Dietary Therapies Show Short-term Effectiveness for Childhood Drug-Resistant Epilepsy

Dietary therapies were associated with significant reductions in the frequency of seizure for pediatric patients with drug-resistant epilepsy (DRE), with the modified Atkins diet showing superior tolerability and effectiveness short term than other interventions. Results from the meta-analysis were published in JAMA Pediatrics.

Comprising nearly 30% of cases for children with epilepsy, DRE is a difficult to treat condition that is linked with greater seizure burden and mortality risk. Epilepsy surgery is a curative treatment option for surgically amenable DRE, but for patients with nonsurgical DRE, specific neurometabolic disorders, or those who fail 2 or more appropriately chosen antiseizure medications while awaiting epilepsy surgery, alternative modalities such as dietary therapies have also shown potential.

“Despite advances in the understanding of dietary therapies in children with DRE, no quantitative comparison exists between different dietary interventions,” said the study authors. “Amalgamating various direct and indirect treatment assessments may help in reaching robust inferences and thereby guide therapeutic decision-making.”

They conducted a systematic review and network meta-analysis of randomized clinical trials comparing different dietary therapies (ketogenic diet, modified Atkins diet, and low glycemic index therapy) for the short-term, intermediate term, and long-term management of childhood DRE (age ≤ 18 years).

For the analysis, studies in the PubMed, Embase, Cochrane, and Ovid databases published from inception to April 2022, using the search terms ketogenic diet, medium chain triglyceride diet, modified Atkins diet, low glycemic index therapy, and refractory epilepsy, were eligible.

Short-term (3 months) 50% or higher and 90% or higher reduction in seizure frequency and treatment withdrawal due to adverse events were the primary efficacy and safety outcomes assessed. The proportion with seizure freedom in the short term and the efficacy outcomes in the intermediate (4 to 6 months) and long term (12 months) were also analyzed.

Of 2158 citations, 12 randomized clinical trials (907 patients) qualified for inclusion, in which efficacy was examined short term in 10 trials, intermediate term in 4 trials, and long term in one trial. Among the study cohort, the mean (SD) age at seizure onset was 1.4 (1.6) years and the mean (SD) seizure frequency was 27.1 (31.8) per day.

Primary outcome findings showed that all dietary interventions were more efficacious than care as usual for 50% or higher seizure reduction (low glycemic index therapy: OR, 24.7; 95% CI, 5.3-115.4; modified Atkins diet: OR, 11.3; 95% CI, 5.1-25.1; ketogenic diet: OR, 8.6; 95% CI, 3.7-20.0), with no significant difference found between the 3 dietary interventions.

For short-term analyses on 90% or higher reduction in seizure frequency compared with care as usual, a statistically significant number of participants achieved the outcome with the ketogenic diet (OR, 6.5; 95% CI, 2.3-18.0) and modified Atkins diet (OR, 5.1; 95% CI, 2.2-12.0). Findings of the other analyses showed similar, significant efficacy for the dietary therapies in the management of childhood DRE:

• Compared with care as usual, a statistically significant number of participants had achieved 50% or higher seizure reduction with ketogenic diet in the intermediate term (OR, 4.5; 95% CI, 1.2-17.0)
• The 3 dietary therapies were comparable in terms of intermediate term 90% or higher seizure reduction
• Ketogenic diet (OR, 5.0; 95% CI, 1.3-19.5) and modified Atkins diet (OR, 4.4; 95% CI, 1.3-14.5) were better than care as usual for achieving seizure freedom
  

Regarding safety, adverse event–related discontinuation rates were significantly higher for ketogenic diet (OR, 8.6; 95% CI, 1.8-40.6) and modified Atkins diet (OR, 6.5; 95% CI, 1.4-31.2) compared with care as usual. Indirectly, no significant difference between dietary therapies in efficacy and safety outcomes were identified.

Clinical heterogeneity in the included studies, imprecision, and unavailability of robust evidence for indirect comparison between different dietary interventions and for intermediate and long-term outcomes of these therapies were cited as limitations of the study findings.

“Modified Atkins diet had better tolerability, higher probability for 50% or higher seizure reduction, and comparable probability for 90% or higher seizure reduction and may be a sounder option than ketogenic diet,” concluded the study authors. “Direct head-to-head comparison studies are needed to confirm these findings.”

Reference

Devi N, Madaan P, Kandoth N, Bansal D, Sahu JK. Efficacy and safety of dietary therapies for childhood drug-resistant epilepsy: A systematic review and network meta-analysis. JAMA Pediatr. Published online January 30, 2023. doi:10.1001/jamapediatrics.2022.5648