Drug-resistant epilepsy: Drug target hypothesis and beyond the receptors

Epilepsy is a chronic neurological disorder that affects more than 50 million people worldwide. Despite a recent introduction of antiseizure drugs for the treatment of epileptic seizures, one-third of these patients suffer from drug-resistant epilepsy (DRE). The therapeutic target hypothesis is a cited theory to explain DRE. According to the target hypothesis, the failure to achieve seizure freedom leads to alteration of the structure and/or function of the antiseizure medication (ASM) target. However, this hypothesis fails to explain why patients with DRE do not respond to antiseizure medications of different targets. This review presents different conditions, such as epigenetic mechanisms and protein-protein interactions that may result in alterations of diverse drug targets using different mechanisms. These novel conditions represent new targets to control DRE.