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

From the Guidelines

Restless leg syndrome can be effectively managed with gabapentin enacarbil, as it has been shown to improve disease severity, sleep quality, and quality of life with a moderate effect size, according to the American Academy of Sleep Medicine clinical practice guideline 1. The treatment of restless legs syndrome (RLS) involves a variety of pharmacological and non-pharmacological approaches.

Key Considerations

• The American Academy of Sleep Medicine recommends the use of gabapentin enacarbil over no gabapentin enacarbil in adults with RLS, with a strong recommendation and moderate certainty of evidence 1.
• Gabapentin enacarbil has been shown to improve disease severity, sleep quality, and quality of life with a moderate effect size, and the adverse effects, including somnolence and dizziness, have a small effect size 1.
• Other treatment options, such as pregabalin, IV ferric carboxymaltose, and IV low molecular weight iron dextran, may also be considered, but the evidence is less strong or more conditional 1.

Treatment Options

• Gabapentin enacarbil: recommended as a first-line treatment for RLS, with a strong recommendation and moderate certainty of evidence 1.
• Pregabalin: may be considered as an alternative treatment option, with a strong recommendation and moderate certainty of evidence 1.
• Iron supplementation: may be recommended for patients with iron deficiency, with a conditional recommendation and moderate certainty of evidence 1.

Important Considerations

• The cost of gabapentin enacarbil is considered high, which may reduce health equity, but direct evidence is lacking 1.
• Patients who are at high risk of side effects with gabapentin enacarbil may choose other treatment options 1.
• Medications may need adjustment over time as some can cause augmentation—worsening symptoms or earlier onset—with prolonged use.

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. A variety of measures were used to assess the effects of treatment, including the IRLS scale and Clinical Global Impression-Global Improvement (CGI-I) scores 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

Ropinirole is effective in the treatment of Restless Legs Syndrome (RLS). The medication has been shown to significantly reduce symptoms of RLS, as measured by the International RLS Rating Scale (IRLS) and Clinical Global Impression-Global Improvement (CGI-I) scores, in three randomized, double-blind, placebo-controlled trials 2. Key benefits of ropinirole for RLS treatment include:

• Significant reduction in RLS symptoms
• Improvement in sleep disturbance and daytime somnolence
• Positive impact on activities of daily living and mood The recommended dosage of ropinirole for RLS is 0.25 mg once daily, taken 1-3 hours before bedtime, with flexible dosing up to a maximum of 4 mg once daily.

From the Research

Restless Leg Syndrome Treatment Options

• Dopaminergic agents, such as levodopa and dopamine agonists (pramipexole, ropinirole, and rotigotine), are considered first-line treatment for restless legs syndrome (RLS) 3, 4, 5
• Alpha-2-delta ligands, including gabapentin, gabapentin enacarbil, and pregabalin, are also effective for RLS without known occurrence of augmentation or impulse control disorders 4, 6, 7
• Non-dopaminergic treatment options, such as opioids, may be considered for patients with severe augmentation of symptoms or treatment failure with dopamine agonists 7

Medication Comparison

• Dopamine agonists are more effective in treating periodic limb movements (PLMs) 7
• Alpha-2-delta ligands are more effective in consolidating sleep 7
• Gabapentin and ropinirole provide similarly well-tolerated and effective treatment of PLMS and sensorimotor symptoms in patients with idiopathic RLS 6

Treatment Considerations

• Pharmacological treatment should be limited to patients who suffer from clinically relevant RLS with impaired sleep quality or quality of life 3
• Treatment on demand is a clinical need in RLS cases that present intermittent symptoms 3
• The lowest effective dose of dopaminergic agents should be used for the shortest possible period of time to reduce the risk of augmentation 7