Global burden of antidepressant-associated seizures from 1967 to 2023: A comparative analysis of the international pharmacovigilance database

Hanseul Cho; Kyeongmin Lee; Sheng-Min Wang; Hayeon Lee; Soeun Kim; Tae Hyeon Kim; Guillaume Fond; Laurent Boyer; Louis Jacob; Selin Woo; Suein Choi; Dong Keon Yon

doi:10.1016/j.jad.2025.04.024

Global burden of antidepressant-associated seizures from 1967 to 2023: A comparative analysis of the international pharmacovigilance database

J Affect Disord. 2025 Apr 4:381:215-223. doi: 10.1016/j.jad.2025.04.024. Online ahead of print.

Authors

Hanseul Cho¹, Kyeongmin Lee², Sheng-Min Wang³, Hayeon Lee⁴, Soeun Kim⁵, Tae Hyeon Kim⁶, Guillaume Fond⁷, Laurent Boyer⁷, Louis Jacob⁸, Selin Woo⁹, Suein Choi¹⁰, Dong Keon Yon¹¹

Affiliations

¹ Department of Medicine, Kyung Hee University College of Medicine, Seoul, South Korea; Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea.
² Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea; Department of Regulatory Science, Kyung Hee University, Seoul, South Korea.
³ Department of Psychiatry, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
⁴ Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea; Department of Electronics and Information Convergence Engineering, Kyung Hee University, Yongin, South Korea.
⁵ Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea; Department of Precision Medicine, Kyung Hee University College of Medicine, Seoul, South Korea.
⁶ Department of Medicine, Kyung Hee University College of Medicine, Seoul, South Korea; Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea; Department of Precision Medicine, Kyung Hee University College of Medicine, Seoul, South Korea.
⁷ CEReSS-Health Service Research and Quality of Life Center, Assistance Publique-Hôpitaux de Marseille, Aix Marseille University, Marseille, France.
⁸ Research and Development Unit, Parc Sanitari Sant Joan de Déu, CIBERSAM, ISCIII, Barcelona, Spain; Department of Physical Medicine and Rehabilitation, Lariboisière-Fernand Widal Hospital, AP-HP, Université Paris Cité, Paris, France; Epidemiology of Ageing and Neurodegenerative Diseases (EpiAgeing), Inserm U1153, Université Paris Cité, Paris, France.
⁹ Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea. Electronic address: dntpfls@naver.com.
¹⁰ Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul, South Korea; Pharmacometrics Institute for Practical Education and Training (PIPET), College of Medicine, The Catholic University of Korea, Seoul, South Korea. Electronic address: mychloe00@gmail.com.
¹¹ Department of Medicine, Kyung Hee University College of Medicine, Seoul, South Korea; Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea; Department of Regulatory Science, Kyung Hee University, Seoul, South Korea; Department of Electronics and Information Convergence Engineering, Kyung Hee University, Yongin, South Korea; Department of Pediatrics, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea. Electronic address: yonkkang@gmail.com.

PMID: 40189065
DOI: 10.1016/j.jad.2025.04.024

Abstract

Background: Although antidepressants have been implicated in seizure risk, comprehensive safety data examining this risk across different antidepressants remains limited.

Methods: Data from Vigibase, an international pharmacovigilance database, encompassing 131,255,418 reports from 1967 to 2023, was analyzed. Reporting odds ratio (ROR) and information component (IC) were calculates to identify disproportionate associations between 17 antidepressants and seizures.

Results: Among 2,275,638 reports on antidepressants, 23,331 reported seizures. Antidepressants as a whole were associated with higher reporting frequency of seizures compared with all medications. Among antidepressant classes, tricyclic antidepressants (TCA; ROR [95 % CI]: 2.71 [2.58-2.84]; IC [IC0.25] 1.42 [1.34]), were the most frequently reported in combination with seizures, followed by selective serotonin reuptake inhibitors (SSRIs; 2.27 [2.22-2.32]; 1.16 [1.13]) and serotonin-norepinephrine reuptake inhibitors (SNRIs; 1.31 [1.27-1.36]; 0.39 [0.33]). Regarding individual antidepressants, agomelatine and desvenlafaxine were the only medications without a significant disproportionate association with seizures. Among the remaining antidepressants, bupropion (8.57 [8.34-8.80]; 3.04 [3.00]) and clomipramine (4.69 [4.29-5.13]; 2.20 [2.05]) had the highest disproportionality measure estimates, whereas vortioxetine and duloxetine had the lowest disproportionality in reporting. Escitalopram (2.17 [2.04-2.31]; 1.11 [1.01]), the active enantiomer of citalopram, and desvenlafaxine (0.93 [0.82-1.05]; -0.11 [-0.31]), the active metabolite of venlafaxine, were less frequently reported for seizures compared to their parent compounds.

Conclusion: Our findings align with earlier studies indicating that SNRIs and SSRIs carry a lower risk of seizures, whereas bupropion and clomipramine are linked to a higher risk. Agomelatine, vortioxetine, and SNRIs like desvenlafaxine and duloxetine may potentially be safe alternatives.

Keywords: Antidepressants; Global; Pharmacovigilance; Seizures; World Health Organization.