(A-084) Effectiveness and Safety of Vortioxetine versus Other Antidepressants in Patients with Major Depression Disorder

Background: Vortioxetine is a serotonin modulator for major depressive disorder (MDD), yet real-world evidence on its comparative effectiveness and safety relative to other antidepressants remains limited.

Objectives: To assess the effectiveness and safety of Vortioxetine compared to other classes of antidepressants, including serotonin-norepinephrine reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors (SSRIs), mirtazapine, tricyclic antidepressants (TCAs), atypical agents, and other serotonin modulators in MDD patients.

Methods: This retrospective cohort study used electronic health records from the TriNetX Global Collaborative Network (2019–2023), including adults with MDD initiating Vortioxetine or other antidepressants. Multiple pairwise comparisons were conducted, where Vortioxetine was separately compared to each class. Primary effectiveness outcomes were suicide attempts and intentional self-harm; safety outcomes included cognitive impairment (dementia, Alzheimer’s disease, degenerative nervous diseases), sexual dysfunction, and neurological side effects (insomnia, dizziness, tremor, stroke, headache). 1:1 propensity score matching was used to balance baseline characteristics, and hazard ratios (HRs) were estimated using Cox proportional hazards models.

Results: The study identified 15,383 to 31,926 Vortioxetine users, compared to 327,196 to 2,377,293 users of other antidepressants. After matching, 15,375 to 31,698 patients per cohort were analyzed. The mean age was approximately 50 years, with 30% male participants. Median follow-up ranged from 729 to 885 days. For effectiveness, suicide attempt and intentional self-harm event rates ranged from 4 to 8 per 1,000 patients, with HRs between 0.51 (0.40–0.65) and 1.09 (0.87–1.36), indicating a trend favoring Vortioxetine. For safety, cognitive impairment, sexual dysfunction, and neurological side effect event rates were 77–95, 14–23, and 254–290 per 1,000 patients, respectively. Vortioxetine was associated with a higher risk of sexual dysfunction (HR 1.27–1.60), except compared to TCAs (HR=1). It showed a lower risk of cognitive and neurological impairments compared to TCAs and other serotonin modulators (HRs 0.80–0.88), while comparisons with other antidepressants were neutral.

Conclusions: Vortioxetine demonstrated a potential advantage in reducing suicide attempts and intentional self-harm risk. While it exhibited lower cognitive and neurological risks than TCAs and serotonin modulators, it was associated with an increased risk of sexual dysfunction. These findings provide valuable real-world insights for clinical decision-making in depression treatment.