Abstract
This retrospective cohort study evaluated the tolerability, efficacy, and safety of adjunctive cannabidiol (CBD) therapy in pediatric-onset intractable epilepsy across diverse genetic and nongenetic etiologies. Twenty-nine patients aged 6 to 24 years, treated at Korea University Hospitals between April 2019 and May 2024, were included. The median follow-up duration was 14.3 months. Confirmed genetic etiologies included SCN1A-related epilepsy (6.9%); GABRB3-, SCN2A-, KCNT1-, KIF1A-, and COL4A1-related epilepsies (3.4% each); Angelman syndrome and Down syndrome (3.4% each). Presumed genetic etiologies included hemimegalencephaly (3.4%) and cortical dysplasia (6.9%). Acquired causes included hypoxic brain injury (6.9%) and CNS infection (10.3%). In 41.4% of cases, the etiology was unidentified; among them, 58.3% had a history of infantile spasms. At CBD initiation, patients were receiving a median of 5 antiseizure medications, most commonly valproic acid (93.1%), clobazam (82.8%), and levetiracetam (75.9%). The median maintenance dose of CBD was 14.2 mg/kg/d. The retention rate was above 86% at both 12 and 24 months. At 12 months, 79.3% achieved a ≥50% reduction in seizure frequency, and 34.5% achieved a ≥75% reduction without generalized motor seizures. One patient with a GABRB3 variant achieved seizure freedom. Adverse events occurred in 37.9%, most commonly somnolence and lethargy. These were mild and resolved with antiseizure medication adjustments. CBD was discontinued in 3 patients due to pneumonia, lethargy, or seizure aggravation. CBD therapy demonstrated favorable retention, efficacy, and safety profiles in pediatric-onset intractable epilepsy across a spectrum of etiologies.