Sci Rep. 2025 Aug 6;15(1):28713. doi: 10.1038/s41598-025-13487-1.ABSTRACTPeripheral nerve stimulation (PNS) demonstrates promise for some neurological conditions. However, its effectiveness for essential tremor (ET) requires further research. In this randomized, double-blind, sham-controlled trial, we investigated the safety and efficacy of a single, 40-minute PNS session in ET. Eighty-eight participants (age: 63.5 [52.5, 70.3], male: 57.95%) were assigned to active PNS stimulation (n = 45) or sham procedure (n = 43). Efficacy was assessed using accelerometer-measured tremor amplitude (m/s²), clinician-rated tremor severity using the Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS), patients' own experience with daily activities using the Bain and Findley Activities of Daily Living scale (BF-ADL), and their perceived improvement based on the Clinical Global Impression-Improvement scale (CGI-I). Assessments were conducted at baseline, immediately post-stimulation, and at multiple intervals up to 90 min (extending to 24 h for subjective outcomes). Temporal changes in outcomes over time were evaluated using the Generalized Estimating Equation (GEE). The effects of group, time, and their interaction (group*time) on the outcomes were subsequently assessed using GEE. GEE analyses revealed significant group*time interaction for tremor amplitude (B = - 51.61, 95%CI [- 94.60, - 8.62], p = 0.019). However, no significant group*time interactions were observed for TETRAS, BF-ADL, and CGI-I. This study indicated the effect of PNS on reducing ET amplitude. ID: IRCT20161212031362N2.PMID:40770217 | DOI:10.1038/s41598-025-13487-1