Medical Management of Epilepsy: General Principles

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The four broad categories of epilepsy syndromes are idiopathic generalized, symptomatic generalized, idiopathic localization-related and symptomatic localization-related. The importance of making a syndromic diagnosis is illustrated by juvenile myoclonic epilepsy, a common idiopathic generalized epilepsy syndrome in which patients may experience absence, myoclonic and convulsive (clonic-tonic-clonic or tonic-clonic) seizures. If phenytoin (Dilantin) or carbamazepine (Tegretol) is used for treatment, the nonconvulsive seizures are often worsened. In contrast, valproate (Depakote) provides complete seizure control in most patients.

While patients with generalized-onset epilepsies (such as juvenile myoclonic epilepsy) respond best to valproate, any of the major medications (except ethosuximide [Zarontin]) may be effective in patients with localization-related (partial-onset) epilepsy. In patients with partial epilepsy, large studies have consistently demonstrated similar efficacy for phenytoin, carbamazepine, valproate, primidone (Mysoline) and phenobarbital, although the barbiturates are often poorly tolerated as a result of their sedating properties.1416

Thus, in patients with localization-related epilepsies, drug selection is heavily influenced by the side effect profile, cost and dosing frequency of each agent (Table 3). The long-term cosmetic consequences (which include coarsening of the facial features, gingival hyperplasia, hirsutism and enlargement of the lips) for many patients taking chronic phenytoin therapy, for example, make this a poor first choice for children and young adults. Yet, the once-daily dosing scheme and low cost make it an attractive agent for other patients. Carbamazepine, especially the new extended-release preparations, is an excellent choice for many children and adults with localization-related epilepsies. Valproate, in addition to being the drug of choice for most of the generalized epilepsies, is also efficacious in the treatment of the localization-related syndromes. Accordingly, it is a good first choice in patients in whom the epilepsy syndrome is not clearly defined.

Once the preferred medication has been chosen, therapy should be initiated at an appropriate dosing schedule and increased at an appropriate dosing increment and rate (Table 3). For any of the antiepileptic drugs, we recommend that dosage increases continue—regardless of serum drug levels—until complete seizure control is achieved or until persistent, unacceptable side effects occur.

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