Zhang Junjiao, Yan Rui, Cui Yusha, Su Dongning, Feng Tao
Center for movement disorders, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
China National Clinical Research Center for Neurological Diseases, Beijing, China.
EClinicalMedicine. 2024 Oct 18;77:102889. doi: 10.1016/j.eclinm.2024.102889. eCollection 2024 Nov.
Essential tremor (ET) significantly impacts patients' daily lives and quality of life, presenting a considerable challenge in clinical practice. In recent years, novel therapeutic regimens have been investigated in randomized controlled trials (RCTs). This study aims to investigate and evaluate the relative efficacy and safety of various therapeutic interventions for ET.
We did a systematic review and Bayesian Model-based Network Meta-analysis (NMA) of RCTs. Following PRISMA-NMA guidelines, a comprehensive database search was conducted up to April 1, 2024 to identify RCTs focused on ET treatments. The Bayesian Markov Chain Monte Carlo (MCMC) method was utilized for the analysis, evaluating the relative efficacy and safety of treatments using standardized mean difference (SMD) and log odds ratios (log ORs), respectively. Additionally, the Surface Under the Cumulative Ranking Curve (SUCRA) was applied to assess the relative efficacy of the treatment modalities. PROSPERO registration: CRD42023415752.
This study included 33 RCTs involving 1251 patients, covering 19 oral medication treatments and six non-oral medication treatments. NMA showed that deep brain stimulation (DBS) (SMD = -4.93; 95% CI: [-7.73, -2.13]), CX-8998 (SMD = -2.69; 95% CI: [-5.26, -0.14]), atenolol (SMD = -2.36; 95% CI: [-4.70, -0.10]), and propranolol (SMD = -1.59; 95% CI: [-2.25, -0.67]) showed relative efficacy compared to placebo, with DBS demonstrating relative efficacy compared to 15 other treatment methods. However, GRADE assessment indicated that the evidence level for these conclusions was "low" or "very low." According to SUCRA rankings, DBS (0.97) ranked first in relative efficacy, followed by CX-8998 (0.80), thalamotomy (0.79), atenolol (0.76), metoprolol (0.66), propranolol (0.64), magnetic resonance guided focus ultrasound (MR-FUS) (0.624), ICI-118551 (0.620), nimodipine (0.61) and phenobarbitone (0.59). In terms of safety, as a network graph could not be constructed, DBS and thalamotomy were excluded from the NMA, while other effective treatments showed no significant differences in safety compared to placebo.
Our study results indicate that CX-8998, propranolol, and atenolol demonstrate relative efficacy and safety in treating ET. DBS is effective for medication-resistant ET and ranks first in relative efficacy, though our NMA lacks safety data for DBS. Given the low overall grade of evidence, these results should be applied cautiously in clinical practice. Further large-scale, head-to-head RCTs are needed.
This work was supported by grants from the National Nature Science Foundation of China (Grant No. 82271459).
特发性震颤（ET）严重影响患者的日常生活和生活质量，给临床实践带来了巨大挑战。近年来，在随机对照试验（RCT）中对新的治疗方案进行了研究。本研究旨在调查和评估ET各种治疗干预措施的相对疗效和安全性。
我们对RCT进行了系统评价和基于贝叶斯模型的网络荟萃分析（NMA）。按照PRISMA-NMA指南，截至2024年4月1日进行了全面的数据库检索，以识别聚焦于ET治疗的RCT。采用贝叶斯马尔可夫链蒙特卡罗（MCMC）方法进行分析，分别使用标准化均数差（SMD）和对数比值比（log ORs）评估治疗的相对疗效和安全性。此外，应用累积排序曲线下面积（SUCRA）评估治疗方式的相对疗效。PROSPERO注册编号：CRD42023415752。
本研究纳入了33项涉及1251例患者的RCT，涵盖19种口服药物治疗和6种非口服药物治疗。NMA显示，与安慰剂相比，脑深部电刺激（DBS）（SMD = -4.93；95%CI：[-7.73，-2.13]）、CX-8998（SMD = -2.69；95%CI：[-5.26，-0.14]）、阿替洛尔（SMD = -2.36；95%CI：[-4.70，-0.10]）和普萘洛尔（SMD = -1.59；95%CI：[-2.25，-0.67]）显示出相对疗效，与其他15种治疗方法相比，DBS显示出相对疗效。然而，GRADE评估表明这些结论的证据水平为“低”或“非常低”。根据SUCRA排名，DBS（0.97）在相对疗效方面排名第一，其次是CX-8998（0.80）、丘脑切开术（0.79）、阿替洛尔（0.76）、美托洛尔（0.66）、普萘洛尔（0.64）、磁共振引导聚焦超声（MR-FUS）（0.624）、ICI-118551（0.620）、尼莫地平（0.61）和苯巴比妥（0.59）。在安全性方面，由于无法构建网络图，DBS和丘脑切开术被排除在NMA之外，但与安慰剂相比，其他有效治疗在安全性方面无显著差异。
我们的研究结果表明，CX-8998、普萘洛尔和阿替洛尔在治疗ET方面显示出相对疗效和安全性。DBS对药物难治性ET有效，在相对疗效方面排名第一，尽管我们的NMA缺乏DBS的安全性数据。鉴于总体证据等级较低，这些结果在临床实践中应谨慎应用。需要进一步开展大规模的、直接比较的RCT。
本研究得到了中国国家自然科学基金（批准号：82271459）的资助。
