Valproate and clonazepam comedication in patients with intractable epilepsy

The efficacy and the potential risk of inducing convulsive or nonconvulsive status epilepticus with the combination of valproate (VPA) and clonazepam (CZP), with or without other anticonvulsant drugs, in 55 patients with intractable epilepsy was evaluated. The patients were treated with VPA and CZP concomitantly for from 3 to 72 months (mean 21.7 months). Trough VPA serum levels ranged from 26 to 96 micrograms/ml). Trough CZP serum levels ranged from 5 to 63 ng/ml (mean 22.6 ng/ml). The treatment seizure frequency was compared with baseline values before combination treatment. Seizure improvement was obtained in 7 of 8 patients with absence seizures, 8 of 9 patients with myoclonic seizures, 19 of 39 patients with complex partial seizures, 3 of 14 patients with primary generalized tonic-clonic seizures, 8 of 23 patients with secondarily generalized tonic-clonic seizures, and 3 of 14 patients with atonic seizures. No single case of status epilepticus or exacerbation of seizures of any type was seen.