What are alternative treatments to ropinirole (Dopamine Agonist) for patients with Restless Legs Syndrome (RLS)?

Alternative Treatments to Ropinirole for Restless Legs Syndrome

Alpha-2-delta ligands (gabapentin, gabapentin enacarbil, or pregabalin) are strongly recommended as first-line therapy for patients with Restless Legs Syndrome, replacing dopamine agonists like ropinirole due to their better efficacy and lower risk of augmentation. 1

First-Line Alternatives to Ropinirole

• Alpha-2-delta ligands are now the preferred first-line treatment for RLS:

  • Gabapentin (strong recommendation, moderate certainty of evidence) 1
  • Gabapentin enacarbil (strong recommendation, moderate certainty of evidence) 1
  • Pregabalin (strong recommendation, moderate certainty of evidence) 1

• Iron therapy should be considered for patients with low iron stores:

  • Oral ferrous sulfate if ferritin ≤75 ng/mL or transferrin saturation <20% (conditional recommendation, moderate certainty) 1
  • IV ferric carboxymaltose for patients with appropriate iron parameters who don't respond to oral therapy (strong recommendation, moderate certainty) 1
  • IV iron sucrose for patients with end-stage renal disease if ferritin <200 ng/mL and transferrin saturation <20% (conditional recommendation, moderate certainty) 1

Second-Line and Alternative Treatments

• Opioids can be effective for refractory cases or when treating augmentation from dopaminergic agents:

  • Extended-release oxycodone and other opioids (conditional recommendation) 1
  • Methadone and buprenorphine have shown efficacy with relatively low risks of abuse in appropriately screened patients 1

• Non-pharmacological options:

  • Bilateral high-frequency peroneal nerve stimulation (conditional recommendation, moderate certainty of evidence) 1
  • Vitamin C for patients with end-stage renal disease (conditional recommendation) 1

Why Avoid Ropinirole and Other Dopamine Agonists

• The American Academy of Sleep Medicine suggests against the standard use of dopamine agonists including ropinirole (conditional recommendation, moderate certainty of evidence) due to significant risk of augmentation with long-term use 1, 2

• Augmentation is characterized by:

  • Worsening and earlier onset of symptoms in patients initially controlled on medication 2
  • Increased symptom intensity and spread of symptoms to other body parts 1
  • Earlier symptom onset during the day 2

• Dopamine agonists like ropinirole have a higher risk of causing dizziness and somnolence, which can directly increase fall risk 1

Managing Patients Currently on Ropinirole

• If augmentation has developed, consider:
  • Taking medication doses earlier in the day 2
  • Splitting existing doses into early evening and bedtime doses 2
  • Gradually transitioning to an alpha-2-delta ligand 1
  • Using opioids temporarily to relieve worsening symptoms when decreasing or eliminating dopamine agonists 1

Initial Assessment Before Starting Alternative Treatment

• Check serum iron studies, including ferritin and transferrin saturation, in all patients with clinically significant RLS 1
• Address potential exacerbating factors, including alcohol, caffeine, antihistaminergic medications, serotonergic medications, and antidopaminergic medications 1
• Evaluate for untreated obstructive sleep apnea 1
• Distinguish RLS from mimics such as neuropathy, akathisia, positional discomfort, and nocturnal leg cramps 1

Medications to Specifically Avoid

• The American Academy of Sleep Medicine specifically recommends against:
  • Cabergoline (strong recommendation, moderate certainty) 1
  • Bupropion, carbamazepine, clonazepam, valproic acid, and valerian (conditional recommendations) 1

Special Considerations

• For patients with end-stage renal disease, consider gabapentin (conditional recommendation, very low certainty) 1
• For pediatric RLS, consider ferrous sulfate (conditional recommendation, very low certainty) 1
• When using alpha-2-delta ligands, evaluate risk factors for misuse and monitor for side effects including dizziness and somnolence 1