ISSN:0001-6314    

DOI:10.1111/j.1600-0404.1973.tb02275.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

ISSN:0001-6314    

DOI:10.1111/j.1600-0404.1973.tb02276.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

ABSTRACTThe effect of clonazepam (Ro 5‐4023) was studied in 20 patients whose seizures were not satisfactorily controlled by conventional anti‐epileptic treatment. Theinitial effect, i. e. the reduction in the number of seizures observed during the first month, was significant in 18 of the 20 patients. Relief from seizures was obtained in 9 patients. In most patients, seizures recurred in a milder form after 1–3 months of treatment. In some cases, however, a further increase in the dosage controlled the condition. Thelong‐term improvementwas marked improvement (75 per cent reduction in seizure frequency) in 8, moderate (50 per cent) in 3, while no effect was noted in 4 patients. There was no definite relation between the effect of clonazepam upon seizures and the type of drug used for previous medication. The dosage of clonazepam varied from 2–10 mg. In order to obtain relief from seizures, the use of clonazepam doses near the limits of tolerance seemed unavoidable, especially in severe focal epilepsies. The most common side effects observed were drowsiness and lethargy. No dangerous side effects were noted. Combinations of clonazepam and primidone or phenobarbital were prone to produce drowsiness, even in small doses of the benzodiazepine compound, while clonazepam in combination with hydantoines or carbamazepine was better

ISSN:0001-6314    

DOI:10.1111/j.1600-0404.1973.tb02277.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

ABSTRACTIn a controlled trial based on 21 patients with psychomotor seizures and insufficient response to conventional anti‐epileptic treatment, the benzodiazepine derivative Ro 5‐4023 (clonazepam) combined with previous anti‐epileptic drugs was compared with placebo combined with the same previous anti‐epileptic drugs. The trial was single‐blind, crossover with sequential analysis. In a daily dosage of usually 6 mg clonazepam was significantly superior to placebo. Side‐effects in form of somnolence, fatigue, drowsiness and coordination disturbances occurred in most of the patients, but could be easily controlled by slow increase or slight reduction of dosage. Further studies with clonazepam alone seem to b

ISSN:0001-6314    

DOI:10.1111/j.1600-0404.1973.tb02278.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

ABSTRACTFrom a material of 179 cases of various forms of childhood epilepsy treated with clonazepam (Ro 5‐4023) the results in 79 cases with two major forms—syndrome of infantile spasms with hypsarrhythmia and petit mal variant or Lennox‐syndrome—are presented. The overall effect was complete clinical and EEG control in about one third of the cases, and partial improvement of seizure and/or hypersynchronous EEG activity in a large part of the cases. Clonazepam can therefore be considered as a very important new anti‐epileptic medicament for treatment of these forms of severe childhood

ISSN:0001-6314    

DOI:10.1111/j.1600-0404.1973.tb02279.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

ABSTRACTThe effectiveness of Rivotril® (Clonazepam, Ro 5‐4023) when used either as the sole anti‐convulsant or in combination with other drugs in institutionalised mentally retarded children with epilepsy is reported. The material comprised 37 children—19 girls and 18 boys—aged 4 to 19 years. Minor motor seizures—especially akinetic‐myoclonic attacks—were seen in 34 children either alone or in combination with other epileptic seizures. In 3 children the only seizure type was grand mal attacks. A history of infantile spasms preceding the actual symptoms was found in 9 children. In 3 children Valium® and in 22 children Mogadon® was the first drug of choice. These drugs were discontinued on account of pronounced drowsiness and in 2 cases also hypersalivation. Electroencephalographic registrations were performed in 31 children, a petit mal variant pattern being found in 20 cases and an equivocal pattern in 6 cases. Rivotril was instituted in gradually increasing doses. The final satisfactory dose varied between 0.03 and 0.33 mg/kg/day. In 4 children the akinetic seizures apparently diminished in frequency, the remaining attacks, however, being more violent. In these cases 0.25–0.50 g Diamox® provided partial relief.A drug interactionwith phenytoin apparently occurred in 7 children (19 per cent) such that the serum concentration of phenytoin exceeded 20 μg/ml and symptoms of intoxication appeared.Side effectssuch as drowsiness were seen in 5 children, vertigo and ataxia in 1, hypersalivation in 1, and muscular hypotonia in 2 children. These side effects were transitory in all but 1 case with drowsiness and the 2 cases with hypotonia. In the first‐mentioned one the drug was completely discontinued. Rivotril was judged to increase the anti‐convulsive effect to complete or clearly improved seizure control, i.e. more than 50 per cent control, in 29 children (78 per cent). In comparison with other benzodiazepines Rivotril is the best anti‐convulsant available for minor seizures. This fact is mainly based on the finding of minimal side effects. The anticonvulsive response was probably somewhat better than or did not significantly di

ISSN:0001-6314    

DOI:10.1111/j.1600-0404.1973.tb02280.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

ABSTRACTThe relationship between the rate of dosage increase of clonazepam (Ro 5‐4023) and the number of patients with side‐effects was investigated, with special reference to the number of cases in which clonazepam had to be discontinued. Out‐patients in the age group of 18 to 50 years treated for non‐symptomatic epilepsy with an insufficient result were included. The patients were allocated to one of two groups. The initial dose was 1 mg. The maintenance dose, 8 mg, was reached within 1 week in group 1, and within 3 weeks in group 2. Side‐effects were registered in 96 per cent of the patients in group 1, in 85 per cent in group 2. Of the 26 patients in group 1, 11—i.e. 42 per cent—had the drug discontinued owing to severe side‐effects. Group 2 included 27 patients. Clonazepam had to be stopped in 3 cases, i.e. 11 per cent. In the study ofBirket‐Smith et al.(1972) 36 patients were given the same initial dose as in this study. They reached the maintenance dose of 6 mg within 2 weeks. Considering the number of cases in which clonazepam had to be stopped, a highly significant difference was found between our one‐week group and the two‐weeks group mentioned. The difference between our one‐week and our three‐weeks group was also significant, whereas no difference was found between the two‐weeks and the three‐weeks group. It is concluded justifiable to prefer a schedule according to which the maintenance dose is reached within 2 weeks. However, individualizing the rate of increasing the

ISSN:0001-6314    

DOI:10.1111/j.1600-0404.1973.tb02281.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

ABSTRACTClinical trials for periods of 3 months to 3 years in 100 children treated as outpatients (two‐thirds of them had had previous unsuccessful treatment before receiving clonazepam (Ro 5‐4023) as an adjunct while one‐third were new cases treated with clonazepam alone) yielded the following main results: 1. Clonazepam is suitable for long‐term treatment. It has a greater consistency of action than nitrazepam. “Relapses” are encountered for the most part in cases exhibiting a phasic course (Lennox‐syndrome, psychomotor epilepsies). 2. Freedom from seizures was obtained in 44 per cent of cases. Differences in the susceptibility to treatment of the various types of seizure cannot be demonstrated with certainty. 3. This renders it difficult to define a precise range of indications in terms of seizure type. By contrast, the EEG changes that are immediately evident on i. v. administration (“injection test”) serve as a useful criterion in selecting suitable cases for oral maintenance therapy. 4. The initial side effects considered by many particularly troublesome in the early days of clinical testing were largely due to excessive dosage or too rapid incrementation. Maintenance doses of 0.05 to a maximum of 0.2 mg/kg per day usually suffice and are well tolerated if the increase is effected at a suitable slow rate. 5. The better results seen with clonazepam alone would seem to be related to the type of patient selected (e. g. new cases, often with the “injection test” as a

ISSN:0001-6314    

DOI:10.1111/j.1600-0404.1973.tb02282.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

ABSTRACTAn attempt was made to quantify changes in EEG abnormalities after an i.v. injection of clonazepam (Ro 5‐4023). The number of spikes and sharp‐waves per 30 sec and percentage of the total duration of generalized paroxysms (with/without spike‐ or sharp‐wave components) were calculated differentially. Epileptic patients with marked EEG abnormalities were selected for the study. The EEG tracings from which the calculation were made were recorded approx. 10 min before and after (the completion of) the injection of 1–2 mg clonazepam. In the 2 patients who continuously had spike‐and‐wave discharges only during hyperventilation (HV), the calculations were made exceptionally from 4‐min‐samples with 3 min of HV initially. Some marked differences are seen in the effects of clonazepam on the EEG abnormalities. The clinical consequences of these differences will be tested in

ISSN:0001-6314    

DOI:10.1111/j.1600-0404.1973.tb02283.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY

摘要:

ABSTRACTClonazepam (Ro 5‐4023) was tested in 65 instances of clinical and electroencephalographic status epilepticus. In 37 cases a scalp EEG was obtained during injection of the drug, which was mostly by the i. v. route. In 6 cases the drug was injected in the course of Stereo‐EEG exploration. Especially by intravenous administration and even in very small doses the drug rapidly produced a clinical effect. Of the patients 83.3 per cent responded either at once or after a second injection (1–4 mg). Particularly patients with primary generalized or focal, secondary generalized seizures responded favourably to the treatment. Improvement of the scalp EEG correlated with clinical effectiveness. Stereo‐EEG showed abolition of both spontaneous and evoked seizure discharges in various brain structures or limitation of their spread from the depths to the isocortex, thus facilitating localization of t

ISSN:0001-6314    

DOI:10.1111/j.1600-0404.1973.tb02284.x

出版商:Blackwell Publishing Ltd    

年代:1973

数据来源: WILEY