Review The Pharmacological Treatment for Uremic Restless Legs Syndrome: Evidence-Based Review Ma ´rcio Moyse ´s de Oliveira, MD, PhD, 1,2,3 Cristiane Fiquene Conti, MD, PhD, 1,2,3 Juliana Spelta Valbuza, PhD, 1,2,3 Luciane Bizari Coin de Carvalho, PhD, 1,3 and Gilmar Fernandes do Prado, MD, PhD 1,3 * 1 Department of Emergency Medicine and Evidence Based Medicine (UNIFESP), Universidade Federal de Sa˜o Paulo, Sa˜o Paulo, Brazil 2 Brazilian Cochrane Center (UNIFESP), Universidade Federal de Sa˜o Paulo, Sa˜o Paulo, Brazil 3 Sao Paulo Hospital Sleep Laboratory (UNIFESP), Universidade Federal de Sa˜o Paulo, Sa˜o Paulo, Brazil Abstract: Restless legs syndrome (RLS) is a common and of- ten misdiagnosed entity among the general population and it may be more common among dialysis patients, with an esti- mated prevalence of 6.6 to 21.5%. The treatment for uremic RLS has been controversial and therefore a systematic synthe- sis of the evidence is needed in order to evaluate the effective- ness and safety of treatments for uremic RLS. This was a systematic review of randomized or quasi-randomized double- blind trials on treatments for uremic RLS. The outcomes con- sidered were relief of RLS symptoms marked on a validated scale, subjective sleep quality, sleep quality measured using night polysomnography and actigraphy, quality of life meas- ured subjectively, and adverse events associated with these treatments. Six eligible clinical trials were included. The results from subjective analyses in these studies were divergent, although objective analyses in one trial showed that there was a statistically significant improvement in periodic leg move- ment while asleep in the treatment group. No combined analy- sis (meta-analysis) was performed. The most common adverse event seen was gastrointestinal symptoms. Only a few thera- peutic trials on patients with uremia with RLS have been pub- lished, and there is insufficient scientific evidence to favor any specific therapeutic regimen for uremic-associated RLS. Ther- apy using levodopa, dopaminergic agonists, anticonvulsants, and clonidine tend to be effective, but further studies are needed. Ó 2010 Movement Disorder Society Key words: systematic review; restless legs syndrome; uremic; end-stage renal disease Restless legs syndrome (RLS) is a fairly common sleep-related disorder. It is a sensory motor disorder characterized by a distressing urge to move the legs and sometimes also other parts of the body, usually accompanied by a marked sense of discomfort or pain in the legs or other affected body parts. 1 It is more common among women 2 and it affects at least 2.7 to 5% of adults. 3 Physical examinations on patients with RLS typi- cally show normal results. The characteristic clinical symptoms of RLS include well-defined criteria that have been described in the literature. 4,5 RLS may occur in an idiopathic form or secondary to other conditions such as pregnancy, iron deficiency, rheumatoid arthritis, spinal cord injuries, and peripheral nerve injuries, and is one of the more distressing con- comitants of end-stage renal disease (ESRD). The management of RLS among patients with renal disease remains a medical dilemma. Recent studies using the International Restless Legs Syndrome Study Group (IRLSSG) criteria 4 have reported that the prevalence was 6.6 to 21.5% among dialysis patients, 6–9 compared with 5% for the general population. Furthermore, 20% of hemodialysis patients have reported premature discontin- uation of dialysis sessions because of RLS symptoms. 10 Potential conflict of interest: Nothing to report. The first two authors contributed equally to this work. *Correspondence to: Gilmar F Prado, Rua Claudio Rossi, 394 Sao Paulo – SP, CEP 01547-000, Brazil E-mail: gilmarunifesp@yahoo.com.br Received 19 February 2009; Revised 15 August 2009; Accepted 13 November 2009 Published online 11 June 2010 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/mds.22955 1335 Movement Disorders Vol. 25, No. 10, 2010, pp. 1335–1342 Ó 2010 Movement Disorder Society