Clonazepamによる難治性てんかんの治療成績

Treatment of Epileptic Seizures with Clonazepam

I．はじめに

　発作の抑制を図ることは，てんかんの治療に際してまず第一になされなければならないことである。周知のごとくphenobarbitalやdiphenylhydantoinが，すぐれた抗けいれん剤として登場して以来30数年を越え，この間数多くの抗てんかん剤が次々と開発され，てんかん患者に多くの光明をもたらしている。しかし，てんかん患者の15％前後は充分な発作の抑制が得られずに難治性てんかんのレッテルをはられており，さらにすぐれた抗てんかん剤の出現が待ち望まれているのが現状であろう。我々は，今回日本ロシュ株式会社より新しい抗てんかん剤clonazepam（Hoffmann-La Roche社で開発されたbenzodiazepineに属する化合物5-(o-chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepin-2-one）の提供をうけて治療を試みたが，価値ある薬剤の1つであるとの知見が得られたので，ここにその詳細を報告することとした。

　Clonazepam, a new antiepileptic drug, was administered to 32 epileptic patients who had been hardly responding to other antiepileptics. The average dose for the first administration was 0.05 mg/kg/day, the average maintenance dose was 0.08 mg/kg/day and the average period of treatment was 25.7 weeks. The following results were obtained:

　1. The evaluation at an early stage of treatment (after 5 weeks) showed that in 11 cases it was indicated to be remarkably effective (+++), in 7 cases effective (++), in another 7 fairly effective (+) and in 7 cases no effect (-). Effects on the epileptic seizure types ; for 10 cases of psychomotor seizure, 2 cases showed (+++), 2 cases (++), 4 cases (+) and 2 cases no effect. For 6 cases of Lennox syndrome group, 2 cases were (++), 1 case (+) and 3 cases no effect. Two cases of myoclonic seizure+C1 showed a remarkable effect (+++). For 5 cases of autonomic seizure, 3 showed (+++), 1 (+) and 1 no effect (-).

　2. In a long term evaluation (more than 10 weeks), 3 cases having been remarkably effective (+++) and 2 cases of (++) at the early stage turned completely ineffective, while a case of (+++) was reduced to (++).

　3. Nine of 32 were improved, with the decrease in the frequency of seizures, in psychiatric symptoms such as irritability, excitability, restlessness, impatience and uneasiness, which had been observed before the administration with clonazepam. On the other hand, these psychiatric symptoms were aggravated in 4 cases.

　4. By the electroencephalographic comparison before and after the administration of 23 cases, it was found that 6 cases showed an improvement together with a reduction in frequency of seizures, 15 remained unchanged, 1 was aggravated with the recurrence of seizures, while 1 case showed the normal EEG value on both occasions.

　5. Of 32 cases 28 have been administered with other benzodiazepines. Nitrazepam was used in 20 cases at a dose level of 2 to 15 mg. Among them 3 cases responded favorably to nitrazepam temporarily and 17 remained completely unaffected. By the administration with clonazepam, 14 cases were improved in the range of (+) to (+++) at the early stage and 4 turned to be negative at the later stage.

　6. Adverse reactions were seen in 26 cases such as unsteadiness, dizziness, drowsiness and blankness; but 9 cases recovered soon from these.

　In various examinations, 7 cases showed a rise in the serum alkaline phosphatase value which could not immediately be attributed to clonazepam administration, since 4 cases out of 7 had shown high scores before the administration and 3 others had been already administered with various antiepileptics, but any other abnormalities were not found.

　7. Clonazepam is considered to have the best antiepileptic effect among other benzodiazepines and it also seems to possess an emotional sedative effect. Clonazepam is, therefore, considered to be one of the drugs to be tried on cases with epileptic seizures which were unable to respond satisfactorily to the administration with other antiepileptic drugs.