Treatment

The following drugs have been used in the management of restless legs syndrome:

• dopamine agonists
  • non-ergotamine dopamine agonists e.g. pramipexole, ropiniprole (1)
    • drug of choice for patients with daily symptoms (2)
  • ergotamine dopamine agonists e.g. cabergoline, pergolide
    • less preferred due to its side effects
      
      
• levodopa
  • used in patients who are intolerant to dopamine agonists
  • provides relief in intermittent symptoms
  • can be used as a prophylaxis drug e.g. – during long plane trips, car rides, or theatre events (2)
    
    
• anti-epileptic agents
  • gabapentin is useful in patients with coexisting neuropathic pain and in haemodialysis patients (1,3)
    
    
• opioids
  • weak opioids (codeine or tramadol) can be used intermittently or daily for painful RLS (3,4)
    
    
• benzodiazepines
  • e.g. clonazepam 0.5-2 mg 30 minutes before retiring (6)
  • used intermittently in sleep onset insomnia caused by RLS
    
    
• imipramine e.g. 25 mg 30 minutes before retiring (6)

Other treatments reported to be effective include:

• clonidine
• carbamazepine

Notes:

• a Drug and Therapeutics Bulletin review concluded that (7) '..Based on the limited available evidence, dopamine agonists may be worth trying in some patients whose symptoms are severe. However no dopamine agonists are licensed for this indication...Other drugs that are used include opioids, antiepileptics and benzodiazepines, but their use cannot be justified on current evidence.'
• a more recent study found that cabergoline is an efficacious and well-tolerated option for the treatment of restless legs symptoms during the night and the day (8)
• a suggested treatment plan for use of medication in restless legs syndrome has been outlined (5) "
  • start treatment with a dopamine agonist (all newer agonists such as pergolide, cabergoline, pramipexole and ropinirole are effective and should be given as a single dose in the evening)
  • if patients are intolerant to dopamine agonists then levodopa (Sinemet or Madopar) should be given at night-time before bed. 80-82% of paitents taking levodopa may develop augmentation or rebound
  • if levodopa is no longer effective or if symptoms start appearing in the early morning (rebound phenomenon) or evening/daytime with spread to upper limb (augmentation), then dopamine agonists may be reintroduced. At this stage cabergoline may be particularly useful as this drug works given once daily. Dopamine agonists with shorter half-life may need to be given up to 3 times a day
  • if symptoms are resistant then an antiepileptic drug such as carbamazepine or gabapentin may be tried. These drugs inhibit the hyperactivity of the nervous system that may be related to the symptoms. Gabapentin may be particularly useful for haemodialysis patients because it is dialyzable and has a long half-life, and for 'painful' RLS
  • severe unremitting painful RLS may need to be treated by strong painkillers such as Codeine, Tramadol, Oxycodone or Propoxyphene under specialist guidance
  • bedtime sedatives such as clonazepam or zopiclone may be useful in some cases with severe insomnia. These may also exert a beneficial effect by reducing nervous activity and by increasing muscle relaxation
  • in some severe cases unresponsive to above, patients may need hospitalisation and treatment with subcutaneous apomorphine given overnight by a pump in specialist centres.."

Reference:

• (1) Bayard M et al. Restless legs syndrome. AFP 2008;78(2)
• (2) Gamaldo C.E. et al. Rest legs syndrome – A clinical update. Chest 2006;130(5):1596-1604
• (3) RLS:UK website www.restlesslegs.org.uk (accessed 18/5/06)
• (4) Yee B, Killick R. Restless legs syndrome. Aust Fam Physician 2009;38(5)
• (5) Moore AP. Commentary on "Pergolide reduced involuntary periodic leg movements and improved sleep in the restless legs syndrome". Evidence-Based Medicine 2000 Jan-Feb:21. Comment on Wetter TC, Stiasny K, Winkelmann J, et al. A randomized controlled study of pergolide in patients with restless legs syndrome. Neurology (1999), 52, 944-50.
• (6) Prescriber (2001), 12 (3), 93-97.
• (7) Drug and Therapeutics Bulletin (2003), 41 (11), 81-3.
• (8) Stiansny-Kolster K et al. Effective cabergoline treatment in idiopathic restless legs syndrome. Neurology 2004;63:2272-9