What are the treatments for Restless Leg Syndrome (RLS)?

From the Guidelines

Treatment of Restless Leg Syndrome (RLS)

Restless leg syndrome (RLS) can be effectively managed with pharmacological and non-pharmacological interventions.

• Pharmacological interventions:
  • Iron supplementation: Ferrous sulfate is suggested for use in adults with RLS, particularly those with appropriate iron status 1.
  • Opioids: Extended-release oxycodone and other opioids may be used for moderate to severe cases of RLS, with caution due to the risk of central sleep apnea and respiratory depression 1.
  • Bilateral high-frequency peroneal nerve stimulation: This non-invasive, non-pharmacological treatment receives a conditional recommendation for initial success in short-term sham-controlled studies and a longer observational extension 1.
• Non-pharmacological interventions:
  • Addressing exacerbating factors: The first step in managing RLS should be addressing factors such as alcohol, caffeine, antihistaminergic, serotonergic, antidopaminergic medications, and untreated obstructive sleep apnea 1.
  • Lifestyle modifications: Regular exercise, stress reduction, and avoiding triggers that worsen symptoms can also be beneficial.

Special Considerations

• Pregnancy: Prescribers should consider the pregnancy-specific safety profile of each treatment being considered 1.
• End-stage renal disease (ESRD): Gabapentin, IV iron sucrose, and vitamin C may be used in adults with RLS and ESRD, with conditional recommendations against levodopa and rotigotine 1.
• Pediatric RLS: Oral iron supplementation may be used in cases of iron deficiency, with consideration of potential side effects such as constipation 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.

Treatments for Restless Leg Syndrome (RLS) include:

• Ropinirole: a dopamine agonist that has been shown to be effective in reducing symptoms of RLS in clinical trials 2 2
• Flexible dosing: initiating therapy at 0.25 mg ropinirole once daily, with titration based on clinical response and tolerability over 7 weeks to a maximum of 4 mg once daily Key points:
• Ropinirole has been demonstrated to be effective in the treatment of RLS in randomized, double-blind, placebo-controlled trials
• The medication should be taken between 1 and 3 hours before bedtime
• Long-term maintenance of efficacy in the treatment of RLS was demonstrated in a 36-week trial 2 2

From the Research

Non-Pharmacological Treatments

• Repetitive transcranial magnetic stimulation, exercise, compression devices, counterstrain manipulation, infrared therapy, and standard acupuncture may reduce Restless Leg Syndrome (RLS) severity 3
• Vibration pads, cryotherapy, yoga, compression devices, and acupuncture may improve some sleep-related outcomes in RLS 3
• Good sleep hygiene is considered essential to improve comorbid insomnia in RLS patients 4
• Massaging the affected legs, taking hot baths, and performing mentally demanding tasks have been reported to reduce RLS symptoms 4
• Intradialytic stretching exercise and aromatherapy massage may be potential non-pharmacological interventions for RLS in end-stage kidney disease patients, but with limited confidence of evidence 5
• Cool dialysate has been found to produce the largest RLS severity score reduction in end-stage kidney disease patients 5

Pharmacological Treatments

• Dopaminergic agents, such as pramipexole and ropinirole, are considered first-line treatment for RLS 4, 6, 7
• Opioids, such as oxycodone-naloxone, may be effective in refractory RLS cases 6
• Anticonvulsants, such as gabapentin, may be effective in reducing RLS severity and improving sleep quality 6, 5
• Benzodiazepines, such as clonazepam, may be used to improve sleep quality in RLS patients, but with modest therapeutic effects on RLS symptoms 4, 6
• IV iron may be a pharmacological approach for RLS treatment, but with different levels of evidence of efficacy 6