Combination of Sodium Valproate and Clonazepam in the Treatment of Symptomatic West Syndrome and Lennox Syndrome

Abstract

Combination therapy of sodium valproate (VPA) and clonazepam (CZP) was instituted in 18 children suffering from intractable epilepsy; 13 with symptomatic West syndrome and 5 with Lennox syndrome. The required daily doses of VPA ranged from 20.0 to 59.7mg/kg (mean 32.8), and those of CZP ranged from 0.03 to 0.19mg/kg (mean 0.08). At the first month of this therapy, complete seizure control was achieved in 5 out of 13 patients with West syndrome (38.5%), and in 1 out of 5 patients with Lennox syndrome (20.0%). The frequency of seizures were reduced by more than 50% in 15 cases (83.3%). The maximum effect occurred from 2 to 28 days (mean 10.4 days) after starting the treatment.
After follow-up for 12-46 months (mean, 24.7 months), this combination therapy was still effective in 7 cases (46.7%), and 5 cases (33.3%) were seizure-free.
In our studies, therapeutic benefit was evident at serum levels (samples taken 3 hours after the morning dose) of 49.0 to 148.0μg/ml (mean 93.8) for VPA, and of 5.4 to 50.5 ng/ml (mean 19.2) for CZP. This combination therapy was effective against tonic spasms, tonic seizures and myoclonic seizures.
Twelve cases (66.7%) had symptomatic side effects. Drowsiness (50.0%), increased salivary secretion (50.0%), thrombocytopenia (22.2%), and minor seizure status (5.6%) were seen. These side effects were dose-related and reversible.
This combination therapy of VPA and CZP may be effective against symptomatic West and Lennoxsyndromes, when serum levels are maintained between 50 and 100μg/ml for VPA, 10 and 35ng/ml for CZP.