The first line of therapy in a girl with juvenile myoclonic epilepsy: Should it be valproate or a new agent?

Juvenile myoclonic epilepsy is a common idiopathic generalized epileptic syndrome that includes generalized myoclonic seizures and commonly generalized tonic–clonic and generalized absence seizures. Before the emergence of the newer antiepileptic drugs (AEDs) in the 1990s, valproate was the usual first-line treatment in both men and women. However, the frequent adverse effect of weight gain and the risk of teratogenicity have resulted in a search for alternative first-line therapies in women. Four new AEDs— lamotrigine, topiramate, levetiracetam, and zonisamide—have been used as monotherapy or adjunctive therapy for juvenile myoclonic epilepsy in small patient series. Because they are not associated with weight gain and because they may have less risk of teratogenicity than valproate, they have been proposed as alternative first-line agents in women who have childbearing potential. However, the new AEDs may not be effective for all the seizure types of juvenile myoclonic epilepsy, and valproate appeared overall more effective in a large comparative trial in idiopathic generalized epilepsy. In addition, valproate is often effective at lower doses that have less teratogenicity, and an extended-release preparation may be less likely to produce weight gain. The current review presents evidence and arguments supporting the use of a new AED and those supporting the use of valproate as the first-line treatment in a girl with newly diagnosed juvenile myoclonic epilepsy. The review then concludes with a compromise approach.