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

From the Guidelines

Restless leg syndrome (RLS) can be effectively managed through a combination of lifestyle changes and medications, with ferrous sulfate suggested for use over no ferrous sulfate in patients with appropriate iron status 1. The treatment of RLS should prioritize non-pharmacological approaches, such as establishing good sleep habits, avoiding caffeine, alcohol, and nicotine, and engaging in regular moderate exercise during the day. For mild RLS, these approaches may be sufficient, but if iron deficiency is present, iron supplementation with ferrous sulfate 325 mg daily with vitamin C to enhance absorption can help. Some key points to consider in the treatment of RLS include:

• The use of ferrous sulfate over no ferrous sulfate in patients with appropriate iron status 1
• The potential use of dipyridamole, although with low certainty of evidence 1
• The consideration of extended-release oxycodone and other opioids for moderate to severe symptoms, with moderate certainty of evidence 1
• The potential use of bilateral high-frequency peroneal nerve stimulation as a non-invasive, non-pharmacological treatment 1
• The avoidance of certain medications, such as levodopa, pramipexole, and ropinirole, due to the risk of augmentation and other adverse effects 1 It is essential to weigh the potential benefits and risks of each treatment option and to consider the individual patient's needs and circumstances. Ultimately, the goal of treatment is to alleviate symptoms, improve quality of life, and reduce morbidity and mortality associated with RLS.

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. 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

Treatment of Restless Leg Syndrome (RLS) with Ropinirole:

• Ropinirole is effective in the treatment of RLS, as demonstrated by statistically significant differences in mean change from baseline in the IRLS scale total score and percentage of patients rated as responders on the CGI-I.
• The recommended dosing is flexible, with patients initiating therapy at 0.25 mg once daily and titrating up to a maximum of 4 mg once daily based on clinical response and tolerability.
• Long-term maintenance of efficacy in the treatment of RLS was demonstrated in a 36-week trial, with patients who continued on ropinirole showing a significantly lower relapse rate compared to those randomized to placebo 2, 2. Key Points:
• Ropinirole is effective in treating RLS
• Flexible dosing is recommended, with a maximum dose of 4 mg once daily
• Long-term efficacy was demonstrated in a 36-week trial

From the Research

Treatment Options for Restless Leg Syndrome

• Non-pharmacological measures such as massage or temperate baths can provide adequate symptom control for some people with RLS 3.
• First-line management options include iron-replacement therapy, gabapentin, pregabalin, and dopamine agonists such as pramipexole, ropinirole, and rotigotine 3, 4.
• Second-line therapies include intravenous iron infusion and opioids such as tramadol, oxycodone, and methadone 3.
• Alternative treatments including mind-body interventions, lifestyle interventions, and neutraceuticals may also be effective, although evidence is limited 5.
• Dopaminergic agents are considered first-line treatment for RLS, with levodopa, pramipexole, and ropinirole being well-studied options 4, 6.

Pharmacological Treatment

• Dopaminergic agents, such as pramipexole and ropinirole, are effective for RLS but may be associated with side effects such as daytime sleepiness, impulse control disorders, and augmentation 4, 6.
• Alpha-2-delta ligands, including gabapentin and pregabalin, are effective for RLS without known occurrence of augmentation or impulse control disorders, although sedation and dizziness can occur 4.
• Opioids may be used for refractory RLS, although evidence is limited and they should be used with caution 3, 7.

Non-Pharmacological Treatment

• Regular physical activity is recommended for the treatment of RLS symptoms 5.
• Oral iron supplementation should be considered for people with RLS who have low ferritin levels 5.
• Mental alerting activities, avoidance of substances or medications that may exacerbate RLS, and oral and intravenous iron supplementation are outlined as nonpharmacologic approaches 7.