Efficacy and Tolerance of Synthetic Cannabidiol for Treatment of Drug Resistant Epilepsy
Efficacy and Tolerance of Synthetic Cannabidiol for Treatment of Drug Resistant Epilepsy
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DOI：
10.3389/fneur.2019.01313
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发表时间：
2019-12-10
影响因子：
3.4
通讯作者：
Jacobs, Julia
中科院分区：
文献类型：
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作者：
Klotz, Kerstin A.;Grob, Daniel;Jacobs, Julia
目的：对照和开放标签试验已经证实大麻二醇对某些癫痫脑病的疗效。然而，植物来源的大麻二酚产品几乎是独家使用的。合成大麻二酚的疗效以前从未被研究过。本研究的目的是评估合成大麻二醇在耐药癫痫患者中的耐受性和疗效。方法：在这项前瞻性开放研究(DRKS00013177)中，耐药癫痫患者在先前稳定的抗惊厥治疗基础上再接受合成大麻二醇治疗。起始剂量为5毫克/公斤/天，向上滴定至最高50毫克/公斤/天。主要疗效终点为3个月时运动发作的月次。结果：2017年4月至2019年5月，35名患者纳入研究。平均年龄19.7岁(SD 14.6)。运动发作的平均频率从基线的每月21.8%(IQR7.5-52.5%)下降到3个月时的8.5%(IQR3.7-28.3p<；0.001)，效果不受AED改变和辍学的影响。调整后的减少百分比为40.0%(IQR 18.2-58.5)。报告的不良事件有25例(71.4%)，最常见的是嗜睡(40%)、腹泻(34.3%)和食欲不振(20%)。2例(5.7%)因AE停止治疗。中位疗程为321天(36-824天)。到目前为止，有21名患者(60%)正在接受治疗。结论：本研究合成CBD治疗耐药癫痫的有效性和耐受性类似于使用植物来源CBD的开放标签研究。关于经济和生态方面，合成大麻二醇可能是植物来源大麻二醇的合理替代品。
Objective: Controlled and open label trials have demonstrated efficacy of cannabidiol for certain epileptic encephalopathies. However, plant derived cannabidiol products have been used almost exclusively. Efficacy of synthetically derived cannabidiol has not been studied before. The objective of this study was to evaluate tolerability and efficacy of synthetic cannabidiol in patients with pharmacoresistant epilepsy. Methods: In this prospective, open-label study (DRKS00013177), patients with pharmacoresistant epilepsy received synthetic cannabidiol in addition to their previously stable anticonvulsive treatment. Starting dose was 5 mg/kg/day, up-titrated to a maximum of 50 mg/kg/day. Primary efficacy endpoint was monthly frequency of motor seizures at 3 months. Results: Between April 2017 and May 2019, 35 patients were enrolled in the study. Mean age was 19.7 years (SD 14.6). Median motor seizure frequency decreased from 21.8 (IQR 7.5-52.5) seizures per month at baseline to 8.5 (IQR 3.7-28.3, p < 0.001) at 3 months, effect not influenced by AED changes and drop-outs. Adjusted percentage reduction was 40.0% (IQR 18.2-58.5). Adverse events (AE) were reported in 25 patients (71.4%), most frequently somnolence (40%), diarrhea (34.3), and loss of appetite (20%). Two patients (5.7%) discontinued treatment due to AE. Median (range) of treatment duration was 321 days (range 36-824). With ongoing treatment up to date in 21 patients (60%). Conclusion: Efficacy and tolerance in our study of synthetic CBD treatment in pharmacoresistant epilepsy is similar to open label studies using plant derived CBD. Regarding economic and ecological aspects, synthetic cannabidiol might be a reasonable alternative to plant derived cannabidiol.