Pharmacogenetics in epilepsy treatment: sense or nonsense?

Epilepsy is the most common serious chronic neurological disorder. Treatment consists mainly of antiepileptic drugs (AEDs), with more than 15 different molecules available. However, AED treatment is often problematic because of unpredictability of drug response, adverse drug reactions and optimal dosing in individual patients. Moreover, up to one in three patients with epilepsy are refractory to currently available AEDs. Pharmacogenetic studies explore the contribution of genetic variants to interindividual differences in drug response. An increasing number of pharmacogenetic association studies in epilepsy are being reported. Nevertheless, at present only one association is firmly established, namely that of the HLA-B*1502 allele with severe cutaneous adverse drug reactions on carbamazepine therapy in the Han Chinese population. It is likely that large collaborations looking at multiple genes encoding entire drug pathways, or even the entire human genome, together with new pharmacogenetic strategies will result in the discovery of other genetic variants involved in AED response. Although several challenges remain, it is hoped that, ultimately, these findings will lead to the development of predictive tests, resulting in a more efficacious and safer AED treatment, and to the development of new AEDs with novel mechanisms of action, particularly aimed at patients with drug-refractory epilepsy.