Efficacy and compliance of carbohydrate-restricted diets for treating drug-resistant epilepsy: A network meta-analysis of randomized controlled trials

Abstract

Background

Drug-resistant epilepsy (DRE) presents a significant clinical challenge since many patients fail to respond adequately to pharmacological treatments, resulting in persistent seizures and a great decline in quality of life. This highlights the urgent need for alternative or adjunctive therapeutic strategies. Carbohydrate-restricted diets have emerged as promising adjunctive treatments for epilepsy. However, while the efficacy of these diets has been well-established in pediatric populations, their effectiveness on adult DRE patients remains underexplored. This study aims to evaluate and compare the efficacy of various carbohydrate-restricted diets in treating DRE among all age groups, providing valuable insights into their potential clinical applications.

Methods

PRISMA guidelines for network meta-analysis were followed. Randomized controlled trials (RCTs) comparing the efficacy of different carbohydrate-restricted diets in DRE patients, and published in PubMed, Embase, Cochrane, and Web of Science up to 22 December 2023 were screened. The primary outcomes were >50 %, >90 % seizure frequency reduction from the baseline and seizure freedom. Secondary outcomes included compliance and adverse events. Random-effects models with a Bayesian-based approach were employed to estimate between-group comparisons, with results presented as odds ratios (OR) and 95 % credible intervals (CrI).

Results

A total of 17 RCTs involving 1468 DRE patients were included. The diets evaluated were the ketogenic diet (KD), modified Atkins diet (MAD), and low glycemic index treatment (LGIT). For >50 % and >90 % seizure reduction from baseline, all three diets resulted in significant efficacy compared to the normal diet. Notably, MAD was the only diet that demonstrated a statistically significant association with seizure freedom (OR 7.36, 95 % CrI 2.21–60.36), compared to the normal diet, while its lower compliance (OR 0.39, 95 % CrI 0.18–0.76) was likely influenced by the inclusion of adult subjects. Adverse effects were reported across all three diets with similar profiles, highlighting the need for individualized monitoring.

Conclusions

This meta-analysis indicated that in RCTs, the included diet therapies were overall equivalent in efficacy and side effects, with the MAD showing a higher chance of seizure freedom. Compliance was lower with the MAD, but this was likely due to a preponderance of adult studies using this therapy.