Evaluating the mediating role of executive functions for antiepileptic drugs' effects on IQ in children and adolescents with epilepsy

Abstract Several studies suggest that antiepileptic drug (AED) treatment may permanently or reversibly affect intelligence (intelligence quotient [IQ]) in children and adolescents with epilepsy. Since AED treatment preferentially affects attention and executive functions, we evaluated the potentially mediating effect of executive functions in regard to the adverse effects of drug treatment on intelligence. In a retrospective observational study, 178 children and adolescents with refractory and mostly localization-related epilepsies were evaluated in regard to the interrelation of IQ (Wechsler Intelligence Scale for Children [WISC III] short-form), executive functions (EpiTrack-Junior®, a cognitive AED screening test), and drug treatment (drug load). The results indicate that a low IQ was evident in 23%, impaired executive functions in 59% of the patients. Executive functions correlated to IQ (r = 0.60) and the symbol digits and picture arrangement subtests (R 2  = 0.46) in particular. Odds ratios for impaired executive functions compared to being off drug (33% impaired) increased from 2.0 with one drug (53% impaired) to 9.5 (83% impaired) with at least three drugs. A mediation analysis revealed that drug dependent differences in executive functions mediate the negative effect of the AED load on intelligence. Hence, executive functions appear to link adverse cognitive side effects of AED treatment to intelligence. Considering Catell's two factor model of intelligence, AEDs preferentially affect the aspects of fluid intelligence. The overall impact of AED on intelligence appears mild. It may become relevant, however, when drug-induced impairments persist over longer time intervals during sensitive developmental phases. This issue needs to be addressed in future longitudinal studies.