Some Common Issues in the Use of Antiepileptic Drugs

ABSTRACT

Since 1993, eight new antiepileptic drugs (AEDs) have become available in the United States for the treatment of epilepsy: felbamate, gabapentin, lamotrigine, topiramate, tiagabine, levetiracetam, oxcarbazepine, and zonisamide. Of the older AEDs, six continue to be widely used: phenobarbital, phenytoin, primidone, ethosuximide, carbamazepine, and valproate. As a result, there is a relatively large number of alternative AEDs for the treatment of any given type of epilepsy. This has been particularly beneficial for patients with generalized epilepsies, both idiopathic and symptomatic. Given the wide availability of effective agents, the toxicity and pharmacokinetic profile of an AED have become major factors in the selection process. A number of common clinical situations may benefit from the abundance of AEDs. Chronic toxicity observed with some of the older AEDs such as osteoporosis, gingival hyperplasia, or alterations in reproductive endocrine function may be avoided with the use of the newer agents. The obese patient with epilepsy may benefit from the use of AEDs such as topiramate or zonisamide, which have a tendency to produce weight loss. In patients with a history of drug-induced skin rash, AEDs such as valproate, gabapentin, topiramate, tiagabine, and levetiracetam carry a lower risk of cross-reactivity. In patients sensitive to cognitive dysfunction, drugs with a favorable profile include gabapentin, tiagabine, lamotrigine, oxcarbazepine, and levetiracetam. A more favorable pharmacokinetic profile is observed in the majority of the newer AEDs in contraposition to the classic agents. Good absorption, linear kinetics, and low drug-drug interaction potential make these drugs easier to use. The newer AEDs are eliminated through different combinations of liver metabolism and direct renal excretion, thus providing a wider variety of choices in patients with failure of one of these organs. Some specific problems have been found with some of the newer AEDs. Hyponatremia, known to occur rarely with carbamazepine use, appears to be more common with oxcarbazepine. Felbamate has been associated with a high incidence of aplastic anemia and liver failure and should be used exceptionally. Acute angle closure glaucoma has been observed with the use of topiramate. This complication occurs early in the course of therapy and reverses rapidly with discontinuation of the drug, so physician and patient awareness of this problem is very important. In this article several common clinical situations in the management of patients with epilepsy are presented in the form of case studies. These cases illustrate some current aspects of the use of the AEDs and will give some guidelines to help the treating physician in the increasingly complex process of AED selection.

KEYWORDS

Antiepileptic drugs - toxicity - pharmacokinetics - felbamate - gabapentin - lamotrigine - topiramate - tiagabine - levetiracetam - oxcarbazepine - zonisamide - valproate - phenobarbital - phenytoin - primidone - ethosuximide - carbamazepine

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