Clobazam as a new antiepileptic drug and clorazepate dipotassium as an alternative antiepileptic drug in Japan.
OBJECTIVE
To confirm the efficacy and to clarify the problems of clobazam (CLB) as a new antiepileptic drug (AED) and clorazepate (CLP) as an alternative AED in Japan.


METHODS
CLB and CLP were added on or replaced with conventional AEDs in 55 and 170 patients with refractory epilepsies, respectively. Short-term efficacy was studied after at least 2 months of CLB administration and at least 4 weeks of CLP administration. Long-term efficacy was examined in 31 cases with CLB for > or =6 months and in 86 cases with CLP for > or =6 months. CLB was initiated at 0.15-0.40 mg/kg and increased by 0.1-0.2 mg/kg every 1-2 weeks up to 0.28-1.25 mg/kg. CLP was started at 0.3-0.7 mg/kg and increased by 0.2-0.3 mg/kg every 1-2 weeks up to 2.5 mg/kg. Tolerance was examined in 42 cases with CLB for > or =3 months and 112 cases with CLP for > or =4 weeks.


RESULTS
CLB was effective, defined as > or =50% reduction in seizure frequency, in 71% of the short-term subjects and 81% of the long-term subjects. Short-term efficacy was better in symptomatic localization-related epilepsies, but long-term efficacy did not differ according to seizure classification. Short-term efficacy was not different by seizure types or EEG findings. CLP was effective in 70% of the short-term subjects and 80% of the long-term subjects. CLP was more effective in patients with localization-related epilepsies or in patients with partial seizures or focal epileptiform discharges on EEG. Adverse effects developed in 47% of CLB cases and 31% of CLP cases, but the incidence was reduced by lower initial doses and slow dose titration. Tolerance occurred in 24% of CLB cases and 48% of CLP cases, half within 3-4 months after the initiation of CLB and half by 2 months after the start of CLP. Upon rechallenge, 70% of CLB-tolerant cases and 50% of CLP-tolerant cases responded to each drug again by increasing or maintaining the dosage.


CONCLUSIONS
Excellent efficacy of CLB and excellent and prolonged efficacy of CLP for refractory epilepsies were confirmed. Frequent tolerance and adverse effects were major problems, but were manageable.
Sugai
Kenji
K
Department of Child Neurology, National Center Hospital for Mental, Nervous and Muscular Disorders, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan. sugaik@ncnpmusashi.gr.jp
D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use*; D000078306:Clobazam; D003009:Clorazepate Dipotassium / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D004827:Epilepsy / Q000145:classification / Q000188:drug therapy*; D005500:Follow-Up Studies; D006801:Humans; D007564:Japan; D008137:Longitudinal Studies; D016896:Treatment Outcome
D000927:Anticonvulsants; D001569:Benzodiazepines; D000078306:Clobazam; D003009:Clorazepate Dipotassium