What are the recommended medications for treating restless legs syndrome (RLS)?

Medication Management for Restless Legs Syndrome

Alpha-2-delta ligands (pregabalin or gabapentin) should be considered as first-line treatment for restless legs syndrome (RLS) due to their efficacy and favorable long-term safety profile with minimal risk of augmentation. 1

First-Line Treatment Options

Alpha-2-Delta Ligands

• Pregabalin or gabapentin are recommended as first-line treatments by the American Academy of Sleep Medicine 1
• Benefits:
  • Effective symptom control
  • Low risk of augmentation (paradoxical worsening of symptoms)
  • Better long-term safety profile compared to dopaminergic agents
• Dosing considerations:
  • Require dose adjustment in patients with renal impairment
  • Lower starting doses and slower titration recommended for older adults

Iron Supplementation

• Should be initiated when:
  • Serum ferritin ≤ 75 ng/mL or transferrin saturation < 20% in adults 1
  • Serum ferritin < 50 ng/mL in children 1
• Administration routes:
  • Oral iron for ferritin ≤ 75 ng/mL
  • IV iron if ferritin is between 75-100 ng/mL or if oral iron is not tolerated
• Testing recommendations:
  • Morning testing
  • Avoid iron supplements for 24 hours before testing

Second-Line Treatment Options

Dopamine Agonists

• Options include ropinirole, pramipexole, or rotigotine patch 1, 2
• FDA-approved for moderate-to-severe RLS 2
• Dosing recommendations:
  • Start with lowest possible dose (e.g., ropinirole 0.25 mg once daily) 2
  • Titrate based on clinical response over 7 weeks
  • Maximum dose of ropinirole for RLS: 4 mg once daily 2
  • Take 1-3 hours before bedtime 2
• Clinical efficacy:
  • Significant improvement in RLS symptoms compared to placebo
  • Responder rates of 53-73% in clinical trials 2
• Important caution: Recommended for short-term use only due to high risk of augmentation 1, 3

Opioids

• Low-dose opioids can be considered for:
  • Severe to very severe RLS 1
  • Cases where other therapies have failed
  • Facilitating taper of dopamine agonists
• Cautions:
  • Risk of central sleep apnea
  • Respiratory depression
  • Potential for dependence

Treatment Algorithm

1. Assess iron status - Check serum ferritin and transferrin saturation

   • If deficient: Start iron supplementation as first step

2. Initial pharmacotherapy:

   • First choice: Alpha-2-delta ligands (pregabalin or gabapentin)
   • Alternative: Low-dose dopamine agonists if alpha-2-delta ligands contraindicated or not tolerated

3. For patients with inadequate response:

   • Increase dose of current medication within recommended range
   • Consider switching to alternative first-line agent
   • For persistent symptoms: Consider adding or switching to dopamine agonist (short-term)

4. For severe, refractory cases:

   • Consider low-dose opioids
   • Consider combination therapy

Special Populations

Chronic Kidney Disease/ESRD

• Gabapentin or pregabalin (with dose adjustment) as first-line 1
• IV iron sucrose for ESRD patients with ferritin < 200 ng/mL and transferrin saturation < 20% 1
• Consider cool dialysate for patients on hemodialysis 1

Children

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

Monitoring and Management of Augmentation

• Regular follow-up to assess symptom control

• Monitor for signs of augmentation with dopamine agonists:

  • Earlier onset of symptoms
  • Increased symptom intensity
  • Spread of symptoms to other body parts
  • Shorter duration of effect from medication

• If augmentation occurs:

  • For mild augmentation: Divide the dose, advance timing, or slightly increase dose 4
  • For severe augmentation: Switch to alpha-2-delta ligand or rotigotine 4
  • In very severe cases: Consider opioid therapy 4

Non-Pharmacological Approaches

• Regular aerobic and resistance exercise 1
• Maintain regular sleep schedule
• Avoid substances that worsen RLS: caffeine, alcohol, antihistamines, certain antidepressants 1
• Bilateral high-frequency peroneal nerve stimulation as alternative therapy 1