What are the treatment options for Restless Legs Syndrome (RLS)?

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Last updated: June 22, 2025View editorial policy

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From the Guidelines

Restless Legs Syndrome (RLS) treatment should prioritize the use of gabapentin enacarbil, gabapentin, or pregabalin as first-line pharmacological treatments, as recommended by the American Academy of Sleep Medicine (AASM) with strong evidence 1. When considering treatment options for RLS, it's essential to evaluate the severity of symptoms and impact on quality of life. For mild RLS, lifestyle modifications such as regular exercise, good sleep hygiene, avoiding caffeine and alcohol, and consistent sleep schedules should be tried first.

  • Iron supplementation with ferrous sulfate 325 mg taken with vitamin C to enhance absorption is recommended for patients with low ferritin levels (below 75 ng/mL) 1.
  • The AASM suggests the use of ferrous sulfate over no ferrous sulfate in patients with appropriate iron status (conditional recommendation, moderate certainty of evidence) 1.
  • Gabapentin enacarbil, gabapentin, and pregabalin are effective first-line options with less risk of augmentation, and their use is recommended by the AASM with strong evidence (strong recommendation, moderate certainty of evidence) 1. Some key points to consider when treating RLS include:
  • Regular monitoring is essential to assess treatment efficacy and potential side effects, particularly with long-term use of dopamine agonists, which can lead to augmentation (worsening of symptoms).
  • Treatment should be individualized based on symptom severity, comorbidities, and patient preferences, with the goal of reducing discomfort and improving sleep quality.
  • Other treatment options, such as opioids, may be considered for severe or refractory cases, but their use should be carefully evaluated due to potential risks and side effects 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.

The treatment options for Restless Legs Syndrome (RLS) include:

  • Ropinirole: a dopamine agonist that has been shown to be effective in reducing symptoms of RLS, with a mean dose of approximately 2 mg/day.
  • Flexible dosing: patients can be titrated based on clinical response and tolerability over 7 weeks to a maximum of 4 mg once daily.
  • Long-term maintenance: efficacy in the treatment of RLS was demonstrated in a 36-week trial, with patients who were responders at Week 24 showing a significantly lower relapse rate compared with patients randomized to placebo 2, 2. Key points:
  • Ropinirole has been shown to be effective in reducing symptoms of RLS.
  • Flexible dosing can be used to titrate patients based on clinical response and tolerability.
  • Long-term maintenance of efficacy has been demonstrated in clinical trials.

From the Research

Treatment Options for Restless Legs Syndrome (RLS)

The treatment of RLS can be divided into non-pharmacological interventions and pharmacological therapies.

  • Non-pharmacological interventions:
    • Good sleep hygiene is considered essential to improve comorbid insomnia 3
    • Massaging the affected legs, taking hot baths, and performing mentally demanding tasks have been reported to reduce RLS symptoms 3
    • Lifestyle modification may also be helpful 4
  • Pharmacological therapies:
    • Dopaminergic agents, such as levodopa and dopamine agonists (e.g., pergolide, pramipexole, cabergoline, and ropinirole), are considered the first-line treatment for RLS 3, 5, 6, 4, 7
    • Opioids are prescribed to patients with severe conditions, especially those unresponsive to other treatments 3, 5, 7
    • Anticonvulsants, such as gabapentin, are used as second-line treatment 3, 5, 4, 7
    • Benzodiazepines, including clonazepam and nitrazepam, are widely prescribed to improve sleep quality in patients with RLS, but their therapeutic effects on RLS symptoms are modest 3

Special Considerations

  • Correction of iron deficiency improves symptoms in patients with low ferritin levels 4
  • High-dose intravenous iron is a promising but still experimental approach 5
  • Patients with painful symptoms may respond favorably to anticonvulsants such as gabapentin and carbamazepine 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

[Update on the treatment of restless legs syndrome].

Brain and nerve = Shinkei kenkyu no shinpo, 2009

Research

Restless legs syndrome.

Handbook of clinical neurology, 2011

Research

Current treatment options for restless legs syndrome.

Expert opinion on pharmacotherapy, 2003

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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