The new antiepileptic drugs: Pharmacological and clinical aspects

In recent years several new drugs (oxcarbazepine, lamotrigine, topiramate, gabapentin, zonisamide, tiagabine, fosphenytoin, vigabatrin and felbamate) have been added to the therapeutic armamentarium against epilepsy. Some of these represent structural modifications of pre-existing compounds, others were developed with the specific objective of modifying neurotransmitter fu nction, and many more were found to be clinically useful even though their mode of action is unclear or differs from that originally planned. The phar macokinetics of these drugs differ widely from one agent to another. Some ( gabapentin and vigabatrin) are eliminated unchanged in urine and have littl e or no interaction potential; others (tiagabine, lamotrigine, topiramate, oxcarbazepine, zonisamide, felbamate) are subject to induction of metabolis m by concomitant anticonvulsants; lamotrigine is vulnerable to metabolic in hibition by valproate, and felbamate is a powerful enzyme inhibitor in addi tion to being an inducer of the metabolism of carbamazepine and steroid ora l contraceptives. All new antiepileptic drugs have been found to be effecti ve in improving seizure control in patients with partial and secondarily ge neralized seizures. However, lamotrigine, topiramate, zonisamide and felbam ate appear to have broader efficacy against both partial and many generaliz ed seizure types, while vigabatrin is also valuable in the: management of i nfantile spasms. In monotherapy studies, new drugs have nor been found to b e more efficacious than older agents, but some may offer limited advantages in terms of improved tolerability. On the other hand, serious toxicity res tricts considerably the use of vigabatrin and felbamate. Overall, new drugs represent valuable tools in the fight against epilepsy, but because of lim ited experience and cost considerations their first-line use cannot be reco mmended in most situations.