Chiang Sharon, Moss Robert, Misra Sunita N, Carrazana Enrique, Rabinowicz Adrian L
Department of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, California, USA.
Departments of Physiology and Psychiatry and the Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, California, USA.
Epilepsia. 2025 Feb;66(2):369-378. doi: 10.1111/epi.18195. Epub 2024 Nov 28.
Benzodiazepine rescue medications are established as therapy for acute termination of seizure clusters. A post-hoc analysis of a clinical trial of seizure cluster treatment with diazepam nasal spray found a potential longer-term impact over a year of treatment. In this retrospective analysis, we tested the hypothesis that benzodiazepine-treated seizure clusters are associated with prolonged time to the next seizure cluster compared with untreated seizure clusters in a patient-reported real-world database.
We analyzed data on self-reported seizures and benzodiazepine rescue medication administration in the Seizure Tracker™ database between 2007 and 2022. Kaplan-Meier analysis was used to compare treated vs untreated seizure clusters with respect to time to start of the next seizure cluster or immediate-use medication administration. Mixed-effects analysis was used to compare the number of seizures per cluster for treated and untreated seizure clusters. Robustness of findings was evaluated across three operational seizure-cluster definitions: ≥2 seizures in 4 hours as primary analysis and in 6 and 24 hours as sensitivity analyses.
A total of 10 889 benzodiazepine immediate-use medication administrations (n = 220 patients) met inclusion criteria. Benzodiazepine rescue administrations were followed by longer time to the next seizure cluster or rescue administration, compared with untreated seizure clusters, corresponding to a median of 4.9 days following treated seizure clusters and a median of 0.8 days following untreated seizure clusters. This prolongation was driven by a minority of patients (accounting for 45.9% of seizure clusters in the sample) and patients were more likely to be women. The number of seizures per cluster was lower when treatment was administered earlier in the seizure cluster.
These retrospective real-world data suggest that the effect of benzodiazepines on termination of seizure clusters may be more pronounced when administration occurs earlier after onset, and support a hypothesis of a possible longer-term effect of benzodiazepines beyond immediate-use acute seizure termination.
苯二氮䓬类急救药物已被确立为急性终止癫痫发作丛集的治疗方法。一项关于地西泮鼻喷雾剂治疗癫痫发作丛集的临床试验的事后分析发现，治疗一年可能有更长期的影响。在这项回顾性分析中，我们在一个患者报告的真实世界数据库中检验了这一假设，即与未治疗的癫痫发作丛集相比，接受苯二氮䓬类药物治疗的癫痫发作丛集与下次癫痫发作丛集发作时间延长有关。
我们分析了2007年至2022年期间癫痫发作追踪器™数据库中自我报告的癫痫发作和苯二氮䓬类急救药物使用的数据。采用Kaplan-Meier分析来比较治疗组和未治疗组癫痫发作丛集至下次癫痫发作丛集开始或立即使用药物的时间。采用混合效应分析来比较治疗组和未治疗组癫痫发作丛集每丛集的癫痫发作次数。在三种操作性癫痫发作丛集定义下评估研究结果的稳健性：以4小时内发作≥2次为主要分析，6小时和24小时内发作≥2次为敏感性分析。
共有10889次苯二氮䓬类立即使用药物给药（n = 220例患者）符合纳入标准。与未治疗的癫痫发作丛集相比，苯二氮䓬类急救给药后至下次癫痫发作丛集或急救给药的时间更长，治疗后的癫痫发作丛集中位数为4.9天，未治疗的癫痫发作丛集中位数为0.8天。这种延长是由少数患者驱动的（占样本中癫痫发作丛集的45.9%），且患者更可能为女性。在癫痫发作丛集早期进行治疗时，每丛集的癫痫发作次数较少。
这些回顾性真实世界数据表明，苯二氮䓬类药物对癫痫发作丛集终止的作用在发作后早期给药时可能更显著，并支持苯二氮䓬类药物除了立即使用以急性终止癫痫发作外可能有更长期作用的假设。
