Ketogenic diet therapies for the treatment of drug-resistant epilepsy in children and adults: A systematic review

Epilepsy is a common treatable neurological condition characterized by recurrent involuntary brain activity manifested in seizures. It is estimated that around 30% of patients with this disease do not respond to initial pharmacological treatments, developing drug-resistant epilepsy. Among the non-pharmacological treatment options are ketogenic diet therapies (KDT) in its various forms. The objective of this study is to systematically review the randomized controlled trials investigating the use of KDTs in pediatric and adult drug-resistant epilepsy, according to Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. The following databases: Embase, PubMed/Medline, LILACS, and the Cochrane Library, were searched and studies fitting the inclusion and exclusion criteria were included for analysis. Randomized controlled trials (RCT) with a minimum follow-up of 28 days were included. There were 1193 articles retrieved after duplicates were removed and 17 met the inclusion criteria. Eleven studies included children (up to 12 yrs) and six included adolescents from 13 years old and adults. Follow-up ranged from 6 to 24 months. In children, 37% may achieve a reduction in seizure frequency of 50% or more with in any form of KDT (moderate-certainty evidence). In addition, about 6 more children per 100 may achieve a ≥ 90% reduction, although this is supported by low-certainty evidence. In adolescents and adults, KDT may lead to a ≥ 50% reduction in seizure frequency in 16 more individuals per 100 compared with usual care (moderate-certainty evidence), but its impact on a 90% or greater reduction is uncertain due to the limited number of reported events and imprecision in available studies. Side effects in children showed no significant differences compared to usual care (low certainty), while in adults, the impact remains uncertain (very low certainty). Adherence to treatment may be slightly lower with KDT in both children and adults/adolescents compared to usual treatment, though results are inconsistent. Regarding quality of life and cognitive and behavioral outcomes, studies are scarce, heterogeneous, and of very low certainty, limiting the ability to draw strong conclusions.