Topiramate, has much the same mode of action and probably a broader effectiveness as tiagabine. It will rarely cause serious dermatologic side effects, especially if used with valproate, and appears to induce renal stones in 1.5 percent of patients, lower in women. Angle-closure glaucoma has also been reported as a complication. A minor problem has been the development of hyperchloremic metabolic acidosis. It has high teratogenicity in most studies.
Lacosamide, a potent drug for seizures that have a focal onset and generalize or remain focal, is currently used mainly as an adjunctive therapy. Like levetiracetam, its mechanism of action is not entirely known but it has been shown to modulate voltage-gated sodium channel activity. It may be titrated upward rapidly and has limited pharmacokinetic interactions but its effective range of blood levels is narrow; also like levetiracetam, it is renally excreted. The availability of an intravenous preparation is also notable. The main but infrequent side effects are headache and diplopia. The drug may prolong the P-R interval and worsen heart failure.
Ethosuximide and valproate are equally effective for the treatment of absence seizures, the former having fewer cognitive side effects according to a study by Glauser and colleagues. The use of ethosuximide is virtually limited to this indication. It is good practice, so as to avoid excessive sleepiness, to begin with a single dose of 250 mg of ethosuximide per day and to increase it every week until the optimum therapeutic effect is achieved. Methsuximide (Celontin) is useful in individual cases where ethosuximide and valproate have failed. In patients with benign absence attacks that are associated with photosensitivity, myoclonus, and clonic-tonic-clonic seizures (including juvenile myoclonic epilepsy), valproate is the drug of choice. Valproate is particularly useful in children who have both absence and grand mal attacks, as the use of this drug alone often permits the control of both types of seizures. The concurrent use of valproate and clonazepam has been known to produce absence status.
Zonisamide, similar to topiramate, seems to be useful for myoclonic epilepsy but its main use is currently as an adjuvant in al epilepsy. It is not predominantly a sodium channel blocker and can be taken in parallel with carbamazepine. Some clinicians have found it to produce fewer cognitive side effects than topiramate.
New antiepileptic medications are being introduced regularly, among the newer ones is brivaracetam that is likely to display to broad activity against seizure types and lack of interaction with other medications seen with levetiracetam. Retigabine, rufinamide, pregabalin, gabapentin, felbamate, eslicarbazepine, several in the diazepine class find special use, mostly in epilepsy clinics that treat recalcitrant seizures. The medications used in the neonatal and infant population are discussed below.
Treatment of Seizures in the Neonate and Young Child
This specialized area of neonatal seizures is discussed by Fenichel and by Volpe and in children by Guerrini. In general, phenobarbital has been preferred for seizure control in infancy. Probably the form of epilepsy that is most difficult to treat is the childhood Lennox-Gastaut syndrome. Some of these patients have as many as 50 or more seizures per day, and there may be no effective combination of anticonvulsant medications. Valproic acid (900 to 2,400 mg/d) will reduce the frequency of spells in approximately half the cases. The newer drugs—lamotrigine, topiramate, vigabatrin—are each effective in approximately 25 percent of cases. Clonazepam also has had limited success. In the special case of Dravet syndrome, a disorder of the sodium channel, antiepileptic drugs that block that same channel are avoided.