Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, Via Conca 71, 60020, Ancona, Italy.
Department of Neuroscience, Biomedicine and Movement Science, University of Verona, Verona, Italy.
CNS Drugs. 2018 Oct;32(10):905-916. doi: 10.1007/s40263-018-0558-9.
Lennox-Gastaut syndrome (LGS) is a severe developmental epileptic encephalopathy, and available interventions fail to control seizures in most patients. Cannabidiol (CBD) is a major chemical of marijuana, which has anti-seizure properties and different mechanisms of action compared with other approved antiepileptic drugs (AEDs).
The aim was to evaluate the efficacy and safety of CBD as adjunctive treatment for seizures in patients with LGS using meta-analytical techniques.
Randomized, placebo-controlled, single- or double-blinded trials were identified. Main outcomes included the ≥ 50% reduction in baseline drop and non-drop seizure frequency, and the incidence of treatment withdrawal and adverse events (AEs). Risk ratios (RRs) with 95% confidence intervals (CIs) were estimated through the inverse variance method.
Two trials were included involving 396 participants. Patients presenting ≥ 50% reduction in drop seizure frequency during the treatment were 40.0% with CBD and 19.3% with placebo [RR 2.12 (95% CI 1.48-3.03); p < 0.001]. The rate of non-drop seizure frequency was reduced by 50% or more in 49.4% of patients in the CBD and 30.4% in the placebo arms [RR 1.62 (95% CI 1.09-2.43); p = 0.018]. The RR for CBD withdrawal was 4.93 (95% CI 1.50-16.22; p = 0.009). The RR to develop any AE during CBD treatment was 1.24 (95% CI 1.11-1.38; p < 0.001). AEs significantly associated with CBD were somnolence, decreased appetite, diarrhea and increased serum aminotransferases.
Adjunctive CBD resulted in a greater reduction in seizure frequency and a higher rate of AEs than placebo in patients with LGS presenting seizures uncontrolled by concomitant AEDs.
Lennox-Gastaut 综合征（LGS）是一种严重的发育性癫痫性脑病，大多数患者的现有干预措施都无法控制癫痫发作。大麻二酚（CBD）是大麻的主要化学物质，与其他已批准的抗癫痫药物（AED）相比，具有抗癫痫作用和不同的作用机制。
使用荟萃分析技术评估 CBD 作为辅助治疗 LGS 患者癫痫发作的疗效和安全性。
确定了随机、安慰剂对照、单盲或双盲试验。主要结局包括基线降幅和非降幅癫痫发作频率≥50%的减少，以及治疗退出和不良事件（AE）的发生率。通过逆方差法估计风险比（RR）及其 95%置信区间（CI）。
纳入了两项涉及 396 名参与者的试验。在治疗过程中，有 CBD 的患者癫痫发作频率降幅≥50%的比例为 40.0%，安慰剂组为 19.3%[RR 2.12（95% CI 1.48-3.03）；p<0.001]。CBD 组有 49.4%的患者非降幅癫痫发作频率降低了 50%或更多，安慰剂组为 30.4%[RR 1.62（95% CI 1.09-2.43）；p=0.018]。CBD 停药的 RR 为 4.93（95% CI 1.50-16.22；p=0.009）。CBD 治疗期间发生任何 AE 的 RR 为 1.24（95% CI 1.11-1.38；p<0.001）。与 CBD 显著相关的 AE 有嗜睡、食欲减退、腹泻和血清转氨酶升高。
在伴有 AED 治疗仍未控制癫痫发作的 LGS 患者中，辅助使用 CBD 可使癫痫发作频率降低更多，AE 发生率更高。
