How to treat Restless Legs Syndrome (RLS)?

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Last updated: February 16, 2025View editorial policy

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From the Guidelines

The treatment of Restless Legs Syndrome (RLS) typically involves a combination of pharmacological and non-pharmacological interventions.

Treatment Options

  • For mild cases, ferrous sulfate is suggested over no ferrous sulfate in patients with appropriate iron status 1.
  • In more severe cases, extended-release oxycodone and other opioids may be considered over no opioids 1, and bilateral high-frequency peroneal nerve stimulation may be used over no peroneal nerve stimulation 1.
  • Gabapentin may be used in adults with RLS and end-stage renal disease (ESRD) 1.

Important Considerations

  • Dopamine agonists such as levodopa, pramipexole, rotigotine, and ropinirole are not recommended for standard use due to the risk of augmentation 1.
  • IV iron sucrose may be used in adults with RLS and ESRD with a transferrin saturation < 20% 1.
  • Vitamin C may be used in adults with RLS and ESRD 1.

Non-Pharmacological Interventions

  • Addressing exacerbating factors such as alcohol, caffeine, antihistaminergic, serotonergic, and antidopaminergic medications, and untreated obstructive sleep apnea is essential 1.
  • Regular and affordable access to iron infusion is necessary for patients with RLS, particularly those with ESRD 1.

From the FDA Drug Label

The effectiveness of ropinirole in the treatment of RLS was demonstrated in randomized, double-blind, placebo-controlled trials in adults diagnosed with RLS using the International Restless Legs Syndrome Study Group diagnostic criteria Patients were required to have a history of a minimum of 15 RLS episodes/month during the previous month and a total score of ≥15 on the International RLS Rating Scale (IRLS scale) at baseline. All trials employed flexible dosing, with patients initiating therapy at 0.25 mg ropinirole once daily. Patients were titrated based on clinical response and tolerability over 7 weeks to a maximum of 4 mg once daily. All doses were taken between 1 and 3 hours before bedtime.

To treat Restless Legs Syndrome (RLS), the recommended treatment is:

  • Ropinirole (PO), with a starting dose of 0.25 mg once daily, taken between 1 and 3 hours before bedtime
  • The dose can be titrated based on clinical response and tolerability over 7 weeks to a maximum of 4 mg once daily 2
  • The treatment should be initiated in patients with a history of a minimum of 15 RLS episodes/month during the previous month and a total score of ≥15 on the International RLS Rating Scale (IRLS scale) at baseline. Key points to consider:
  • Flexible dosing: Patients can be titrated to a dose that provides optimal relief from RLS symptoms
  • Dose range: The dose of ropinirole can be adjusted between 0.25 mg and 4 mg once daily
  • Timing of dose: The dose should be taken between 1 and 3 hours before bedtime to maximize efficacy.

From the Research

Treatment Options for Restless Legs Syndrome (RLS)

Restless Legs Syndrome (RLS) can be treated through various methods, including pharmacological and non-pharmacological interventions. The following are some of the treatment options:

  • Non-pharmacological interventions:
    • Repetitive transcranial magnetic stimulation, exercise, compression devices, counterstrain manipulation, infrared therapy, and standard acupuncture may reduce RLS severity 3
    • Vibration pads, cryotherapy, yoga, compression devices, and acupuncture may improve some sleep-related outcomes in RLS 3
  • Pharmacological interventions:
    • Dopaminergic agents, such as pramipexole, are effective in treating RLS symptoms without severe side-effects 4
    • α2δ anticonvulsants may be considered as drugs of choice for moderate to severe RLS patients 5
    • Opioids, such as prolonged release oxycodone/naloxone, may be effective in treating RLS symptoms, especially for patients with severe symptoms 6
    • Iron suppletion, α2δ ligands, dopamine agonists, and combinations of these may be considered for moderate to severe primary RLS 7

Considerations for Treatment

When treating RLS, it is essential to consider the following:

  • Augmentation: Dopamine agonists may cause augmentation, which can limit their use for long-term therapy 5
  • Side effects: Opioids are associated with adverse events such as constipation, tolerance, and dependence 6
  • Individualized treatment: Treatment should be tailored to the individual patient's needs and symptoms 5, 7

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Strategies for the treatment of restless legs syndrome.

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2012

Research

Opioids for restless legs syndrome.

The Cochrane database of systematic reviews, 2016

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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