Valproic acid in childhood epilepsy: anticonvulsive efficacy in relation to its plasma levels

Abstract

Plasma levels of valproic acid were monitored for two years in 90 epileptic children. From 34 patients receiving sodium valproate as monotherapy, complete seizure control could be achieved in 28 children (82%) with a mean (+/- SD) plasma level of 65.1 +/- 20.3 micrograms/ml. In 6 patients (18%) seizures recurred. Since their plasma levels were significantly (p = 0.008) higher (91.7 +/- 35.2 micrograms/ml) than in the controlled patients, their disorder might be regraded as resistant to therapy with sodium valproate. The drug seems to be effective in patients with absences, tonic-clonic seizures and partial epilepsy. The most common combination of anticonvulsants administered was valproate/phenobarbital (n = 22). In 14 children of this group (64%) seizures were completely controlled with plasma levels of 54.6 +/- 26.5 micrograms/ml. In the 5 uncontrolled patients (23%) valproate concentrations were lower (33.8 +/- 28.2 micrograms/ml; p = 0.08). 20 children were treated with more than two anticonvulsants. This population probably represents the most severe cases. Therefore it was not surprising that only 7 patients (35%) exhibited complete seizure control with valproate plasma concentrations of 63.1 +/- 51.9 micrograms/ml. In the uncontrolled patients these levels were slightly lower (43.8 +/- 24.8 micrograms/ml). Side effects were observed in 7 patients (21%) receiving sodium valproate alone. Most common effects were increase in appetite (n = 4), and gastrointestinal disturbances (n = 2). Additionally, one patient complained about transient hair loss and one felt tired. In most cases their plasma concentrations were above 70 micrograms/ml. A therapeutic range of 40--90 micrograms/ml is postulated.