Vortioxetine Improves Depression, Shows Mixed Cognitive Effects in Older Adults

Key Clinical Summary

• A systematic review of 12 studies found that vortioxetine was consistently associated with improvements in depressive symptoms among adults aged 65 years and older with major depressive disorder (MDD).
• Cognitive effects were heterogeneous, with observational studies showing improvements in processing speed, attention, and executive function but randomized and comparative studies finding inconsistent effects on global cognition.
• Whether vortioxetine provides cognitive benefits independent of improvements in depressive symptoms remains uncertain, highlighting the need for additional longitudinal randomized studies.

Vortioxetine was consistently associated with reduced depressive symptoms in older adults with MDD, while its effects on cognition were less consistent, according to a systematic review published in the Journal of Affective Disorders. Findings suggested neutral-to-positive effects on cognition that were primarily limited to specific cognitive domains rather than global cognitive functioning.

Study Findings

As a persistent feature of late-life depression, cognitive impairment may contribute significantly to functional decline in MDD. In this study, researchers conducted a systematic review to evaluate the effects of vortioxetine on depressive symptoms and cognitive function specifically among older adults.

Investigators analyzed 12 randomized and observational studies published between January 2010 and January 2025. Eligible studies included adults aged 65 years or older with MDD who received vortioxetine and underwent assessment of cognitive outcomes.

The primary outcomes were changes in cognition measured using validated neuropsychological assessments, while secondary outcomes included depressive symptom severity and functional outcomes.

Across the included studies, vortioxetine was consistently associated with improvements in depressive symptoms. Cognitive outcomes, however, varied according to study design and the measures assessed.

Observational studies demonstrated improvements in specific cognitive domains, including processing speed, attention, and executive function. In contrast, randomized and comparative studies showed inconsistent effects on global cognition and did not demonstrate clear superiority of vortioxetine over placebo or other antidepressants.

Available data on functional outcomes were limited, evaluated in only 5 of the 12 studies, but suggested a modest benefit. The review also found that cognitive improvements observed in randomized controlled trials may be transient, with benefits fading by 26-week endpoints.

Clinical Implications

The findings suggest that vortioxetine may provide consistent antidepressant effects for older adults with MDD, while its potential cognitive effects are less certain. Where cognitive improvements were observed, they were predominantly domain-specific rather than improvements in global cognition.

The available evidence alone does not establish that vortioxetine improves global cognition or provides greater cognitive benefit than placebo or other antidepressants, warranting further investigation.

Expert Commentary

“Interpreting whether vortioxetine exerts a direct procognitive effect requires separating the study designs that generated the evidence,” wrote senior author Ibrahim Makki, MD, MFM, first author Muhammad El-Kassem, MD candidate, both of the Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada, and coauthors.

“…Accordingly, we describe vortioxetine's cognitive profile in late-life depression as promising but not established, and specifically as neutral-to-positive and predominantly domain-specific rather than a proven global procognitive action.” 

The authors concluded that future studies should more closely examine the relationship between mood symptoms and cognitive effects and determine whether the agent provides long-term benefit in this patient population.

Reference
El-Kassem M, Ali M, Madani MT, et al. The effect of vortioxetine on cognitive function in older adults with major depressive disorder: A systematic review. J Affect Disord. Published online September 1, 2026.