Objective: We aimed to evaluate the efficacy of non-invasive peripheral nerve stimulation (PNS) in reducing clinician-rated tremor severity in essential tremor, assess its effects on patient-reported functional ability and global improvement, and characterize its safety and tolerability

Background: Essential tremor (ET) is a common movement disorder with limited effective and well-tolerated treatment options. First-line pharmacotherapies often provide incomplete relief and are poorly tolerated, while invasive neurosurgical interventions are reserved for severe, refractory cases. Wrist-worn non-invasive peripheral nerve stimulation (PNS) has emerged as a novel neuromodulation approach targeting tremor-related neural circuits, but its clinical efficacy remains uncertain.

Method: We systematically searched PubMed, Cochrane Library, Scopus, and Web of Science from inception to 2025 for randomized controlled trials comparing wrist-worn non-invasive PNS with sham or standard care in adults with ET. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Cochrane RoB 2 tool. Primary outcomes were clinician-rated tremor severity measured by the TETRAS Performance Subscale and activities of daily living (ADL). Secondary outcomes included Clinical Global Impression–Improvement (CGI-I). Random-effects meta-analysis was performed, and certainty of evidence was evaluated using GRADE.

Results: Four RCTs including 616 participants were analyzed. PNS significantly improved clinician-rated tremor severity versus control (three studies, n = 263; SMD 0.28, 95% CI 0.10 to 0.46; I² = 0%; moderate-certainty evidence). ADL scores also improved (four studies, n = 397; SMD 0.52, 95% CI 0.06 to 0.98; I² = 44.9%; low-certainty evidence). CGI-I responder rates did not differ significantly (two studies, n = 175; RR 1.46, 95% CI 0.79 to 2.69; high-certainty evidence). PNS was well tolerated, with skin irritation as the most common adverse event. Overall effects were small to moderate and consistent across trials.

Conclusion: Wrist-worn non-invasive PNS provides modest but consistent improvements in tremor severity and daily function in ET, with a favorable safety profile. These findings support PNS as a potential adjunctive therapy and highlight the need for larger, long-term trials to establish sustained clinical benefit.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/comparative-efficacy-of-wrist-worn-non-invasive-peripheral-nerve-stimulation-for-essential-tremor-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials/