Cognitive dysfunction is a core feature of major depressive disorder (MDD). Although both repetitive transcranial magnetic stimulation (rTMS) and vortioxetine have demonstrated procognitive effects, direct comparative evidence remains limited. This study compared the clinical and cognitive outcomes of rTMS and vortioxetine in patients with MDD.

In this 8-week naturalistic study, 40 patients with MDD received either rTMS (n = 25) or vortioxetine (n = 15). Depressive symptoms were assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS). Cognitive performance was evaluated with the Perceived Deficits Questionnaire–Depression (PDQ-D), Trail Making Test Part B (TMT-B), Stroop Test, and Wisconsin Card Sorting Test (WCST). Longitudinal changes were analyzed using linear mixed-effects models. Week-8 outcomes were examined using ANCOVA adjusted for baseline cognitive performance and relevant clinical covariates.

Both groups showed significant improvements in depressive symptoms and cognitive performance over time, with no significant treatment × time interactions. Baseline cognitive performance strongly predicted week-8 outcomes. Domain-specific differences were observed in executive functioning: vortioxetine showed a modest advantage in WCST performance, whereas rTMS showed a non-significant trend toward better Stroop interference performance. No significant differences were detected in processing speed.

rTMS and vortioxetine were associated with comparable improvements in depressive symptoms and cognitive functioning in patients with MDD. Baseline cognitive status appeared to be a stronger predictor of outcome than treatment modality.