Effect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome
Effect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome
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DOI：
10.1056/nejmoa1714631
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发表时间：
2018-05-17
影响因子：
158.5
通讯作者：
Zuberi, Sameer M.
中科院分区：
文献类型：
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作者：
Devinsky, Orrin;Patel, Anup D.;Zuberi, Sameer M.
大麻二酚已被用于严重早发性癫痫患者的治疗抵抗性癫痫发作。我们调查了大麻二酚添加到常规抗癫痫药物治疗方案中治疗Lennox-Gastaut综合征（一种严重发育性癫痫性脑病）患者的跌倒发作的有效性和安全性。在这项在30个临床中心进行的双盲、安慰剂对照试验中，我们随机分配了Lennox-Gastaut综合征患者，（年龄范围，2至55岁），在28天基线期内每周有两次或更多次跌倒发作，接受剂量为20 mg/kg体重的大麻二酚口服溶液（20 mg大麻二酚组）或10 mg/kg（10 mg大麻二酚组）或匹配的安慰剂，每天以两个等分剂量给药，持续14周。主要结果是治疗期间跌倒发作频率（平均每28天）较基线的百分比变化。共有225名患者参加了CRTTSA; 76名患者被分配到20 mg大麻二酚组，73名患者分配到10 mg大麻二酚组，76名患者分配到安慰剂组。在28天基线期内，所有试验组合并的中位跌倒发作次数为85次。在治疗期间，20 mg大麻二酚组的下降癫痫发作频率较基线降低的中位百分比为41.9%，10 mg大麻二酚组为37.2%，安慰剂组为17.2%（20 mg大麻二酚组与安慰剂组相比P = 0.005，10 mg大麻二酚组与安慰剂组相比P = 0.002）。大麻二酚组患者中最常见的不良事件是嗜睡，食欲下降和腹泻;这些事件在高剂量组中发生得更频繁。20 mg大麻二酚组中的6名患者和10 mg大麻二酚组中的1名患者因不良事件而停用试验药物并退出试验。14例谁收到大麻二酚（9%）肝转氨酶concentration.CONCLUSIONSAmong儿童和成人与Lennox-Gastaut综合征，除了大麻二酚的剂量为10毫克或20毫克每公斤每天到一个传统的抗癫痫治疗方案导致下降癫痫发作的频率比安慰剂更大的减少。大麻二酚的不良事件包括肝转氨酶浓度升高。
BACKGROUNDCannabidiol has been used for treatment-resistant seizures in patients with severe early-onset epilepsy. We investigated the efficacy and safety of cannabidiol added to a regimen of conventional antiepileptic medication to treat drop seizures in patients with the Lennox-Gastaut syndrome, a severe developmental epileptic encephalopathy.METHODSIn this double-blind, placebo-controlled trial conducted at 30 clinical centers, we randomly assigned patients with the Lennox-Gastaut syndrome (age range, 2 to 55 years) who had had two or more drop seizures per week during a 28-day baseline period to receive cannabidiol oral solution at a dose of either 20 mg per kilogram of body weight (20-mg cannabidiol group) or 10 mg per kilogram (10-mg cannabidiol group) or matching placebo, administered in two equally divided doses daily for 14 weeks. The primary outcome was the percentage change from baseline in the frequency of drop seizures (average per 28 days) during the treatment period.RESULTSA total of 225 patients were enrolled; 76 patients were assigned to the 20-mg cannabidiol group, 73 to the 10-mg cannabidiol group, and 76 to the placebo group. During the 28-day baseline period, the median number of drop seizures was 85 in all trial groups combined. The median percent reduction from baseline in drop-seizure frequency during the treatment period was 41.9% in the 20-mg cannabidiol group, 37.2% in the 10-mg cannabidiol group, and 17.2% in the placebo group (P = 0.005 for the 20-mg cannabidiol group vs. placebo group, and P = 0.002 for the 10-mg cannabidiol group vs. placebo group). The most common adverse events among the patients in the cannabidiol groups were somnolence, decreased appetite, and diarrhea; these events occurred more frequently in the higher-dose group. Six patients in the 20-mg cannabidiol group and 1 patient in the 10-mg cannabidiol group discontinued the trial medication because of adverse events and were withdrawn from the trial. Fourteen patients who received cannabidiol (9%) had elevated liver aminotransferase concentrations.CONCLUSIONSAmong children and adults with the Lennox-Gastaut syndrome, the addition of cannabidiol at a dose of 10 mg or 20 mg per kilogram per day to a conventional antiepileptic regimen resulted in greater reductions in the frequency of drop seizures than placebo. Adverse events with cannabidiol included elevated liver aminotransferase concentrations.