Medical Policy

Policy Num:      02.007.013
Policy Name:    Tonic Motor Activation for Restless Legs Syndrome
Policy ID           [02.007.013]  [Ac / B / M- / P-]  [1.01.32]

Last Review:    November 04, 2025
Next Review:    November 20, 2026
 

Related Policies:

01.001.020 -  Transcutaneous Electrical Nerve Stimulation and Transcutaneous Afferent Patterned Stimulation

01.001.031 -  Implantable Peripheral Nerve Stimulation for Chronic Pain Conditions

07.001.118 - Percutaneous Electrical Nerve Stimulation, Percutaneous Neuromodulation Therapy, and Restorative Neurostimulation Therapy

Tonic Motor Activation for Restless Legs Syndrome 

Summary

Description

Tonic motor activation (TOMAC) is a peroneal nerve stimulation device that uses electrodes worn on the lower legs to deliver bilateral high-frequency electrical stimulation to the common peroneal nerves located near the fibula in the lower legs. This stimulation is proposed to activate the tibialis anterior muscle, producing sustained, low-level muscle contractions that mimic the effects of voluntary leg movements like walking or stretching, which are activities known to relieve restless legs syndrome RLS symptoms.

Summary of Evidence

For individuals with restless legs syndrome (RLS) who are refractory to medication who receive tonic motor activation (TOMAC), the evidence includes randomized controlled trials (RCTs), nonrandomized studies, and a systematic review and meta-analysis. Relevant outcomes are changes in symptoms, functional outcomes, quality of life, and medication use. The pivotal RCT showed a higher Clinical Global Impression of Improvement (CGI-I) responder rate in the TOMAC group compared to the control group (45% vs. 16%; difference: 28%). They also showed greater reductions in International RLS Study Group Rating Scale (IRLS) scores in the TOMAC group compared to the sham group (-7.2 vs. -3.8). The meta-analysis, which includes the RCT results comparing TOMAC to sham controls, showed significantly reduced IRLS scores (mean difference: -3.66), improved Patient Global Impression of Improvement (PGI-I) response (risk ratio: 3.16), and enhanced sleep quality (MOS-I mean difference: -9.28; MOS-II mean difference: -10.06). Across studies, adverse events were mild with no serious device-related events reported. Limitations included underpowered sample sizes, short study durations, potential loss of blinding due to perceived treatment, a lack of long-term randomized data, and risk of bias from patient-reported outcomes. Sufficiently powered RCTs, with long-term follow-up to investigate safety and durability, are needed to further evaluate the net health outcomes. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Additional Information

Not applicable.

Objective

The objective of this evidence review is to determine whether the use of tonic motor activation improves the net health outcome in individuals with restless legs syndrome who are refractory to medication

Policy Statement

Tonic motor activation as a treatment for restless legs syndrome refractory to medication is considered investigational.

Policy Guidelines

Coding

See the Codes table for details.

Benefit Application

BlueCard/National Account Issues

State or federal mandates (eg, Federal Employee Program) may dictate that certain U.S. Food and Drug Administration‒approved devices, drugs, or biologics may not be considered investigational, and thus these devices may be assessed only by their medical necessity.

Benefits are determined by the group contract, member benefit booklet, and/or individual subscriber certificate in effect at the time services were rendered.  Benefit products or negotiated coverages may have all or some of the services discussed in this medical policy excluded from their coverage.

Background

Restless Legs Syndrome

Restless legs syndrome (RLS) is a neurological condition characterized by an uncontrollable urge to move the legs, often accompanied by uncomfortable sensations. These symptoms typically worsen during periods of rest or inactivity, especially in the evening or at night, and are temporarily relieved by movement. RLS is frequently associated with sleep disturbances and periodic limb movements during sleep (PLMS), which can further impair rest and daytime functioning. When PLMS occurs without RLS or other related disorders, it is classified as periodic limb movement disorder (PLMD). Treatment for RLS generally involves pharmacologic therapy, with options including alpha-2-delta calcium channel ligands, dopaminergic agents, opioids, and benzodiazepines. Therapy is tailored based on symptom severity, patient age, comorbidities, and individual preferences, aiming to improve sleep quality and overall life functioning. Dopaminergic therapies have a known risk of augmentation.

For individuals with refractory RLS, where symptoms persist despite first-line treatments like gabapentinoids, alternative strategies are considered. These include combination pharmacotherapy using different drug classes, low-dose opioids, and a thorough review of iron levels, potential exacerbating substances, behavioral interventions, and bilateral peroneal nerve stimulation.

Tonic Motor Activation

Tonic motor activation (TOMAC), also known as bilateral peroneal nerve stimulation, is proposed to work by delivering bilateral high-frequency electrical stimulation to the common peroneal nerves located near the fibula in the lower legs. This stimulation activates the tibialis anterior muscle, producing sustained, low-level muscle contractions that mimic the effects of voluntary leg movements like walking or stretching, which are activities known to relieve RLS symptoms.

The proposed biological mechanism involves afferent feedback.^1, The stimulation sends signals back to the central nervous system, which may help suppress the abnormal sensory signals that drive the urge to move the legs. By activating the same circuits used during natural movement, TOMAC may modulate spinal and supraspinal pathways involved in RLS pathophysiology.

TOMAC differs from transcutaneous electrical nerve stimulation (TENS) devices. TOMAC targets the common peroneal nerve with a goal of tonic activation of motor pathways to mimic movement with high-frequency, sustained, bilateral stimulation. TENS targets superficial sensory nerves often with the goal of pain relief by administering pulsed, often intermittent, stimulation.

Clinical Pathway

TOMAC is not a first-line therapy for RLS. It is indicated for moderate-to-severe primary RLS that is refractory to pharmacologic treatment. First-line therapies include, iron supplementation, gabapentinoids, lifestyle modifications (eg, regular moderate exercise, sleep habits, etc.).

Regulatory Status

The NTX100 Tonic Motor Activation (TOMAC) System (Noctrix Health, Inc; Pleasanton, CA) received De Novo classification (DEN220059; Product Code: QWD) from the FDA for its intended use "to reduce symptoms of primary moderate-severe Restless Legs Syndrome (RLS) and to improve sleep quality in adults refractory to medication."^2,

Rationale

This evidence review was created in August 2025 with a search of the PubMed database. The most recent literature update was performed through August 20, 2025.

Evidence reviews assess the clinical evidence to determine whether the use of a technology improves the net health outcome. Broadly defined, health outcomes are length of life, quality of life, and ability to function including benefits and harms. Every clinical condition has specific outcomes that are important to patients and to managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of a technology, 2 domains are examined: the relevance and the quality and credibility. To be relevant, studies must represent one or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. Randomized controlled trials are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

Population Reference No. 1

Tonic Motor Activation in Individuals with Restless Legs Syndrome Refractory to Medication

Clinical Context and Therapy Purpose

The purpose of tonic motor activation (TOMAC) in individuals who have restless legs syndrome (RLS) is to provide a treatment option for those who are refractory to medication.

The following PICO was used to select literature to inform this review.

Populations

The relevant population of interest are individuals with RLS who are refractory to medication.

Interventions

The therapy being considered is TOMAC. TOMAC, also known as bilateral peroneal nerve stimulation, is proposed to work by delivering bilateral high-frequency electrical stimulation to the common peroneal nerves located near the fibula in the lower legs. This stimulation activates the tibialis anterior muscle, producing sustained, low-level muscle contractions that mimic the effects of voluntary leg movements like walking or stretching, which are activities known to relieve RLS symptoms.

Comparators

The following therapies are currently being used to treat RLS: iron supplementation, gabapentinoids, and lifestyle modifications (eg, exercise, sleep hygiene, cognitive behavioral therapy, etc.).

Outcomes

The general outcomes of interest are symptom relief, functional outcomes, quality of life, and medication use. Relevant health outcome measures are summarized in Table 1.

Follow-up of at least 6 months is recommended to monitor outcomes.^3,

Table 1. Health Outcome Measures Relevant to Restless Legs Syndrome

  CGI-I: Clinician Global Impression of Improvement; IRLS: International Restless Legs Syndrome Score; MOS: Medical Outcomes Study; PGI-I: Patient Global Impression of Improvement; RLS: restless legs syndrome.

Study Selection Criteria

Methodologically credible studies were selected using the following principles:

• To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;

• In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.

• To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.

• Consistent with a 'best available evidence approach,' within each category of study design, studies with larger sample sizes and longer durations were sought.

• Studies with duplicative or overlapping populations were excluded.

Review of Evidence

Randomized Controlled Trials

The pivotal trial, published by Bogan et al (2023), was a multicenter, randomized, double-blind, sham-controlled clinical trial (RESTFUL Study) evaluating the efficacy and safety of TOMAC for treating medication-refractory RLS (N=133).^7, Adults with moderate-to-severe primary RLS unresponsive to standard medications were randomized 1:1 to receive either active TOMAC or sham treatment for 4 weeks (stage 1), followed by 4 weeks of open-label active TOMAC for all participants (stage 2). The primary endpoint, the Clinical Global Impression of Improvement (CGI-I) responder rate, was significantly higher in the TOMAC group compared to the sham group (45% vs. 16%; difference: 28%; 95% CI: 14% to 43%; p=.00011). Secondary endpoints showed greater reductions in International RLS Study Group Rating Scale (IRLS) scores in the TOMAC group compared to the sham group (-7.2 vs. -3.8; p=.00093). No serious device-related adverse events occurred. Mild discomfort and site irritation were the most common side effects, both resolving quickly and decreasing over time. Limitations included some loss of blinding due to perceived treatment, short study duration, and lack of medication washout.

Singh et al (2024) conducted a multicenter, randomized, participant-blinded, sham-controlled clinical trial evaluating the efficacy and safety of TOMAC for treating moderate-to-severe RLS in both medication-naïve and medication-refractory adults (N=45).^8, Participants were randomized 1:1 to receive either TOMAC or sham treatment over two weeks, with self-administered 30-minute sessions during symptomatic periods. The primary outcome was the change in IRLS score, and secondary outcomes included the Patient Global Impression of Improvement (PGI-I) and sleep quality indices (MOS-I and MOS-II). TOMAC significantly reduced IRLS scores compared to sham (-6.59 vs. -2.17; p=.004) (mean difference = 4.42; 95% CI: 1.57 to 7.26; p=.0040), with similar effect sizes in both medication-naïve and refractory subgroups. PGI-I responder rates were notably higher in the TOMAC group (36% vs. 4%; p=.0073). The device was well tolerated, with no serious adverse events; mild discomfort and site irritation were the most common issues. Limitations included the short treatment duration and underpowered sample.

Buchfuhrer et al (2021) conducted a randomized, participant-blinded, crossover trial investigating the efficacy and safety of TOMAC as a treatment for moderate-to-severe RLS (N=43).^9, Participants self-administered both TOMAC and sham treatments nightly for 14 days each, in randomized order. The TOMAC device delivered 30-minute electrical stimulation sessions to the common peroneal nerve via wearable units. The primary outcome was change in the IRLS, with secondary outcomes including the CGI-I scale and numerical rating scales (NRS) for symptom severity. TOMAC significantly reduced IRLS scores by 6.81 points versus 3.38 for sham (p<.01), and yielded a 66% CGI-I responder rate compared to 17% for sham (p<.01). No moderate or serious device-related adverse events were reported; mild events included transient discomfort and skin irritation. Limitations included potential unblinding due to paresthesia, short treatment duration, and underpowered sample.

A summary of study characteristics and key results are presented in Tables 2 and 3. Study relevance and design and conduct limitations are summarized in Table 4 and 5.

Table 2. Summary of Key Randomized Controlled Trials Characteristics

  IRLS: International Restless Legs Syndrome Score; NR: not reported; RLS: restless legs syndrome; TOMAC: tonic motor activation.

Table 3. Summary of Key Randomized Controlled Trials Results

  CGI-I: Clinician Global Impression of Improvement; IRLS: International Restless Legs Syndrome Score; PGI-I: Patient Global Impression of Improvement.

Table 4. Study Relevance Limitations

  The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.  a Population key: 1. Intended use population unclear; 2. Study population is unclear; 3. Study population not representative of intended use; 4, Enrolled populations do not reflect relevant diversity; 5. Other. b Intervention key: 1. Not clearly defined; 2. Version used unclear; 3. Delivery not similar intensity as comparator; 4. Not the intervention of interest (e.g., proposed as an adjunct but not tested as such); 5: Other. c Comparator key: 1. Not clearly defined; 2. Not standard or optimal; 3. Delivery not similar intensity as intervention; 4. Not delivered effectively; 5. Other. d Outcomes key: 1. Key health outcomes not addressed; 2. Physiologic measures, not validated surrogates; 3. Incomplete reporting of harms; 4. Not establish and validated measurements; 5. Clinically significant difference not prespecified; 6. Clinically significant difference not supported; 7. Other. e Follow-Up key: 1. Not sufficient duration for benefit; 2. Not sufficient duration for harms; 3. Other.

Table 5. Study Design and Conduct Limitations

  CGI-I: Clinician Global Impression of Improvement; ITT: intent to treat. The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment. a Allocation key: 1. Participants not randomly allocated; 2. Allocation not concealed; 3. Allocation concealment unclear; 4. Inadequate control for selection bias; 5. Other. b Blinding key: 1. Participants or study staff not blinded; 2. Outcome assessors not blinded; 3. Outcome assessed by treating physician; 4. Other. c Selective Reporting key: 1. Not registered; 2. Evidence of selective reporting; 3. Evidence of selective publication; 4. Other. d Data Completeness key: 1. High loss to follow-up or missing data; 2. Inadequate handling of missing data; 3. High number of crossovers; 4. Inadequate handling of crossovers; 5. Inappropriate exclusions; 6. Not intent to treat analysis (per protocol for noninferiority trials); 7. Other. e Power key: 1. Power calculations not reported; 2. Power not calculated for primary outcome; 3. Power not based on clinically important difference; 4. Other. f Statistical key: 1. Analysis is not appropriate for outcome type: (a) continuous; (b) binary; (c) time to event; 2. Analysis is not appropriate for multiple observations per patient; 3. Confidence intervals and/or p values not reported; 4. Comparative treatment effects not calculated; 5. Other.

Nonrandomized Studies

Roy et al (2023) reported results of the 24-week open-label extension of the RESTFUL study evaluating the long-term efficacy and safety of TOMAC in adults with medication-refractory moderate-to-severe primary RLS.^10, Among 44 participants receiving TOMAC, 72.7% were CGI-I responders and 75.0% were PGI-I responders at week 24, with a mean IRLS score reduction of -11.3 points (95% CI: -8.8 to -13.9; p<.0001) compared to baseline. Sleep quality improved significantly (MOS-II: -17.2; MOS-I: -15.8; both p<.0001), and symptom frequency decreased by 46%, from 5.9 to 3.2 days/week. Compared to 59 control participants receiving standard care, TOMAC produced significantly greater improvements across all endpoints (CGI-I: 72.7% vs. 13.6%, p<.0001; IRLS: -11.3 vs. -5.4, p=.0001). Benefits partially persisted after 8 weeks of treatment cessation without rebound above baseline. Safety showed no grade ≥2 device-related adverse events and only mild, transient discomfort in 6.8% of participants. Limitations included non-randomized control assignment, open-label design, and use of patient-reported outcomes.

Buchfuhrer et al (2023) conducted a prospective, open-label, single-arm clinical trial evaluating whether TOMAC could enable opioid dose reduction in patients with refractory RLS.^11, Twenty adults on ≤60 morphine milligram equivalents (MME)/day were enrolled, having failed an average of 3.2 prior RLS medications and maintained stable opioid therapy for an average of 5.3 years. Participants self-administered 30-minute TOMAC sessions bilaterally over the peroneal nerve during symptom onset. Opioid doses were tapered every 2–3 weeks until the CGI-I score exceeded 5. The primary endpoint, ≥20% opioid dose reduction with CGI-I ≤5, was achieved by 70% of participants (14/20), exceeding the prespecified 50% success criterion. The mean opioid dose reduction was 29.9% (SD 23.7%), from 39.0 to 26.8 MME/day. Of 15 participants who had any successful opioid dose reduction the average CGI-I score at the reduced dose was 4.0 (95% CI: 3.3 to 4.7) and the average change in IRLS score from baseline at the reduced dose was 3.4 (95% CI: 0.4 to 6.4). Adherence to TOMAC was 85%, and all adverse events were mild and non-serious. Limitations included the underpowered sample, lack of a control group, short study duration, and open-label design, which may introduce bias.

A summary of study characteristics and key results are presented in Tables 6 and 7.

Table 6. Summary of Key Nonrandomized Study Characteristics

  RLS: restless legs syndrome; TOMAC: tonic motor activation.

Table 7. Summary of Key Nonrandomized Study Results

  aOutomes reported at maximum reduced dose. bOutcomes reported for participants with any successful opioid reduction. CGI-I: Clinician Global Impression of Improvement; CI: confidence interval; IRLS: International Restless Legs Syndrome Score; NR: not reported.

Systematic Reviews and Meta-Analyses

Two systematic reviews and meta-analyses have been published evaluating the efficacy and safety of TOMAC for RLS.^12,13, Winkleman et al (2025) only included 2 of the available RCTs and will not be further discussed in this review.

Mohamed et al (2025) conducted a systematic review and meta-analysis evaluating the efficacy and safety of TOMAC for moderate-to-severe RLS.^12, Three RCTs and an open-label extension study (N=320) were included, with primary outcomes being changes in International IRLS scores, PGI-I responder rates, and sleep quality indices (MOS-I, MOS-II). TOMAC significantly reduced IRLS scores compared to sham (mean difference [MD]: -3.66; 95% CI: -5.07 to -2.25; p<.00001), improved PGI-I response (risk ratio [RR]: 3.16; 95% CI: 1.35 to 7.37; p=.008), and enhanced sleep quality (MOS-I MD: -9.28; p <.00001; MOS-II MD: -10.06; p <.00001). Adverse events were more frequent with TOMAC (RR: 1.68; p=.004) but were mild and self-limiting, with no severe or device-related discontinuations. Limitations include the small number of RCTs with underpowered samples sizes, inclusion of medication-naive individuals in the overall analysis, short follow-up durations, and limited data on long-term safety.

An overview of included trials and characteristics of the systematic review and meta-analysis are summarized in Tables 8 and 9. Results of the systematic review and meta-analysis are summarized in Table 10.

Table 8. Comparison of Trials Included in Systematic Reviews and Meta-Analyses

Table 9. Systematic Reviews and Meta-Analyses Characteristics

  RCT: randomized controlled trial; RLS: restless legs syndrome.  

Table 10. Systematic Reviews and Meta-Analyses Results

  AE: adverse event; CGI-I: Clinician Global Impression of Improvement; IRLS: International Restless Legs Syndrome Score; MOS: Medical Outcomes Study; PGI-I: Patient Global Impression of Improvement; RLS: restless legs syndrome.

Section Summary: Tonic Motor Activation in Individuals with Restless Legs Syndrome Refractory to Medication

The evidence includes randomized controlled trials (RCTs), nonrandomized studies, and a systematic review and meta-analysis. Relevant outcomes are changes in symptoms, functional outcomes, quality of life, and medication use. The pivotal RCT showed a higher Clinical Global Impression of Improvement (CGI-I) responder rate in the TOMAC group compared to the control group (45% vs. 16%; difference: 28%). They also showed greater reductions in International RLS Study Group Rating Scale (IRLS) scores in the TOMAC group compared to the sham group (-7.2 vs. -3.8). The meta-analysis, which includes the RCT results comparing TOMAC to sham controls, showed significantly reduced IRLS scores (mean difference: -3.66), improved Patient Global Impression of Improvement (PGI-I) response (risk ratio: 3.16), and enhanced sleep quality (MOS-I mean difference: -9.28; MOS-II mean difference: -10.06). Across studies, adverse events were mild with no serious device-related events reported. Limitations included underpowered sample sizes, short study durations, potential loss of blinding due to perceived treatment, a lack of long-term randomized data, and risk of bias from patient-reported outcomes. Sufficiently powered RCTs, with long-term follow-up to investigate safety and durability, are needed to further evaluate the net health outcomes.

For individuals with restless legs syndrome (RLS) who are refractory to medication who receive tonic motor activation (TOMAC), the evidence includes randomized controlled trials (RCTs), nonrandomized studies, and a systematic review and meta-analysis. Relevant outcomes are changes in symptoms, functional outcomes, quality of life, and medication use. The pivotal RCT showed a higher Clinical Global Impression of Improvement (CGI-I) responder rate in the TOMAC group compared to the control group (45% vs. 16%; difference: 28%). They also showed greater reductions in International RLS Study Group Rating Scale (IRLS) scores in the TOMAC group compared to the sham group (-7.2 vs. -3.8). The meta-analysis, which includes the RCT results comparing TOMAC to sham controls, showed significantly reduced IRLS scores (mean difference: -3.66), improved Patient Global Impression of Improvement (PGI-I) response (risk ratio: 3.16), and enhanced sleep quality (MOS-I mean difference: -9.28; MOS-II mean difference: -10.06). Across studies, adverse events were mild with no serious device-related events reported. Limitations included underpowered sample sizes, short study durations, potential loss of blinding due to perceived treatment, a lack of long-term randomized data, and risk of bias from patient-reported outcomes. Sufficiently powered RCTs, with long-term follow-up to investigate safety and durability, are needed to further evaluate the net health outcomes. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Suplemental Information

The purpose of the following information is to provide reference material. Inclusion does not imply endorsement or alignment with the evidence review conclusions.

Practice Guidelines and Position Statements

Guidelines or position statements will be considered for inclusion in 'Supplemental Information' if they were issued by, or jointly by, a US professional society, an international society with US representation, or National Institute for Health and Care Excellence (NICE). Priority will be given to guidelines that are informed by a systematic review, include strength of evidence ratings, and include a description of management of conflict of interest.

American Academy of Sleep Medicine

In 2025, the American Academy of Sleep Medicine (AASM) published clinical practice guidelines on the treatment of RLS and periodic limb movement disorder.^14, The AASM gave a conditional recommendation with moderate certainty of evidence for the use of bilateral high-frequency peroneal nerve stimulation over no peroneal nerve stimulation in adults with RLS.

U.S. Preventive Services Task Force Recommendations

Not applicable.

Medicare National Coverage

There is no national coverage determination. In the absence of a national coverage determination, coverage decisions are left to the discretion of local Medicare carriers.

Ongoing and Unpublished Clinical Trials

Some trials that might influence this review are listed in Table 11.

Table 11. Summary of Key Trials

  NCT: national clinical trial. a Denotes industry-sponsored or cosponsored trial.

References

1. Charlesworth JD, Adlou B, Singh H, et al. Bilateral high-frequency noninvasive peroneal nerve stimulation evokes tonic leg muscle activation for sleep-compatible reduction of restless legs syndrome symptoms. J Clin Sleep Med. Jul 01 2023; 19(7): 1199-1209. PMID 36856064
2. Food & Drug Administration. 2023. De Novo Classification Request For NTX100 Tonic Motor Activation (NTX100 TOMAC) System. Decision Summary. https://www.accessdata.fda.gov/cdrh_docs/reviews/DEN220059.pdf. Accessed September 24, 2025.
3. Wilt TJ, MacDonald R, Ouellette J, et al. Treatment for Restless Legs Syndrome [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2012 Nov. (Comparative Effectiveness Reviews, No. 86.) Table D, Future research recommendations. Available from: https://www.ncbi.nlm.nih.gov/books/NBK115378/table/executivesummary.t4/. Accessed September 24, 2025.
4. Ondo WG, Grieger F, Moran K, et al. Post Hoc Analysis of Data from Two Clinical Trials Evaluating the Minimal Clinically Important Change in International Restless Legs Syndrome Sum Score in Patients with Restless Legs Syndrome (Willis-Ekbom Disease). J Clin Sleep Med. Jan 2016; 12(1): 63-70. PMID 26446245
5. Allen R, Oertel W, Walters A, et al. Relation of the International Restless Legs Syndrome Study Group rating scale with the Clinical Global Impression severity scale, the restless legs syndrome 6-item questionnaire, and the restless legs syndrome-quality of life questionnaire. Sleep Med. Dec 2013; 14(12): 1375-80. PMID 24246378
6. Allen RP, Kosinski M, Hill-Zabala CE, et al. Psychometric evaluation and tests of validity of the Medical Outcomes Study 12-item Sleep Scale (MOS sleep). Sleep Med. May 2009; 10(5): 531-9. PMID 18805054
7. Bogan RK, Roy A, Kram J, et al. Efficacy and safety of tonic motor activation (TOMAC) for medication-refractory restless legs syndrome: a randomized clinical trial. Sleep. Oct 11 2023; 46(10). PMID 37458698
8. Singh H, Baker FC, Ojile J, et al. Efficacy and safety of TOMAC for treatment of medication-naïve and medication-refractory restless legs syndrome: A randomized clinical trial and meta-analysis. Sleep Med. Oct 2024; 122: 141-148. PMID 39173210
9. Buchfuhrer MJ, Baker FC, Singh H, et al. Noninvasive neuromodulation reduces symptoms of restless legs syndrome. J Clin Sleep Med. Aug 01 2021; 17(8): 1685-1694. PMID 33949942
10. Roy A, Ojile J, Kram J, et al. Long-term efficacy and safety of tonic motor activation for treatment of medication-refractory restless legs syndrome: A 24-Week Open-Label Extension Study. Sleep. Oct 11 2023; 46(10). PMID 37439365
11. Buchfuhrer MJ, Roy A, Rodriguez S, et al. Adjunctive tonic motor activation enables opioid reduction for refractory restless legs syndrome: a prospective, open-label, single-arm clinical trial. BMC Neurol. Nov 21 2023; 23(1): 415. PMID 37990163
12. Mohamed RG, Sarhan K, Hegazi A, et al. Efficacy and safety of tonic motor activation for the treatment of restless legs syndrome: A meta-analysis of randomized controlled trials. Sleep Med. Aug 2025; 132: 106580. PMID 40381601
13. Winkelman JW, Berkowski JA, DelRosso LM, et al. Treatment of restless legs syndrome and periodic limb movement disorder: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med. Jan 01 2025; 21(1): 153-199. PMID 39324664
14. Winkelman JW, Berkowski JA, DelRosso LM, et al. Treatment of restless legs syndrome and periodic limb movement disorder: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. Jan 01 2025; 21(1): 137-152. PMID 39324694

Codes

Policy History