Clobazam in Long‐Term Epilepsy Treatment: Sustained Responders Versus Those Developing Tolerance
Clobazam in Long‐Term Epilepsy Treatment: Sustained Responders Versus Those Developing Tolerance
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长期癫痫治疗中的氯巴扎姆：持续缓解者与产生耐受性的患者
DOI：
10.1111/j.1528-1157.1995.tb01617.x
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发表时间：
1995
期刊：
影响因子：
5.6
通讯作者：
D. Boisvert
中科院分区：
文献类型：
--
作者：
Avinder Singh;A. Guberman;D. Boisvert
摘要：氯巴占（CLB）是一种结构独特的苯二氮卓类药物（BZD），对所有类型的难治性癫痫发作均具有抗惊厥活性。与其他BZD一样，CLB的主要缺点是出现耐受性。到目前为止，还没有办法预测哪些患者会产生耐受性。我们比较了两组患者的临床特征和治疗变量，这两组患者的癫痫发作最初用CLB控制良好：持续反应的患者和产生耐受性的患者。我们回顾性地从173例连续接受CLB治疗的癫痫不受控制的患者中确定了一组50例非常好的反应者。非常好的反应者定义为在添加CLB后癫痫发作减少>75%并且持续CLB治疗至少1个月的患者。在平均随访37.5 ± 12.8个月时，25例患者继续缓解，25例患者出现耐受性（平均随访17.0 ± 15.7个月）。耐受性定义为在最初非常好的缓解至少1个月后，尽管CLB剂量和血清水平恒定（如可用），但复发水平<50%的前CLB癫痫发作频率。伴随用药无变化。两组之间存在显著差异。持续反应组的癫痫持续时间较短（平均16.5 vs.24.5年，p = 0.015），癫痫病因已知的个体比例较高（48 vs.16%，p = 0.006），CLB水平较高（0.50 vs.0.22 μM，p = 0.017），但N-去甲基-CLB水平无显著差异。某些因素显然可能会影响对氯巴占抗癫痫作用产生耐受性的可能性。
Summary: Clobazam (CLB) is a structurally unique benzodiazepine (BZD) that has anticonvulsant activity in all types of refractory seizures. The main drawback to CLB, as to other BZDs, is the occurrence of tolerance. To date, there has been no way to predict which patients will develop tolerance. We compared clinical features and treatment variables between two groups of patients whose seizures were initially well controlled with CLB: patients with a sustained response and patients who developed tolerance. We retrospectively identified a group of 50 very good responders from among 173 consecutive patients with uncontrolled epilepsy treated with CLB. Very good responders were defined as patients with >75% reduction in seizures after the addition of CLB who continued CLB treatment for at least 1 month. At a mean follow‐up of 37.5 ± 12.8 months, 25 patients continued to respond and 25 developed tolerance (mean follow‐up 17.0 ± 15.7 months).Tolerance was defined as a relapse to a level <50% of pre‐CLB seizure frequency after an initial very good response for a minimum period of 1 month, despite constant CLB dose and, when available, serum levels. There was no change in concomitant medication. Significant differences were noted between the two groups. The sustained response group had a shorter duration of epilepsy (mean 16.5 vs.24.5 years, p = 0.015), a greater proportion of individuals with a known etiology for their epilepsy (48 vs.16%, p = 0.006), and higher CLB levels (0.50 vs.0.22 μM, p = 0.017), but no significant difference in N‐desmethyl‐CLB levels. Certain factors apparently may influence the likelihood of developing tolerance to the antiepileptic effects of clobazam.