What are the best therapies for Restless Legs Syndrome (RLS)?

From the Guidelines

The most effective therapies for restless legs syndrome (RLS) include iron supplementation, particularly IV ferric carboxymaltose, and medications such as gabapentin, pregabalin, and extended-release oxycodone, which should be individualized based on symptom severity, comorbidities, and potential side effects. When considering treatment options for RLS, it is essential to prioritize iron supplementation, as brain-iron deficiency is a leading concept in the pathophysiology of RLS 1. The American Academy of Sleep Medicine (AASM) suggests the use of ferrous sulfate over no ferrous sulfate in patients with appropriate iron status, as well as the use of IV ferric carboxymaltose, which receives a strong recommendation 1. For moderate to severe symptoms requiring medication, first-line options include alpha-2-delta calcium channel ligands like gabapentin and pregabalin, which are effective treatments for RLS, particularly for patients with pain or anxiety 1. Additionally, extended-release oxycodone and other opioids may be considered for severe cases or those with augmentation, but caution should be used due to the risk of central sleep apnea and respiratory depression 1. It is crucial to individualize treatment based on symptom severity, comorbidities, and potential side effects, with regular monitoring for augmentation with dopaminergic medications, which affects up to 70% of patients on long-term therapy. Some key points to consider when treating RLS include:

• Iron supplementation is essential for patients with low ferritin levels below 75 ng/mL
• Gabapentin and pregabalin are effective first-line treatments for moderate to severe RLS symptoms
• Extended-release oxycodone and other opioids may be considered for severe cases or those with augmentation
• Treatment should be individualized based on symptom severity, comorbidities, and potential side effects
• Regular monitoring for augmentation with dopaminergic medications is crucial.

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. In all 3 trials, a statistically significant difference between the treatment group receiving ropinirole and the treatment group receiving placebo was observed at Week 12 for both the mean change from baseline in the IRLS scale total score and the percentage of patients rated as responders (much improved or very much improved) on the CGI-I

Best therapies for restless legs syndrome include:

• Ropinirole: a dopamine agonist that has been shown to be effective in reducing symptoms of RLS in clinical trials 2 Key points:
• Ropinirole has been demonstrated to be effective in reducing symptoms of RLS in adults with a history of at least 15 RLS episodes/month and a total score of ≥15 on the IRLS scale at baseline
• The medication should be initiated at a dosage of 0.25 mg once daily and titrated based on clinical response and tolerability over 7 weeks to a maximum of 4 mg once daily
• Long-term maintenance of efficacy in the treatment of RLS was demonstrated in a 36-week trial 2

From the Research

Therapies for Restless Legs Syndrome

The following therapies have been identified as potential treatments for restless legs syndrome:

• Non-pharmacological measures such as massage or temperate baths, which may provide adequate symptom control for some individuals 3
• Repetitive transcranial magnetic stimulation, exercise, compression devices, counterstrain manipulation, infrared therapy, and standard acupuncture, which have been shown to be significantly more effective for RLS severity than control conditions 4
• Vibration pads, cryotherapy, yoga, compression devices, and acupuncture, which may improve some sleep-related outcomes in RLS patients 4

Pharmacological Therapies

Pharmacological therapies for RLS include:

• Iron-replacement therapy for individuals with reduced body-iron stores 3
• Dopamine agonists such as pramipexole, ropinirole, and rotigotine, which are considered first-line management options 3, 5
• Gabapentin and pregabalin, which are also first-line management options 3
• Opioids such as tramadol, oxycodone, and methadone, which may be used as second-line therapies 3
• Gabapentin, which has been shown to be effective in reducing RLS severity and improving sleep quality in patients with end-stage kidney disease 6

Treatment Considerations

Treatment for RLS should be individualized and based on the severity of symptoms and the presence of any underlying conditions. Non-pharmacological interventions may be beneficial for reducing RLS severity and enhancing sleep, while pharmacological therapies may be necessary for more severe cases 4, 5, 7.