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

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.