Sankar Raman, Chung Steve, Perry Michael Scott, Kuzniecky Ruben, Sinha Saurabh
Division of Pediatric Neurology, David Geffen School of Medicine at UCLA, University of California-Los Angeles, Room 22-474 MDCC, Los Angeles, CA 90095-1752, USA.
J Med Case Rep. 2014 Dec 16;8:429. doi: 10.1186/1752-1947-8-429.
In treating refractory epilepsy, many clinicians are interested in methods used to transition patients receiving clonazepam to clobazam to maintain or increase seizure control, improve tolerability of patients' overall drug therapy regimens, and to enhance quality of life for patients and their families. However, no published guidelines assist clinicians in successfully accomplishing this change safely.
The following three case reports provide insight into the transition from clonazepam to clobazam. First, an 8-year-old Caucasian boy with cryptogenic Lennox-Gastaut syndrome beginning at 3.5 years of age, who was experiencing multiple daily generalized tonic-clonic, absence, myoclonic, and tonic seizures at presentation. Second, a 25-year-old, left-handed, White Hispanic man with moderate mental retardation and medically refractory seizures that he began experiencing at 1 year of age, secondary to tuberous sclerosis. When first presented to an epilepsy center, he had been receiving levetiracetam, valproate, and clonazepam, but reported having ongoing and frequent seizures. Third, a 69-year-old Korean woman who had been healthy until she had a stroke in 2009 with subsequent right hemiparesis; as a result, she became less physically and socially active, and had her first convulsive seizure approximately 4 months after the stroke.
From these cases, we observe that a rough estimate of final clobazam dosage for each mg of clonazepam under substitution is likely to be at least 10-fold, probably closer to 15-fold for many patients, and as high as 20-fold for a few. Consideration and discussion of the pharmacokinetic, pharmacologic, and clinical properties of 1,4- and 1,5-benzodiazepine action provide a rationale on why and how these transitions were successful.
在治疗难治性癫痫时，许多临床医生对将接受氯硝西泮治疗的患者转换为氯巴占的方法感兴趣，以维持或增强癫痫控制效果、提高患者整体药物治疗方案的耐受性，并改善患者及其家庭的生活质量。然而，目前尚无已发表的指南协助临床医生安全地成功完成这一转变。
以下三例病例报告为从氯硝西泮转换为氯巴占提供了见解。第一例，一名8岁白人男孩，3.5岁起患有隐源性 Lennox-Gastaut 综合征，就诊时每日发作多次全身性强直阵挛发作、失神发作、肌阵挛发作和强直发作。第二例，一名25岁的左撇子白人西班牙裔男子，中度智力障碍，1岁起患有药物难治性癫痫，继发于结节性硬化症。首次就诊于癫痫中心时，他一直在服用左乙拉西坦、丙戊酸盐和氯硝西泮，但仍报告有持续且频繁的癫痫发作。第三例，一名69岁的韩国女性，2009年中风前身体健康，中风后出现右半身轻瘫；因此，她的身体和社交活动减少，中风后约4个月首次出现惊厥发作。
从这些病例中，我们观察到，替换时每毫克氯硝西泮的最终氯巴占剂量粗略估计可能至少为其10倍，对许多患者而言可能更接近15倍，少数患者高达20倍。对1,4 - 和1,5 - 苯二氮䓬作用的药代动力学、药理学和临床特性的考虑与讨论，为这些转换为何成功以及如何成功提供了理论依据。
