Estudo clínico do RO-5-4023 no tratamento de epilepsias

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.

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Discontinuation of Clonazepam After Long‐Term Treatment

Specht

Boenigk

Wolf

1989

Epilepsia

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Frequent unwanted side effects and development of tolerance are the main disadvantages of clonazepam (CZP) in long-term treatment of epileptic patients. A review of the literature shows that CZP tolerance more often appears in severe forms of childhood epilepsy (West and Lennox-Gastaut syndromes) than in other epileptic syndromes. We prospectively studied the consequences of CZP discontinuation in 40 consecutive children with difficult-to-treat epilepsies and multiple-drug therapy. The CZP was reduced stepwise in a variable daily reduction rate (0.003-0.16 mg/kg), while serum levels of the comedication were kept unchanged. In only three children (7.5%), CZP was believed to have had some antiepileptic effect; in 30 (75%) it had been ineffective, whereas in six (15%), a decrease in seizure frequency after CZP discontinuation even suggested a negative therapeutic effect. Discontinuation symptoms, mostly in the form of a transitory exacerbation of seizure frequency, occurred in 19 children (47.5%). These children had a significantly higher CZP dose and longer duration of treatment than did children without discontinuation symptoms, but there was no difference between the two groups related to the rate of CZP discontinuance.

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Estudo clínico do RO-5-4023 no tratamento de epilepsias

Cited by 4 publications

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Clonazepam

Clonazepam

Valproate and Clonazepam Comedication in Patients with Intractable Epilepsy

Discontinuation of Clonazepam After Long‐Term Treatment

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