BY 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.1,2 These first-generation 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.
Pierre-Louis SJC. New Drugs: Which Should Be Included in the Formulary? Epilepsy: All New Drugs Should Be Included. Arch Neurol. 2000;57(2):272–273. doi:10.1001/archneur.57.2.272
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