Premature Mortality and Causes of Death Among People With Epilepsy: A Nationwide Population-Based Incident Cohort Study

Abstract

Background and objectives: People with epilepsy (PWE) are at risk of premature death with considerable variability according to the study population. We aimed to estimate the risk and causes of death in PWE according to age, disease severity, disease course, comorbidities, and socioeconomic status in Korea.

Methods: We conducted a nationwide population-based retrospective cohort study using the National Health Insurance database linked with the national death register. Newly treated PWE from 2008 to 2016 who were identified by antiseizure medication (ASM) prescriptions and diagnostic codes for epilepsy/seizure were included and observed until 2017. We assessed all-cause and cause-specific crude mortality rates and standardized mortality ratios (SMRs).

Results: Among 138,998 PWE, 20,095 deaths were identified, and the mean follow-up period was 4.79 years. The SMR was 2.25 in the overall group of PWE, with a higher value in the younger age group at diagnosis and a shorter time interval after diagnosis. The SMR in the monotherapy group was 1.56, while that in the group with 4 or more ASMs was 4.93. PWE without any comorbidities had an SMR of 1.61. PWE who were rural residents had a higher SMR than those who were urban residents (2.47 vs 2.03, respectively). The causes of death among PWE were cerebrovascular disease (18.9%, SMR 4.50), malignant neoplasms outside the CNS (15.7%, SMR 1.37), malignant neoplasms of the CNS (6.7%, SMR 46.95), pneumonia (6.0%, SMR 2.08), and external causes (7.2%, SMR 2.17), including suicide (2.6%, SMR 2.07). Epilepsy itself and status epilepticus accounted for 1.9% of the overall death. The excess mortality associated with pneumonia and external causes was persistently high, whereas the excess mortality associated with malignancy and cerebrovascular diseases tended to decrease with increasing time since diagnosis.

Discussion: This study showed excess mortality in PWE, even in those without comorbidities and those receiving monotherapy. Regional disparities and sustained risks of deaths from external causes over 10 years imply potential points of intervention. In addition to active control of seizures, education about injury prevention, monitoring for suicidal ideation, and efforts to improve accessibility to epilepsy care are all required to reduce mortality.