What is the recommended treatment (Rx) for restless legs syndrome?

Treatment of Restless Legs Syndrome (RLS)

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

First-Line Treatment Options

Alpha-2-Delta Ligands

• Pregabalin or gabapentin are recommended as first-line therapy due to:
  • Strong efficacy in symptom control
  • Lower risk of augmentation compared to dopaminergic agents
  • Particularly beneficial for patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD) with appropriate dose adjustment 1

Iron Therapy

• Should be first-line treatment for patients with low iron stores:
  • Initiate if ferritin ≤75 ng/mL or transferrin saturation <20%
  • Oral ferrous sulfate for most patients
  • IV ferric carboxymaltose for inadequate response to oral iron
  • IV iron sucrose specifically for ESRD patients with ferritin <200 ng/mL and transferrin saturation <20% 1

Second-Line Treatment Options

Dopamine Agonists

• Ropinirole, pramipexole, or rotigotine patch can be effective but are recommended for short-term use only due to risk of augmentation 1
• Ropinirole has demonstrated efficacy in clinical trials with significant improvements in RLS symptoms compared to placebo 2
• Dosing considerations for ropinirole:
  • Starting dose: 0.25 mg once daily
  • Titration based on response and tolerability over 7 weeks
  • Maximum dose: 4 mg once daily
  • Administration: 1-3 hours before bedtime 2

Opioids

• Extended-release oxycodone is conditionally recommended for moderate to severe RLS, particularly for patients who have failed other therapies 1
• Requires careful monitoring for respiratory depression and central sleep apnea 1

Non-Pharmacological Approaches

• Regular aerobic and resistance exercise
• Good sleep hygiene practices
• Avoidance of substances that may worsen RLS:
  • Caffeine
  • Alcohol
  • Antihistamines
  • Most antidepressants 1
• Alternative therapies to consider:
  • Bilateral high-frequency peroneal nerve stimulation
  • Cool dialysate for patients on hemodialysis 1

Management of Augmentation

Augmentation is a paradoxical worsening of RLS symptoms that occurs primarily with dopaminergic treatment, characterized by:

• Earlier onset of symptoms during the day
• Increased symptom intensity
• Shorter latency to symptom onset during rest
• Spread of symptoms to other body parts
• Shorter duration of relief from medication 1, 3

If augmentation occurs:

1. Gradually taper and discontinue the dopaminergic agent
2. Transition to alpha-2-delta ligands or opioids
3. Consider IV iron therapy 1
4. Low-dose opioids are specifically recommended for managing dopamine agonist-related augmentation 1

Special Populations

Chronic Kidney Disease/ESRD

• Gabapentin or pregabalin (with dose adjustment) as first-line therapy 1
• IV iron sucrose for those with ferritin <200 ng/mL and transferrin saturation <20% 1

Pregnant Patients

• Prioritize non-pharmacological approaches due to safety concerns 1

Children

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

Monitoring and Follow-up

• Regular assessment of symptom control
• Minimal dose increases over time
• Close monitoring for medication side effects, particularly augmentation in patients on dopamine agonists 1

The shift from dopaminergic agents to alpha-2-delta ligands as first-line therapy represents a significant change in RLS treatment paradigms, driven by increasing recognition of the risks of augmentation with long-term dopaminergic therapy 1, 3, 4.