What is the treatment for Restless Legs Syndrome (RLS)?

Treatment for Restless Legs Syndrome (RLS)

Alpha-2-delta ligands such as pregabalin or gabapentin should be used as first-line pharmacologic therapy for Restless Legs Syndrome due to their strong evidence of efficacy and favorable long-term safety profile compared to dopaminergic agents. 1

Diagnostic Approach

• Diagnosis requires:
  • An urge to move the legs with or without uncomfortable sensations
  • Symptoms that worsen at rest
  • Relief with movement
  • Worsening of symptoms in the evening/night

Treatment Algorithm

Step 1: Iron Assessment and Therapy

• Check ferritin levels and transferrin saturation
• Initiate iron therapy if:
  • Ferritin ≤75 ng/mL or transferrin saturation <20%
  • Use oral ferrous sulfate for most patients
  • Consider IV ferric carboxymaltose for inadequate response to oral iron
  • For ESRD patients with ferritin <200 ng/mL and transferrin saturation <20%, use IV iron sucrose 1

Step 2: First-Line Pharmacologic Treatment

• Alpha-2-delta ligands (preferred first-line)
  • Gabapentin or pregabalin
  • Advantages: no risk of augmentation, effective for long-term use
  • Suitable for patients with chronic kidney disease with dose adjustment 1

Step 3: Alternative Pharmacologic Options

• Dopamine agonists (short-term use)
  • Ropinirole: Start at 0.25 mg once daily, titrate based on response over 7 weeks to maximum 4 mg daily
  • Take 1-3 hours before bedtime
  • Clinical trials showed significant improvement in RLS symptoms compared to placebo 2
  • Mean effective dose of pramipexole ~0.3 mg
  • Caution: Risk of augmentation (paradoxical worsening of symptoms) with long-term use 1

Step 4: Refractory Cases

• Opioids
  • Extended-release oxycodone for moderate to severe RLS
  • Recommended for patients who have failed other therapies
  • Monitor for respiratory depression and central sleep apnea 1

Non-Pharmacological Approaches

• Regular aerobic resistance exercise 1
• Good sleep hygiene practices:
  • Consistent sleep-wake schedule
  • Limiting stimulants 1
• Bilateral high-frequency peroneal nerve stimulation 1
• Compression devices, which have shown effectiveness in improving sleep-related outcomes 3
• Massage, hot baths, and mentally demanding tasks may reduce symptoms 4

Special Populations

Patients on Hemodialysis

• Cool dialysate is recommended 1
• Gabapentin with dose adjustment is recommended for ESRD patients 1

Pregnant Patients

• Prioritize non-pharmacological approaches due to safety concerns 1

Children

• Iron therapy should be first-line for children with low iron stores
• Limited evidence for medications in children with no FDA-approved options 1

Monitoring and Follow-up

• Regular monitoring for medication side effects, particularly for:

  • Dopamine agonists: Watch for augmentation
  • Alpha-2-delta ligands: Monitor for sedation
  • Opioids: Watch for dependence and respiratory effects 1

• If augmentation occurs with dopamine agonists:

  • Gradually taper and discontinue
  • Transition to alpha-2-delta ligands or opioids 1

Treatment Selection Considerations

• Severity of symptoms
• Comorbid conditions (especially kidney disease)
• Iron status
• Patient preference regarding side effect profiles

Remember that RLS requires treatment only when it significantly impacts nighttime sleep or daily activities, and medication doses should be kept to the minimum required for acceptable symptom reduction 5.