Farmacos antiepilepticos

168

THE NEW ENGLAND JOURNAL OF MEDICINE

Jan. 18, 1996

REVIEW ARTICLE
lying neurologic lesion, and presence or absence of a family history.6 INDICATIONS FOR TREATMENT Most patients with recurrent epileptic seizures require treatment. The exceptions are patients with provoked seizures and those with episodes separated by years. The question of whether to treat a single seizure iscontroversial. Patients who have had an unprovoked seizure have a substantial chance of recurrent events (i.e., epilepsy), with the frequency ranging from 31 to 71 percent, depending on other risk factors.7,8 Patients with an underlying neurologic abnormality or cerebral lesion or a specific syndrome, such as juvenile myoclonic epilepsy, should probably be treated. The decision about treatment withantiepileptic drugs should be made after an extensive discussion with the patient about the risks and benefits of treatment and of no treatment. The best drug for the particular type of seizure is selected and administered in a dose high enough to bring the plasma drug concentration into a target (therapeutic) range without unacceptable side effects. The goal should be the restoration of a normal lifethrough complete control of seizures with the use of a single drug that has no side effects. DRUG Carbamazepine, phenytoin, valproic acid, phenobarbital, and primidone are all effective in reducing the frequency of partial seizures.9,10 There are conflicting data on whether carbamazepine is more effective than valproic acid.10-14 Carbamazepine and phenytoin are the drugs of choice for partialseizures. In Europe, some clinicians choose valproic acid instead of phenytoin, because of the relative tendency of the liver to be unable to metabolize the drug load (saturation kinetics), which makes it difficult to use without monitoring the plasma drug concentrations, and because of the perception that phenytoin has more side effects. Phenobarbital is relegated to use as a second-line drug in mostcases, since it tends to cause sedation and depression in adults and hyperactivity and aggression in children. For patients with tonic–clonic seizures, valproic acid, phenytoin, and carbamazepine are all effective. Valproic acid is the drug of choice for patients with tonic– clonic seizures and spike-wave discharges on the electroencephalogram and for patients with other forms of generalized epilepsy,particularly myoclonic jerks and absence seizures. Ethosuximide is also a useful drug for absence seizures. For patients who have both absence seizures and tonic–clonic seizures or myoclonic jerks, valproic acid is preferable. Substantial data have accumulated on the clinical pharmacokinetics of the established antiepileptic drugs (Table 3). The indications for their use and guidelines for dosesin children and in adolescents and adults are
OF

DRUG THERAPY ALASTAIR J. J. WOOD, M.D., Editor

ANTIEPILEPTIC DRUGS
AND

MARTIN J. BRODIE, M.D., MARC A. DICHTER, M.D.

A

T a conservative estimate, 50 million people worldwide have epilepsy. The annual incidence ranges from 20 to 70 cases per 100,0001 and the point prevalence is 0.4 to 0.8 percent.2 The incidence rates are highest inchildhood, plateau from the age of 15 to 65 years, and rise again among the elderly. Overall, 5 percent of persons report a seizure at some time in their lives. This figure excludes febrile convulsions, which occur in approximately 5 percent of children. These data suggest that there is a substantial rate of remission, even among persons who never receive treatment with an antiepileptic drug.3About 30 percent of patients with seizures have an identifiable neurologic or systemic disorder,4 and the remainder have either idiopathic or cryptogenic epilepsy. The diagnosis is based on the description of the seizures and the clinical context in which they occur, often supplemented by the results of electroencephalography. Treatment with an antiepileptic drug is usually begun when the patient has...