Adverse event reports of seizure for insomnia medication from 1967 to 2023

Abstract Insomnia may negatively impact seizure control; however, the corresponding evidence remains limited. This study analyzed the seizure risk associated with various insomnia medications using a comprehensive pharmacovigilance database and identified safe options for patients at high risk of se...

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Main Authors: Tae Hyeon Kim, Kyeongmin Lee, Jiyoung Hwang, Suhyun Lee, Hyesu Jo, Hanseul Cho, Hayeon Lee, Hye Jeong Baek, Jiseung Kang, Christa J. Nehs, Guillaume Fond, Laurent Boyer, Eun Kyoung Chung, Dong Keon Yon
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Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-11314-1
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author Tae Hyeon Kim
Kyeongmin Lee
Jiyoung Hwang
Suhyun Lee
Hyesu Jo
Hanseul Cho
Hayeon Lee
Hye Jeong Baek
Jiseung Kang
Christa J. Nehs
Guillaume Fond
Laurent Boyer
Eun Kyoung Chung
Dong Keon Yon
author_facet Tae Hyeon Kim
Kyeongmin Lee
Jiyoung Hwang
Suhyun Lee
Hyesu Jo
Hanseul Cho
Hayeon Lee
Hye Jeong Baek
Jiseung Kang
Christa J. Nehs
Guillaume Fond
Laurent Boyer
Eun Kyoung Chung
Dong Keon Yon
author_sort Tae Hyeon Kim
collection DOAJ
description Abstract Insomnia may negatively impact seizure control; however, the corresponding evidence remains limited. This study analyzed the seizure risk associated with various insomnia medications using a comprehensive pharmacovigilance database and identified safe options for patients at high risk of seizures. VigiBase, a database of adverse drug reaction reports from over 140 countries, comprises 35 million reports published from 1967 to 2023. Medications for insomnia include benzodiazepines, Z-drugs, antidepressants, atypical antipsychotics, first-generation H1 antagonists, orexin receptor agonists, melatonin, and melatonin receptor agonists. We assessed the association between insomnia medications and seizure risk by analyzing the reported odds ratio (ROR) with 95% confidence intervals (CI) and the information component (IC) with IC025. In total, 17,967 cases of seizures associated with insomnia medications were reported, revealing a significant association (ROR, 2.12 [95% CI, 2.09 to 2.15]; IC, 1.05 [IC025, 1.03]). Based on the mechanism of action, seizures were significantly associated with benzodiazepines (ROR, 2.56 [95% CI, 2.49 to 2.64]; IC, 1.34 [IC025, 1.29]), Z-drugs (ROR, 1.58 [1.49 to 1.69]; IC, 0.66 [0.56]), antidepressants (ROR, 2.52 [2.43 to 2.61]; IC, 1.32 [1.26]), atypical antipsychotics (ROR, 1.92 [1.88 to 1.97]; IC, 0.93 [0.89]), first-generation H1 antagonists (ROR, 2.08 [1.98 to 2.19]; IC, 1.05 [0.96]), and melatonin (ROR, 1.81 [1.49 to 2.20]; IC, 0.84 [0.51]). In contrast, orexin receptor antagonists (ROR, 0.81 [95% CI, 0.61 to 1.07]; IC, − 0.30 [IC025, − 0.77]) and melatonin receptor agonists (ROR, 1.20 [0.80 to 1.81]; IC, 0.26 [− 0.44]) showed no significant association with seizures. Although the disproportionality analysis did not allow causal interpretation, our study highlights significant variations in seizure signal among insomnia medications.
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spelling doaj-art-3bc8ba83531647f78edbe59c8b6a656d2025-08-20T03:42:31ZengNature PortfolioScientific Reports2045-23222025-07-0115111110.1038/s41598-025-11314-1Adverse event reports of seizure for insomnia medication from 1967 to 2023Tae Hyeon Kim0Kyeongmin Lee1Jiyoung Hwang2Suhyun Lee3Hyesu Jo4Hanseul Cho5Hayeon Lee6Hye Jeong Baek7Jiseung Kang8Christa J. Nehs9Guillaume Fond10Laurent Boyer11Eun Kyoung Chung12Dong Keon Yon13Department of Precision Medicine, Kyung Hee University College of MedicineCenter for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of MedicineCenter for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of MedicineDepartment of Pharmacy, College of Pharmacy, Kyung Hee UniversityCenter for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of MedicineCenter for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of MedicineCenter for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of MedicineDepartment of Regulatory Science, Graduate School, Kyung Hee UniversitySchool of Health and Environmental Science, College of Health Science, Korea UniversityDivision of Sleep Medicine, Harvard Medical SchoolCEReSS-Health Service Research and Quality of Life Center, Assistance Publique-Hôpitaux de Marseille, Aix Marseille UniversityCEReSS-Health Service Research and Quality of Life Center, Assistance Publique-Hôpitaux de Marseille, Aix Marseille UniversityDepartment of Regulatory Science, Graduate School, Kyung Hee UniversityDepartment of Precision Medicine, Kyung Hee University College of MedicineAbstract Insomnia may negatively impact seizure control; however, the corresponding evidence remains limited. This study analyzed the seizure risk associated with various insomnia medications using a comprehensive pharmacovigilance database and identified safe options for patients at high risk of seizures. VigiBase, a database of adverse drug reaction reports from over 140 countries, comprises 35 million reports published from 1967 to 2023. Medications for insomnia include benzodiazepines, Z-drugs, antidepressants, atypical antipsychotics, first-generation H1 antagonists, orexin receptor agonists, melatonin, and melatonin receptor agonists. We assessed the association between insomnia medications and seizure risk by analyzing the reported odds ratio (ROR) with 95% confidence intervals (CI) and the information component (IC) with IC025. In total, 17,967 cases of seizures associated with insomnia medications were reported, revealing a significant association (ROR, 2.12 [95% CI, 2.09 to 2.15]; IC, 1.05 [IC025, 1.03]). Based on the mechanism of action, seizures were significantly associated with benzodiazepines (ROR, 2.56 [95% CI, 2.49 to 2.64]; IC, 1.34 [IC025, 1.29]), Z-drugs (ROR, 1.58 [1.49 to 1.69]; IC, 0.66 [0.56]), antidepressants (ROR, 2.52 [2.43 to 2.61]; IC, 1.32 [1.26]), atypical antipsychotics (ROR, 1.92 [1.88 to 1.97]; IC, 0.93 [0.89]), first-generation H1 antagonists (ROR, 2.08 [1.98 to 2.19]; IC, 1.05 [0.96]), and melatonin (ROR, 1.81 [1.49 to 2.20]; IC, 0.84 [0.51]). In contrast, orexin receptor antagonists (ROR, 0.81 [95% CI, 0.61 to 1.07]; IC, − 0.30 [IC025, − 0.77]) and melatonin receptor agonists (ROR, 1.20 [0.80 to 1.81]; IC, 0.26 [− 0.44]) showed no significant association with seizures. Although the disproportionality analysis did not allow causal interpretation, our study highlights significant variations in seizure signal among insomnia medications.https://doi.org/10.1038/s41598-025-11314-1InsomniaSeizureWorld Health OrganizationPharmacovigilance
spellingShingle Tae Hyeon Kim
Kyeongmin Lee
Jiyoung Hwang
Suhyun Lee
Hyesu Jo
Hanseul Cho
Hayeon Lee
Hye Jeong Baek
Jiseung Kang
Christa J. Nehs
Guillaume Fond
Laurent Boyer
Eun Kyoung Chung
Dong Keon Yon
Adverse event reports of seizure for insomnia medication from 1967 to 2023
Scientific Reports
Insomnia
Seizure
World Health Organization
Pharmacovigilance
title Adverse event reports of seizure for insomnia medication from 1967 to 2023
title_full Adverse event reports of seizure for insomnia medication from 1967 to 2023
title_fullStr Adverse event reports of seizure for insomnia medication from 1967 to 2023
title_full_unstemmed Adverse event reports of seizure for insomnia medication from 1967 to 2023
title_short Adverse event reports of seizure for insomnia medication from 1967 to 2023
title_sort adverse event reports of seizure for insomnia medication from 1967 to 2023
topic Insomnia
Seizure
World Health Organization
Pharmacovigilance
url https://doi.org/10.1038/s41598-025-11314-1
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