Epilepsy is a chronic neurological disorder characterized by repeated unprovoked seizures resulting from abnormal and excessive electrical activity in the brain. Former studies on epilepsy-related mortality have focused only on recent decades, restricting insights into long term mortality trends.

From 1968 to 2023, a total of 103,842 deaths were attributed to epilepsy. The AAMR showed an overall upward trajectory, rising from (1.38) in 1968 to (2.46 ) in 2023 (AAPC: 1.02, 95% CI: 0.54 to 1.51, p< 0.01). Males consistently had higher AAMRs than females (men: 1.8, women: 1) in 1968 to (men: 2.8, women: 2.1) in 2023, with incline for both sexes (men: AAPC: 0.92, p< 0.01, women: AAPC: 1.24, p< 0.01). Racial disparities persisted, with Black individuals having higher AAMRs than White individuals both in 1968 (4.5 vs 1.1) and in 2023 (4 vs 2.4). Regionally, the Midwest recorded the highest AAMR (1999: 1.2, 2023: 2.6, AAPC: 1.32, p< 0.01). Among age groups, older adults reported the highest CMR (1968: 1.1, 2023: 5.8).

Our retrospective analysis demonstrates an overall increasing trend in mortality from epilepsy over the past five decades. Persistent disparities were seen with significantly higher mortality burden among males, Black individuals, the elderly and residents of Midwest region highlighting the underlying differences in healthcare access, socioeconomic factors, and availability of specialized neurologic care.