The effect of vortioxetine on cognitive function in older adults with major depressive disorder: A systematic review

Cognitive impairment is a persistent feature of late-life depression, contributing to functional decline and complicating differentiation from early neurocognitive disorders. Conventional antidepressants often demonstrate limited direct procognitive effects. Vortioxetine, a multimodal antidepressant, has been proposed to improve depressive symptoms and cognitive functioning, but its effects in older adults remain unclear.

To evaluate the impact of vortioxetine on cognitive function and depressive symptoms in older adults with depression.

A systematic review was conducted in accordance with PRISMA guidelines. MEDLINE, EMBASE, CINAHL, and Cochrane CENTRAL were searched for studies published between January 2010 and January 2025. Eligible studies included randomized and observational studies involving adults aged ≥65 years with major depressive disorder treated with vortioxetine reporting cognitive outcomes. Studies with fewer than 10 participants, non-human studies, and non-English publications were excluded. Twelve studies met the inclusion criteria.

Primary outcomes included changes in cognitive function assessed using validated neuropsychological measures. Secondary outcomes included depressive symptom severity and functional outcomes.

Vortioxetine was consistently associated with improvements in depressive symptoms. Cognitive findings were heterogeneous: observational studies demonstrated improvements in domain-specific measures, including processing speed, attention, and executive function, whereas randomized and comparative studies showed inconsistent effects on global cognition and no clear superiority over placebo or other antidepressants. Functional outcomes were limited but suggested a modest benefit.

Vortioxetine was associated with consistent reductions in depressive symptoms and with neutral-to-positive, predominantly domain-specific cognitive effects in late-life depression. Its effect on global cognition, and whether any cognitive benefit is independent of mood improvement, remain uncertain. Further longitudinal randomized studies are needed to clarify its clinical role.