Ketogenic Diet for the Treatment of Refractory Epilepsy in Children: A Systematic Review of Efficacy

To systematically review and synthesize the available evidence on the efficacy of the ketogenic diet in reducing seizure frequency for children with refractory epilepsy. Medline searches were performed using the keywords epilepsy/therapy, dietary therapy, and epilepsy, and the text word ketogenic diet. The Cochrane Library of clinical trials was searched using the term ketogenic diet. Bibliographies of recent review articles and relevant primary research reports, as well as Current Contents were reviewed for additional relevant citations. Studies were selected for inclusion in the review that reported the reduction of seizure frequency following treatment with the ketogenic diet in children with refractory epilepsy. The outcome measures used were the percentage of patients with: 1) complete elimination of seizures, 2) >90% reduction in seizures, and 3) >50% reduction in seizures. The evidence consists entirely of uncontrolled studies. Of 11 studies identified for this review, 9 are retrospective series of patients from a single institution. Two studies are prospective, 1 of which is a multicenter trial. The results of these studies are consistent in showing that some children benefit from the ketogenic diet, demonstrated by a significant reduction in seizure frequency. Estimates of the rates of improvement by combined analysis (confidence profile method) are complete cessation of all seizures in 16% of children (95% confidence interval [CI]: 11.0-21.7); a greater than 90% reduction in seizures in 32% (95% CI: 25.3-39.8); and a greater than 50% reduction in seizures in 56% (95% CI: 41.2-69.7). It is unlikely that this degree of benefit can result from a placebo response and/or spontaneous remission. Although controlled trials are lacking, the evidence is sufficient to determine that the ketogenic diet is efficacious in reducing seizure frequency in children with refractory epilepsy.