What is the treatment approach for a patient with Restless Leg Syndrome (RLS)?

Treatment Approach for Restless Leg Syndrome (RLS)

Alpha-2-delta ligands such as pregabalin or gabapentin are recommended as first-line pharmacological treatments for RLS due to their efficacy and favorable long-term safety profile. 1

Diagnostic Confirmation

• Confirm diagnosis using established clinical criteria:
  • Urge to move the legs
  • Symptoms beginning or worsening during rest/inactivity
  • Symptoms partially or totally relieved by movement
  • Symptoms worse in evening or night
  • Symptoms not solely attributable to another medical condition

Initial Assessment and Management

Step 1: Address Exacerbating Factors

• Eliminate or reduce:
  • Alcohol
  • Caffeine
  • Antihistamines
  • Serotonergic medications
  • Antidopaminergic medications
  • Treat untreated obstructive sleep apnea 2

Step 2: Laboratory Testing

• Serum ferritin and transferrin saturation (morning testing, avoiding iron supplements/foods for 24 hours prior)
• Consider additional tests to rule out secondary causes:
  • Thyroid function tests
  • HbA1c
  • Urine albumin:creatinine ratio 1

Step 3: Iron Supplementation

• Initiate iron supplementation based on ferritin levels:
  • Oral or IV iron if serum ferritin ≤ 75 ng/mL or transferrin saturation < 20%
  • IV iron only if serum ferritin between 75-100 ng/mL 2, 1

Pharmacological Treatment Algorithm

First-Line Treatment

• Alpha-2-delta ligands:
  • Pregabalin: Start at 75 mg at bedtime, titrate up to 300 mg daily as needed
  • Gabapentin: Start at 300 mg at bedtime, titrate up to 1800 mg daily as needed
  • Particularly beneficial for patients with comorbid pain or anxiety 1
  • First choice for patients with chronic kidney disease or end-stage renal disease (with dose adjustment) 1

Second-Line Treatment

• Dopamine agonists (short-term use only due to augmentation risk):
  • Ropinirole: Start at 0.25 mg 1-3 hours before bedtime, titrate up to maximum 4 mg daily 3
  • Pramipexole: Start at 0.125 mg 1-3 hours before bedtime, titrate up to 0.5 mg daily
  • Rotigotine patch: Start at 1 mg/24 hours, titrate up to 3 mg/24 hours 1
  • Monitor closely for augmentation (paradoxical worsening of symptoms)

Third-Line Treatment

• Low-dose opioids for moderate to severe RLS that has failed other therapies:
  • Extended-release oxycodone for severe to very severe RLS
  • Use with caution due to risk of central sleep apnea and respiratory depression 1, 4

Non-Pharmacological Approaches

• Regular aerobic and resistance exercise
• Maintaining regular sleep schedule
• Bilateral high-frequency peroneal nerve stimulation
• For patients on hemodialysis: consider cool dialysate 1

Special Considerations

Augmentation

• Watch for earlier symptom onset, increased intensity, or spread to other body parts
• Management of augmentation:
  • Switch from dopamine agonists to alpha-2-delta ligands
  • Consider IV iron therapy if ferritin < 100 ng/mL
  • In severe cases, consider opioid therapy 5, 4

Pregnancy

• Consider pregnancy-specific safety profiles of treatments
• Non-pharmacological approaches preferred
• Iron supplementation if deficient 2

Follow-up and Monitoring

• Regular follow-up to assess symptom control
• Periodic reassessment of iron status
• Monitor for medication side effects, particularly augmentation with dopamine agonists 1

Important Caveats

• Dopamine agonists, while effective in the short term, carry significant risk of augmentation with long-term use, making alpha-2-delta ligands preferable for initial therapy 4
• Levodopa has higher rates of augmentation than other dopaminergic agents and is generally not recommended as first-line therapy 6
• Treatment should be taken 1-3 hours before bedtime for optimal symptom control 3