Safe and Effective Diet Therapies for the Treatment of Drug Resistant Epilepsy

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

Nearly 30% of children with epilepsy have a digital rectal examination, a form of epilepsy that is currently difficult to treat. DRE can often be treated with epilepsy surgery, but when 2 or more chosen anticonvulsant drugs do not work on a child awaiting surgery, diet therapy may be used.

KDs have shown promising results limited by adhesion difficulties over 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 to investigate the comparative safety and effectiveness of these dietary therapies in the treatment of DRE, the researchers conducted a meta-analysis on this topic.

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, low glycemic index therapy and refractory epilepsy. GoogleScholar, ClinicalTrials.gov, and some article reference lists were used for manual searching.

Studies used for the analysis included randomized clinical trials (RCTs) that assessed the safety and effectiveness of dietary therapies such as MAD, KD, and LGIT. Two review authors independently performed selection and data extraction for the studies.

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

A significant reduction in seizure rate was measured as the primary outcome of the analysis. This was measured by the proportion of 50% or more or 90% or more reduction in short-term seizures. The absence of crisis in the medium and long term was also assessed.

The safety outcomes measured included treatment discontinuation due to adverse events (AEs) and other reported AEs.

There were 11 open-label and 1 single-blind 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 observed between 2 studies, leading to a total population of 907 participants.

Participants had an average age of 4.6 years at enrollment and 67% of participants were boys. The average age of onset of seizures in patients was 1.4 years, with an average 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, 4 intermediate, and 1 long-term outcomes.

All 3 dietary therapies were shown to be more effective than usual care for a 50% or greater reduction in seizures. No major differences were found between the 3 dietary therapies. Significantly more patients also achieved a 90% or greater seizure reduction when taking MAD or KD compared to usual care, but the 2 dietary therapies did not show significant differences between them.

Ten percent of patients taking dietary therapies were seizure-free, with KD and MAD leading more consistently to seizure-free. There were no significant differences between these dietary therapies.

Participants were significantly more likely to discontinue care due to AEs while taking KD or MAD compared to standard care. These cases of abandonment did not differ significantly from each other.

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

Overall, MAD showed better tolerability, a 50% or greater likelihood of seizure reduction, and a 90% or greater seizure reduction, making it the most reasonable option for management digital rectal examination.

Reference

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