The Clinical Pharmacology of the New Antiepileptic Drugs

Conventional anticonvulsants have important limitations in terms of efficacy and tolerability, and there is a clear need for new agents to be developed. After a quiescent period which lasted for more than two decades, several promising new compounds have undergone clinical evaluation and a few of these (vigabatrin, lamotrigine, oxcarbazepine, zonisamide) are now commercially available in some countries. Some of the new agents represent structural analogues of pre-existing drugs in an attempt to improve the therapeutic index of the latter (e.g., oxcarbazepine), while others were rationally designed to interfere selectively with inhibitory (vigabatrin) or excitatory (NMDA receptor antagonists) neurotransmission in the brain. Many other compounds were discovered more or less serependitiously and their mode of action is poorly understood. The present article provides a concise review of the clinical pharmacology of the new anticonvulsants which have undergone most extensive clinical testing in patients with epilepsy. Topics discussed include clinical pharmacokinetics, drug interactions, efficacy data in selected epileptic syndromes or seizure types, and adverse effects profile. Although the precise role of these new agents in the overall management of epilepsy remains to be clearly defined, their availability already provides a valuable tool which can be usefully exploited to improve prognosis, especially in patients with the more severe forms of the disease.