Effect Modification of Alcohol Use on Epilepsy: NHIS Longitudinal Study

Introduction: The relationship between epilepsy and alcohol use is complex and clinically significant. Alcohol acts as a neurochemical modulator capable of lowering the seizure threshold during both intoxication and withdrawal, while chronic misuse may contribute to epileptogenesis through neuronal injury, metabolic stress, and neurotransmitter dysregulation. However, the long-term impact of alcohol use on mortality among people with epilepsy (PWE) remains insufficiently characterized. The purpose of this study was to assess all-cause mortality risk among individuals with epilepsy based on alcohol use history, stratified by race/ethnicity. Methods: Data from the 2008-2018 National Health Interview Survey (NHIS) were linked to mortality outcomes on 31 December 2019 from the National Death Index (NDI) for U.S. adults aged 18 years and older. PWE and alcohol use were determined using self-reported data. Survival probabilities were estimated using weighted Kaplan-Meier methods, and hazard ratios were calculated using Cox proportional hazards models adjusted for demographic and clinical covariates. Results: Our results indicated that among PWE, alcohol use was associated with increased all-cause mortality. The unadjusted hazard ratio (HR) for alcohol use among individuals with epilepsy was 1.30, increasing to 1.40 after multivariable adjustment. In contrast, alcohol use alone without epilepsy was not associated with elevated mortality risk after adjustment. When stratified by race, the combined effect of epilepsy and alcohol use was significantly associated with increased mortality among Black individuals but not White individuals. Conclusions: In this nationally representative cohort, the combined presence of epilepsy and alcohol use was associated with higher all-cause mortality compared with alcohol use alone. Racial differences were observed, underscoring the need for integrated clinical care and further research into genetic, biological, and social determinants influencing epilepsy outcomes.