Restless legs syndrome (RLS) is a neurological movement disorder characterized by sensory symptoms and motor disturbances. While the underlying cause remains unknown, it is suggested that 20–25% of people with RLS are affected seriously enough to require pharmacological treatment. Dopamine agonists (DAs) are the most common treatment and act by increasing the low levels of dopamine to which RLS is often attributed. A growing literature highlights the debilitating and distressing nature of this condition from the patient’s perspective. While sleep problems are most commonly reported, the impact of RLS on quality of life (QOL) is wide ranging, affecting relationships with partners, sex life, family life, social life, leisure activities, friendships, everyday activities, concentration, travel, career/work, sleep, and health.
We conducted a systematic review of clinical trials in which DAs have been evaluated in terms of RLS-specific QOL, i.e. their impact on the QOL of people with RLS, and critically reviewed the development history and measurement properties of RLS-specific QOL instruments.
A systematic search using terms synonymous with RLS, DAs and QOL was conducted using Scopus software, which includes MEDLINE, Psyc-INFO, EMBASE, and CINAHL. Our search covered publications from 2000 (prior to which RLS-specific QOL measures did not exist) to August 2009. Trials were included in our review if they evaluated DAs for the treatment of adults with RLS and reported evaluation using an RLS-specific QOL measure. We also ran citation searches to identify papers reporting the development history and measurement properties of the identified RLS-specific QOL instruments.
Three measures of RLS-specific QOL have been developed in recent years and are reviewed here: the Restless Legs Syndrome Quality of Life (RLSQOL) questionnaire, the Restless Legs Syndrome Quality of Life Instrument (RLS-QLI), and the Quality of Life Restless Legs Syndrome (QOL-RLS) measure. Critical review indicates that each has limitations (particularly in terms of published developmental history and content validity). Eleven trials of DAs were identified that included assessment of RLS-specific QOL (nine using the RLSQOL and two using the QOL-RLS). In all studies, significant improvements in RLS-specific QOL were observed, although these were mostly short term (12 weeks) and large placebo effects were also noted.
In people with RLS, the use of DAs has been shown to improve RLS-specific QOL. Longer-term, large-scale studies may be needed to confirm these findings and demonstrate statistically significant improvements in RLS-specific QOL at lower doses. Further development of the RLS-specific QOL measures is needed to ensure that the full impact of RLS (and the full benefit of new treatments) on aspects of life identified as important to individuals is captured in future studies.
Pramipexole Cabergoline Ropinirole Rotigotine Severe Sleep Problem
This is a preview of subscription content, log in to check access
The authors thank UCB Pharma for funding a strategic review upon which this publication is based in part. Since the original funded work (and in preparation for publication), the review was updated. UCB Pharma has not been involved in the preparation of this manuscript nor requested to approve it. The authors also thank Matt Reaney, MSc (previously of AHP Research), for his contribution to the earlier report upon which this publication is based in part.
Jane Speight and Ana Howarth have previously been engaged in consultancy work in RLS for UCB Pharma.
Evidente VG, Adler CH. How to help patients with restless legs syndrome: discerning the indescribable and relaxing the restless. Postgrad Med 1999 Mar; 105(3): 59–61,65-66,73-4PubMedCrossRefGoogle Scholar
Allen RP, Walters AS, Montplaisir J, et al. Restless legs syndrome prevalence and impact: REST general population study. Arch Intern Med 2005 Jun 13; 165(11): 1286–92PubMedCrossRefGoogle Scholar
Speight J, Reaney M, Showunmi O. A qualitative study to inform the development of a new measure assessing the individualised impact of restless legs syndrome (RLS) on quality of life [abstract]. Value Health 2007; 10(6): A391Google Scholar
Kohnen R, Benes H, Heinrich CR, et al. Development of the disease-specific Restless Legs Syndrome Quality of Life (RLS-QoL) questionnaire [abstract]. Mov Disord 2002; 17Suppl. 5: P743Google Scholar
Atkinson MJ, Allen RP, DuChane J, et al. Validation of the Restless Legs Syndrome Quality of Life Instrument (RLS-QLI): findings of a consortium of national experts and the RLS Foundation. Qual Life Res 2004; 13(3): 679–93PubMedCrossRefGoogle Scholar
Abetz L, Vallow SM, Kirsch J, et al. Validation of the Restless Legs Syndrome Quality of Life questionnaire. Value Health 2005; 8(2): 157–67PubMedCrossRefGoogle Scholar
Chaudhuri KR. The restless legs syndrome: time to recognise a very common movement disorder. Pract Neurol 2003; 3: 204–13CrossRefGoogle Scholar
Allen RP, Picchietti D, Hening WA, et al. 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 Mar; 4(2): 101–19PubMedCrossRefGoogle Scholar
Hening W, Walters AS, Allen RP, et al. 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 May; 5(3): 237–46PubMedCrossRefGoogle Scholar
Möller JC, Unger M, Stiasny-Kolster K, et al. Restless legs syndrome (RLS) and Parkinson’s disease (PD): related disorders or different entities? J Neurol Sci 2010; 289(1–2): 135–7PubMedCrossRefGoogle Scholar
National Institutes of Health, National Institute of Neurological Disorders and Stroke. Restless legs syndrome fact sheet. Bethesda (MD): NINDS, 2001 Apr [online]. Available from URL: http://www.ninds.nih.gov/disorders/restless_legs/detail_restless_legs.htm [Accessed 2010 Jan 26]Google Scholar
Berger K, Kurth T. RLS epidemiology: frequencies, risk factors and methods in population studies. Mov Disord 2007; 22Suppl. 18: S420–3PubMedCrossRefGoogle Scholar
Abetz L, Allen R, Follet A, et al. Evaluating the quality of life of patients with restless legs syndrome. Clin Ther 2004; 26(6): 925–35PubMedCrossRefGoogle Scholar
Kushida C, Martin M, Nikam P, et al. Burden of restless legs syndrome on health-related quality of life. Qual Life Res 2007; 16(4): 617–24PubMedCrossRefGoogle Scholar
McCrink L, Allen RP, Wolowacz S, et al. Predictors of health-related quality of life in sufferers with restless legs syndrome: a multi-national study. Sleep Med 2007; 8(1): 73–83PubMedCrossRefGoogle Scholar
Schlesinger I, Erikh I, Avizohar O, et al. Cardiovascular risk factors in restless legs syndrome. Mov Disord 2009; 24(11): 1587–92PubMedCrossRefGoogle Scholar
Trenkwalder C, Garcia-Borreguero D, Montagna P, et al. Ropinirole in the treatment of restless legs syndrome: results from the TREAT RLS 1 study, a 12 week, randomised, placebo controlled study in 10 European countries. J Neurol Neurosurg Psychiatry 2004; 75(1): 92–7PubMedGoogle Scholar
Walters AS, Ondo WG, Dreykluft T, et al. Ropinirole is effective in the treatment of restless legs syndrome: TREAT RLS 2. A 12-week, double-blind, randomized, parallel-group, placebo-controlled study. Mov Disord 2004; 19(12): 1414–23PubMedCrossRefGoogle Scholar
Abetz L, Arbuckle R, Allen RP, et al. The reliability, validity and responsiveness of the Restless Legs Syndrome Quality of Life questionnaire (RLSQoL) in a trial population. Health Qual Life Outcomes 2005; 3: 79PubMedCrossRefGoogle Scholar
Cuellar NG, Strumpf NE, Ratcliffe SJ. Symptoms of restless legs syndrome in older adults: outcomes on sleep quality, sleepiness, fatigue, depression, and quality of life. J Am Geriatr Soc 2007; 55(9): 1387–92PubMedCrossRefGoogle Scholar
Kushida CA, Allen RP, Atkinson MJ. Modeling the causal relationships between symptoms associated with restless legs syndrome and the patient-reported impact of RLS. Sleep Med 2004; 5(5): 485–8PubMedCrossRefGoogle Scholar
Kohnen R, Allen RP, Benes H, et al. Assessment of restless legs syndrome: methodological approaches for use in practice and clinical trials. Mov Disord 2007; 22Suppl. 18: S485–94PubMedCrossRefGoogle Scholar
O’Connor D, Green S, Higgins JPT, editors. Defining the review question and developing criteria for including studies. In: Higgins JPT, Green S, editors. Cochrane handbook for systematic reviews of interventions. Version 5.0.2, updated September 2009 [online]. Available from URL: http://www.cochrane-handbook.org [Accessed 2010 Jan 26]Google Scholar
US Department of Health and Human Services FDA Center for Drug Evaluation and Research, US Department of Health and Human Services FDA Center for Biologics Evaluation and Research, US Department of Health and Human Services FDA Center for Devices and Radiological Health. Guidance for industry: patient report outcome measures. Use in clinical medical product development to support labelling claims: draft guidance. Health Qual Life Outcomes 2006; 4: 79CrossRefGoogle Scholar
ProQOLid: patient-reported outcome and quality of life instruments database [online]. Available from URL: http://www.proQOLid.org [Accessed 2010 Jan 26]Google Scholar
Oertel WH, 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(3): 228–39PubMedCrossRefGoogle Scholar
Trenkwalder C, Benes H, Grote L, et al. Cabergoline compared to levodopa in the treatment of patients with severe restless legs syndrome: results from a multi-center, randomized, active controlled trial. Mov Disord 2007; 22(5): 696–703PubMedCrossRefGoogle Scholar
Oertel WH, Benes H, Bodenschatz R, et al. Efficacy of cabergoline in restless legs syndrome: a placebo-controlled study with polysomnography (CATOR). Neurology 2006; 67(6): 1040–6PubMedCrossRefGoogle Scholar
Trenkwalder C, Stiasny-Kolster K, Kupsch A, et al. Controlled withdrawal of pramipexole after 6 months of open-label treatment in patients with restless legs syndrome. Mov Disord 2006; 21(9): 1404–10PubMedCrossRefGoogle Scholar
Winkelman JW, Sethi KD, Kushida CA, et al. Efficacy and safety of pramipexole in restless legs syndrome. Neurology 2006; 67(6): 1034–9PubMedCrossRefGoogle Scholar
Ferini-Strambi L, Aarskog D, Partinen M, et al. Effect of pramipexole on RLS symptoms and sleep: a randomized, double-blind, placebo-controlled trial. Sleep Med 2008; 9(8): 874–81PubMedCrossRefGoogle Scholar
Bogan RK, Fry JM, Schmidt MH, et al. Ropinirole in the treatment of patients with restless legs syndrome: a US-based randomized, double-blind, placebo-controlled clinical trial. Obstet Gynecol Surv 2006; 61(8): 527–8CrossRefGoogle Scholar
Montplaisir J, Karrasch J, Haan J, et al. Ropinirole is effective in the long-term management of restless legs syndrome: a randomized controlled trial. Mov Disord 2006; 21(10): 1627–35PubMedCrossRefGoogle Scholar
Garcia-Borreguero D, Grunstein R, Sridhar G, et al. A 52-week open-label study of the long-term safety of ropinirole in patients with restless legs syndrome. Sleep Med 2007; 8(7–8): 742–52PubMedCrossRefGoogle Scholar
Oertel WH, Benes H, Garcia-Borreguero D, et al. One year open-label safety and efficacy trial with rotigotine transdermal patch in moderate to severe idiopathic restless legs syndrome. Sleep Med 2008; 9(8): 865–73PubMedCrossRefGoogle Scholar
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(7): 595–604PubMedCrossRefGoogle Scholar
Kenney C, Jankovic J. Rotigotine transdermal patch in the treatment of Parkinson’s disease and restless legs syndrome. Expert Opin Pharmacother 2007; 8(9): 1329–35PubMedCrossRefGoogle Scholar