Sleep & Movement Disorders

Overview

Restless legs syndrome (RLS), also called Willis–Ekbom disease, is a neurological sensorimotor disorder that produces an urge to move the legs—usually with unpleasant sensations—when a person is resting. Movement brings at least temporary relief, and symptoms are typically worse in the evening or at night. RLS can severely disrupt sleep, concentration, mood, and quality of life even though the neurological examination may be normal.

The major treatment change in 2025–2026 is not a new pill. It is a change in strategy: check iron carefully, remove aggravating factors, and favor non-dopaminergic treatment for chronic persistent RLS. The American Academy of Sleep Medicine now strongly recommends gabapentin enacarbil, gabapentin, pregabalin, and—when iron indices and clinical circumstances support it—intravenous ferric carboxymaltose. It suggests against the standard long-term use of levodopa and dopamine agonists because of augmentation, a paradoxical medication-induced worsening of RLS.²³

• Iron thresholds in RLS are different from anemia thresholds. A ferritin result that is “normal” on a general laboratory report may still be relevant to RLS. Ferritin must be interpreted with transferrin saturation and the clinical setting.
• Gabapentinoids are preferred first-line medication for many adults with chronic persistent symptoms. They do not cause dopaminergic augmentation, although sedation, dizziness, edema, weight gain, respiratory risk, and misuse potential still require attention.
• Dopamine agonists are not forbidden. They may remain reasonable for selected patients after shared decision-making, but doses should remain low and patients must be monitored for augmentation and impulse-control problems.
• Low-dose opioids have a legitimate specialist role in severe refractory RLS, particularly during difficult withdrawal from a dopamine agonist, but they require careful screening, monitoring, and risk mitigation.⁴⁷
• A prescription nerve-stimulation system is available for selected medication-refractory adults. The NTX100 ToMAc system was authorized through FDA De Novo review in April 2023; a June 2026 final rule codified its device classification and was not a new 2026 treatment approval.⁸¹⁰

Evidence cutoff: This article reflects publicly available evidence and U.S. regulatory information through July 10, 2026. Medication and device selection must be individualized; patients taking a dopamine agonist should not stop it abruptly without a supervised taper.

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What RLS Feels Like

The five essential diagnostic features are summarized by the word URGE:

• U — Urge: an urge to move the legs, usually accompanied by uncomfortable sensations.
• R — Rest: symptoms begin or worsen during sitting or lying down.
• G — Gets better with movement: walking, stretching, or moving the legs provides partial or complete relief while the movement continues.
• E — Evening: symptoms occur mainly in the evening or night, or are worse then than during the day.
• Not explained by another condition: leg cramps, positional discomfort, arthritis, edema, neuropathy, anxiety-related restlessness, and habitual foot movement can mimic RLS.¹

Patients use many words—crawling, pulling, aching, buzzing, electric, internal itching, pressure, or simply an unbearable need to move. The sensation is usually deep rather than on the skin. Arms or other body regions may be involved in severe disease or dopaminergic augmentation.

RLS is not the same as periodic limb movements

Periodic limb movements of sleep are repetitive movements recorded during sleep. They are common in RLS but also occur in people without RLS. A sleep study is not needed to diagnose typical RLS and a high limb-movement count alone does not establish a disorder requiring treatment.

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Why RLS Happens

Brain iron and network signaling

RLS is associated with altered iron handling in the brain and with changes in dopaminergic, glutamatergic, and adenosine signaling. It is not accurately described as a simple dopamine deficiency. That distinction matters because a dopamine drug can relieve symptoms rapidly yet, with repeated exposure, make the underlying symptom pattern worse.

Genetic susceptibility

RLS often runs in families, especially when symptoms begin earlier in life. Common genetic variants influence susceptibility, but routine genetic testing is not needed for typical RLS.

Secondary and aggravating conditions

• Iron deficiency, with or without anemia; frequent blood donation; blood loss; pregnancy; or impaired absorption
• Chronic kidney disease, especially end-stage kidney disease
• Pregnancy, usually with improvement after delivery
• Peripheral neuropathy or selected spinal-cord disorders
• Untreated sleep apnea, chronic sleep deprivation, and shift work
• Alcohol, caffeine, nicotine, and medications that worsen symptoms

A new RLS-like syndrome in one leg, with marked pain, swelling, weakness, or numbness, should prompt evaluation for another diagnosis rather than automatic treatment as primary RLS.

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Diagnosis and Testing

RLS is diagnosed from the clinical history. A useful interview establishes when symptoms occur, what triggers them, whether movement helps, how much sleep is lost, whether arms are involved, and whether medication timing has shifted over time.

Iron studies are part of the core evaluation

Testing generally includes ferritin, serum iron, total iron-binding capacity, and transferrin saturation, ideally as a morning fasting sample when feasible and without recent iron supplementation. Ferritin can be falsely reassuring during inflammation, infection, liver disease, or cancer, so transferrin saturation adds important context.⁵⁴

The 2026 algorithm broadens consideration of intravenous iron for chronic persistent RLS. It supports IV iron in selected patients with transferrin saturation below 45% and ferritin in the 75–300 μg/L range, or with ferritin below 75 μg/L when oral iron cannot be absorbed or tolerated, has failed after an adequate trial, or a faster response is clinically important.⁴ These are RLS-specific treatment thresholds—not evidence that everyone with a ferritin below 300 needs iron.

Iron safety: Iron treatment should be guided by laboratory results and medical supervision. Unnecessary iron can cause toxicity. IV formulations also differ in dosing, infusion reactions, hypophosphatemia risk, cost, and insurance coverage.

Additional testing

Kidney function, blood count, pregnancy status, and other studies are selected according to the history. Polysomnography is reserved for suspected sleep apnea, parasomnia, narcolepsy, or another sleep disorder—not for routine confirmation of RLS.

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The 2026 Treatment Approach

Step 1: Address aggravating factors

• Use a consistent sleep schedule and avoid chronic sleep deprivation.
• Review caffeine, alcohol, nicotine, and heavy evening exercise.
• Evaluate and treat sleep apnea when suspected.
• Review medications that can worsen symptoms, including sedating antihistamines, many serotonin-enhancing antidepressants, dopamine-blocking antipsychotics, and anti-nausea drugs.
• Do not abruptly stop a needed psychiatric or anti-nausea medication; adjust it only with the prescribing clinician.

Step 2: Treat iron deficiency or low iron availability

Oral iron may be reasonable when indices are low and absorption is expected. IV iron is considered when oral treatment is not tolerated or absorbed, has not worked, or the clinical situation meets guideline criteria. Benefits may take several weeks and should be assessed with symptom severity and repeat laboratory testing—not ferritin alone.²⁴⁵

Step 3: Choose medication according to phenotype and risk

Why dopamine agonists moved out of the default first-line position

Augmentation should be suspected when symptoms begin earlier than before treatment, become more intense, require earlier or higher dosing, take less time to appear at rest, or spread to the arms or trunk. A patient may mistakenly interpret this as worsening disease and increase the dose, which can deepen the cycle.⁶⁴

Management generally includes reassessing iron, introducing a non-dopaminergic treatment, and gradually tapering the dopamine agonist. Rebound symptoms can be severe. The 2026 algorithm emphasizes that the dose should not simply be increased in response to suspected augmentation and that tapering may need to proceed slowly over weeks or months.⁴

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Prescription Nerve Stimulation: What Is New—and What Is Not

The NTX100 Tonic Motor Activation system is a nonimplantable prescription device worn below both knees. It applies low-amplitude stimulation near the common peroneal nerves. FDA authorized it for adults with primary moderate-to-severe RLS that is refractory to medications, with the goal of reducing symptoms and improving sleep quality.⁸

In the pivotal sham-controlled study, active treatment improved RLS symptom outcomes over four weeks in medication-refractory adults, and a longer open-label extension provided additional safety and durability information.⁹ The FDA decision summary notes that the pivotal primary and key secondary endpoints were assessed at four weeks and that long-term durability had not yet been established at the time of authorization.⁸

The June 26, 2026 Federal Register notice formally codified the device category. It should not be described as a new FDA clearance occurring in June 2026.¹⁰

The system is not suitable for every patient. The FDA summary lists contraindications involving pacemakers, implanted defibrillators, other implanted electronic devices, or implanted metal near the treatment site. Labeling and clinician screening should be reviewed in full.

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Intermittent, Chronic, and Refractory RLS

• Intermittent RLS: symptoms occur infrequently enough that behavioral measures or carefully selected as-needed treatment may be sufficient.
• Chronic persistent RLS: symptoms are frequent and require regular treatment; iron and gabapentinoids are central to the modern strategy.
• Refractory RLS: symptoms remain uncontrolled despite appropriate treatment, or treatment is limited by augmentation or adverse effects. Re-check the diagnosis, iron status, adherence, sleep apnea, medication triggers, and substance use before escalating therapy.

Severe refractory RLS can cause profound sleep deprivation, depression, and suicidal thinking. Low-dose opioids may be appropriate in specialist care after assessment of substance-use history, respiratory risk, drug interactions, and monitoring requirements.⁷⁴

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Pregnancy, Kidney Disease, and Older Adults

Pregnancy-associated RLS often improves after delivery. Non-drug strategies and iron assessment are emphasized, and medication decisions should involve obstetric and sleep or neurological expertise. In kidney disease, iron status, dialysis factors, medication clearance, and other causes of leg discomfort require special attention.

Older adults are particularly vulnerable to dizziness, falls, cognitive effects, and respiratory depression from gabapentinoids, sedatives, and opioids. Lower starting doses and slower titration are often appropriate.

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A Practical Plan

1. Confirm the URGE pattern and exclude mimics.
2. Measure ferritin and transferrin saturation rather than relying on hemoglobin alone.
3. Correct aggravating sleep, medication, and substance factors.
4. Use gabapentinoids or iron-based treatment when appropriate before defaulting to long-term dopamine therapy.
5. Screen for augmentation at every follow-up in anyone taking levodopa or a dopamine agonist.
6. Refer severe, refractory, or complex augmentation cases to an experienced clinician.

Bottom line: RLS is treatable, but modern treatment is no longer “start a dopamine agonist and keep increasing it.” The 2026 approach begins with diagnostic precision and iron, favors non-dopaminergic therapy for many patients, uses dopamine drugs selectively, and recognizes specialist low-dose opioids and prescription nerve stimulation as options for difficult refractory disease.

At Los Altos Neurology, RLS evaluation includes confirmation of the clinical pattern, iron and medication review, assessment for neuropathy and sleep disorders, recognition of augmentation, and an individualized plan that balances sleep benefit with long-term safety.

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References

1. Allen RP, Picchietti DL, Garcia-Borreguero D, et al. Sleep Med. 2014;15:860-873. doi:10.1016/j.sleep.2014.03.025. International Restless Legs Syndrome Study Group diagnostic criteria.
2. Winkelman JW, Berkowski JA, DelRosso LM, et al. J Clin Sleep Med. 2025;21:137-152. doi:10.5664/jcsm.11390. AASM clinical practice guideline for treatment of RLS and periodic limb movement disorder.
3. Winkelman JW, Berkowski JA, DelRosso LM, et al. J Clin Sleep Med. 2025;21:153-199. doi:10.5664/jcsm.11388. AASM systematic review, meta-analysis, and GRADE assessment.
4. Silber MH, Buchfuhrer MJ, Earley CJ, et al. Mayo Clin Proc. Published online May 26, 2026. An Updated Algorithm for the Management of Restless Legs Syndrome.
5. Allen RP, Picchietti DL, Auerbach M, et al. Sleep Med. 2018;41:27-44. Evidence-based and consensus guidelines for iron treatment of RLS.
6. Garcia-Borreguero D, Silber MH, Winkelman JW, et al. Sleep Med. 2016;21:1-11. Guidelines for first-line RLS treatment and management of dopaminergic augmentation.
7. Winkelman JW, Lammers GJ, Stiasny-Kolster K, et al. Mayo Clin Proc. 2018;93:59-67. Appropriate use of opioids in refractory restless legs syndrome.
8. U.S. Food and Drug Administration. DEN220059. Decision date April 17, 2023. FDA De Novo decision summary: NTX100 Tonic Motor Activation System.
9. Bogan RK, Roy A, Kram J, et al. Sleep. 2023;46:zsad190. Randomized trial of tonic motor activation for medication-refractory RLS.
10. U.S. Food and Drug Administration. Federal Register. June 26, 2026. FDA final rule classifying the external lower-extremity nerve stimulator for RLS.

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