Efficacy and safety of dopamine agonists in restless legs syndrome

Sleep Medicine

Volumn 13, Issue 3, 2012, Pages 228-236

  Hornyak, Magdolna ^a   Trenkwalder, Claudia ^b,c   Kohnen, Ralf ^d,e   Scholz, Hanna ^a  

^a UNIVERSITY OF FREIBURG   (Germany)

^b Centre for Parkinson Syndromes and Movement Disorders   (Germany)

^c UNIVERSITY OF GÖTTINGEN   (Germany)

^d Research Pharmaceutical Services Inc   (United States)

^e UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

Author keywords

Dopamine agonists; Meta analysis; Quality of life; Restless legs syndrome; Safety; Treatment efficacy

Indexed keywords

CABERGOLINE; DOPAMINE RECEPTOR STIMULATING AGENT; LEVODOPA; LISURIDE; PERGOLIDE; PLACEBO; PRAMIPEXOLE; ROPINIROLE; ROTIGOTINE; SUMANIROLE;

CLINICAL GLOBAL IMPRESSION SCALE; DRUG DOSE TITRATION; DRUG EFFECT; DRUG EFFICACY; DRUG RESPONSE; DRUG SAFETY; DRUG WITHDRAWAL; HUMAN; META ANALYSIS; PERIODIC LIMB MOVEMENT DISORDER; PRIORITY JOURNAL; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL (TOPIC); RESTLESS LEGS SYNDROME; REVIEW; SLEEP QUALITY; SYSTEMATIC REVIEW; TREATMENT DURATION; TREATMENT OUTCOME; UNSPECIFIED SIDE EFFECT;

DOPAMINE AGONISTS; HUMANS; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RESTLESS LEGS SYNDROME;

EID: 84857239411     PISSN: 13899457     EISSN: 18785506     Source Type: Journal    
DOI: 10.1016/j.sleep.2011.09.013     Document Type: Review

References (56)

1. Walters A.S. Toward a better definition of the restless legs syndrome. The International restless legs syndrome study group. Mov Disord 1995, 10:634-642.
2. Allen R.P., Picchietti D., Hening W.A., Trenkwalder C., Walters A.S., Montplaisir J. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 2003, 4:101-119.
3. Montplaisir J., Boucher S., Poirier G., Lavigne G., Lapierre O., Lesperance P. Clinical, polysomnographic, and genetic characteristics of restless legs syndrome: a study of 133 patients diagnosed with new standard criteria. Mov Disord 1997, 12:61-65.
4. Stiasny-Kolster K., Kohnen R., Moller J.C., Trenkwalder C., Oertel W.H. Validation of the 'L-DOPA test' for diagnosis of restless legs syndrome. Mov Disord 2006, 21:1333-1339.
5. Kushida C., Martin M., Nikam P., et al. Burden of restless legs syndrome on health-related quality of life. Qual Life Res 2007, 16:617-624.
6. Talati R., Phung O.J., Mather J., Coleman C.I. Effect of non-ergot dopamine agonists on health-related quality of life of patients with restless legs syndrome. Ann Pharmacother 2009, 43:813-821.
7. Hening W., Walters A.S., Allen R.P., Montplaisir J., Myers A., Ferini-Strambi L. Impact, diagnosis and treatment of restless legs syndrome (RLS) in a primary care population: the REST (RLS epidemiology, symptoms, and treatment) primary care study. Sleep Med 2004, 5:237-246.
8. Trenkwalder C., Paulus W. Restless legs syndrome: pathophysiology, clinical presentation and management. Nat Rev Neurol 2010, 6:337-346.
9. Walters A.S., Rye D.B. Review of the relationship of restless legs syndrome and periodic limb movements in sleep to hypertension, heart disease, and stroke. Sleep 2009, 32:589-597.
10. Hening W. The clinical neurophysiology of the restless legs syndrome and periodic limb movements. Part I: diagnosis, assessment, and characterization. Clin Neurophysiol 2004, 115:1965-1974.
11. Trenkwalder C., Paulus W. Why do restless legs occur at rest? Pathophysiology of neuronal structures in RLS. Neurophysiology of RLS (Part 2). Clin Neurophysiol 2004, 115:1975-1988.
12. Trenkwalder C., Hening W.A., Montagna P., et al. Treatment of restless legs syndrome: an evidence-based review and implications for clinical practice. Mov Disord 2008, 23:2267-2302.
13. Baker W.L., White C.M., Coleman C.I. Effect of nonergot dopamine agonists on symptoms of restless legs syndrome. Ann Fam Med 2008, 6:253-262.
14. Hansen R.A., Song L., Moore C.G., et al. Effect of ropinirole on sleep outcomes in patients with restless legs syndrome: meta-analysis of pooled individual patient data from randomized controlled trials. Pharmacotherapy 2009, 29:255-262.
15. Quilici S., Abrams K.R., Nicolas A., et al. Meta-analysis of the efficacy and tolerability of pramipexole versus ropinirole in the treatment of restless legs syndrome. Sleep Med 2008, 9:715-726.
16. Zintzaras E., Kitsios G.D., Papathanasiou A.A., et al. Randomized trials of dopamine agonists in restless legs syndrome: a systematic review, quality assessment, and meta-analysis. Clin Ther 2010, 32:221-237.
17. Scholz H., Trenkwalder C., Kohnen R., Kriston L., Riemann D., Hornyak M. Dopamine agonists for restless legs syndrome. Cochrane Database System Rev 2011, 3:CD006009.
18. Walters A.S., LeBrocq C., Dhar A., et al. Validation of the International restless legs syndrome study group rating scale for restless legs syndrome. Sleep Med 2003, 4:121-132.
19. American Academy of Sleep Medicine. Periodic limb movement disorder. In: The international classification of sleep disorders: diagnostic & coding manual. 2nd ed. Westchester, IL: American Academy of Sleep Medicine; 2005. pp. 182-6.
20. Zucconi M., Ferri R., Allen R., et al. The official World Association of Sleep Medicine (WASM) standards for recording and scoring periodic leg movements in sleep (PLMS) and wakefulness (PLMW) developed in collaboration with a task force from the International Restless Legs Syndrome Study Group (IRLSSG). Sleep Med 2006, 7:175-183.
21. National Institute of Mental Health. Clinical global impressions. In: Guy W, editor. ECDEU assessment manual for psychopharmacology. Revised edn. Rockville, MD: NIMH; 1976.
22. Kohnen R., Benes H., Heinrich C., Kurella B. Development of the disease-specific restless legs syndrome quality of life (RLS-QoL) questionnaire. Mov Disord 2002, 17:P743.
23. Abetz L., Vallow S.M., Kirsch J., Allen R.P., Washburn T., Earley C.J. Validation of the restless legs syndrome quality of life questionnaire. Value Health 2005, 8:157-167.
24. Mantel N., Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 1959, 22:719-748.
25. DerSimonian R., Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986, 7:177-188.
26. Adler C.H., Hauser R.A., Sethi K., et al. Ropinirole for restless legs syndrome: a placebo-controlled crossover trial. Neurology 2004, 62:1405-1407.
27. Pieta J., Millar T., Zacharias J., Fine A., Kryger M. Effect of pergolide on restless legs and leg movements in sleep in uremic patients. Sleep 1998, 21:617-622.
28. Wetter T.C., Stiasny K., Winkelmann J., et al. A randomized controlled study of pergolide in patients with restless legs syndrome. Neurology 1999, 52:944-950.
29. Montplaisir J., Nicolas A., Denesle R., Gomez-Mancilla B. Restless legs syndrome improved by pramipexole: a double-blind randomized trial. Neurology 1999, 52:938-943.
30. Higgins J., Green S.P. Cochrane Handbook for Systematic Reviews of Interventions 2008, Wiley-Blackwell, Oxford.
31. Egger M., Davey Smith G., Schneider M., Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997, 315:629-634.
32. Walters A.S., Hening W.A., Kavey N., Chokroverty S., Gidro-Frank S. A double-blind randomized crossover trial of bromocriptine and placebo in restless legs syndrome. Ann Neurol 1988, 24:455-458.
33. Cohen J. Statistical Power Analysis for the Behavioral Sciences 1988, Erlbaum Associates, Hillsdale, NJ; Hove. 2nd ed.
34. Trenkwalder C., Kohnen R., Allen R.P., et al. Clinical trials in restless legs syndrome - recommendations of the European RLS Study Group (EURLSSG). Mov Disord 2007, 22(Suppl. 18):S495-504.
35. Benes H., Walters A.S., Allen R.P., Hening W.A., Kohnen R. Definition of restless legs syndrome, how to diagnose it, and how to differentiate it from RLS mimics. Mov Disord 2007, 22:S401-S408.
36. Benes H., Kohnen R. Transdermal lisuride in patients with severe restless legs syndrome: results from a placebo- and ropinirole-controlled, double-blind, randomized, multicenter, 12-week efficacy and tolerability study. Sleep 2008, 31(Suppl.):A266.
37. Siddiqui F., Strus J., Ming X., Lee I.A., Chokroverty S., Walters A.S. Rise of blood pressure with periodic limb movements in sleep and wakefulness. Clin Neurophysiol 2007, 118:1923-1930.
38. Manconi M., Ferri R., Zucconi M., et al. Effects of acute dopamine-agonist treatment in restless legs syndrome on heart rate variability during sleep. Sleep Med 2011, 12:47-55.
39. Buscemi N., Vandermeer B., Friesen C., et al. The efficacy and safety of drug treatments for chronic insomnia in adults: a meta-analysis of RCTs. J Gen Intern Med 2007, 22:1335-1350.
40. Conti C.F., de Oliveira M.M., Andriolo R.B., et al. Levodopa for idiopathic restless legs syndrome: evidence-based review. Mov Disord 2007, 22:1943-1951.
41. Kohnen R. The promises of meta-analyses in current RLS research: is 1+1 more than 2?. Sleep Med 2008, 9:709-711.
42. Arnulf I., Leu-Semenescu S. Sleepiness in Parkinson's disease. Parkinson Relat Disord 2009, 15(Suppl. 3):S101-S104.
43. Benes H. TULIR study group. Transdermal lisuride in patients with idiopathic restless legs syndrome: results from a placebo-controlled, double-blind, randomized, multicenter, 12-week dose-finding study. Sleep Med 2005, 6(Suppl. 2):S156.
44. Hening W.A., Allen R.P., Ondo W.G., et al. Rotigotine improves restless legs syndrome: a 6-month randomized, double-blind, placebo-controlled trial in the United States. Mov Disord 2010, 25:1675-1683.
45. Oertel W.H., Benes H., Garcia-Borreguero D., et al. Efficacy of rotigotine transdermal system in severe restless legs syndrome: a randomized, double-blind, placebo-controlled, six-week dose-finding trial in Europe. Sleep Med 2008, 9:228-239.
46. Partinen M., Hirvonen K., Jama L., et al. Efficacy and safety of pramipexole in idiopathic restless legs syndrome: a polysomnographic dose-finding study - the PRELUDE study. Sleep Med 2006, 7:407-417.
47. Stiasny-Kolster K., Kohnen R., Schollmayer E., Moller J.C., Oertel W.H. Patch application of the dopamine agonist rotigotine to patients with moderate to advanced stages of restless legs syndrome: a double-blind, placebo-controlled pilot study. Mov Disord 2004, 19:1432-1438.
48. Trenkwalder C., Benes H., Poewe W., et al. Efficacy of rotigotine for treatment of moderate-to-severe restless legs syndrome: a randomised, double-blind, placebo-controlled trial. Lancet Neurol 2008, 7:595-604.
49. Garcia-Borreguero D., Winkelman J., Adams A., et al. Efficacy and tolerability of sumanirole in restless legs syndrome: a phase II, randomized, double-blind, placebo-controlled, dose-response study. Sleep Med 2007, 8:119-127.
50. Allen R., Becker P.M., Bogan R., et al. Ropinirole decreases periodic leg movements and improves sleep parameters in patients with restless legs syndrome. Sleep 2004, 27:907-914.
51. Benes H., Mattern W., Peglau I., et al. Ropinirole improves depressive symptoms and restless legs syndrome severity in RLS patients: a multicentre, randomized, placebo-controlled study. J Neurol 2011, 258:1046-1054.
52. Bogan R.K., Fry J.M., Schmidt M.H., Carson S.W., Ritchie S.Y. Ropinirole in the treatment of patients with restless legs syndrome: a US-based randomized, double-blind, placebo-controlled clinical trial. Mayo Clin Proc 2006, 81:17-27.
53. Kushida C.A., Geyer J., Tolson J.M., Asgharian A. Patient- and physician-rated measures demonstrate the effectiveness of ropinirole in the treatment of restless legs syndrome. Clin Neuropharmacol 2008, 31:281-286.
54. GSK. ROR 104836. A randomised, double-blind, placebo-controlled, parallel group study to evaluate the efficacy and safety of ropinirole for 26 weeks and to further evaluate the incidence of augmentation and rebound for a further 40 weeks open-label extension treatment period in subjects suffering from moderate to severe restless legs syndrome. Brentford, United Kingdom: GlaxoSmithKline; 2009. Available at: (last Accessed 2/11/2009). http://www.gsk-clinicalstudyregister.com.
55. Boehringer Ingelheim. BI 248.616, 2008: A phase IV randomised, double-blind, active and placebo-controlled, 6-week trial to investigate the efficacy and safety of a starting (and fixed) dose 0.25mg pramipexole (Mirapex®) in patients with idiopathic restless legs syndrome. Ingelheim, Germany: Boehringer Ingelheim; 2008. Available at: (last Accessed 04/03/2009). http://trials.boehringer-ingelheim.com/res/trial/data/pdf/248.616_U08-3876_upload19194.pdf.
56. Kelly M., Mistry P. Tolerability of a forced-dose escalating regimen of ropinirole in patients with RLS. (GSK SKF-101468/207). Mov Disord 2005, 20:S63.