The effects of vortioxetine on cognitive dysfunction in patients with inadequate response to current antidepressants in major depressive disorder: A short-term, randomized, double-blind, exploratory study versus escitalopram

Background: Major Depressive Disorder (MDD) is a heterogeneous disease characterized by emotional, physical and cognitive symptoms. This study explored the effects of vortioxetine versus escitalopram on outcomes of cognition, functioning and mood symptoms in depressed patients with inadequate response to current antidepressant treatment. Methods: In this parallel-group, active-comparator study, adult patients (18-65 years, N = 101) with MDD, with inadequate response to current antidepressant monotherapy, were randomized 1: 1 to 8 weeks' double-blind treatment with flexible doses (10-20 mg/day) of either vortioxetine or escitalopram. Primary and key secondary efficacy measures were the Digit Symbol Substitution Test (DSST), analyzed using a mixed model for repeated measurements, and the University of San Diego Performance-based Skills Assessment - Brief (UPSA-B), analyzed using analysis of covariance (last observation carried forward method). Results: At week 8, DSST and UPSA-B performance had improved in both treatment groups, with no statistically significant treatment differences. Numerical improvements across measures of cognition, functioning and mood symptoms generally favored vortioxetine. Most adverse events were mild or moderate, with nausea being the most common adverse event. Limitations: This was an exploratory study with small sample sizes implying limited statistical power. Conclusion: Although this explorative study did not meet primary endpoints, the results confirm vortioxetine in doses of 10-20 mg/day as an efficacious and well-tolerated antidepressant switch treatment. The overall direction of numerical effect sizes across cognition endpoints support previous findings that vortioxetine specifically benefits cognitive function in MDD.