THE NEW-GENERATION OF ANTIEPILEPTIC DRUGS - ADVANTAGES AND DISADVANTAGES

1 After a hiatus of over 20 years, several new antiepileptic drugs (vi gabatrin, lamotrigine, gabapentin, oxcarbazepine, topiramate, felbamat e, zonisamide and tiagabine) have reached or approached the registrati on phase. 2 Compared with older agents, many new drugs exhibit simpler pharmacokinetics. This is especially true for vigabatrin and gabapent in, which are renally eliminated and have a low interaction potential. 3 Unlike most of the older agents, vigabatrin, lamotrigine, gabapenti n and tiagabine are devoid of significant enzyme inducing or inhibitin g properties. Topiramate, oxcarbazepine and felbamate may induce the m etabolism of steroid oral contraceptives. In addition, felbamate also acts as a metabolic inhibitor. 4 To date, the efficacy of new drugs ha s been evaluated extensively only under add-on conditions in patients with partial seizures (with or without secondary generalization) refra ctory to conventional treatment. However, there is evidence that lamot rigine, zonisamide, felbamate and, possibly, topiramate may also be ef fective in generalized epilepsies. 5 In placebo-controlled studies, ty pically between 15 and 40% of patients with difficult-to-treat partial epilepsy have shown an improvement (defined as a 50% or greater decre ase in seizure frequency) after addition of a new drug. Only a small m inority of these patients achieved complete seizure control. 6 Compare d with older agents, some of the new drugs may have a better tolerabil ity profile. Felbamate, however, has been associated with a high risk of aplastic anaemia and hepatotoxicity. 7 At present, the main use of the new agents is in patients refractory to first-line drugs such as c arbamazepine or valproate, and further studies are required to charact erize their activity spectrum as well as their potential value in mono therapy. In most patients, new drugs cannot be recommended for first-l ine use until evidence is obtained that potential advantages in tolera bility or ease of use outweigh the drawback of their high cost.