Marketed new antiepileptic drugs: are they better than old-generation agents?

Until a decade ago, the pharmacologic armamentarium for the management of epilepsy was restricted to a little more than a handful of drugs that had been introduced 20 to 70 years earlier. This situation has changed dramatically, with as many as nine new-generation drugs (oxcarbazepine, gabapentin, lamotrigine, levetiracetam, tiagabine, topiramate, zonisamide, vigabatrin, and felbamate, in addition to the water-soluble phenytoin prodrug fosphenytoin) having been introduced in Europe, the United States, or other parts of the world. These drugs represent a welcome addition because they produce an appreciable reduction in seizure frequency in up to 40% to 50% of patients who had been refractory to older-generation drugs. However, only a few patients with truly refractory disease can be made seizure-free by these new drugs, and the search for more effective anticonvulsants should continue. Although in patients with newly diagnosed epilepsy the efficacy of new-generation drugs is not superior to that of older agents, some of the newer drugs offer advantages in terms of improved tolerability, ease of use, and reduced interaction potential. However, the increased availability of treatment options implies that drug choice in patients with epilepsy is more complicated than in the past, and there is a concern that inadequate knowledge of indications, contraindications, and mode of use of the newer drugs could result in some patients receiving suboptimal treatment or being exposed to undue risks from side effects and drug interactions. Although measurement of plasma drug concentrations is often used to adjust the dosage of classic antiepileptic drugs, therapeutic drug monitoring has been claimed to be of little or no value with newer-generation drugs. This view has been challenged in light of the evidence that pharmacokinetic variability contributes to an important extent to differences in dosage requirements for most of these drugs.