What has been the impact of new drug treatments on epilepsy?

Abstract

Nearly two dozen antiseizure medications (ASMs) with different mechanisms of action have been introduced over the past three decades with the aim of providing better efficacy or safety profile than the previous drugs. Several new ASMs with improvement on a classic drug family or have novel mechanisms of action have been recently approved for epilepsy. The present review explored recent studies or guidelines on new agents and discussed the potential impact of these novel treatments on epilepsy management and future directions of research. Long-term cohort studies showed that, collectively, the second-generation did not improve the overall prognosis of epilepsy. Individual monotherapy studies showed similar efficacy of second-generation (levetiracetam and zonisamide) and third-generation (eslicarbazepine acetate and lacosamide) ASMs compared to controlled-release carbamazepine for the treatment of focal epilepsy. However, there appears to be no evidence to support any second-generation or third-generation ASMs to be as efficacious as valproate monotherapy for generalized and unclassified epilepsies. Cannabidiol adjunctive treatments were found to be efficacious for Dravet syndrome and Lennox-Gastaut syndrome. Although most newer generation ASMs are less prone to drug-drug interactions, stiripentol and cannabidiol can elevate the plasma concentration of N-desmethylclobazam, the active metabolite of clobazam. Generally speaking, the second-generation ASMs have lower teratogenic risk than the older drugs but there is scant study on neurodevelopmental effect of third-generation ASMs. Although the newer generation ASMs may not have improved the overall seizure control they have advantages in terms of drug-drug interactions and teratogenicity, and thus offer valuable individualized options in the treatment of epilepsy.