NEW ANTIEPILEPTIC DRUGS - A REVIEW OF THEIR CURRENT STATUS AND CLINICAL POTENTIAL

Approximately 20 to 30% of patients with newly diagnosed epilepsy do n ot have their seizures controlled with currently available antiepilept ic drugs. The clinical need for new antiepileptic drugs is therefore c lear. In recent years, as our understanding of the molecular basis of epilepsy has unfolded, several novel candidate antiepileptic drugs hav e become available for clinical evaluation. The major emphasis has bee n on the development of more potent and effective antiepileptic drugs, and also drugs with fewer adverse effects than existing therapies. Th is has resulted in 7 new drugs being licenced around the world in the last 5 years (felbamate, gabapentin, lamotrigine, oxcarbazepine, pirac etam, vigabatrin and zonisamide). In addition, 7 other promising drugs are in various stages of development [eterobarb, fosphenytoin, leveti racetam (ubc L059), remacemide, stiripentol, tiagabine and topiramate] . Numerous advantages over existing antiepileptic drugs can be identif ied for some of these new drugs. A mechanism of action has been determ ined for lamotrigine, tiagabine and vigabatrin. This may prove particu larly useful therapeutically since it allows a more rational treatment strategy. Eterobarb, fosphenytoin, oxcarbazepine and remacemide are p rodrugs. This is a particular advantage for fosphenytoin, which is met abolised to phenytoin. Gabapentin, piracetam and topiramate are not me tabolised and vigabatrin is minimally metabolised. These drugs do not exhibit significant binding to blood proteins. Therefore, these drugs are not susceptible to significant pharmacokinetic drug interactions. Oxcarbazepine also exhibits minimal drug interactions. This is in cont rast to felbamate, lamotrigine and stiripentol, drugs with which pharm acokinetic interactions can be clinically problematic. All drugs, with the exception of piracetam, are effective treatments for partial or s econdarily generalised seizures. Piracetam and zonisamide are effectiv e in myoclonus, and felbamate has been licenced for use in children wi th Lennox-Gastaut syndrome. All 14 drugs have the potential to induce adverse effects, mostly CNS-related. Whilst treatment recommendations can be made for some of the drugs, these cannot be considered definiti ve since they are based largely on data from controlled clinical studi es in highly selected patients. Further treatment recommendations for different seizure types and epilepsy syndromes will inevitably develop as clinical experience with the drugs increases.