This publication is provided for historical reference only and the information may be out of date.
Research Focus for Clinicians
In response to a request from the public, a review was undertaken to evaluate the evidence regarding the potential benefits and adverse effects associated with various treatments for restless legs syndrome (RLS). This review did not cover other sleep disorders such as periodic limb movement disorder. The systematic review included 53 reports of randomized clinical trials and observational studies published through June 2012. The online version of this summary and the full report are available at www.effectivehealthcare.ahrq.gov/restless-legs.cfm. This summary is provided to inform discussions with patients of options and to assist in decisionmaking along with consideration of a patient’s values and preferences. However, reviews of evidence should not be construed to represent clinical recommendations or guidelines.
Background
RLS† is a neurological disorder characterized by unpleasant sensations in the legs and an irresistible urge to move them. The essential diagnostic criteria for RLS were established by the International RLS (IRLS) Study Group. Any RLS diagnosis requires that all four of these essential criteria be met:
- An urge to move the legs, usually accompanied by uncomfortable or unpleasant sensations in the legs
- Unpleasant sensations or the urge to move begin or worsen during periods of rest or inactivity such as lying or sitting
- Unpleasant sensations or the urge to move are partly or totally relieved by movement such as walking, bending, stretching, et cetera, at least as long as the activity continues
- Unpleasant sensations or the urge to move are worse in the evening or at night than during the day, or only occur in the evening or night
RLS varies in symptom severity‡ and frequency. Mild RLS may cause minor annoyance, but severe RLS can negatively affect work, social activities, and function. RLS-induced sleep deprivation and daytime fatigue are common reasons RLS patients seek treatment. Severe RLS can be a chronic progressive disorder that may require long-term treatment.
Prevalence estimates for RLS in the United States range from 1.5 to 7.4 percent in adults. The variation reflects different approaches to diagnosing RLS and defining its frequency and severity. The etiology of primary RLS is unknown, but the disorder might occur secondary to other conditions such as iron deficiency, end-stage renal disease, and pregnancy. Insufficient sleep and sleep disorders such as sleep apnea might exacerbate symptoms of RLS.
Treatment options for RLS include nonpharmacologic and pharmacologic strategies. Nonpharmacologic treatment approaches include pneumatic compression devices, near- infrared light therapy, lower body resistance exercise, and using botanical preparations. The major classes of pharmacologic agents used are listed in Table 1. The choice of pharmacologic agent used to treat RLS depends on the frequency and severity of symptoms.
Table 1
Pharmacologic Interventions Assessed in This Comparative Effectiveness Review.
Dopaminergic agents can result in a treatment complication called augmentation. Augmentation is a drug-induced exacerbation of symptoms characterized by greater symptom intensity, onset earlier in the day, and shorter latency during inactivity. With augmentation, symptoms may also spread to the arms, trunk, and face. Recent studies suggest augmentation is more likely to occur with levodopa when compared with dopamine agonists. Augmentation can lead to poorer outcomes, a switch to other classes of medication, or treatment discontinuation.1,2 Augmentation is usually considered as resolved when the medication triggering augmentation has been discontinued or when the patient has been switched to another medication.1,2
Clinicians face uncertainty related to defining RLS, assessing disease severity, and evaluating the risks and benefits of treatment. While these challenges apply to both primary care and specialty settings, they may be more pronounced in primary care.
- 1.
- Garcia-Borreguero D, Hogl B, Ferini-Strambi L, et al. Mov Disord. 2012;27(2):277–83. [PubMed: 22328464]
- 2.
- Allen RP, Adler CH, Du W, et al. Sleep Med. 2011;12(5):431–9. [PubMed: 21493132]
Conclusion
When compared with placebo, dopamine agonists and alpha-2-delta ligands reduce RLS symptoms and improve patient-reported sleep outcomes and disease-specific quality of life. Moderate-level evidence suggests benefits of intravenous iron on symptoms of RLS. No eligible studies assessed opioids or sedative hypnotics as treatment for RLS. These agents also have potentially serious adverse effects. Some nonpharmacologic interventions such as compression stockings, near-infrared light, or exercise improve RLS symptoms (evidence level low to moderate). Adverse effects of pharmacologic therapies and long-term treatment withdrawals due to adverse effects or lack of efficacy are common. Evidence from observational studies suggests that augmentation is common across dopaminergic agents. The studies included in this review were conducted in adults with moderate to severe RLS. The long-term effectiveness and applicability of the assessed RLS therapies for adults with milder or less frequent RLS symptoms, individuals with secondary RLS, and children are unknown.
Clinical Bottom Line
Table 2
Individual Outcomes and Strength of Evidence in Placebo-Controlled Studies of Dopamine Agonists.
Table 3
Individual Outcomes and Strength of Evidence in Placebo-Controlled Studies of Alpha-2-Delta Ligands.
Gaps in Knowledge
- Most studies included in this review were efficacy studies. No studies making head-to-head comparison between RLS medications were identified. The included studies did not permit reliable conclusions about comparative benefits and harms.
- The current evidence base consists almost exclusively of pharmacologic treatments. The effectiveness of nonpharmacologic treatments including herbal therapy, mind-body medicine, and manipulative treatments is not known. Additionally, the effectiveness of over-the-counter iron supplements is not known.
- Most of the studies included in this review were conducted in patients with moderate to severe RLS. The effectiveness of the assessed treatments in patients with mild RLS is unknown.
- No evidence was found about the effectiveness of therapies in specific subgroups such as children, older adults with multiple comorbidities, or individuals with secondary RLS (including those with iron deficiency or end-stage renal disease and pregnant women).
- The long-term durability of treatment benefits remains unknown.
- Little is known about patient characteristics that may lead to augmentation.
- The included studies do not consistently report on the use of objective criteria for sleep assessment.
- There is a paucity of information on the effects of environmental factors on RLS and their impact on treatment outcomes.
What To Discuss With Your Patients and Their Caregivers
- What RLS is, and that it is a treatable condition
- That RLS can become a chronic condition that requires treatment in moderate to severe cases
- The currently available pharmacologic and nonpharmacologic therapies for RLS
- The available evidence for the effectiveness of the various treatments for RLS with regard to disease symptoms, quality of life, and sleep outcomes
- The available evidence for the harms of the various treatments for RLS
- The possibility that the patient might develop augmentation if he/she is taking levodopa or dopamine agonists
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Ask the patient at each visit if he/she is experiencing symptoms of augmentation.
Resource for Patients
Options for Treating Restless Legs Syndrome, A Review of the Research for Adults, is a free companion to this clinician research summary. It can help patients talk with their health care professionals about the many options for treating RLS.
Ordering Information
For electronic copies of Options for Treating Restless Legs Syndrome, A Review of the Research for Adults, this clinician research summary, and the full systematic review, visit www.effectivehealthcare.ahrq.gov/restless-legs.cfm. To order free print copies of this clinician research summary, call the AHRQ Publications Clearinghouse at 800-358-9295.
Source
The information in this summary is based on Treatment for Restless Legs Syndrome, Comparative Effectiveness Review No. 86, prepared by the Minnesota Evidence-based Practice Center under Contract No. 290-2007-10064-I for the Agency for Healthcare Research and Quality, November 2012. Available at www.effectivehealthcare.ahrq.gov/restless-legs.cfm. This summary was prepared by the John M. Eisenberg Center for Clinical Decisions and Communications Science at Baylor College of Medicine, Houston, TX.
Footnotes
- †
Also referred to as Willis-Ekbom disease
- ‡
RLS can be defined as mild, moderate, severe, or very severe based on the IRLS Rating Scale. The IRLS is a 10-item scale with scores ranging from 0 (no symptoms) to 40. Scores ≤10 are considered as mild, scores 11–20 as moderate, scores 21–30 as severe, and scores >30 as very severe RLS.
Publication Details
Author Information and Affiliations
Authors
John M. Eisenberg Center for Clinical Decisions and Communications Science1.Affiliations
Publication History
Issued: August 30, 2013.
Copyright
Publisher
Agency for Healthcare Research and Quality (US), Rockville (MD)
NLM Citation
John M. Eisenberg Center for Clinical Decisions and Communications Science. Treatment for Restless Legs Syndrome. 2013 Aug 30. In: Comparative Effectiveness Review Summary Guides for Clinicians [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2007-.