Treatment Options in Intractable Restless Legs Syndrome/Willis-Ekbom Disease (RLS/WED)

Current Treatment Options in Neurology

Volumn 18, Issue 2, 2016, Pages 1-9

  Rinaldi, Fabrizio ^a,b   Galbiati, Andrea ^a,c   Marelli, Sara ^a,c   Ferini Strambi, Luigi ^a,c   Zucconi, Marco ^a  

^a SAN RAFFAELE HOSPITAL   (Italy)

^b UNIVERSITY OF BRESCIA   (Italy)

^c VITA SALUTE SAN RAFFAELE UNIVERSITY   (Italy)

Author keywords

Augmentation; Dopamine agonists; Intractable RLS WED; Non pharmacological treatments; Opioids; Restless legs syndrome Willis Ekbom disease

Indexed keywords

ALPHA 2 DELTA CALCIUM CHANNEL DERIVATIVE; ANTICONVULSIVE AGENT; APOMORPHINE; BENZODIAZEPINE DERIVATIVE; CABERGOLINE; CALCIUM CHANNEL AFFECTING AGENT; CARBAMAZEPINE; CLONAZEPAM; CODEINE; DEXTROPROPOXYPHENE; DOPAMINE RECEPTOR STIMULATING AGENT; ETIRACETAM; FERRIC CARBOXYMALTOSE; GABAPENTIN ENACARBIL; IRON DERIVATIVE; IRON DEXTRAN; LAMOTRIGINE; LEVODOPA; METHADONE; MORPHINE; NALOXONE; OPIATE DERIVATIVE; OXYCODONE; PERGOLIDE; PRAMIPEXOLE; PREGABALIN; ROPINIROLE; ROTIGOTINE; TRAMADOL; UNCLASSIFIED DRUG; UNINDEXED DRUG;

BRAIN DEPTH STIMULATION; COMORBIDITY; DRUG EFFICACY; DRUG TOLERABILITY; EXERCISE; HEALTH CARE AVAILABILITY; HUMAN; HYGIENE; INTRACTABLE RESTLESS LEGS SYNDROME; INTRATHECAL DRUG ADMINISTRATION; IRON THERAPY; LIFESTYLE MODIFICATION; RESTLESS LEGS SYNDROME; REVIEW; SLEEP QUALITY; SYMPTOMATOLOGY; TRANSCRANIAL MAGNETIC STIMULATION; TREATMENT PLANNING; WILLIS EKBOM DISEASE;

EID: 84958170304     PISSN: 10928480     EISSN: 15343138     Source Type: Journal    
DOI: 10.1007/s11940-015-0390-1     Document Type: Review

References (43)

1. Allen RP, Picchietti DL, Garcia-Borreguero D, Ondo WG, Walters AS, Winkelman JW, et al. International Restless Legs Syndrome Study Group. Restless legs syndrome/Willis-Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria–history, rationale, description, and significance. Sleep Med. 2014;15:860–73. This paper provides an important description and historical overview that brings to the updated diagnostic criteria for RLS/WED.
2. Manconi M, Ferri R, Zucconi M, Oldani A, Fantini ML, Castronovo V, et al. First night efficacy of pramipexole in restless legs syndrome and periodic leg movements. Sleep Med. 2007;8:491–7. This study demonstrates the immediate efficacy and tolerability of pramipexole in RLS/WED patients.
3. Mackie S, Winkelman JW. Long-term treatment of restless legs syndrome (RLS): an approach to management of worsening symptoms, loss of efficacy, and augmentation. CNS Drugs. 2015;29:351–7.
4. Trenkwalder C, Beneš H, Grote L, García-Borreguero D, Högl B, Hopp M, et al. (2013). Prolonged release oxycodone–naloxone for treatment of severe restless legs syndrome after failure of previous treatment: a double-blind, randomised, placebo-controlled trial with an open-label extension. Lancet Neurol. 2013;12:1141–50. This study provides evidence for the employment of opioids in RLS/WED treatment when first-line drugs have no efficacy.
5. Tzonova D, Larrosa O, Calvo E, Granizo JJ, Williams AM, De la Llave Y, et al. Breakthrough symptoms during the daytime in patients with restless legs syndrome (Willis-Ekbom disease). Sleep Med. 2012;13:151–5.
6. García-Borreguero D, Allen R, Kohnen R, et al. Loss of response during long-term treatment of restless legs syndrome: guidelines approved by the International Restless Legs Syndrome Study Group for use in clinical trials. Sleep Med. 2010;11(9):956–7.
7. Winkelman JW, Johnston L. Augmentation and tolerance with long-term pramipexole treatment of restless legs syndrome (RLS). Sleep Med. 2004;5(1):9–14.
8. Akpinar S. Treatment of restless legs syndrome with levodopa plus benserazide. Arch Neurol. 1982;39:739.
9. Garcıa-Borreguero D, Kohnen R, Silber MH, et al. The long-term treatment of restless legs syndrome/Willis-Ekbom disease: evidence-based guidelines and clinical consensus best practice guidance: a report from the International Restless Legs Syndrome Study Group. Sleep Med. 2013;14(7):675–84. These guidelines give an evidenced-based approach for long term-treatment of RLS/WE.
10. Silber MH, Becker PM, Earley C. Garcia-Borreguero D, Ondo WG, Medical Advisory Board of the Willis-Ekbom Disease Foundation. Willis-Ekbom Disease Foundation revised consensus statement on the management of restless legs syndrome. Mayo Clin Proc. 2013;88(9):977–86.
11. Lisa Klingelhoefer,A Ilaria Cova,B Sheena GuptaC and Kallol Ray ChaudhuriD, A review of current treatment strategies for restless legs syndrome (Willis–Ekbom disease), Royal College of Physicians 2014
12. Takahashi M, Ikeda J, Tomida T, Hirata K, Hattori N, Inoue Y. Daytime symptoms of restless legs syndrome—clinical characteristics and rotigotine effectiveness. Sleep Med. 2015;16(7):871–6. doi:10.1016/j.sleep.2015.03.006.
13. Högl B, Garcia-Borreguero D, Kohnen R, et al. Progressive development of augmentation during long-term treatment with levodopa in restless legs syndrome: results of a prospective multi-center study. J Neurol. 2010;257:230–7.
14. Tings T, Stiens G, Paulus W, Trenkwalder C, Happe S. Treatment of restless legs syndrome with subcutaneous apomorphine in a patient with short bowel syndrome. J Neurol. 2005;252(3):361–3.
15. Allen RP, Earley CJ. Augmentation of the restless legs syndrome with carbidopa/ levodopa. Sleep. 1996;19:205–13.
16. Rinaldi F, Galbiati A, Marelli S, Cusmai M, Gasperi A, Oldani A, Zucconi M, Padovani A, Ferini-Strambi L. Defining the phenotype of Restless Legs Syndrome/Willis-Ekbom Disease (RLS/WED): a clinical and polysomnographic study, J Neurol. 2016
17. Allen RP, Chen C, Garcia-Borreguero D, Polo O, DuBrava S, Miceli J, et al. Comparison of pregabalin with pramipexole for restless legs syndrome. N Engl J Med. 2014;370(7):621–31.
18. Allen RP, Walters AS, Montplaisir J, et al. Restless legs syndrome prevalence and impact: REST general population study. Arch Intern Med. 2005;165(11):1286–92. To the best of our knowledge this paper is the first large-scale, multinational, population-based profile study that employs the full standard criteria for RLS/WED.
19. Trenkwalder C, Benesˇ H, Grote L, et al. Prolonged release oxycodone-naloxone for treatment of severe restless legs syndrome after failure of previous treatment: a double-blind, randomised, placebo-controlled trial with an open-label extension. Lancet Neurol. 2013;12(12):1141–50.
20. Silver N, Allen RP, Senerth J, Earley CJ. A 10-year, longitudinal assessment of dopamine agonists and methadone in the treatment of restless legs syndrome. Sleep Med. 2011;12(5):440–4.
21. Ondo WG. Methadone for refractory restless legs syndrome. Mov Disord. 2005;20(3):345–8.
22. Earley CJ, Connor J, Garcia-Borreguero D, et al. Altered brain iron homeostasis and dopaminergic function in restless legs syndrome (Willis-Ekbom Disease). Sleep Med. 2014;15(11):1288–301.
23. Hornyak M, Kaube H. Long-term treatment of a patient with severe restless legs syndrome using intrathecal morphine. Neurology. 2012;79(24):2361–2. doi:10.1212/WNL.0b013e318278b5e7. Epub 2012 Nov 28.
24. Ghosh A, Basu D. Restless legs syndrome in opioid dependent patients. Indian J Psychol Med. 2014;36(1):85–7.
25. Trenkwalder C, Hening WA, Montagna P, et al. Treatment of restless legs syndrome: an evidence-based review and implications for clinical practice. Mov Disord. 2008;23(16):2267–302.
26. Walters AS, Wagner ML, Hening WA, et al. Successful treatment of the idiopathic restless legs syndrome in a randomized double-blind trial of oxycodone versus placebo. Sleep. 1993;16(4):327–32.
27. Wang J, O’Reilly B, Venkataraman R, Mysliwiec V, Mysliwiec A. Efficacy of oral iron in patients with restless legs syndrome and a low-normal ferritin: a randomized, double-blind, placebo-controlled study. Sleep Med. 2009;10(9):973–5.
28. Ondo W. Intravenous iron dextran for severe refractory restless legs syndrome. Sleep Med. 2010;11:494–6. These are two relevant studies investigating respectively oral and intravenous iron efficacy in RLS/WED syndrome.
29. Auerbach M, Pappadakis J, Bahrain H, et al. Safety and efficacy of rapidly administered (one hour) one gram of low molecular weight iron dextran (INFeD) for the treatment of iron deficient anemia. Am J Hematol. 2011;86:860–2.
30. Allen R, Auerbach S, Bahrain H, et al. The prevalence and impact of restless legs syndrome n patients with iron deficiency anemia. Am J Hematol. 2013;88:261–4.
31. Cho Y, Allen R, Earley C. Lower molecular weight intravenous iron dextran for restless legs syndrome. Sleep Med. 2013;14:274–7.
32. Schneider J, Krafft A, Manconi M, Hübner A, Baumann C, Werth E, et al. Open-label study of the efficacy and safety of intravenous ferric carboxymaltose in pregnant women with restless legs syndrome. Sleep Med. 2015;16(11):1342–7. doi:10.1016/j.sleep.2015.08.006. Epub 2015 Aug 20.
33. Silber MH, Ehrenberg BL, Allen RP, et al. An algorithm for the management of restless legs syndrome. Mayo Clin Proc. 2004;79(7):916–22.
34. The International Restless Legs Syndrome Study Group (IRLSSG). White paper summary of recommendations for the prevention and treatment of RLS/WED augmentation, 2015, http://irlssg.org/wp-content/uploads/2015/05/Summary-of-recommendations-RLS-Augmentation-13Aug2015.pdf. These white paper provides new although yet unpublished guidelines for treatment and prevention of augmentation.
35. Mitler MM, Browman CP, Menn SJ, Gujavarty K, Timms RM. Nocturnal myoclonus: treatment efficacy of clonazepam and temazepam. Sleep. 1986;9(3):385–92.
36. Schenck CH, Mahowald MW. Long-term, nightly benzodiazepine treatment of injurious parasomnias and other disorders of disrupted nocturnal sleep in 170 adults. Am J Med. 1996;100:333–7.
37. Della Marca G, Vollono C, Mariotti P, Mazza M, Mennuni GF, Tonali P. Levetiracetam can be effective in the treatment of restless legs syndrome with periodic limb movements in sleep: report of two cases. J Neurol Neurosurg Psychiatry. 2006;77:566–7.
38. Aukerman MM, Aukerman D, Bayard M, Tudiver F, Thorp L, Bailey B. Exercise and restless legs syndrome: a randomized controlled trial. J Am Board Fam Med. 2006;19:487–93.
39. Giannaki CD, Sakkas GK, Karatzaferi C, Maridaki MD, Koutedakis Y, Hadjigeorgiou GM, Stefanidis I. Combination of exercise training and dopamine agonists in dialysis patients with RLS: A randomized double-blind placebo controlled study. ASAIO journal (American Society for Artificial Internal Organs: 1992) 2015. This study suggests that exercise training plus low dose DA could represent a valid alternative to high dosage DA in order to reduce symptoms’ severity in RLS/WED.
40. Hornyak M, Grossmann C, Kohnen R, Schlatterer M, Richter H, Voderholzer U, et al. Cognitive behavioural group therapy to improve patients’ strategies for coping with restless legs syndrome: a proof-of-concept trial. J Neurol Neurosurg Psychiatry. 2008;79:823–5.
41. Lin YC, Feng Y, Zhan SQ, Li N, Ding Y, Hou Y, et al. Repetitive transcranial magnetic stimulation for the treatment of restless legs syndrome. Chin Med J. 2015;128(13):1728.
42. Koo YS, Kim SM, Lee C, Lee BU, Moon YJ, Cho YW, et al. Transcranial direct current stimulation on primary sensorimotor area has no effect in patients with drug-naïve restless legs syndrome: a proof-of-concept clinical trial. Sleep Med. 2015;16(2):280–7. This is a well-designed and controlled study that shows the inefficacy of tDCS in reducing RLS/WED symptomatology.
43. Heide AC, Winkler T, Helms HJ, Nitsche MA, Trenkwalder C, Paulus W, et al. Effects of transcutaneous spinal direct current stimulation in idiopathic restless legs patients. Brain Stimul. 2014;7(5):636–42.