Efficacy of the modified atkins diet in adults with pharmacoresistant epilepsy

Abstract

Background: Approximately 30% of patients with epilepsy are pharmacoresistant and, therefore, alternative therapeutic interventions should be considered to reduce seizure-related morbidity and mortality. The ketogenic diet (KD) has been increasingly used as an adjuvant therapeutic strategy for seizure control in adult patients with pharmacoresistant epilepsy (PRE). Objective: To evaluate the impact of the Modified Atkins Diet (MAD) on seizure frequency of adult patients with PRE. Methods: This is a prospective case series with recruitment since 2018 - ongoing. Adult patients with confirmed diagnosis of epilepsy according to ILAE’s latest guidelines (2017, 2022, 2025), minimum follow-up of 1 year, not candidates for surgery, and on stable pharmacological treatment for at least 1 month prior to study entry with at least one antiseizure medication (ASM), with no evidence of progressive neurological disease or uncontrolled psychiatric condition were included. All patients were followed at a specialized epilepsy center by an expert epileptologist and a team of nutritionists specialized in KD therapy. Exclusion criteria included individuals under 18 years, pregnant or breastfeeding women, patients with contraindications to the KD (inborn errors of metabolism, uncontrolled diabetes, nephrolithiasis, pancreatitis, and renal or hepatic disease), non-epileptic or functional dissociative seizures, and individuals or caregivers unable to understand instructions or reliably complete seizure diaries. Efficacy was assessed after three months of diet, considering therapeutic response as ≥50% reduction in seizure frequency compared to baseline. A p < 0.05 was considered statistically significant. Results: Thirty-one adults with PRE initiated the MAD therapy: 16 females (51.6%), with a mean age of 35.2 ± 9.7 years (range 18–57). Most patients were diagnosed with focal epilepsy (85%). The most commonly used ASM prior to the KD were clobazam (63.3%), levetiracetam (56.7%), carbamazepine (33.3%), and lamotrigine (33.3%). Most patients were on polytherapy, mean number was 2,83 ± 1,26 ASM per patient (range 2-5). Of these, 17 patients completed at least three months of follow-up and were included in the efficacy analysis. Reasons for drop out were mainly: lack of efficacy, adverse effects (gastrointestinal issues, weight loss), diet too restrictive and/or high-cost. The responder rate (≥50% seizure reduction) was 52,9%, with 17,6% achieving seizure freedom. A reduction in median monthly seizure frequency from 7.5 seizures/month at baseline to 4,5 seizures/month after three months was observed. However, this reduction was not statistically significant (paired Wilcoxon test, p = 0.57). Conclusion: The MAD was associated with a reduction in seizure frequency in patients with PRE; however, this reduction did not reach statistical significance. Tolerability and adherence remain major challenges of this therapy.