Short-term efficacy and safety of dietary therapies in children with drug-resistant epilepsy: A network meta-analysis

Objective: To assess the short-term comparative efficacy and safety of different dietary therapies in childhood DRE. Methods: A systematic literature search of PubMed and Embase (till January 2022) was done. Randomized controlled trials(RCTs) comparing different dietary therapies [Ketogenic diet(KD), modified Atkins diet(MAD), low glycemic index therapy(LGIT)], and care as usual(CAU) were included. Short-term (3 months) ≥50% reduction in seizure frequency, seizure freedom, and adverse event(AE)-related treatment withdrawal were the primary efficacy and safety outcomes. A network meta-analysis was done and the hierarchy of competing interventions was defined using the surface under the cumulative ranking curve. Results: Twelve RCTs with 907 participants were evaluated. As compared with CAU, a statistically significant number of participants achieved ≥50% seizure reduction [LGIT(OR:24.7; 95% CI:5.3-115.4), MAD(OR:11.3; 95% CI:5.1-25.1), KD(OR:8.6; 95% CI:3.7- 20.0)] and seizure freedom [KD (OR:5.0; 95% CI:1.3-19.5), MAD (OR:4.4; 95% CI:1.3-14.5), LGIT (OR:1.8; 95% CI:0.2-14.3)] with different dietary therapies. LGIT(0.92) and KD (0.81) had the highest ranking probability for achieving ≥50% seizure reduction and seizure freedom respectively. During the treatment period, the dietary therapies like KD (OR: 9.5; 95% CI: 2.0-45.3) and MAD (OR: 5.8; 95% CI: 1.2-28.1) had to be withdrawn for 44/633 (7%) participants due to AEs as compared with CAU. However, on indirect comparison, there was no significant difference for safety outcomes. Conclusion: KD, MAD, and LGIT are efficacious in short-term as compared with CAU. Although KD followed by MAD had the highest probability for seizure freedom, future head-to-head trials comparing different dietary therapies are the need of the hour.
Keywords: drug resistant epilepsy, ketogenic diet, modified Atkins diet, childhood epilepsy