What are the initial steps for testing and treating restless leg syndrome?

Initial Testing and Treatment for Restless Legs Syndrome

For patients with restless legs syndrome (RLS), the initial testing should include serum iron studies (ferritin and transferrin saturation), and first-line treatment should be gabapentin or pregabalin rather than dopamine agonists due to the risk of augmentation. 1

Initial Diagnostic Evaluation

Essential Testing

• Iron studies: Check morning serum ferritin and transferrin saturation (calculated from iron and total iron binding capacity)
  • Testing should be done in the morning, avoiding iron-containing supplements/foods for at least 24 hours prior to blood draw 1
  • Iron deficiency is a major treatable cause of RLS

Screening Questions for RLS

When evaluating a patient with suspected RLS, ask:

• "What does it feel like?"
• "Does it vary over the day and is it worse later in the day/evening?"
• "Is it relieved by movement?"
• "Does it come back again a few minutes after you sit or lie back down?"
• "Does your bed partner complain that you have twitchy legs or make kicking movements in your sleep?" 1

Rule Out Exacerbating Factors

• Assess for factors that can worsen RLS symptoms:
  • Alcohol and caffeine consumption
  • Medications: antihistamines, serotonergic drugs, antidopaminergic medications
  • Untreated obstructive sleep apnea 1
  • Xerostomia ("dry mouth") which may prompt increased fluid intake 1

Treatment Algorithm

Step 1: Address Iron Status

• If ferritin ≤ 75 ng/mL or transferrin saturation < 20%: Initiate iron supplementation
  • Oral ferrous sulfate (conditional recommendation, moderate evidence) 1
  • For patients with inadequate response to oral iron, consider IV iron therapy:
    • IV ferric carboxymaltose (strong recommendation, moderate evidence) 1
    • IV low molecular weight iron dextran or ferumoxytol (conditional recommendations) 1

Step 2: First-Line Pharmacologic Treatment

• Alpha-2-delta ligands (strong recommendations, moderate evidence):
  • Gabapentin enacarbil
  • Gabapentin
  • Pregabalin 1

Step 3: Second-Line Options (if first-line fails)

• Dipyridamole (conditional recommendation, low evidence) 1
• Bilateral high-frequency peroneal nerve stimulation (conditional recommendation, moderate evidence) 1
• Extended-release oxycodone or other opioids for severe, refractory cases (conditional recommendation, moderate evidence) 1, 2

Special Considerations for CKD/ESRD Patients

• Gabapentin is the first-line treatment (conditional recommendation) 2
• IV iron sucrose for patients with ferritin < 200 ng/mL and transferrin saturation < 20% 2
• Vitamin C supplementation may be beneficial (conditional recommendation) 2

Important Cautions

Avoid Dopamine Agonists as First-Line Treatment

• The 2025 American Academy of Sleep Medicine guidelines represent a significant change from previous recommendations
• Dopamine agonists (ropinirole, pramipexole, rotigotine) are no longer recommended as first-line due to the risk of augmentation 1
• Augmentation is characterized by:
  • More intense symptom severity
  • Earlier symptom occurrence during the day
  • Symptom spread from legs to arms or other body regions 3

Medications to Avoid

• Valproic acid (conditional recommendation against use) 1
• Cabergoline (strong recommendation against use) 1
• Levodopa (conditional recommendation against standard use) 1
• Valerian (conditional recommendation against use) 1

Monitoring and Follow-Up

• Regularly reassess iron status, particularly if symptoms worsen
• Monitor for medication side effects
• If using opioids, watch for dependence, tolerance, and side effects (constipation, nausea, somnolence) 2

By following this evidence-based approach to testing and treatment, clinicians can effectively manage RLS while minimizing the risk of treatment complications such as augmentation.