Dietary therapies safe and efficient for treating drug-resistant epilepsy

Dietary therapies show short term efficacy against childhood drug-resistant epilepsy (DRE), but ketogenic diets (KDs) show worse tolerability when compared to a modified Atkins diet (MAD), according to a recent study.

Nearly 30% of children with epilepsy experience DRE, a form of epilepsy which is currently difficult to treat. DRE can often be treated through epilepsy surgery, but when 2 or more chosen antiseizure medications fail to work on a child waiting for surgery, a dietary therapy may be used.

KDs have shown promising results limited by adherence difficulties in the past centuries. Recently, less restrictive options have been explored, including the modified Atkins diet (MAD) and low glycemic index therapy (LGIT).

As there is a need for investigations into the comparative safety and efficacy of these dietary therapies in treating DRE, investigators conducted a meta-analysis on this subject.

PubMed, Embase, Cochrane, and Ovid databases were used for a preliminary search, with keywords entered including ketogenic diet,medium chain triglyceride diet, modified Atkins diet, lowglycemic index therapy, andrefractory epilepsy. GoogleScholar, ClinicalTrials.gov, and certain reference lists from articles were used for a manual search.

Studies used for the analysis included randomized clinical trials (RCTs) which evaluated the safety and efficacy of dietary therapies such as MAD, KD, and LGIT. Two authors independently carried out data screening and extraction for the studies. 

Variables extracted included publication year, country, participant demographics, baseline characteristics, interventiondetails, reported outcomes, and other relevant information. Disagreements between the 2 authors were discussed and consulted with a third author.

A significant reduction in the rate of seizures was measured as the primary outcome of the analysis. This was measured through the proportion of 50% or higher or 90% or higher short-term seizure reduction. Intermediate and long-term seizure freedom were also evaluated. 

Safety outcomes measured included treatment withdrawal because of adverse events (AE) and other reported AEs.

There were 11 open-label and 1 single-blinded RCT comparing 3 dietary therapies with each other, or usual care included in the analysis. In these studies, 676 patients were assigned to dietary interventions while 257 were assigned to usual care. A common group of patients was seen between 2 studies, leading to a total study population of 907 participants.

Participants had a mean age of 4.6 years at enrollment, and 67% of participants were boys. The mean age of seizure onset in patients was 1.4 years, with a mean seizure rate of 27.1 seizures per day. Outcomes at 3 months were assessed in 9 trials, 4 to 6 months in 5, and 12 months in 1. For efficacy, 10 trials examined short-term results, 4 intermediate, and 1 long-term.

All 3 dietary therapies showed more efficacy than usual care for 50% or higher seizure reduction. No major differences were found between the 3 dietary therapies. Many more patients also reached 90% or higher seizure reduction when taking MAD or KD compared to usual care, but the 2 dietary therapies did not show significant differences between each other.

Ten percent of patients taking dietary therapies achieved seizure freedom, with KD and MAD more consistently leading to seizure freedom. There were not significant differences between these dietary therapies.

Participants were significantly more likely to withdraw from care because of AEs when taking KD or MAD compared to standard care. These cases of discontinuation did not significantly differ between each other. 

Common AEs from KD included constipation, lack of energy, vomiting, hunger, diarrhea, hypercalciuria, abdominal pain, and dyslipidemia. Common AEs from MAD included constipation, lack of energy, vomiting, anorexia, dyslipidemia, and hypercalciuria.

Overall, MAD showed better tolerability, probability for 50%or more seizure reduction, and 90% or more seizure reduction, making it the most reasonable option for DRE management.

Reference

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