What are the treatment options for restless leg syndrome?

Treatment Options for Restless Legs Syndrome

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

Diagnosis and Initial Evaluation

• RLS is characterized by:

  • An urge to move the legs accompanied by uncomfortable sensations
  • Symptoms that begin or worsen during periods of rest
  • Relief with movement
  • Worsening of symptoms in the evening or night 1

• Laboratory evaluation:

  • Ferritin testing is the primary laboratory evaluation for RLS 1
  • Complete blood count, basic metabolic panel, and liver function tests should be considered 1
  • Evaluate for secondary causes: renal disease, diabetes, medication side effects, and thyroid disorders 1

Treatment Algorithm

Step 1: Iron Supplementation

• Check serum ferritin and transferrin saturation in all patients with RLS 1
• Supplement iron if:
  • Ferritin ≤75 ng/mL or transferrin saturation <20% 1
  • Use oral iron supplementation for most patients
  • IV iron sucrose for ESRD patients with ferritin <200 ng/mL and transferrin saturation <20% 1

Step 2: Non-Pharmacologic Approaches

• Regular aerobic and resistance exercise 1
• Moderate exercise regimen 1
• Lifestyle modifications:
  • Smoking cessation
  • Alcohol avoidance
  • Caffeine reduction or elimination
  • Discontinuation of potentially exacerbating medications 1

Step 3: Pharmacologic Therapy for Moderate to Severe RLS

First-line:

• Alpha-2-delta ligands:
  • Pregabalin or gabapentin 1
  • Particularly beneficial in patients with comorbid pain or anxiety
  • Lower risk of augmentation compared to dopamine agonists
  • Gabapentin is first-line for patients with CKD or ESRD 1

Second-line:

• Dopamine agonists (short-term use only 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
  • Titrate based on clinical response and tolerability over 7 weeks to a maximum of 4 mg once daily for ropinirole 2

Third-line:

• Opioids for severe cases that fail to respond to first and second-line treatments:
  • Extended-release oxycodone for severe to very severe RLS 1
  • Use with caution due to risk of central sleep apnea and respiratory depression 1

Special Considerations

Augmentation

• A paradoxical worsening of symptoms with dopaminergic treatment 1
• Characterized by:
  • Earlier symptom onset
  • Increased symptom intensity
  • Spread of symptoms to other body parts 1
• Risk is high with dopamine agonists (30-80% of patients) 1
• Prevention strategies:
  • Keep dopamine agonist dose as low as possible
  • Use longer-acting agents like rotigotine patch
  • Maintain high serum ferritin levels 1

Geriatric Patients

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

Patients with End-Stage Renal Disease

• Gabapentin as first-line therapy
• Consider vitamin C supplementation
• Cool dialysate may be beneficial 1

Monitoring and Follow-up

• Regular follow-up to assess symptom control and adjust treatment as needed 1
• Monitor for medication side effects, particularly augmentation with dopamine agonists 1
• Reassess ferritin levels periodically and supplement when <50 ng/mL 1

Treatment Efficacy

• Ropinirole has demonstrated significant improvement in RLS symptoms compared to placebo in multiple clinical trials, with mean changes in IRLS scale scores of -11 to -13.5 points versus -8 to -9.8 points for placebo 2
• Long-term maintenance of efficacy with ropinirole has been demonstrated in a 36-week trial, with significantly lower relapse rates compared to placebo (32.6% versus 57.8%) 2