What workup is needed for Restless Legs Syndrome (RLS)?

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Last updated: April 16, 2025View editorial policy

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From the Guidelines

The workup for restless leg syndrome (RLS) should include a thorough medical history, physical examination, and basic laboratory tests, with a focus on checking iron levels, including ferritin, as iron deficiency is a common cause of RLS, as suggested by the American Academy of Sleep Medicine clinical practice guideline 1. The diagnosis of RLS is primarily clinical, based on four key criteria: an urge to move the legs with uncomfortable sensations, symptoms that worsen during rest, relief with movement, and symptoms that worsen in the evening or night. Some key points to consider in the workup include:

  • Checking iron levels, including ferritin, as iron deficiency is a common cause of RLS 1
  • Reviewing medications, as certain drugs like antidepressants, antihistamines, and antipsychotics can worsen symptoms 1
  • Considering lifestyle modifications, such as regular exercise, stress reduction, and avoiding triggers like caffeine and alcohol 1
  • Evaluating the need for iron supplementation, if deficient, or medications like dopamine agonists, gabapentin, or benzodiazepines, depending on symptom severity 1 It's also important to note that the American Academy of Sleep Medicine suggests against the standard use of certain medications, such as levodopa, pramipexole, and ropinirole, due to the risk of augmentation and other adverse effects 1. Overall, a comprehensive approach to diagnosing and managing RLS is essential to improve patient outcomes and quality of life.

From the Research

Diagnosis and Evaluation

  • 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 2.
  • 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, especially when augmentation develops 2.
  • A thorough subjective evaluation and complete neurologic examination are key in the diagnosis of RLS 3.

Treatment Options

  • Non-pharmacological measures such as massage or temperate baths may be adequate for some people with RLS 2.
  • 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 2.
  • 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 2.
  • Iron therapy probably improves restlessness and RLS severity in comparison to placebo, and may not increase the risk of side effects in comparison to placebo 4.

Special Considerations

  • RLS may be primary (idiopathic) or secondary to pregnancy or a variety of systemic disorders, especially iron deficiency, and chronic renal insufficiency 2.
  • Genetic predisposition with a family history is common 2.
  • Treatment of RLS in pregnancy and childhood is discussed in the updated algorithm for the management of RLS 5.
  • Referral to a neurologist or sleep specialist should be considered if initial treatment plans are ineffective 3.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Restless Legs Syndrome: Contemporary Diagnosis and Treatment.

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2021

Research

Iron for the treatment of restless legs syndrome.

The Cochrane database of systematic reviews, 2019

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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