Treatment for essential tremor: a systematic review and Bayesian Model-based Network Meta-analysis of RCTs

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).