Antiepileptic drugs in patients with malignant brain tumor: beyond seizures and pharmacokinetics

In neurological malignancies, antiepileptic drugs ( AED s) are frequently used to control the seizure activity that accompanies the disorder. There is a growing body of evidence on the importance of AED selection for reasons other than pharmacokinetics ( PK ) properties. Epigenetic modifications may occur in glioblastomas, such as changes in gene methylation and histone acetylation states. Secondary mechanisms of AED drug action which impact these epigenetic modifications could play a significant role in patient survival outcomes. Both valproic acid ( VPA ) and carbamazepine have histone deacetylase ( HDAC ) inhibitory activities, and levetiracetam and VPA reduce the activity of O6‐methylguanine‐ DNA methyltransferase ( MGMT ), a DNA ‐repair molecule implicated in resistance to alkylating agents used for chemotherapy. The use of AED s for purposes other than seizure prophylaxis and their selection based on non‐ PK properties present a potential paradigm shift in the field of neuro‐oncology.