How to manage Restless Leg Syndrome (RLS)?

Management of Restless Legs Syndrome (RLS)

Alpha-2-delta ligands such as pregabalin or gabapentin should be used as first-line pharmacological treatment for Restless Legs Syndrome due to their efficacy and favorable long-term safety profile compared to dopamine agonists. 1

Initial Assessment and Non-Pharmacological Management

Iron Status Evaluation

• Check serum ferritin and transferrin saturation in the morning (patient should avoid iron supplements for 24 hours before testing) 1
• Iron supplementation thresholds:
  • Adults: Oral or IV iron if serum ferritin ≤ 75 ng/mL or transferrin saturation < 20%
  • IV iron only if serum ferritin is between 75-100 ng/mL
  • Children: Iron supplementation if serum ferritin < 50 ng/mL 1

Lifestyle Modifications

• Regular aerobic and resistance exercise for physically capable patients 1
• Maintain regular sleep schedule 1
• Avoid substances that worsen RLS: caffeine, alcohol, antihistamines, and certain antidepressants 1

Pharmacological Treatment Algorithm

First-Line Therapy

• Alpha-2-delta ligands (pregabalin or gabapentin) 1
  • Better long-term safety profile
  • Lower risk of augmentation compared to dopamine agonists
  • First choice for patients with chronic kidney disease (with dose adjustment) 1

Second-Line Therapy

• Dopamine agonists (ropinirole, pramipexole, rotigotine patch) 1, 2
  • Ropinirole starting dose: 0.25 mg once daily 1-3 hours before bedtime
  • Titration schedule:
    • Days 1-2: 0.25 mg
    • Days 3-7: 0.5 mg
    • Week 2: 1 mg
    • Week 3: 1.5 mg
    • Week 4: 2 mg
    • Week 5: 2.5 mg
    • Week 6: 3 mg
    • Week 7: 4 mg (maximum recommended dose) 2
  • Monitor closely for augmentation (paradoxical worsening of symptoms)
  • Recommended for short-term use only 1

Third-Line Therapy

• Low-dose opioids for moderate to severe RLS that has failed other therapies 1
  • Can facilitate taper and discontinuation of dopamine agonists
  • Use with caution due to risk of central sleep apnea and respiratory depression

Special Populations

Chronic Kidney Disease/End-Stage Renal Disease

• Gabapentin or pregabalin (first-line) with dose adjustment 1
• IV iron sucrose if ferritin < 200 ng/mL and transferrin saturation < 20% 1
• Consider cool dialysate for patients on hemodialysis 1
• For patients on hemodialysis taking ropinirole:
  • Starting dose: 0.25 mg once daily
  • Maximum dose: 3 mg/day
  • No supplemental doses needed after dialysis 2

Children

• Iron therapy as first-line for those with low iron stores 1
• Limited data on dopaminergic medications in children 1

Alternative Therapies

• Bilateral high-frequency peroneal nerve stimulation 1
• Regular physical activity has demonstrated benefits 3

Monitoring and Follow-up

• Regular assessment of symptom control
• Monitor for medication side effects, particularly augmentation with dopamine agonists 1
• When discontinuing ropinirole, gradual reduction of the daily dose is recommended to prevent withdrawal symptoms 2

Pitfalls and Caveats

• Augmentation is a major concern with dopamine agonists, characterized by earlier symptom onset, increased intensity, and spread to other body parts
• Avoid using dopamine agonists in patients with a history of impulse control disorders
• Ensure RLS is not confused with neuropathy, cramps, or other conditions with similar symptoms 4
• Doses of dopamine agonists should be kept to the minimum required for acceptable symptom reduction 4