Pharmacologic Therapy

Whether antiepileptic drug therapy should be initiated after a first seizure remains a topic of debate. The data regarding the likelihood of recurrent seizures after a first seizure are wanting or questionable, and estimates of the rate of recurrence after a single unprovoked seizure range widely. Certain findings and characteristics do seem to increase the likelihood of recurrence after a first seizure, including EEG abnormalities, previous neurologic injury, partial seizures, and a family history of seizures. Also, it is not known whether anti-epileptic pharmacologic therapy following a single seizure alters the subsequent risk of epilepsy. Because of these uncertainties and because antiepileptic pharmacologic therapy is associated with a significant incidence of adverse effects, often exceeding the risk of recurrent seizures, many family physicians elect not to prescribe antiepileptic medications for most patients after a single seizure.

Although many agents are available for the treatment of seizures, carbamazepine (Tegretol), phenytoin (Dilantin), phenobarbital, and divalproex (Depakote) have been traditional first-line therapies for most patients with epilepsy. Increasing availability of newer agents to treat seizures has often resulted in more favorable side effect profiles. Phenobarbital is the oldest agent but has certain disadvantages. Its adverse effects include irritability, decreased cognition, and hyperactivity or lethargy. The degree of sedation and cognitive effects produced at therapeutic dosages are frequently significant enough that many family physicians do not prescribe phenobarbital as a first-line agent. The recommended dosage for common antiepileptics and adverse effects are summarized in Table 42-5. Most patients with epilepsy can achieve remission with the use of a single medication. Because the addition of another antiepileptic agent is usually associated with an increase in adverse drug effects, patients not controlled with one agent should be given a trial of a different agent rather than combining agents early in the course of treatment. Treatment with more than one agent is usually attempted only after a number of trials of monotherapy have failed.

Family physicians should exercise caution when measuring levels of antiepileptic drugs. Therapeutic ranges for most antiepileptics are only guidelines for treatment. Some patients achieve therapeutic remission without significant side effects with drug concentrations ordinarily toxic. Other patients develop intolerable side effects with subtherapeu-tic serum levels. Serum levels of most antiepileptic drugs should generally be determined when remission of seizures is achieved or the patient develops significant side effects. Drug concentrations can also provide evidence of compliance. More frequent serum testing is necessary for patients taking more than one agent, pregnant women, older adults, patients with hepatic or renal dysfunction, and patients taking medications for other medical problems. Box 42-8 lists drugs used to treat other medical conditions that can lower the seizure threshold. Nevertheless, serum levels should not be the primary basis for decisions regarding antiepileptic drug dosing. Seizure control and the development of adverse effects related to drug therapy are more important than serum levels alone.

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