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

From the Guidelines

Restless leg syndrome (RLS) should be treated with ferrous sulfate in adults with appropriate iron status, as suggested by the American Academy of Sleep Medicine (AASM) in their 2025 clinical practice guideline 1. The treatment of RLS involves a multifaceted approach, including lifestyle modifications and pharmacological interventions.

Key Recommendations

• The AASM suggests the use of ferrous sulfate over no ferrous sulfate in patients with appropriate iron status 1.
• The AASM also suggests the use of dipyridamole, extended-release oxycodone, and bilateral high-frequency peroneal nerve stimulation in certain cases 1.

Pharmacological Treatments

The AASM provides conditional recommendations against the standard use of several medications, including:

• Levodopa, pramipexole, transdermal rotigotine, ropinirole, bupropion, carbamazepine, clonazepam, and valproic acid 1.

Special Considerations

• In adults with RLS and end-stage renal disease (ESRD), the AASM suggests the use of gabapentin, IV iron sucrose, and vitamin C in certain cases 1.
• The AASM also provides recommendations for the treatment of RLS in children and periodic limb movement disorder (PLMD) 1.

Lifestyle Modifications

In addition to pharmacological treatments, lifestyle modifications play a crucial role in managing RLS symptoms.

• Regular exercise, good sleep hygiene, avoiding caffeine and alcohol, and ensuring adequate iron levels are essential for reducing symptoms.
• Reviewing current medications with a doctor is also important, as certain medications can exacerbate RLS symptoms.

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 symptoms of RLS, as measured by the International RLS Rating Scale (IRLS scale) and the Clinical Global Impression-Global Improvement (CGI-I) scores.
• Statistically significant differences were observed between ropinirole and placebo in three randomized, double-blind, placebo-controlled trials.
• The mean dose of ropinirole at Week 12 was approximately 2 mg/day.
• Long-term maintenance of efficacy in the treatment of RLS was demonstrated in a 36-week trial 2

From the Research

Definition and Characteristics of Restless Leg Syndrome

• Restless legs syndrome (RLS) is characterized by an uncomfortable urge to move the legs while at rest, relief upon movement or getting up to walk, and worsened symptom severity at night 3.
• RLS may be primary (idiopathic) or secondary to pregnancy or a variety of systemic disorders, especially iron deficiency, and chronic renal insufficiency 3, 4.
• Symptoms vary considerably in age at onset, frequency, and severity, with severe forms affecting sleep, quality of life, and mood 4.

Diagnosis and Evaluation

• Evaluation begins with a thorough history and examination, and iron measures, including ferritin and transferrin saturation, should be checked at presentation and with worsened symptoms 3.
• Augmentation is characterized by more intense symptom severity, earlier symptom occurrence, and often, symptom spread from the legs to the arms or other body regions 3, 4.

Treatment Options

• First-line management options include iron-replacement therapy in those with evidence for reduced body-iron stores or, alternatively, with prescribed gabapentin or pregabalin, and dopamine agonists such as pramipexole, ropinirole, and rotigotine 3.
• Second-line therapies include intravenous iron infusion in those who are intolerant of oral iron and/or those having augmentation with intense, severe RLS symptoms, and opioids including tramadol, oxycodone, and methadone 3.
• Alternative treatments such as mind-body interventions (conventional exercise, yoga, and acupuncture), non-pharmacologic lifestyle interventions (pneumatic compression devices, light therapy, and cognitive-behavioral therapy), and neutraceuticals (vitamins, valerian, and Chinese herbs) may be considered, although evidence is limited 5.
• Dopaminergic therapy is currently the treatment of choice, usually initiated with a long-acting dopamine agonist, thereby avoiding some of the complications associated with levodopa 6.