Does Missing Medication Acutely Change Seizure Risk? A Prospective Study

Objective The objective of this study was to determine whether missing individual doses of anti‐seizure medications (ASMs) elevate short‐term seizure risk in people with drug‐resistant epilepsy. Methods In a prospective, community‐based cohort, adults with drug‐resistant epilepsy (≥ 3 seizures/month) or their caregivers recorded seizures and ASM intake with smartphone applications for 10 months each. Individual level analysis modeled the relationships between ASM adherence with seizure occurrence, as well as with a simplified seizure forecast via a 90‐day moving average (“Napkin method”). Group‐level analysis with a mixed‐effects model was performed to examine the relationship between ASM adherence and simplified forecasts, while controlling for differences in individual seizure frequency via random effects. Results Twenty‐seven participants (median age = 29 years) contributed 7,853 person‐days. Individual analysis showed that only a small (n = 2) number of participants had a weak relationship between ASM adherence with seizure occurrence. Group‐level analysis showed that seizure occurrence was highly linked to the Napkin method, but not ASM adherence. Interpretation Among individuals with frequent, drug‐resistant epilepsy, occasional missed ASM doses did not measurably raise immediate seizure risk. Whereas sustained nonadherence remains a clinical concern, clinicians may reassure patients that infrequent brief lapses are unlikely to trigger seizures acutely, yet they should continue emphasizing overall adherence for long‐term seizure control. ANN NEUROL 2026