Control of epilepsy is achieved with a single agent in most patients. However, seizures are refractory in approximately 20 percent of patients with generalized epilepsy and 35 percent of those with partial epilepsy. In a review article, Devinsky discusses therapeutic considerations for patients who have refractory seizures.

The author suggests that magnetic resonance imaging (MRI) be performed to exclude a structural lesion when the severity or frequency of seizures continues to increase despite stable, therapeutic plasma levels of the antiepileptic drug. MRI can also identify surgically treatable causes of seizures, including cavernous angiomas and low-grade gliomas.

The possibility of noncompliance with drug therapy should be considered regardless of the patient's age, intellectual ability or socioeconomic status. Adherence to therapy can be monitored by serum drug levels. Lifestyle factors such as sleep deprivation, emotional stress, menstruation, flickering lights and alcohol withdrawal may also induce seizures.

The choice of antiepileptic drug is based on the type of seizure and, if possible, the epileptic syndrome. A single agent should initially be used, with systematic increases in the dosage and plasma level until the seizures are controlled or the side effects become intolerable. Before a drug is stopped because of a perceived lack of efficacy, the dosing schedule and any other seizure-provoking events should be assessed. According to the author, the adequacy of the trial is defined not by time but by frequency of the seizures: the more frequent the seizures, the less time is required for determining drug efficacy in a particular patient.

If the seizures persist after monotherapy with two different drugs, a combination of two drugs should be used. In one study, combination therapy resulted in cessation of seizures in 10 percent of patients and improved control in 40 percent. Treatment with more than one drug increases the risk of drug interactions. Frequent monitoring of plasma levels may reduce the risk.

Four new antiepileptic medications for adjunctive treatment of partial epilepsy have been introduced since 1993. These include gabapentin, lamotrigine, topiramate and tiagabine; the efficacy of these drugs is uncertain. Another new agent, felbamate, was found to cause aplastic anemia and hepatic failure in one in 2,500 users. These adverse effects have limited its use.

The author states that referral to a neurologist should be considered for patients whose seizures are not controlled within three months. If control is not achieved by one year, referral to a specialized epilepsy center is indicated.

Surgery is an underused option in patients with refractory epilepsy. It is effective in controlling seizures in two thirds of carefully selected patients and reduces the frequency and severity of seizures in many additional patients. The vagus nerve stimulator, a new therapy, is an implantable, programmable, pacemaker-like device that connects two electrodes to the left vagus nerve. In a randomized controlled trial, 30 percent of patients had a reduction of more than 50 percent in the frequency of their seizures.

Long-term treatment of epilepsy requires a dialogue between the physician and the patient. The goals of therapy and success of prescribed treatments may be viewed differently by physicians and patients. Some patients may be content knowing they will not be completely seizure-free and prefer not to take multiple medications. A good resource for patients is the Epilepsy Foundation, Landover, Md. (telephone: 1-800-EFA-1000).