POST-MARKETING SAFETY PROFILE OF ANTIDEPRESSANTS IN 2013 TO 2025
Author(s)
Anoop Singh, Pharm D1, Zhanghe Chen, MS1, Xiaomo (Shawn) Xiong, MS, PhD2, Arun Kumar, MS, PharmD, PhD3, Marepalli B Rao3, Ana L. Hincapie4, Emma C. Palmer, PharmD5, Jeff Jianfei Guo6;
1University of Cincinnati, PhD Student, Cincinnati, OH, USA, 2James L Winkle College of Pharmacy, University of Cincinnati, Blue Ash, OH, USA, 3Cincinnati, OH, USA, 4USA, 5Morrow, OH, USA, 6James L Winkle College of Pharmacy, University of Cincinnati, USA
1University of Cincinnati, PhD Student, Cincinnati, OH, USA, 2James L Winkle College of Pharmacy, University of Cincinnati, Blue Ash, OH, USA, 3Cincinnati, OH, USA, 4USA, 5Morrow, OH, USA, 6James L Winkle College of Pharmacy, University of Cincinnati, USA
OBJECTIVES: To analyze the reporting patterns of adverse events and outcomes across serotonin-norepinephrine reuptake inhibitors (SNRI’s) and N-methyl-D-aspartate (NMDA) receptor antagonists in the US FDA- Adverse Event reporting System (FAERS) using medication-focused disproportionality analysis
METHODS: A retrospective disproportionality analysis of FAERS data (2013-2025) evaluated major AEs and serious outcomes (death, hospitalization, congenital anomaly, disability, required intervention, life-threatening events) for SNRIs and NMDAs. Safety signals were assessed using established ROR‑ and PRR-based criteria.
RESULTS: A total of 4,09,802 AEs reports from 3,81,581 case patients (age range from 1 to 81 years), females (92.9%). The most reported AEs were drug withdrawal syndrome, nausea, dizziness, fatigue, paresthesia, insomnia, headache, and anxiety. Outcomes (n=3,68,737), comprising 1,94,798 other serious outcomes (OT, 52.8%), 1,13,890 hospitalizations (HO, 30.8%), 28,675 deaths (DE, 7.7%), 17,107 life‑threatening events (LT, 4.63%), 10,779 disabilities (DS, 2.93%), 2,594 congenital anomalies (CA, 0.70%), and 894 required interventions (RI, 0.24%). Levomilnacipran showed strong disproportionality signal for CA Reporting Odd Ratio (ROR 11.4, 95% CI 9.9-13.1) and elevated signals for DS (3.09), LT (1.98), RI (1.86), and DE (1.82), while Milnacipran showed strong signal for RI (7.31, 5.3-10.0); Venlafaxine had elevated reporting for CA (2.58, 2.38-2.79) and Ketamine for LT events (3.50, 3.35-3.66), with additional significant serious‑outcome signals for Esketamine, Vortioxetine, Venlafaxine, Ketamine, Duloxetine, and Milnacipran, and Levomilnacipran-CA Proportional Reporting Ratios (PRR 10.71, 95% CI 9.40-12.20) showed the strongest PRR signal, Milnacipran-RI (7.21, 5.30-9.80) and Ketamine-LT (3.17, 3.05-3.30).
CONCLUSIONS: Findings show numerous serious AE’s associated with duloxetine, milnacipran, ketamine, and venlafaxine, which can lead to other serious outcomes, including hospitalization. It is necessary to continue and systematically monitor the safety associated with antidepressants and other associated medications.
METHODS: A retrospective disproportionality analysis of FAERS data (2013-2025) evaluated major AEs and serious outcomes (death, hospitalization, congenital anomaly, disability, required intervention, life-threatening events) for SNRIs and NMDAs. Safety signals were assessed using established ROR‑ and PRR-based criteria.
RESULTS: A total of 4,09,802 AEs reports from 3,81,581 case patients (age range from 1 to 81 years), females (92.9%). The most reported AEs were drug withdrawal syndrome, nausea, dizziness, fatigue, paresthesia, insomnia, headache, and anxiety. Outcomes (n=3,68,737), comprising 1,94,798 other serious outcomes (OT, 52.8%), 1,13,890 hospitalizations (HO, 30.8%), 28,675 deaths (DE, 7.7%), 17,107 life‑threatening events (LT, 4.63%), 10,779 disabilities (DS, 2.93%), 2,594 congenital anomalies (CA, 0.70%), and 894 required interventions (RI, 0.24%). Levomilnacipran showed strong disproportionality signal for CA Reporting Odd Ratio (ROR 11.4, 95% CI 9.9-13.1) and elevated signals for DS (3.09), LT (1.98), RI (1.86), and DE (1.82), while Milnacipran showed strong signal for RI (7.31, 5.3-10.0); Venlafaxine had elevated reporting for CA (2.58, 2.38-2.79) and Ketamine for LT events (3.50, 3.35-3.66), with additional significant serious‑outcome signals for Esketamine, Vortioxetine, Venlafaxine, Ketamine, Duloxetine, and Milnacipran, and Levomilnacipran-CA Proportional Reporting Ratios (PRR 10.71, 95% CI 9.40-12.20) showed the strongest PRR signal, Milnacipran-RI (7.21, 5.30-9.80) and Ketamine-LT (3.17, 3.05-3.30).
CONCLUSIONS: Findings show numerous serious AE’s associated with duloxetine, milnacipran, ketamine, and venlafaxine, which can lead to other serious outcomes, including hospitalization. It is necessary to continue and systematically monitor the safety associated with antidepressants and other associated medications.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
RWD81
Topic
Real World Data & Information Systems
Disease
SDC: Neurological Disorders