The efficacy and safety of ketogenic diet therapy among adolescents and adults with drug resistant epilepsy: A systematic review and meta-analysis.

Ketogenic diet therapy (KDT), characterised by its high-fat, low-carbohydrate composition, is a valuable approach to reducing seizures in children with drug resistant epilepsies (DRE). Uncertainty remains regarding its benefits in adolescents and adults. This systematic review and metanalysis critically evaluated evidence efficacy, safety and tolerability of KDT in adolescents and adults with DRE. Analysis was also undertaken on epilepsy and KDT subtypes, side effects, attrition proportions and reasons for KDT cessation, along with effects beyond seizure control including mood and quality of life outcomes. Of the 1846 articles screened, 33 met the inclusion criteria, 3 randomised controlled trials, 17 prospective and 13 retrospective case series and included 1019 people with DRE. The overall proportion with seizure reduction >50 % was 42.82 % (95 %CI 34.14-51.69). Subgroup analysis suggested that 53.4 % (95 %CI: 16.92-88.20 of individuals with generalised DRE responded to KDT, compared to 14.4 % (95 %CI: 0.00-42.25) with focal DRE. The efficacy was not found to be associated with KDT type. Restrictiveness and compliance challenges led to an overall attrition proportion of 20.95 % (95 %CI 12.06-31.19). Findings suggested that KDTs were safe and generally well tolerated. Taken together, there is increasing evidence to support use of KDT as an adjunctive treatment for some people with DRE. The knowledge generated is pertinent to establishing guidelines, optimising the use of KDT in specific epilepsy populations to improve therapeutic management.