Efficacy and safety of tonic motor activation (TOMAC) for restless legs syndrome as adjunctive and monotherapy: An individual participant data systematic review and meta-analysis

Abstract

Introduction: Tonic motor activation (TOMAC) is a non-pharmacological treatment for moderate-to-severe medication-refractory Restless Legs Syndrome (RLS). This bilateral wearable device applies high-frequency electrical stimulation to the peroneal nerve, engaging the therapeutic mechanism while minimizing sleep discomfort. A recent meta-analysis evaluated TOMAC in RLS using aggregate data, which precluded subgroup analyses. The aim of our systematic review and meta-analysis was to extract individual participant data to enable the evaluation of TOMAC as adjunctive treatment and monotherapy in RLS.

Methods: This study was registered on PROSPERO (CRD420251005571). Web of Science, Scopus, and PubMed were searched, from inception to March 31, 2025, to identify studies evaluating TOMAC for RLS. Risk of bias (Cochrane Risk of Bias Tool and Downs and Black checklist) and quality of evidence (Oxford Centre for Evidence-Based Medicine 2011 guidelines) of eligible studies were assessed. Primary outcomes were changes in International RLS Study Group Rating Scale (IRLS) score for efficacy and in Medical Outcomes Study Sleep Problem Index II (MOS-II) score for sleep improvement. Main safety outcome was the incidence of device-related adverse events. Subgroup analyses evaluated TOMAC as adjunctive therapy and as monotherapy, as well as by age, RLS age-of-onset, sex, RLS severity, and stimulation amplitude.

Results: Five studies from the United States were extracted including three randomized-controlled-trials with 252 participants for analyses (69 monotherapy/183 adjunctive TOMAC therapy). Relative to sham, TOMAC significantly reduced IRLS score both as adjunctive therapy (MD: 3.39, p = 0.0001) and monotherapy (mean difference [MD]: 3.80, p = 0.0047), and significantly reduced MOS-II score both as adjunctive therapy (MD: 8.23, p = 0.0006) and monotherapy (MD: 9.65, p = 0.0236). There were no significant differences in IRLS MD based on age, age of RLS onset, sex, RLS severity, and stimulation amplitude. Mild discomfort was the only adverse event with higher prevalence for TOMAC than sham.

Conclusion: These results suggest that TOMAC is a tolerable non-pharmacological treatment that reduces RLS symptoms and improves sleep, both as adjunctive therapy and as monotherapy.

Keywords: Meta-analysis; Neuromodulation; Neurostimulation; Restless legs syndrome; Tonic motor activation.