Data Sheet 1_Post-market safety profile and suicide risk signals of vortioxetine: a real-world pharmacovigilance study.xlsx

BackgroundVortioxetine inhibits 5-HT transporter-mediated 5-HT reuptake and simultaneously regulates the activities of various 5-HT receptors to exert an antidepressant effect. It has been proven to be a highly effective antidepressant that can significantly improve depressive symptoms. However, the real-world evidence of vortioxetine-associated suicidal signals is very limited. We explored the vortioxetine-related suicidal signals by mining the US FDA Adverse Event Reporting System (FAERS) database.
MethodsThis study used the disproportionality method to systematically evaluate the vortioxetine-related adverse events (AEs). Data were collected from the fourth quarter (Q4) of 2013 to the second quarter (Q2) of 2025 in the FAERS database. The report was analyzed by four signal detection methods, namely, reported odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). The contingency table was analyzed to compare the proportion of suicide-related reports across different subgroups.
ResultsA total of 13,698 vortioxetine-related reports were cleaned from the FAERS database. From these reports, 27 system organ classes (SOCs) and 173 preferred terms (PTs) were identified. The top three SOCs were psychiatric disorders, general disorders and administration site conditions, and gastrointestinal disorders. Significant suicide-related signals were detected for suicidal ideation (ROR = 19.87), suicide attempt (ROR = 7.05), completed suicide (ROR = 4.73), suicidal behavior (ROR = 13.57), and suicide threat (ROR = 15.47). The contingency table analysis revealed that sex (χ2 = 48.77, p < 0.001) and age (χ2 = 30.17, p < 0.001) were significant factors associated with suicide-related reporting. Although the highest proportion of suicide-related reports occurred in the 25- to 64-year age group (12.90%), the ≤24-year age group also contributed a meaningful proportion (8.86%), consistent with the FDA black box warning for antidepressants. No significant association was observed with weight (p = 0.64).
ConclusionThis study aligns with regulatory warnings and underscores the importance of clinical vigilance when prescribing vortioxetine. Enhanced monitoring is recommended for all patients, with particular attention given to younger populations during treatment initiation. Due to the inherent limitations of spontaneous reporting systems, these findings should be interpreted as hypothesis-generating signals requiring confirmation through controlled studies.