Effect of concurrent anti-seizure medications on the efficacy of the ketogenic diet in children with epilepsy

Objective: The ketogenic diet (KD) is a well-established therapeutic option for children with non-surgical drug-resistant epilepsy (DRE). At the time of KD initiation, most children are already on anti-seizure medications (ASM), which are continued and adjusted during KD treatment. The purpose of this study was to determine whether specific ASM, alone or in combination, are associated with positive seizure outcomes when used concurrently with KD. Methods: This was a retrospective chart review of children, aged 1 month to 18 years, with DRE treated with KD at the Hospital for Sick Children from Jan 2011 to Feb 2022. Data included demographics, epilepsy etiology, seizure type, and ASM used. Children with seizure frequency data available for at least 3 months without dose modification were eligible for analysis. Children with ≥50% reduction in seizures from baseline were classified as responders. The proportions of responders on each anti-seizure medication were calculated.

Results: A total of 127 children (55 boys) were enrolled. The most common ASM used in monotherapy or in combinations included levetiracetam, clobazam, valproate, phenobarbital, oxcarbazepine, and lamotrigine. The >50% reduction in seizure responder rate was the highest among children treated with Lamotrigine (75%), followed by Topiramate (68.5%), Phenobarbital (63.3%), Valproate (63.3%), Levetiracetam (61.5%) and Clobazam (54.8%).

Conclusion: Children treated with lamotrigine in combination with KD were found to have the highest responder rate in this retrospective cohort. Further analyses will examine the effects of age, epilepsy etiology, and seizure type in combination with ASM on seizure outcomes in children treated with KD.
Keywords: ketogenic diet, drug-resistant epilepsy, lamotrigine, topiramate, clobazam