Melody Ryan; John T. Slevin


Am J Health Syst Pharm. 2006;63(17):1599-1612. 

In This Article

Editor's Note

Please note: The following announcement supersedes any information contained in this article. On March 30, 2007, Novartis, in compliance with an FDA request, suspended marketing and sales of its irritable bowel/constipation drug tegaserod maleate (Zelnorm) after an analysis of its clinical database pointed to a higher incidence of myocardial infarction, stroke, and unstable angina among patients taking the drug. For updated information on this issue, see the Medscape Alert Center on tegaserod.

Abstract and Introduction


Purpose: The signs and symptoms, epidemiology, etiology, pathophysiology, diagnosis, pharmacologic and nonpharmacologic treatments, and options and guidelines for the treatment of restless legs syndrome (RLS) are reviewed.
Summary: RLS was first described in the 17th century and further characterized in 1945. RLS is a common disorder, occurring in about 10% of the population. Patients with RLS often describe the urge to move, uncomfortable sensations, and pain, which begin or worsen during rest or inactivity such as lying or sitting. Symptoms of RLS make sleeping difficult for many patients, and significant daytime difficulties result from the condition. RLS can either be primary or arise from secondary causes that lead to iron deficiency. There is a familial component in primary RLS, but its underlying mechanisms remain unknown. Of individuals with conditions associated with iron-deficiency states, including pregnancy, renal failure, and anemia, 25-30% may develop RLS. The goals of RLS treatment include improving its symptoms and the patient's quality of life. There are limited data on the treatment of RLS. Pharmacologic therapies include iron replacement, dopaminergic agents (e.g., levodopa), dopamine agonists, anticonvulsants, opioids, and benzodiazepines. There have been no systematic trials of nonpharmacologic therapies for RLS, but good sleep hygiene and avoidance of alcohol, caffeine, and nicotine may improve symptoms.
Conclusion: RLS is a common disorder thought to involve abnormal iron metabolism and dopaminergic systems. Nonpharmacologic therapy should be suggested for all patients with RLS, but pharmacologic therapy may be required, and evidence is strongest for levodopa and dopamine agonists.


The first clinical description of restless legs syndrome (RLS) is generally attributed to the 17th century British anatomist and physician, Thomas Willis,[1] who described "so great a Restlessness and Tossings of their Members ensue that the diseased are no more able to sleep than if they were in a place of the greatest Torture." He was also the first to suggest a treatment, opioids. In 1945, the syndrome was more completely characterized by Ekbom[2] who, in a presentation of 53 cases, described its classic clinical features and also offered treatments. A half century later, the International RLS Study Group (IRLSSG) published a set of criteria to allow for a more uniform diagnosis that was recently revised and expanded (Appendix A) at an IRLSSG/National Institutes of Health workshop (Workshop).[3] RLS is defined as a symptomatic urge to move the legs, usually accompanied or caused by uncomfortable or unpleasant sensations deep within the legs. These sensations begin or are worsened during periods of rest or inactivity and are partially or totally relieved by movement. The sensations are worse or only present in the evening or night. This article describes RLS and reviews its treatment.


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