Section Review Central & Peripheral Nervous Systems: New anti-epileptic drugs

Abstract

Standard anti-epileptic drugs (AEDs) are unable to control seizures in as many as 30 - 50% of patients with epilepsy. The overall incidence of unacceptable side-effects, necessitating withdrawal of the drug, is approximately 10%. Furthermore, most of the standard AEDs only possess anti-seizure effects and do not prevent the progression of the epileptic process, i.e., they have no anti-epilepto-genic or neuroprotective effects. The clinical need for new AEDs is, therefore, clear and during the past decade approximately twenty to thirty agents have reached various stages of clinical evaluation. Whereas previously most AEDs were developed by empiric screening, development of many of the newer AEDs has been based upon rational consideration of the pathophysiologic mechanisms underlying seizures. Generally, many of the newer AEDs can be categorised as those that reduce excitaiory transmission or enhance inhibitory transmission. However, despite the growing trend towards rational drug design, the mechanisms of action for several new AEDs remain uncertain. Seven newer AEDs (felbamate, gabapentin. lamotrigine, oxcarbazepine, piracetam, vigabatrin and zonisamide) have been licensed around the world during the last few years. The objective of this review is to evaluate the place of recently licensed AEDs in the therapy of epilepsy and to present some of the newer, promising AEDs that are in various stages of development.