NEW CHALLENGES IN THE TREATMENT OF EPILEPSY

An increased understanding of the pathogenesis of epilepsy and the bas ic mechanisms of action of antiepileptic drugs has made rational antie pileptic dme design possible, resulting in the marketing of seven new compounds: felbamate, gabapentin, lamotrigine, oxcarbazepine, progabid e, vigabatrin and zonisamide. Their clinical and pharmacokinetic prope rties are reviewed. Felbamate, effective against partial seizures and Lennox-Gastaut syndrome, can induce fatal aplastic anemia and acute li ver failure, which already resulted in the withdrawal of the drug. Gab apentin, licensed as adjunctive therapy in partial seizures, appears t o have the most promising pharmacokinetic properties. Lamotrigine has a broad antiepileptic spectrum and is well tolerated. Oxcarbazepine ha s the same antiepileptic profile as cabamazepine, but has fewer side e ffects. Progabide appears to be of limited therapeutic value and can i nduce fatal hepatotoxicity. Vigabatrin is most effective in partial se izures and is well tolerated. Zonisamide has a broad anticonvulsant sp ectrum, including myoclonic epilepsy, but at a cost of an increased in cidence of nephrolithiasis. There is no evidence that these newer drug s are any more potent than existing ones and the major benefits may we il be in terms of reducing adverse effects and simplifying clinical us e, Two major limitations are that none of these drugs are available in injectable form and that their treatment cost is high.