title: Efficacy of low-dose, add-on therapy of clobazam (CLB) is produced by its major metabolite, N-desmethyl-CLB.
abstract: We evaluated the efficacy of low-dose, add-on therapy of CLB in adults with refractory epilepsy. 28 patients were included: 12 with temporal lobe epilepsy (TLE), 14 with extratemporal lobe epilepsy (ETLE) and 2 with symptomatic generalized epilepsy (SGE). CLB was added with the initial dose of 2.5 mg/day and increased to the optimal dose (mean, 5.6 mg/day). The mean observation period was 7.9 months. As compared with the baseline period, 14 out of 28 patients (50%) obtained an obviously good seizure control: 6 seizure free and 8 more than 50% of seizure reduction. The 14 patients comprised of 4 TLE, 8 ETLE and 2 SGE. In seizure type analysis, 26% of complex partial seizures (CPS), 64% of simple partial seizures (SPS) and 86% of generalized tonic-clonic seizures (GTC) showed a good control. Blood level of N-desmethyl-CLB in the steady state was higher in seizure-free group of 6 patients, and N-desmethyl-CLB blood level/dose per kg body weight correlated significantly to seizure control (p=0.0167). Our data show that even in low dose CLB was effective to patients with refractory epilepsy who had higher blood level of N-desmethyl-CLB.
authors.affiliation: Department of Neurology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawaharacho, Sakyoku, Kyoto, 606-8507, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Akio
authors.initials: A
authors.lastname: Ikeda
authors.forename: Tahamina
authors.initials: T
authors.lastname: Begum
authors.forename: Kiyohito
authors.initials: K
authors.lastname: Terada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shibasaki
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000097:blood / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000097:blood / Q000627:therapeutic use*; D000078306:Clobazam; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D001569:Benzodiazepines; D000078306:Clobazam; C024581:N-desmethylclobazam