Cereghino James J, Cloyd James C, Kuzniecky Ruben I
Oregon Health and Science University, Epilepsy Center, Portland 97239, USA.
Arch Neurol. 2002 Dec;59(12):1915-20. doi: 10.1001/archneur.59.12.1915.
To evaluate the efficacy and tolerability of diazepam (DZP) rectal gel (Diastat; Elan Pharmaceuticals, Dublin, Ireland) for the treatment of acute repetitive seizures in adult patients in 2 multicenter, double-blind, placebo-controlled parallel studies.
Ninety-six adults 18 years or older with acute repetitive seizures, 70 of whom received treatment, were randomized into the 2 studies. Active and placebo medications were supplied in prefilled, identical-appearing delivery systems. In study 001, patients received a second dose 4 hours after the initial treatment. Patients in study 003 received only 1 treatment. Patients were observed for 12 hours after the first dose.
There was a significant reduction in seizure frequency in patients who received DZP compared with the placebo group. The median number of seizures per hour in the group treated with DZP rectal gel was 0.00, vs 0.13 in the placebo group (P =.002). In addition, significantly more DZP rectal gel-treated patients remained seizure-free during the 12-hour observation period (71% [22/31] vs 28% [11/39]). Using Kaplan-Meier life-table analysis, time to the next seizure was found to be significantly longer in DZP rectal gel-treated than placebo-treated patients (P<.001). Global assessment as provided by the caregivers was in favor of DZP rectal gel for both study 001 (P =.17) and study 003 (P =.02). Dizziness and somnolence were the only central nervous system adverse events that occurred more frequently in patients receiving DZP rectal gel than in those receiving placebo.
In adults, rectal DZP formulated as Diastat significantly reduced the likelihood of seizure recurrence during an episode of acute repetitive seizures, with minimal safety concerns.
在两项多中心、双盲、安慰剂对照平行研究中,评估地西泮(DZP)直肠凝胶(Diastat;爱尔兰都柏林伊兰制药公司)治疗成年患者急性重复性癫痫发作的疗效和耐受性。
96名18岁及以上患有急性重复性癫痫发作的成年人(其中70人接受治疗)被随机纳入这两项研究。活性药物和安慰剂通过预填充、外观相同的给药系统提供。在研究001中,患者在初始治疗4小时后接受第二剂。研究003中的患者仅接受1次治疗。首剂给药后对患者观察12小时。
与安慰剂组相比,接受DZP治疗的患者癫痫发作频率显著降低。DZP直肠凝胶治疗组每小时癫痫发作的中位数为0.00,而安慰剂组为0.13(P = 0.002)。此外,在12小时观察期内,接受DZP直肠凝胶治疗且无癫痫发作的患者明显更多(71% [22/31] 对28% [11/39])。使用Kaplan-Meier生存表分析发现,DZP直肠凝胶治疗的患者至下次癫痫发作的时间明显长于安慰剂治疗的患者(P<0.001)。护理人员进行的整体评估表明,在研究001(P = 0.17)和研究003(P = 0.02)中,DZP直肠凝胶均更具优势。头晕和嗜睡是接受DZP直肠凝胶治疗的患者比接受安慰剂治疗的患者更频繁出现的仅有的中枢神经系统不良事件。
在成年人中,以Diastat形式配制的直肠DZP可显著降低急性重复性癫痫发作期间癫痫复发的可能性,且安全性担忧极小。