Jarrar Randa, Stern John M, Becker Danielle A, Davis Charles, Rabinowicz Adrian L, Carrazana Enrique
Department of Neurology, Phoenix Children's Hospital, 1919 E Thomas Rd Ambulatory Building, Floor 3, Phoenix, AZ 85016, USA.
Department of Neurology, Geffen School of Medicine, University of California Los Angeles, Los Angeles 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.
Epilepsy Behav. 2024 Oct;159:109987. doi: 10.1016/j.yebeh.2024.109987. Epub 2024 Aug 23.
Benzodiazepines are used in first-line rescue therapy as immediate-use seizure medication for the treatment of seizure clusters and prolonged seizures. Their use varies across clinical practices and conditions, and they can be used promptly when indicated. Clinical studies have demonstrated seizure termination within 2 min when diazepam nasal spray is used to treat seizure clusters within 5 min, but the response when treating longer duration seizures in a cluster remains to be characterized.
To describe and assess timing and dosing of diazepam nasal spray in the subset of prolonged seizures within seizure clusters in a larger dataset of all treated seizure clusters collected during a long-term safety study of diazepam nasal spray.
Using timing data recorded in seizure diaries, this post hoc analysis and associated sensitivity analyses focused on prolonged seizures treated 5 to 15 min after the seizure start. Measures included time to treatment administration and time to seizure termination. Second-dose data were used as a proxy for effectiveness.
In this group of seizure clusters treated 5 to 15 min after seizure start, median time drug administration was 6 min after seizure start, median time from drug administration to seizure termination was 7 min, and median overall seizure duration was 15 min. Sensitivity analyses by age, epilepsy type, and high seizure frequency confirmed this pattern. Use of a second dose occurred in 9.3 % of episodes, with the majority of second doses administered ≤ 4 h after the first dose. Safety results from the overall study showed 82.2 % of patients had ≥ 1 treatment-emergent adverse event (TEAE) irrespective of relationship to treatment, during a mean participation of ∼ 1.5 years. In addition, 30.7 % patients had a serious TEAE, and 18.4 % had TEAEs deemed at least possibly related to the study drug, none of which were serious. No events of cardiorespiratory depression were reported.
Although immediate use of diazepam nasal spray (within 5 min) resulted in quicker seizure termination, a treatment delay of 5 to 15 min still produced rapid termination of the seizure cluster with high first-dose effectiveness and an overall acceptable safety profile. These findings suggest that diazepam nasal spray maintains effectiveness in prolonged seizures within a cluster with delayed treatment.
苯二氮䓬类药物作为即刻使用的抗癫痫药物用于一线抢救治疗，以治疗癫痫丛集发作和癫痫持续状态。其使用因临床实践和病情而异，在有指征时可迅速使用。临床研究表明，当使用地西泮鼻喷雾剂在5分钟内治疗癫痫丛集发作时，癫痫发作可在2分钟内终止，但在治疗丛集中持续时间较长的癫痫发作时的反应仍有待明确。
在一项地西泮鼻喷雾剂长期安全性研究中收集的所有治疗的癫痫丛集发作的更大数据集中，描述和评估地西泮鼻喷雾剂在癫痫丛集发作中癫痫持续状态亚组的给药时间和剂量。
利用癫痫日记中记录的时间数据，这项事后分析及相关敏感性分析聚焦于癫痫发作开始后5至15分钟治疗的癫痫持续状态。测量指标包括给药时间和癫痫发作终止时间。第二剂数据用作有效性的替代指标。
在这组癫痫发作开始后5至15分钟治疗的癫痫丛集发作中，给药中位时间为癫痫发作开始后6分钟，从给药到癫痫发作终止的中位时间为7分钟，癫痫发作总中位持续时间为15分钟。按年龄、癫痫类型和高癫痫发作频率进行的敏感性分析证实了这一模式。9.3%的发作使用了第二剂，大多数第二剂在第一剂后≤4小时给药。整个研究的安全性结果显示，在平均参与约1.5年期间，82.2%的患者发生了≥1次治疗中出现的不良事件（TEAE），无论其与治疗的关系如何。此外，30.7%的患者发生了严重TEAE，18.4%的患者发生了被认为至少可能与研究药物相关的TEAE，均不严重。未报告心肺抑制事件。
尽管立即使用地西泮鼻喷雾剂（5分钟内）可更快地终止癫痫发作，但治疗延迟5至15分钟仍能迅速终止癫痫丛集发作，首剂有效性高，总体安全性可接受。这些发现表明，地西泮鼻喷雾剂在治疗延迟的丛集性癫痫持续状态中仍保持有效性。
