Proton Pump Inhibitor Use and Incident Epilepsy in the UK Biobank: Evidence From Pharmacovigilance and Multi‐Omics Analyses
- 1Department of Neurology The First Affiliated Hospital of Wenzhou Medical University Wenzhou Zhejiang Province People's Republic of China
- 2Key Laboratory of Alzheimer's Disease of Zhejiang Province, Institute of Aging Wenzhou Medical University Wenzhou Zhejiang Province People's Republic of China
- 3Key Laboratory of Novel Nuclide Technologies on Precision Diagnosis and Treatment & Clinical Transformation of Wenzhou City Wenzhou Zhejiang Province People's Republic of China
Abstract
Aims: Proton pump inhibitors (PPIs) are widely used, but their association with incident epilepsy remains uncertain. We examined this association in the UK Biobank and integrated evidence from pharmacovigilance and multi‐omics.
Methods: We included 492,858 UK Biobank participants without epilepsy at baseline. Cox models, age‐ and sex‐stratified analyses, active‐comparator analyses against H2RA users, propensity score matching, competing‐risk models, and sensitivity analyses were performed. FAERS disproportionality, Olink proteomics, and NMR metabolomics provided supportive evidence.
Results: Baseline PPI use was associated with incident epilepsy after full adjustment (HR 1.43, 95% CI 1.29–1.59) and in the PPI‐H2RA propensity score‐matched analysis (HR 1.41, 95% CI 1.03–1.94). In the GP‐linked subset, requiring an ASM prescription within 365 days after diagnosis yielded HR 1.47 (95% CI 1.07–2.02). FAERS showed a PPI‐epilepsy reporting signal (ROR 1.70, 95% CI 1.61–1.79). Proteomic and metabolomic analyses identified immune‐inflammatory and metabolic associations.
Conclusion: Baseline PPI use was associated with incident epilepsy in the UK Biobank. Active‐comparator, outcome‐definition, and prescription‐supported analyses supported the primary association. Pharmacovigilance and molecular findings provided complementary evidence but did not establish causality.
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BibTeX
@article{li2026proton,
title = {{Proton Pump Inhibitor Use and Incident Epilepsy in the UK Biobank: Evidence From Pharmacovigilance and Multi‐Omics Analyses}},
author = {Minghao Li and Yiqian Li and Yuxi Zhang and Balkissou Seebo Saibou and Yifei Chen and Jiayi Xing and Chao Jin and Yuchen Xu and Jiahe Lin and Xinshi Wang},
journal = {CNS Neuroscience \& Therapeutics},
year = {2026},
month = nov,
doi = {10.1002/cns.71223},
url = {https://doi.org/10.1002/cns.71223},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Proton Pump Inhibitor Use and Incident Epilepsy in the UK Biobank: Evidence From Pharmacovigilance and Multi‐Omics Analyses
AU - Minghao Li
AU - Yiqian Li
AU - Yuxi Zhang
AU - Balkissou Seebo Saibou
AU - Yifei Chen
AU - Jiayi Xing
AU - Chao Jin
AU - Yuchen Xu
AU - Jiahe Lin
AU - Xinshi Wang
PY - 2026
DA - 2026/11/04
JO - CNS Neuroscience & Therapeutics
DO - 10.1002/cns.71223
UR - https://doi.org/10.1002/cns.71223
AB - Aims: Proton pump inhibitors (PPIs) are widely used, but their association with incident epilepsy remains uncertain. We examined this association in the UK Biobank and integrated evidence from pharmacovigilance and multi‐omics. Methods: We included 492,858 UK Biobank participants without epilepsy at baseline. Cox models, age‐ and sex‐stratified analyses, active‐comparator analyses against H2RA users, propensity score matching, competing‐risk models, and sensitivity analyses were performed. FAERS disproportionality, Olink proteomics, and NMR metabolomics provided supportive evidence. Results: Baseline PPI use was associated with incident epilepsy after full adjustment (HR 1.43, 95% CI 1.29–1.59) and in the PPI‐H2RA propensity score‐matched analysis (HR 1.41, 95% CI 1.03–1.94). In the GP‐linked subset, requiring an ASM prescription within 365 days after diagnosis yielded HR 1.47 (95% CI 1.07–2.02). FAERS showed a PPI‐epilepsy reporting signal (ROR 1.70, 95% CI 1.61–1.79). Proteomic and metabolomic analyses identified immune‐inflammatory and metabolic associations. Conclusion: Baseline PPI use was associated with incident epilepsy in the UK Biobank. Active‐comparator, outcome‐definition, and prescription‐supported analyses supported the primary association. Pharmacovigilance and molecular findings provided complementary evidence but did not establish causality.
SN - 1755-5930
SN - 1755-5949
ER -