Assessment of antiseizure medication adherence based on postmortem toxicology and claimed prescriptions in cases of sudden unexpected death in epilepsy.

Abstract

Objective: Individuals with epilepsy are at a higher risk of dying suddenly and without explanation, known as sudden unexpected death in epilepsy (SUDEP). Seizures are a risk factor for SUDEP, and nonadherence to antiseizure medication (ASM) increases this risk. We aimed to assess adherence to ASMs at the time of death among young SUDEP cases by comparing prescription claims with postmortem toxicology at an individual level.

Methods: We identified all forensically autopsied SUDEP cases by assessing autopsy reports, toxicology reports, and Danish health registries from a previously identified nationwide population of sudden unexplained deaths in Denmark. We included cases aged 1-35 and 36-49 years between 2000-2019 and 2007-2019, respectively. We assessed adherence to ASMs by examining discrepancies or consistencies between any register-based claimed prescriptions and postmortem toxicology findings, resulting in four possible outcomes: evidence of adherence, nonadherence, nontreatment or undertreatment, and nonprescribed medication.

Results: Of 477 sudden unexplained deaths, 84 (18%) were identified as SUDEP. Among the SUDEP cases, 73 (87%) claimed ASMs before death and 67 (80%) had ingested ASM according to postmortem findings. Evidence of nonadherence was found in 16 (19%) SUDEP cases, constituting 22% (n = 16/73) of SUDEP cases who claimed ASM before death. Adherence was observed in 53 SUDEP cases (63%), comprising 73% (n = 53/73) of SUDEP cases who claimed ASM before death. Nonadherent SUDEP cases tended toward a higher prevalence of psychiatric diseases when compared with the remaining SUDEP cases.

Significance: By uniquely matching register-based prescription data with postmortem toxicology findings, we ascertained that 73% of SUDEP cases adhered to their claimed ASM, underscoring the necessity for continued vigilance in seizure management. However, improving medication adherence may possess preventive potential for SUDEP, as 22% exhibited nonadherence to their claimed ASM.