Clinical Risk Factors for Suicide in Persons With Epilepsy: A Nationwide Population-Based Case-Control Study

Individuals with epilepsy face an elevated risk of suicide, but risk factors for suicide remain incompletely understood.

We conducted a nationwide case-control study in Sweden to investigate clinical characteristics associated with suicide risk in persons with epilepsy. Persons with epilepsy were identified through Swedish nationwide registers, with epilepsy diagnoses validated through medical record review.

Cases were individuals who died by suicide between 2006 and 2011, validated through autopsy reports, and controls were derived from the source population using similar validation procedures. Characteristics included epilepsy type, etiology, tonic-clonic seizure (TCS) frequency, antiseizure medication (ASM) treatment, living conditions, and psychiatric comorbidity.

Odds ratios (ORs) with 95% CIs were estimated using conditional logistic regression. The study included 111 suicide cases and 1,147 controls.

Suicide cases had a mean age at epilepsy onset of 20 years, and 35% were female. Alcohol abuse (OR 11.81, 95% CI 6.25-22.30) and other substance abuse (OR 10.71, 95% CI 4.52-25.38) showed stronger associations than depression (OR 2.94, 95% CI 1.56-5.53) and anxiety disorders (OR 2.93, 95% CI 1.57-5.44).

Living alone was associated with increased risk (OR 2.59, 95% CI 1.58-4.26). Recent TCS showed a dose-response relationship, with the highest risk among individuals experiencing 4-10 TCS in the preceding year (OR 5.01, 95% CI 2.2-11.3).

Structural and unknown epilepsy etiologies were associated with elevated risk (OR 3.07, 95% CI 1.0-9.5 and OR 8.80, 95% CI 2.9-27.1, respectively). ASM treatment was associated with lower suicide risk (monotherapy OR 0.51, 95% CI 0.27-0.95; polytherapy OR 0.21, 95% CI 0.1-0.5), and nonadherence was associated with higher risk (OR 3.02, 95% CI 1.8-5.1).

This study identified a distinct risk profile for suicide in persons with epilepsy, highlighting alcohol and substance abuse, living alone, seizure burden, nonadherence, and structural or unknown etiologies as key risk factors.

The stronger associations for substance abuse may reflect characteristics specific to epilepsy populations and the focus on completed suicide. Screening for substance abuse and improved seizure control may contribute to suicide prevention.

Major limitations include the modest number of cases and incomplete information on prior suicidal behavior.