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
