B Y THE THIRD quarter of the 20th century, 5 major antiepileptic drugs (AED) had been recognized and compared in clinical trials for their efficacy in partial and secondarily generalized seizures and adverse-effect profile: phenytoin, phenobarbital, carbamazepine, primidone, and valproate sodium. These firstgeneration drugs leave about 20% of patients with uncontrolled seizures and cause adverse effects such as drowsiness, dizziness, diplopia, gingival hyperplasia, hirsutism, memory impairment, tremor, and excessive weight gain. Phenytoin, owing to its saturation kinetics, requires careful blood level monitoring. Carbamazepine occasionally causes neutropenia and hyponatremia, and requires frequent dosing. Valproate causes thrombocytopenia and alopecia at high doses. All of these drugs except valproate induce liver enzymes and may potentiate drug interactions; this latter feature is enhanced by the high affinity for serum protein of phenytoin, carbamazepine, and valproate. Although all these drugs are associated with some risks of fetal malformations, carbamazepine and valproate are specifically recognized for additional risks of fetal neural tube defect. Because of the number of patients with refractory partial seizures and the adverse effects of available drugs, 2 things have happened in the last quarter of the century: the number of epilepsy surgery centers has increased dramatically, and, through a concerted effort by both government and the pharmaceutical industry, new AEDs have been developed at a frantic pace. These new developments have brought more choice in the management of epilepsy, but at considerable financial costs. Felbamate, gabapentin, lamotrigine, topiramate, and tiagabine hydrochloride were all marketed in the United States during the last decade as adjunct therapy for partial and secondarily generalized seizures. Lamotrigine was recently approved for monotherapy. As a group, these second-generation drugs seem to have novel mechanisms of action, fewer drug interactions, and perhaps better adverseeffect profiles, although they have not been adequately compared with each other or with previous drugs. They are also substantially more expensive than the first-generation AEDs. The most common adverse effects include dizziness, drowsiness, skin rash, and mental slowing. The need for drug level monitoring and the potential for teratogenicity of the new AEDs have not been established. Felbamate was found to be useful in children with symptomatic generalized epilepsies of the Lennox-Gastaut type, while lamotrigine seems to work in the idiopathic generalized epilepsies. The use of felbamate, however, was substantially reduced owing to a high incidence of aplastic anemia. In addition, several old AEDs have been reformulated. Rectal diazepam is used in the home environment for clusters of seizures, thus preventing a visit to the emergency department. Fosphenytoin is a precursor of phenytoin that can be mixed with dextrose, administered intramuscularly, and given faster than phenytoin, properties that are cherished by emergency department staff. Two extended-release carbamazepine formulations now allow twice daily dosing of that drug and therefore better compliance. An intravenous valproate can replace the oral form when needed, thus preventing interruption of treatment. As expected, these new formulations are generally more expensive than their predecessors. In sum, the second-generation AEDs grew out of a systematic drug development program that recognized a need for new drugs because the first-generation drugs failed to control seizures in many patients or caused clinically significant adverse effects. These new drugs may play a role in some of the refractory generalized epileptic syndromes of childhood and may be easier to administer. They also tend to have more specific sites of action, based on our evolving understanding of the pathophysiology of the epilepsies. However, since they have not been adequately compared with older AEDs, it seems appropriate to start treatment with selected first-generation drugs and move to the more expensive secondgeneration drugs only when indicated. The new formulations of established AEDs were created to respond to specific needs of patients and specific clinical situations, and should be used accordingly. Thus, there is room for the old drugs, the new drugs, and the new formulations of old drugs in hospital formularies. The cost of these new AEDs is certainly of concern. However, denying their use to hospitals and health care providers may be to the The Department of Neurological Sciences, Cook County Hospital/Rush Medical College, Chicago, Ill. CONTROVERSIES IN NEUROLOGY