Efficacy and safety of valproic acid versus phenytoin as sole therapy for newly diagnosed primary generalized tonic-clonic seizures

Abstract

Treatment with antiepileptic drugs is recommended for patients who have had two unprovoked tonic-clonic seizures because data from epidemiologic studies suggest that a third seizure is likely to occur. Phenytoin has been the most commonly prescribed agent for several decades; since it was introduced in the late 1970s, valproic acid (valproate) has been reported to be effective for primary generally tonic-clonic seizures. We designed a multicenter study to compare the efficacy and safety of valproate and phenytoin as sole therapeutic agents for the treatment of patients with newly diagnosed primary generalized tonic-clonic seizures. Patients were randomized in a 2:1 ratio to valproate (n = 86) or phenytoin (n = 50); the investigation was an open-label study. Patients were followed for 6 months. After a 4-week titration period, median serum concentrations were 68.1 ± 3.1 mg/ml for valproate and 10.3 ± 0.9 mg/ml for phenytoin. The 6-month recurrence rates for generalized tonic-clonic seizures were 36 ± 6% for valproatetreated patients and 46 ± 8% for phenytoin-treated patients ( p = 0.473). Overall, the data indicated no significant differences in the efficacy or safety of valproate and phenytoin in the treatment of primary generalized tonic-clonic seizures.