NEWER ANTIEPILEPTIC DRUGS - TOWARDS AN IMPROVED RISK-BENEFIT RATIO

Epilepsy is one of the most common neurological disorders. Even though existing antiepileptic drugs can render 80% of newly diagnosed patien ts seizure free, a significant number of patients have chronic intract able epilepsy causing disability with considerable socioeconomic impli cations. There is, therefore, a need for more potent and effective ant iepileptic drugs and drugs with fewer adverse effects, particularly CN S effects. Drugs for the treatment of partial seizures are particularl y needed. With major advances in our understanding of the basic neurop athology, neuropharmacology and neurophysiology of epilepsy, numerous candidate novel antiepileptic drugs have been developed in recent year s.This review comparatively evaluates the pharmacokinetics, efficacy a nd adverse effects of 12 new antiepileptic drugs namely vigabatrin, la motrigine, gabapentin, oxcarbazepine, felbamate, tiagabine, eterobarb, zonisamide, remacemide, stiripentol, topiramate and levetiracetam (uc b-L059). Of the 12 drugs, vigabatrin, lamotrigine and gabapentin have recently been marketed in the UK. Five of these new drugs have known m echanisms of action (vigabatrin, lamotrigine, tiagabine, oxcarbazepine and eterobarb), which may provide for a more rational approach to the treatment of epilepsy. Oxcarbazepine, remacemide and eterobarb are pr odrugs. Vigabatrin, gabapentin and topiramate are more promising on th e basis of their pharmacokinetic characteristics in that they are excr eted mainly unchanged in urine and not susceptible to significant phar macokinetic interactions. In contrast, lamotrigine, felbamate and stir ipentol exhibit significant drug interactions. Essentially, all the dr ugs are effective in partial or secondarily generalised seizures and a re effective to varying degrees in other seizure types. Particularly w elcome is the possible effectiveness of zonisamide in myoclonus and fe lbamate in Lennox-Gastaut syndrome. In relation to adverse effects, CN S effects are observed with all drugs, however, gabapentin. remacemide and levetiracetam appear to exhibit least. There is also the possibil ity of rational duotherapy, using drugs with known mechanisms of actio n, as an additional therapeutic approach. The efficacy of these 12 ant iepileptic drug occurs despite the fact that candidate antiepileptic d rugs are evaluated under highly unfavourable conditions, namely as add -on therapy in patients refractory to drug management and with high se izure frequency. Thus, whilst candidate drugs which do become licensed are an advance in that they are effective and/or are associated with less adverse effects than currently available antiepileptic drugs in t hese patients, it is possible that these drugs may exhibit even more i mproved risk-benefit ratios when used in normal clinical practice.