What are the treatment options for restless legs syndrome?

Treatment Options for Restless Legs Syndrome

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

Diagnosis and Assessment

• RLS is characterized by:

  • Urge to move the legs with uncomfortable sensations
  • Symptoms begin/worsen during rest
  • Relief with movement
  • Worsening in evening/night 1

• Laboratory evaluation priorities:

  • Ferritin level (values <50 ng/mL consistent with RLS diagnosis)
  • Iron supplementation recommended for ferritin levels <75 ng/mL 1

Treatment Algorithm

First-Line Approaches:

1. Non-pharmacological interventions (should be tried first or alongside medications):

   • Regular aerobic and resistance exercise
   • Proper hydration throughout the day
   • Sleeping with head of bed elevated (10°)
   • Compression stockings if venous pooling suspected
   • Smoking cessation, alcohol avoidance, caffeine reduction 1

2. First-line pharmacological options:

   • Alpha-2-delta ligands: pregabalin or gabapentin
     • Lower risk of augmentation compared to dopamine agonists
     • First choice for moderate to severe RLS 1
     • Particularly recommended for patients with chronic kidney disease 1

3. Iron supplementation:

   • For patients with ferritin <75 ng/mL
   • IV iron sucrose is first-line for end-stage renal disease patients with ferritin <200 ng/mL and transferrin saturation <20% 1

Second-Line Approaches:

1. Dopamine agonists (short-term use recommended due to augmentation risk):

   • Ropinirole: Starting dose 0.25 mg orally 1-3 hours before bedtime 1, 2
   • Pramipexole: Starting dose 0.125 mg orally 2-3 hours before bedtime 1
   • Rotigotine patch 1

   Clinical trials showed significant improvement with ropinirole compared to placebo:

   • Mean change in IRLS scale scores: -11 to -13.5 points (vs -8 to -9.8 for placebo)
   • Response rates: 53-73% (vs 40-57% for placebo) 2

2. For severe cases unresponsive to first-line treatments:

   • Opioids may be considered with caution due to risk of central sleep apnea and respiratory depression 1
   • Extended-release oxycodone for severe to very severe RLS 1

Managing Treatment Complications

Augmentation

Augmentation is a major concern with dopamine agonists, characterized by:

• Earlier symptom onset
• Increased symptom intensity
• Spread of symptoms to other body parts 1

Management of augmentation:

1. Add an alpha-2-delta ligand while maintaining the dopamine agonist
2. Once adequate symptom relief is achieved with the alpha-2-delta ligand, very slowly down-titrate and discontinue the dopamine agonist 3
3. This approach can lead to dramatic long-term relief of symptoms 3

Special Populations

• Chronic kidney disease/ESRD patients:

  • Gabapentin as first-line treatment
  • IV iron sucrose for those with low iron parameters
  • Consider vitamin C supplementation
  • Cool dialysate during hemodialysis 1

• Elderly patients:

  • Start with lower doses and titrate slowly
  • Monitor for orthostatic hypotension with dopamine agonists 1

Monitoring and Follow-up

• Regular monitoring for medication side effects, particularly augmentation with dopamine agonists
• Check ferritin levels regularly
• Assess symptom control and adjust treatment as needed 1

Pitfalls to Avoid

• Prolonged use of dopamine agonists increases augmentation risk
• Overlooking iron deficiency as a treatable cause
• Abrupt discontinuation of dopamine agonists can cause severe rebound symptoms 1, 3
• Using benzodiazepines as primary therapy (not recommended by guidelines) 1