New challenges in the treatment of epilepsy

An increased understanding of the pathogenesis of epilepsy and the basic mechanisms of action of antiepileptic drugs has made rational antiepileptic dme design possible, resulting in the marketing of seven new compounds: felbamate, gabapentin, lamotrigine, oxcarbazepine, progabide, vigabatrin and zonisamide. Their clinical and pharmacokinetic properties are reviewed. Felbamate, effective against partial seizures and Lennox-Gastaut syndrome, can induce fatal aplastic anemia and acute liver failure, which already resulted in the withdrawal of the drug. Gabapentin, licensed as adjunctive therapy in partial seizures, appears to have the most promising pharmacokinetic properties. Lamotrigine has a broad antiepileptic spectrum and is well tolerated. Oxcarbazepine has the same antiepileptic profile as cabamazepine, but has fewer side effects. Progabide appears to be of limited therapeutic value and can induce fatal hepatotoxicity. Vigabatrin is most effective in partial seizures and is well tolerated. Zonisamide has a broad anticonvulsant spectrum, including myoclonic epilepsy, but at a cost of an increased incidence of nephrolithiasis. There is no evidence that these newer drugs are any more potent than existing ones and the major benefits may weil be in terms of reducing adverse effects and simplifying clinical use, Two major limitations are that none of these drugs are available in injectable form and that their treatment cost is high.