measures between subjects in the 5 mg vortioxetine and placebo groups at week 6. 
HAMD-24 total score in subjects with baseline HAMA >19 in the 5 mg vortioxetine 
group was improved at weeks 3-6 compared to the placebo group (nominal p value 
<0.05). The most common AEs for the vortioxetine and placebo groups were nausea 
(19.1 and 9.4%), headache (17.1 and 15.1%) and diarrhoea (11.4 and 7.0%), 
respectively. In this study of adults with MDD, 5 mg vortioxetine did not differ 
significantly from placebo in reducing depression symptoms after 6 wk of 
treatment.