Efficacy of antiepileptic drugs in the era of pharmacogenomics: A focus on childhood

Abstract

Background: In recent years advances in the field of pharmacogenomics have expanded the concept for more individualized treatments. Our aim is to provide literature data about the relationship between genetic polymorphisms and efficacy of antiepileptic drugs in children.

Methods: Pubmed was used as the main medical database source. Only original research papers were considered. No year-of-publication restriction was placed. Quality of evidence was assessed according to American Academy of Neurology guidelines.

Results: A total of 12 cross-sectional and case-control studies fulfilled our selection criteria. ABCB1 gene was associated with drug responsiveness in 2 out of 6 studies and ABCC2 gene in 1 out of 1 studies. SCN1A gene was also associated with seizure control in 4 out of 5 studies. Cytochrome P450 genes were found to significantly affect drug responsiveness in 2 out of 4 studies, while polymorphisms of uridinediphosphateglucuronosyltransferaseUGT2B7 gene predisposed to drug-resistance in 1 out of 2 studies.

Conclusion: Variability in genes coding for sodium channels, drug transporters and cytochrome P450 enzymes can have a significant impact on response to antiepileptic drugs. Larger prospective studies with better stratification of samples are needed to shed light on these associations.

Keywords: Antiepileptic drugs; Children; Epilepsy; Pharmacogenetics; Pharmacogenomics.