Trends in antiseizure medication monotherapy for pediatric epilepsy in the United States

National prescribing trends for antiseizure medication (ASM) in children with epilepsy over the past decade are unclear. Despite the 2021 SANAD II trials supporting lamotrigine and valproate for focal and generalized epilepsies, respectively, it is unknown if their use increased. This study evaluated ASM prescriptions in the U.S. before and after publication of high-quality clinical trials.

A retrospective cross-sectional cohort study was conducted using the Epic Cosmos Dataset, a national electronic health record repository covering over 300 million patients. Children with epilepsy aged 4-18 years prescribed their first ASM between 2015 and 2024 were included, excluding those with absence epilepsy. The primary outcome was the prescribed ASM, analyzed by year and patient demographics.

Among 146 395 children with a single ASM prescription, levetiracetam was most common (58%), increasing from 47% in 2015 to 66% in 2024. Lamotrigine and valproate declined (10%-5.5% and 12%-7.5%, respectively). Females were prescribed less valproate (5% vs. 12% in males). Odds of lamotrigine prescription (OR, 95% CI) were lowest among patients in the highest social vulnerability index quartile (0.71, 0.67-0.75), Black (0.39, 0.36-0.42), Asian (0.49, 0.42-0.57), Hispanic/Latino (0.60, 0.56-0.64), and male (0.60, 0.57-0.62) patients.

While a reduction in valproate was anticipated given increasing teratogenic concerns, lamotrigine prescriptions for children in the U.S. declined despite evidence of its superiority over other commonly used ASMs. This trend is more prominent in racial and ethnic minorities and those with higher social vulnerability. Interventions are needed to ensure children receive evidence-based, equitable care.

Some seizure medications work better than others, and clinical trials have shown lamotrigine to be among the most effective and best-tolerated first treatments for children with epilepsy. Using a large national database of over 146 000 children, we found that lamotrigine prescriptions declined steadily from 2015 to 2024, while the use of levetiracetam, a less effective alternative, continued to rise. This trend was most pronounced in Black, Hispanic, and socially vulnerable children, suggesting that many children are not receiving evidence-based care and that existing inequities in epilepsy treatment are worsening.