What is the recommended treatment for restless leg syndrome?

Treatment of Restless Legs Syndrome

Alpha-2-delta ligands (pregabalin or gabapentin) are recommended 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 Evaluation

RLS is characterized by:

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

Key diagnostic steps:

• Assess ferritin levels (primary laboratory evaluation)
  • Iron supplementation recommended for ferritin <75 ng/mL or transferrin saturation <20%
• Consider additional testing:
  • Complete blood count
  • Basic metabolic panel
  • Liver function tests
  • Thyroid function tests
  • HbA1c
  • Urine albumin:creatinine ratio

Treatment Algorithm

Step 1: Address Secondary Causes and Non-Pharmacological Approaches

• Treat iron deficiency (if ferritin <75 ng/mL)
• Implement lifestyle modifications:
  • Regular aerobic and resistance exercise
  • Smoking cessation
  • Alcohol avoidance
  • Caffeine reduction/elimination
  • Discontinue potentially exacerbating medications

Step 2: First-Line Pharmacological Treatment for Moderate to Severe RLS

• Alpha-2-delta ligands:
  • Pregabalin or gabapentin
  • Preferred due to lower risk of augmentation compared to dopamine agonists 1

Step 3: Second-Line Treatment

• Dopamine agonists (short-term use only due to augmentation risk):
  • Ropinirole: Start 0.25 mg orally 1-3 hours before bedtime 1, 2
  • Pramipexole: Start 0.125 mg orally 2-3 hours before bedtime 1
  • Rotigotine patch

FDA trials showed ropinirole significantly reduced RLS symptoms compared to placebo, with mean changes in IRLS scale scores of -11.0 to -13.5 for ropinirole versus -8.0 to -9.8 for placebo across three trials 2.

Step 4: Treatment for Refractory Cases

• Opioids for severe RLS that fails to respond to first and second-line treatments
  • Use with caution due to risk of central sleep apnea and respiratory depression 1
  • Particularly effective for patients with augmentation when reducing dopamine agonists 3

Special Populations

Patients with Chronic Kidney Disease/ESRD:

• Gabapentin as first-line treatment
• IV iron sucrose for ESRD patients with ferritin <200 ng/mL and transferrin saturation <20%
• Consider vitamin C supplementation
• Consider cool dialysate for patients on hemodialysis 1

Monitoring and Follow-up

• Regular monitoring for medication side effects, particularly:

  • Augmentation with dopamine agonists (paradoxical worsening of symptoms)
  • Earlier symptom onset
  • Increased symptom intensity
  • Spread of symptoms to other body parts

• For dopamine agonists:

  • Keep doses as low as possible
  • Consider longer-acting agents like rotigotine patch
  • Maintain high serum ferritin levels to help prevent augmentation 3
  • Limit prolonged use due to high risk of augmentation (30-80% of patients) 1

• For geriatric patients:

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

Non-Pharmacological Interventions

Several non-pharmacological approaches have shown benefit in RLS management:

• Compression devices
• Repetitive transcranial magnetic stimulation
• Infrared therapy
• Counterstrain manipulation
• Standard acupuncture 4

These interventions may be particularly useful for patients with milder symptoms or as adjuncts to pharmacological therapy.