Leestma J E, Annegers J F, Brodie M J, Brown S, Schraeder P, Siscovick D, Wannamaker B B, Tennis P S, Cierpial M A, Earl N L
Chicago Institute of Neurosurgery and Neuroresearch, Illinois, USA.
Epilepsia. 1997 Jan;38(1):47-55. doi: 10.1111/j.1528-1157.1997.tb01076.x.
The present study was conducted to determine the rate of sudden unexplained death in epilepsy (SUDEP) in a well-defined cohort of patients included in the lamotrigine (LTG) clinical development database.
A panel of scientists experienced in the area of SUDEP was assembled and provided with case summaries on all deaths (n = 45) reported during the initial clinical development of LTG. The panel developed a set of criteria for classifying cases as SUDEP (definite or highly probable), possible SUDEP, or non-SUDEP. This classification algorithm was then applied to the LTG cases, and SUDEP rates were calculated using patient-years of exposure as the denominator.
At the time of the study, 4,700 patients (5,747 patient-years of exposure) were included in the worldwide LTG clinical trials database. In this cohort, 45 deaths were reported. Eighteen were judged by the panel to be SUDEP, 6 were defined as possible SUDEP, 20 were judged to be due to other causes (non-SUDEP), and 1 lacked sufficient data from which to make a classification. The overall SUDEP rate (definite/ highly probable SUDEP and possible SUDEP combined) was calculated to be 3.5 in 1,000 patient-years of exposure to LTG.
The rate of SUDEP in this cohort of patients was comparable to the rate that would be expected in young adults with severe epilepsy (the subgroup of patients believed to be at highest risk of SUDEP). The data suggest that the rate of SUDEP in the LTG clinical development program is a function of the clinical trial population and is unrelated to drug treatment.
本研究旨在确定拉莫三嗪（LTG）临床开发数据库中一组明确界定的患者的癫痫不明原因猝死（SUDEP）发生率。
组建了一个在SUDEP领域经验丰富的科学家小组，并向其提供了LTG初始临床开发期间报告的所有死亡病例（n = 45）的病例摘要。该小组制定了一套将病例分类为SUDEP（明确或极有可能）、可能的SUDEP或非SUDEP的标准。然后将此分类算法应用于LTG病例，并以暴露的患者年数作为分母计算SUDEP发生率。
在研究时，全球LTG临床试验数据库纳入了4700名患者（5747患者年的暴露时间）。在该队列中，报告了45例死亡。该小组判定其中18例为SUDEP，6例定义为可能的SUDEP，20例判定为其他原因导致（非SUDEP），1例缺乏足够数据进行分类。暴露于LTG的1000患者年中，总体SUDEP发生率（明确/极有可能的SUDEP和可能的SUDEP合并）经计算为3.5。
该队列患者的SUDEP发生率与重度癫痫年轻成人（被认为是SUDEP风险最高的患者亚组）预期的发生率相当。数据表明，LTG临床开发项目中的SUDEP发生率是临床试验人群的一个函数，与药物治疗无关。
