Epilepsy is one of the most common
neurological disorders. Even though existing
antiepileptic drugs can render 80% of newly diagnosed patients seizure free, a significant number of patients have chronic
intractable epilepsy causing disability with considerable socioeconomic implications. There is, therefore, a need for more potent and effective
antiepileptic drugs and drugs with fewer adverse effects, particularly CNS effects. Drugs for the treatment of
partial seizures are particularly needed. With major advances in our understanding of the basic neuropathology, neuropharmacology and neurophysiology of
epilepsy, numerous candidate novel
antiepileptic drugs have been developed in recent years. This review comparatively evaluates the pharmacokinetics, efficacy and adverse effects of 12 new
antiepileptic drugs namely
vigabatrin,
lamotrigine,
gabapentin,
oxcarbazepine,
felbamate,
tiagabine,
eterobarb,
zonisamide,
remacemide,
stiripentol,
topiramate and
levetiracetam (ucb-L059). Of the 12 drugs,
vigabatrin,
lamotrigine and
gabapentin have recently been marketed in the UK. Five of these new drugs have known mechanisms 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
prodrugs.
Vigabatrin,
gabapentin and
topiramate are more promising on the basis of their pharmacokinetic characteristics in that they are excreted mainly unchanged in urine and not susceptible to significant pharmacokinetic interactions. In contrast,
lamotrigine,
felbamate and
stiripentol exhibit significant drug interactions. Essentially, all the drugs are effective in partial or secondarily generalised
seizures and are effective to varying degrees in other seizure types. Particularly welcome is the possible effectiveness of
zonisamide in
myoclonus and
felbamate in
Lennox-Gastaut syndrome. In relation to adverse effects, CNS effects are observed with all drugs, however,
gabapentin,
remacemide and
levetiracetam appear to exhibit least. There is also the possibility of rational duotherapy, using drugs with known mechanisms of action, as an additional therapeutic approach. The efficacy of these 12
antiepileptic drug occurs despite the fact that candidate
antiepileptic drugs are evaluated under highly unfavourable conditions, namely as add-on
therapy in patients refractory to
drug management and with high seizure 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 these patients, it is possible that these drugs may exhibit even more improved risk-benefit ratios when used in normal clinical practice.