Hollander Marie, Mayer Thomas, Klotz Kerstin Alexandra, Knake Susanne, von Podewils Felix, Kurlemann Gerhard, Immisch Ilka, Rosenow Felix, Schubert-Bast Susanne, Strzelczyk Adam
Epilepsy Center Frankfurt Rhine-Main, Department of Neurology, Goethe-University Frankfurt, University Medicine Frankfurt, Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany.
Epilepsy Center Kleinwachau, Radeberg, Germany.
Neurol Res Pract. 2025 Jul 22;7(1):49. doi: 10.1186/s42466-025-00408-w.
In randomized controlled trials, add-on cannabidiol (CBD) has been shown to reduce seizure frequency in patients with Lennox-Gastaut syndrome, Dravet syndrome and Tuberous sclerosis complex. Real-world studies provide insights into the drug's profile in other off-label indications. This study evaluated factors predicting efficacy, retention, and tolerability of add-on CBD used for off-label treatment in clinical practice for patients with refractory focal-onset, genetic generalised, and other unclassified epilepsies.
A retrospective cohort study recruiting all patients who had started CBD between 2019 and 2023 for off-label treatment at six German epilepsy centres. Data on baseline and follow-up were obtained from patients' medical records.
A total of 108 patients (mean age 27.3; median 36; range 1.4-68 years, 56 male) were treated with CBD. At three months, 42 (38.9% considering all 108 patients that started CBD) reported at least a 50% reduction in seizures, including 28 patients (25.9%) with a 50-74% reduction, and 14 (13%) with a reduction of 75-99%. Among those 48 patients experiencing tonic-clonic seizures (TCS), at least 50% response was reported by 45.8%, and eight (16.7%) patients were free of TCS. Sex, age, epilepsy syndrome, concomitant clobazam (CLB) use, and the number of concomitant or previous ASMs were not predictive of response. Mean seizure days per month significantly decreased from a mean of 16.8 (median: 13.5) to 14.5 (median 10, p = 0.002). The probability of patients remaining on CBD treatment was 85.2% (n = 92/108, 16 discontinuations) at three months, 73.5% at six months and 61.1% at twelve months; retention was better in children or adolescents compared to adults (log-rank p = 0.014). Using the CGI-C for overall impression, 69 (63.0%) patients were rated as very much, much, or minimally improved; for behaviour, 60 (55.6%) reported within this range of improvement. TEAEs were reported in 41 (38%) patients. The most frequent were diarrhoea (n = 15), sedation (n = 13), and nausea and vomiting (n = 7).
Our results suggest CBD to be an effective ASM, with 50% responder rates similar to those observed in regulatory trials for other ASMs licensed in focal epilepsies. Its off-label use in refractory focal-onset, genetic generalised, and other unclassified epilepsies seems to be safe and well-tolerated.
在随机对照试验中，添加大麻二酚（CBD）已被证明可降低伦诺克斯 - 加斯托综合征、德雷维特综合征和结节性硬化症患者的癫痫发作频率。真实世界研究为该药物在其他未获批适应症方面的情况提供了见解。本研究评估了预测难治性局灶性发作、遗传性全身性和其他未分类癫痫患者在临床实践中使用添加型CBD进行非标签治疗的疗效、持续性和耐受性的因素。
一项回顾性队列研究，纳入了2019年至2023年间在六个德国癫痫中心开始使用CBD进行非标签治疗的所有患者。基线和随访数据来自患者的病历。
共有108例患者（平均年龄27.3岁；中位数36岁；范围1.4 - 68岁，男性56例）接受了CBD治疗。三个月时，42例（考虑所有开始使用CBD的108例患者，占38.9%）报告癫痫发作至少减少50%，其中28例（25.9%）减少50 - 74%，14例（13%）减少75 - 99%。在48例经历强直 - 阵挛发作（TCS）的患者中，45.8%报告至少有50%的反应，8例（16.7%）患者无TCS发作。性别、年龄、癫痫综合征、同时使用氯巴占（CLB）以及同时或既往使用抗癫痫药物（ASM）的数量均不能预测反应情况。每月平均癫痫发作天数从平均16.8天（中位数：13.5天）显著降至14.5天（中位数10天，p = 0.002）。三个月时继续使用CBD治疗的患者概率为85.2%（n = 92/108，16例停药），六个月时为73.5%，十二个月时为61.1%；儿童或青少年的持续性优于成年人（对数秩检验p = 0.014）。使用临床总体印象量表（CGI - C）进行总体评估，69例（63.0%）患者被评为改善非常明显、明显或略有改善；对于行为方面，60例（55.6%）报告在该改善范围内。41例（38%）患者报告了治疗中出现的不良反应（TEAE）。最常见的是腹泻（n = 15）、镇静（n = 13）以及恶心和呕吐（n = 7）。
我们的结果表明CBD是一种有效的抗癫痫药物，50%的反应率与在局灶性癫痫中获批的其他抗癫痫药物的监管试验中观察到的相似。其在难治性局灶性发作、遗传性全身性和其他未分类癫痫中的非标签使用似乎是安全且耐受性良好的。
