Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, Via Conca71, 60020, Ancona, Italy.
Department of Neuroscience, Biomedicine and Movement Science, University of Verona, Verona, Italy.
CNS Drugs. 2020 Mar;34(3):229-241. doi: 10.1007/s40263-020-00708-6.
Dravet syndrome (DS) is one of the most severe forms of drug-resistant epilepsy and available interventions fail to control seizures in most patients. Cannabidiol (CBD) is the first in a new class of antiepileptic drugs with a distinctive chemical structure and mechanism of action.
The aim of this systematic review was to evaluate the efficacy and safety of CBD as adjunctive treatment for seizures in patients with DS using meta-analytical techniques.
We searched for randomized, placebo-controlled, single- or double-blinded trials. Main outcomes included ≥ 50% reduction in baseline convulsive seizure frequency and the incidence of treatment withdrawal and adverse events (AEs). Risk ratios (RRs) with 95% confidence intervals (95% CIs) were estimated through the inverse variance method.
Three trials were included involving 359 participants, 228 for CBD and 131 for placebo groups. In all trials, the active treatment was a plant-derived pharmaceutical formulation of purified CBD oral solution. The pooled RR for 50% response during the treatment was 1.69 (95% CI 1.21-2.36; p = 0.002). Across the trials, treatment was discontinued in 20 (9.0%) and 3 (2.3%) cases in the add-on CBD and placebo groups, respectively; the RR for CBD withdrawal was 3.12 (95% CI 1.07-9.10; p = 0.037). The RR to develop any AE during add-on CBD treatment was 1.06 (95% CI 0.87-1.28; p = 0.561). AEs significantly associated with adjunctive CBD were somnolence, decreased appetite, diarrhea, and increased serum aminotransferases.
Adjunctive CBD resulted in a greater reduction in convulsive seizure frequency than placebo and a higher rate of AEs in patients with DS presenting with seizures uncontrolled by concomitant antiepileptic therapy.
Dravet 综合征（DS）是最严重的耐药性癫痫之一，大多数患者的现有干预措施无法控制癫痫发作。大麻二酚（CBD）是一类新型抗癫痫药物中的首个药物，具有独特的化学结构和作用机制。
本系统评价旨在使用荟萃分析技术评估 CBD 作为附加治疗用于 DS 患者癫痫发作的疗效和安全性。
我们检索了随机、安慰剂对照、单盲或双盲试验。主要结局包括基线抽搐性癫痫发作频率降低≥50%和治疗停药以及不良事件（AE）的发生率。通过逆方差法估计风险比（RR）及其 95%置信区间（95%CI）。
纳入了三项试验，共涉及 359 名参与者，其中 CBD 组 228 名，安慰剂组 131 名。在所有试验中，活性治疗均为植物源性纯化 CBD 口服溶液的药物制剂。治疗期间 50%应答的汇总 RR 为 1.69（95%CI 1.21-2.36；p=0.002）。在所有试验中，分别有 20 例（9.0%）和 3 例（2.3%）参与者因添加 CBD 和安慰剂而停止治疗；添加 CBD 治疗的停药 RR 为 3.12（95%CI 1.07-9.10；p=0.037）。添加 CBD 治疗期间发生任何 AE 的 RR 为 1.06（95%CI 0.87-1.28；p=0.561）。与添加 CBD 相关的 AE 主要有嗜睡、食欲下降、腹泻和血清氨基转移酶升高。
与安慰剂相比，附加 CBD 可显著降低 DS 伴癫痫发作患者的抽搐性癫痫发作频率，并增加癫痫发作频率。
