Regarding initial management of epilepsy...

A 24-year-old man who had been alcoholic since his early teens underwent rehabilitation therapy during which he suffered severe withdrawal symptoms, including a seizure. Subsequently, he had seizures on a regular basis, during which he would turn pale, feel nauseous, become rigid, stop breathing, lose consciousness, and fall to the ground. After a minute, his body would jerk in a violent fashion for an additional 3 or 4 minutes; he would then lapse into a period of flaccid coma, which lasted 30 to 60 minutes more. After recovering consciousness, he had a headache, was disoriented and confused, felt nauseated, and had sore muscles but could remember nothing concerning his seizure. Following a detailed diagnostic workup including electroencephalography, he was put on medication.
Which of the following drugs was most likely used in his initial treatment?
(A) Felbamate
(B) Topiramate
(C) Phenytoin
(D) Ethosuximide
(E) Tiagabine

Answer:
(C) Phenytoin

Discussion: Some 0.5% of the population in the United States is afflicted with some form of epilepsy, in which seizures generally start between 5 and 20 years of age. Most cases have no known cause, but several types of known triggers also exist; among these, as in the case described, is withdrawal from drugs or alcohol after a period of addiction.

Two broad subtypes of epilepsy exist, partial and generalized seizures.

The partial seizures are categorized as either simple or complex, whereas generalized seizures include absence (petit mal), atypical absence, myoclonic, and tonic-clonic (grand-mal). In the latter case, seizures may be isolated, recurrent (with an interval of days, weeks, months, or even years between attacks), serial (with a short period of hours or less between attacks), or repeated (with new sets of convulsions without recovering consciousness in between).
This latter condition is known as status epilepticus and is a medical emergency. For patients with recurrent forms of epilepsy, the goal is to prevent further attacks by administration of an antiepileptic drug. The best drug for initiation of treatment depends upon the type of seizure, and continued use of the same drug depends upon effectiveness and tolerance of side effects by the patient.

The symptoms provided in the vignette consist of tonic-clonic seizures clearly suggesting grand mal epilepsy, and phenytoin (choice C) is commonly used as the drug of first choice. The advantages of this drug include that it is effective in most cases of grand mal usually within 10 days of the initial dose, its side effects can generally be tolerated, and a single daily dose provides the required blood level of 10 to 20 microg/microL. The latter is important because the less often a drug needs to be taken, the greater the compliance.

Felbamate (choice A) can also be used to treat tonic-clonic seizures but is not approved for use as a first line drug because of the risk of aplastic anemia and hepatic dysfunction.

Topiramate (choice B) is only approved for adjunctive treatment in cases of partial seizure and secondary generalized seizure; in addition, somnolence and potential blindness are discouraging side effects; in addition, it must be administered twice daily, which increases the chance of nonadherence.

Use of ethosuximide (choice D) is generally reserved for treatment of petit mal, whereas tiagabine (choice E) is an anticonvulsant primarily used as monotherapy for partial seizures.