Developments in Medical Treatment of Epilepsy

Over the past 20 years, there has been an exponential growth of antiseizure medications (ASM) available. In 1975, the National Institute of Neurological Disorders and Stroke established the Anticonvulsant Drug Development program, in which thousands of new chemical entities were screened for antiseizure activity.¹ Over 20 compounds were found to have possible antiepileptic activity and many have shown promising clinical results.² From 2000 to 2019, when this article was written, there were 11 new ASMs approved by the FDA; although ezogabine was removed from the market in 2017. The increased availability of ASMs provides alternatives for practitioners and people with epilepsy. These medications have unique mechanisms of action, and each has different pharmacologic properties, including drug-drug interactions, pharmacokinetics , and common adverse effects. Older ASMs, such as phenobarbital, phenytoin, and valproic acid work by binding GABA receptors or sodium (Na⁺) channels. The newer medications have different mechanisms and binding sites, including α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, potassium channels, and synaptic vesicle protein 2A (SV2A).

It is important for practitioners to know the pharmacologic profile of each ASM to better understand which ASM may be the best fit for a given individual (Table).^3-13 Despite the increased number of ASMs available, approximately 30% of people with epilepsy do not achieve a reduction in or freedom from seizures with pharmacologic treatment.¹⁴ An unmet need remains to develop more ASMs that can treat various types of seizure disorders, with fewer side effects, minimal drug-drug interactions, and different formulations, as well as disease-modifying treatments.