What is the diagnosis and treatment for Restless Legs Syndrome (RLS)?

From the Guidelines

Restless Leg Syndrome (RLS) should be treated with gabapentin enacarbil as the first-line pharmacological treatment, as it has been shown to significantly 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.

Treatment Options

The treatment of RLS involves a combination of lifestyle modifications and pharmacological interventions. Lifestyle modifications include:

• Regular exercise
• Maintaining a consistent sleep schedule
• Avoiding caffeine and alcohol
• Practicing relaxation techniques If symptoms persist, medications may be necessary. The American Academy of Sleep Medicine recommends the use of gabapentin enacarbil over no gabapentin enacarbil, with a strong recommendation and moderate certainty of evidence 1.

Pharmacological Treatments

Other pharmacological treatments that may be considered include:

• Dopamine agonists such as pramipexole or ropinirole, although their use is not recommended as a standard treatment due to the risk of augmentation 1
• Alpha-2-delta calcium channel ligands like pregabalin, which has been shown to be effective in improving disease severity and sleep quality 1
• Iron supplementation with ferrous sulfate, which is recommended if ferritin levels are below 75 ng/mL 1

Special Considerations

In adults with RLS and end-stage renal disease (ESRD), the use of gabapentin, IV iron sucrose, and vitamin C may be considered, although the certainty of evidence is low to moderate 1.

Monitoring and Follow-up

Regular follow-up is important to monitor symptom control and medication side effects, and to adjust treatment as needed. Patients who are at a high risk of side effects with certain medications may choose other treatment options.

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

Ropinirole is effective in the treatment of Restless Legs Syndrome (RLS).

• The drug has been shown to reduce the severity of RLS symptoms, as measured by the International RLS Rating Scale (IRLS scale) and the Clinical Global Impression-Global Improvement (CGI-I) scores.
• The mean change from baseline in the IRLS scale total score was significantly greater for ropinirole compared to placebo in all three trials.
• The percentage of patients rated as responders (much improved or very much improved) on the CGI-I was also significantly higher for ropinirole compared to placebo in all three trials 2.

From the Research

Definition and Prevalence of Restless Legs Syndrome

• Restless legs syndrome (RLS) is a common condition characterized by paresthesia and an urge to move, with symptoms occurring at rest in the evening or at night, and alleviated by moving the affected extremity 3, 4.
• The population prevalence of RLS is estimated to be approximately 5% 3, with a subgroup of patients having more severe RLS with symptoms occurring 2 or more times a week and causing at least moderate distress, having a prevalence of 1.5% to 2.7% 5.

Treatment Options for Restless Legs Syndrome

• Pharmacological treatment should be limited to those patients who suffer from clinically relevant RLS, that is, when symptoms impair the patient's quality of life, daytime functioning, social functioning or sleep 3, 4.
• Treatment options for RLS include dopaminergic agents, such as pramipexole and ropinirole, which are considered first-line treatment 4, and α-2-δ ligands, such as gabapentin enacarbil and pregabalin 6.
• Nonpharmacologic approaches, including mental alerting activities, avoidance of substances or medications that may exacerbate RLS, and oral and intravenous iron supplementation, are also outlined 5.
• The choice of treatment depends on the severity of symptoms, with dopaminergic agonists being more effective for patients with more severe symptoms 6.

Management of Restless Legs Syndrome

• The management of RLS is considered under the following headings: General Considerations; Intermittent RLS; Chronic Persistent RLS; Refractory RLS; Special Circumstances; and Alternative, Investigative, and Potential Future Therapies 5.
• Algorithms for treatment of RLS include both nonpharmacologic and pharmacologic therapy, with patients being divided into three groups: those with intermittent RLS symptoms, those with daily RLS symptoms, and those whose symptoms are refractory to standard treatments 7.
• The first step in managing RLS is to ensure that there is an adequate diagnosis, and treatment should be tailored to the needs of each individual patient 7.