Delays and Disparities in Uptake of Effective Antiseizure Medications

National prescribing trends suggest many children may receive suboptimal epilepsy therapy.

In the wake of landmark trials (SANAD II) firmly supporting the use of lamotrigine for focal and valproate for generalized epilepsy, neurologists at Nationwide Children’s expected these drugs would be increasingly prescribed. Instead, their analysis of nearly 150,000 children receiving their first antiseizure monotherapy revealed that prescription of lamotrigine and valproate actually declined over time. This divide between what practice should be and what is done is known as a knowledge-practice gap, and it was more severe in socially vulnerable, Black and Hispanic patients. The study was published in Epilepsia Open.

“Lamotrigine is cheaper, well tolerated and more effective — it’s better, but we [pediatric neurologists] don’t prescribe it equitably or as much as we should,” says the study’s lead author Adam Ostendorf, MD, associate division chief of research and co-medical director of the epilepsy surgery program at Nationwide Children’s. “It wasn’t just a one-off, it was a consistent pattern that seems to be worsening.”

The team examined first antiseizure medication prescriptions from 2015 to 2024 in children aged 4 to 18 years. Over this time period, lamotrigine declined from 10% to 5.5% of prescriptions and valproate from 12% to 7.5%. The decline in lamotrigine prescriptions was most profound among socially vulnerable (measured by the social vulnerability index), Black and Hispanic patients. Levetiracetam, a less effective alternative, increased from 47% to 66% of prescriptions over the course of the study.

“We don’t know the reasons behind this prescribing pattern — that’s the challenge,” says Christopher Beatty, MD, MAS, co-medical director of the epilepsy surgery program at Nationwide Children’s and senior author on the study. “We can hypothesize that there is a bias in prescribing, or that certain communities don’t want to risk certain side effects. This study opens the door for more exploration.”

Lamotrigine’s slower initial titration (2-3 months vs 1-2 weeks with other drugs) may also play a role in its poor uptake. However, Drs. Ostendorf and Beatty caution against assuming families cannot manage the prolonged titration.

“When we identify inequity in the care we provide, it’s important to take that extra 5-second mental check and ask ourselves, ‘What’s the reason I’m not using lamotrigine in this patient?’” says Dr. Beatty.

The Nationwide Children’s neurology team has already disseminated the information internally, created a simplified prescription order set and begun measuring their prescription trends. They are also studying other aspects of knowledge-practice gaps in epilepsy care, such as the prescription of ethosuximide for absence seizures, use of implementation science to improve outcomes in status epilepticus (NCT06194747) and the qualitative reasons behind disparities in the uptake of surgery for drug-resistant epilepsy.

“We’re learning more and more that knowledge alone doesn’t change practice,” says Dr. Ostendorf. “We need to marry it with deliberate implementation strategies.”

This article appeared in the 2026 Fall/Winter print issue. Download the issue here. 

References:

1. Ostendorf AP, Eisner M, Abdel-Rasoul M, Ahrens SM, Twanow JD, Goodkin HP, Beatty CW. Trends in antiseizure medication monotherapy for pediatric epilepsy in the United States. Epilepsia Open. 2026 Jun;11(3):1028-1035. doi: 10.1002/epi4.70273.
2. Ostendorf AP, Loddenkemper T, Morgan LA, Appavu B, Farias-Moeller R, Harrar D, Press C, Abend NS, Gaillard WD, Bai S, Eisner M, McHenry L, Kroshus E, Vannatta K, Goodkin HP. Treating seizures faster: The Quality Improvement in Time to Treat Status Epilepticus (QuITT-SE) multicenter randomized stepped wedge clinical trial protocol. Contemporary Clinical Trials. 2025;151:107831. doi: 10.1016/j.cct.2025.107831.

Image Credit: Adobe Stock (header); Nationwide Children’s (portraits)