What are the guidelines for managing Restless Legs Syndrome (RLS) with low ferritin levels and impaired renal function?

From the Guidelines

Restless Legs Syndrome (RLS) management should prioritize iron supplementation with ferrous sulfate for patients with low iron stores (ferritin <75 ng/mL) as the first-line treatment, given its moderate certainty of evidence and negligible cost, as recommended by the 2025 American Academy of Sleep Medicine (AASM) clinical guideline 1.

Key Considerations

• Iron supplementation is crucial for addressing a common underlying cause of RLS symptoms, with the AASM suggesting the use of ferrous sulfate over no ferrous sulfate in patients with appropriate iron status (conditional recommendation, moderate certainty of evidence) 1.
• Dopaminergic agents like ropinirole, pramipexole, and rotigotine are effective but should be used cautiously due to risks of augmentation and side effects like impulse control disorders, with the AASM suggesting against their standard use due to these risks 1.
• Alpha-2-delta ligands such as gabapentin or gabapentin enacarbil are good alternatives, especially for patients with end-stage renal disease or those who cannot tolerate dopamine agonists, as suggested by the AASM for patients with RLS and end-stage renal disease (ESRD) 1.
• Non-pharmacological approaches, including repetitive transcranial magnetic stimulation, compression devices, infrared therapy, exercise, yoga, and acupuncture, can be helpful as adjuncts to medication, with a growing body of evidence supporting their potential benefits [@4@, @5@].

Treatment Approach

• The treatment approach should be individualized, combining medications and non-drug therapies to achieve significant symptom relief and improved quality of life.
• Regular follow-up is essential to monitor symptom progression, assess treatment efficacy, minimize side effects, and prevent augmentation.
• The AASM clinical guideline provides a framework for managing RLS, emphasizing the importance of addressing exacerbating factors, such as alcohol, caffeine, and untreated obstructive sleep apnea, and considering the pregnancy-specific safety profile of each treatment being considered 1.

Medication Considerations

• Ropinirole typically starts at a low dose and is titrated to an effective dose of around 2 mg/day, with the FDA-approved labeling supported by three randomized, double-blind, placebo-controlled trials 1.
• Extended-release oxycodone may be considered for severe, refractory cases, though opioids are generally reserved for last-line therapy due to dependency risks, as suggested by the AASM (conditional recommendation, moderate certainty of evidence) 1.

Non-Pharmacological Therapies

• A 2019 systematic review reported potential benefits from repetitive transcranial magnetic stimulation, compression devices, infrared therapy, counterstrain manipulation, exercise, and yoga, as well as standard acupuncture [@4@, @5@].
• Other promising but less-studied interventions include vibration therapy, cryotherapy, aromatherapy massage, cool dialysate, and intradialytic stretching for ESRD patients, offering low-risk, accessible support for patients with mild to moderate RLS.

From the FDA Drug Label

2.3 Dosing for Restless Legs Syndrome The recommended adult starting dose for RLS is 0.25 mg once daily 1 to 3 hours before bedtime. After 2 days, if necessary, the dose can be increased to 0.5 mg once daily, and to 1 mg once daily at the end of the first week of dosing, then as shown in Table 2 as needed to achieve efficacy. Titration should be based on individual patient therapeutic response and tolerability, up to a maximum recommended dose of 4 mg daily. For RLS, the safety and effectiveness of doses greater than 4 mg once daily have not been established.

The recommended starting dose of ropinirole for Restless Legs Syndrome (RLS) is 0.25 mg once daily, with a maximum recommended dose of 4 mg daily 2.

• The dose can be increased based on individual patient therapeutic response and tolerability.
• Gradual reduction of the daily dose is recommended when discontinuing ropinirole tablets in patients with RLS. Key considerations for dosing include:
• Renal impairment: No dose adjustment is necessary in patients with moderate renal impairment.
• End-stage renal disease: The recommended initial dose is 0.25 mg once daily, with a maximum recommended dose of 3 mg/day in patients receiving regular dialysis.

From the Research

Management of Restless Legs Syndrome

• Restless Legs Syndrome (RLS) is a common neurological sensorimotor disorder that can significantly impact sleep quality, mental health, and overall well-being 3.
• The 2025 American Academy of Sleep Medicine (AASM) clinical guideline emphasizes an individualized, evidence-based approach that combines pharmacological treatments with lifestyle changes and non-drug therapies 3.

Pharmacological Treatments

• Iron supplementation is strongly recommended for adults and children with low or borderline iron stores, given its demonstrated benefit in reducing RLS severity 3.
• Dopaminergic agents such as ropinirole, pramipexole, and rotigotine have long been considered first-line treatments, but the 2025 AASM guideline now advises caution due to risks of augmentation and other adverse effects 3.
• Alpha-2-delta ligands and opioids may be considered for patients with end-stage renal disease (ESRD) or those who cannot tolerate dopamine agonists [3, @7@, @8@].

Non-Pharmacological Therapies

• A growing body of evidence supports non-drug therapies for RLS, especially when used as adjuncts to medical treatment 4, 5.
• Repetitive transcranial magnetic stimulation, exercise, compression devices, counterstrain manipulation, infrared therapy, and standard acupuncture have been shown to be effective in reducing RLS severity 6, 5.
• Vibration pads, cryotherapy, yoga, compression devices, and acupuncture may improve some sleep-related outcomes in RLS 6, 5.

Monitoring and Follow-Up

• Regular follow-up is essential to monitor symptom progression, assess treatment efficacy, minimize side effects, and prevent augmentation (especially with dopaminergic agents) 3.
• Treatment should be re-evaluated regularly, with iron levels, medication adherence, and patient-reported outcomes guiding therapeutic adjustments 3.