The efficacy of vortioxetine 10 and 20 mg/d vs. placebo on cognitive function 
and depression in adults with recurrent moderate-to-severe major depressive 
disorder (MDD) was evaluated. Patients (18-65 yr, N = 602) were randomized 
(1:1:1) to vortioxetine 10 or 20 mg/d or placebo for 8 wk in a double-blind 
multi-national study. Cognitive function was assessed with objective 
neuropsychological tests of executive function, processing speed, attention and 
learning and memory, and a subjective cognitive measure. The primary outcome 
measure was change from baseline to week 8 in a composite z-score comprising the 
Digit Symbol Substitution Test (DSST) and Rey Auditory Verbal Learning Test 
(RAVLT) scores. Depressive symptoms were assessed using the Montgomery-Åsberg 
Depression Rating Scale (MADRS). In the pre-defined primary efficacy analysis, 
both doses of vortioxetine were significantly better than placebo, with mean 
treatment differences vs. placebo of 0.36 (vortioxetine 10 mg, p < 0.0001) and 
0.33 (vortioxetine 20 mg, p < 0.0001) on the composite cognition score. 
Significant improvement vs. placebo was observed for vortioxetine on most of the 
secondary objectives and subjective patient-reported cognitive measures. The 
differences to placebo in the MADRS total score at week 8 were -4.7 (10 mg: 
p < 0.0001) and -6.7 (20 mg: p < 0.0001). Path and subgroup analyses indicate 
that the beneficial effect of vortioxetine on cognition is largely a direct 
treatment effect. No safety concern emerged with vortioxetine. Vortioxetine 
significantly improved objective and subjective measures of cognitive function 
in adults with recurrent MDD and these effects were largely independent of its 
effect on improving depressive symptoms.