What is the treatment for restless legs syndrome?

Treatment for Restless Legs Syndrome

Alpha-2-delta ligands (pregabalin or gabapentin) are recommended as first-line pharmacologic therapy for moderate to severe restless legs syndrome due to their effectiveness and lower risk of augmentation compared to dopamine agonists. 1

Initial Assessment and Non-Pharmacologic Management

Iron Status Evaluation

• Ferritin testing is the primary laboratory evaluation for RLS
• Iron supplementation recommended for:
  • Ferritin levels below 75 ng/mL
  • Transferrin saturation <20%
• Iron deficiency is a major treatable cause of RLS 1

Non-Pharmacologic Approaches

• Regular aerobic and resistance exercise
• Moderate exercise regimen
• Lifestyle modifications:
  • Smoking cessation
  • Alcohol avoidance
  • Caffeine reduction or elimination
  • Discontinuation of potentially exacerbating medications 1

Pharmacologic Treatment Algorithm

First-Line Therapy

• Alpha-2-delta ligands:
  • Pregabalin or gabapentin
  • Particularly beneficial in patients with comorbid pain or anxiety
  • Lower risk of augmentation compared to dopamine agonists 1

Second-Line Therapy

• Dopamine agonists (for short-term management only):
  • Ropinirole: Starting dose 0.25 mg orally 1-3 hours before bedtime
  • Pramipexole: Starting dose 0.125 mg orally 2-3 hours before bedtime
  • Rotigotine: Transdermal patch
  • Caution: High risk of augmentation (30-80% of patients) with prolonged use 1, 2

Third-Line Therapy

• Opioids for severe cases that fail to respond to first and second-line treatments:
  • Extended-release oxycodone for severe to very severe RLS
  • Caution: Risk of central sleep apnea and respiratory depression 1, 3

Special Populations

Patients with Chronic Kidney Disease/ESRD

• Gabapentin: First-line treatment
• IV iron sucrose: First-line for ESRD patients with ferritin < 200 ng/mL and transferrin saturation < 20%
• Consider vitamin C supplementation
• Consider cool dialysate for patients on hemodialysis 1

Geriatric Patients

• Start with lower doses
• Titrate slowly
• Monitor for orthostatic hypotension, especially with dopamine agonists
• Watch for augmentation (earlier symptom onset, increased intensity, spread to other body parts) 1

Management of Augmentation

Augmentation is characterized by:

• Earlier symptom onset
• Increased symptom intensity
• Spread of symptoms to other body parts

If augmentation occurs:

1. Consider switching from dopamine agonist to alpha-2-delta ligand
2. Maintain adequate iron levels (check ferritin and supplement if <50 ng/mL)
3. Consider opioid therapy for severe cases 1, 3

Monitoring and Follow-up

• Regular assessment of symptom control
• Minimal dose increases over time
• Monitor for medication side effects
• Regular follow-up to adjust treatment as needed 1

The evidence strongly supports a structured approach to RLS management, with iron supplementation when indicated and careful selection of pharmacologic therapy based on symptom severity and patient characteristics. The shift toward alpha-2-delta ligands as first-line therapy represents an important evolution in treatment recommendations, primarily due to the significant risk of augmentation with dopamine agonists 1, 3.