What is the recommended workup and treatment for a patient with new onset restless legs syndrome (RLS)?

From the Guidelines

The recommended workup for new onset restless legs syndrome (RLS) should include a complete medical history, physical examination, and laboratory tests to check for iron deficiency, as serum ferritin levels below 75 ng/mL are associated with RLS symptoms. Initial testing should include complete blood count, ferritin, iron saturation, and renal function tests. Treatment begins with addressing any underlying causes, particularly iron deficiency, which may require oral iron supplementation (typically ferrous sulfate 325 mg daily with vitamin C to enhance absorption) when ferritin is below 75 ng/mL, as suggested by the American Academy of Sleep Medicine 1.

Key Considerations

• Non-pharmacological approaches should be tried first, including regular exercise, good sleep hygiene, avoiding caffeine and alcohol, and maintaining a regular sleep schedule.
• For pharmacological treatment, first-line medications include gabapentin, pregabalin, and IV ferric carboxymaltose, which have strong recommendations for use in adults with RLS 1.
• Alpha-2-delta calcium channel ligands like gabapentin (300-1200 mg daily) or pregabalin (75-300 mg daily) are alternatives, especially for patients with pain or anxiety.
• For intermittent symptoms, low-dose opioids may be considered, with a conditional recommendation for extended-release oxycodone and other opioids 1.
• It's essential to monitor for augmentation with dopaminergic medications, where symptoms worsen or begin earlier in the day, which may require medication adjustment.
• Treatment should be individualized based on symptom severity, comorbidities, and patient preferences, considering the latest guidelines from the American Academy of Sleep Medicine 1.

Special Populations

• In adults with RLS and end-stage renal disease (ESRD), the American Academy of Sleep Medicine suggests the use of gabapentin, IV iron sucrose, and vitamin C, with conditional recommendations against levodopa and rotigotine 1.
• In children with RLS, oral iron supplementation is recommended in cases of iron deficiency, with consideration of potential side effects like constipation 1.

From the FDA Drug Label

Restless Legs Syndrome (RLS): The effectiveness of ropinirole hydrochloride in the treatment of RLS was demonstrated in randomized, double-blind, placebo-controlled studies 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.

The recommended workup for a patient with new onset Restless Legs Syndrome (RLS) includes:

• Diagnosing RLS using the International Restless Legs Syndrome Study Group diagnostic criteria
• Assessing the severity of symptoms using the International RLS Rating Scale (IRLS scale)
• Identifying and addressing any potential underlying causes of RLS, such as pregnancy, renal failure, or anemia

The recommended treatment for RLS includes:

• Ropinirole hydrochloride, with a starting dose of 0.25 mg once daily, titrated based on clinical response and tolerability over 7 weeks to a maximum of 4 mg once daily 2
• Doses should be taken between 1 and 3 hours before bedtime
• Treatment efficacy can be assessed using the IRLS Scale and Clinical Global Impression-Global Improvement (CGI-I) scores 2

From the Research

Diagnosis and Workup

• The diagnosis of restless legs syndrome (RLS) is based on four essential criteria: an urge to move, usually associated with paresthesias, onset or exacerbation of symptoms at rest, relief of symptoms with movement, and symptoms manifesting in a circadian pattern 3.
• A supplemental workup including polysomnography, iron profile, and/or neuropathy screen can provide support for the diagnosis and aid in the treatment strategy 3.
• Patients with new onset RLS should undergo a thorough medical history and physical examination to identify any underlying medical conditions that may be contributing to the development of RLS, such as renal failure, systemic iron deficiency, or pregnancy 4, 5.

Treatment Options

• Dopaminergic agents, such as dopamine agonists, are considered the first-line treatment for RLS and are effective in reducing symptoms 4, 5, 6, 7.
• Other treatment options include opioids, anticonvulsants, and benzodiazepines, which may be used as second-line treatments or in combination with dopaminergic agents 5, 6, 3.
• Non-pharmacological interventions, such as good sleep hygiene, massaging the affected legs, taking hot baths, and performing mentally demanding tasks, may also be beneficial in reducing RLS symptoms 6.
• Newer treatment options, such as Neupro (rotigotine) and Horizant (gabapentin enacarbil), have been approved for the treatment of RLS and may provide additional benefits, such as lower rates of augmentation 7.

Individualized Treatment Plan

• The therapeutic plan should be individualized to suit each patient's presentation and needs, taking into account the severity of symptoms, underlying medical conditions, and response to treatment 3, 7.
• Patients with RLS should be regularly monitored for the development of augmentation, which can occur with long-term use of dopaminergic agents, and alternative treatments should be considered if necessary 4, 5, 7.