Guideline:
Practice parameters for the dopaminergic treatment of restless legs syndrome and periodic limb movement disorder
Bibliographic Source(s)
- Littner MR Kushida C Anderson WM Bailey D Berry RB Hirshkowitz M Kapen S Kramer M Lee-Chiong T Li KK Loube DL Morgenthaler T Wise M. Practice parameters for the dopaminergic treatment of restless legs syndrome and periodic limb movement disorder. Sleep 2004 May 1;27(3):557-9. [4 references] PubMed
Guideline Status
This is the current release of the guideline.
Guideline Category
Assessment of Therapeutic Effectiveness
Treatment
Intended Users
Physicians
Guideline Objective(s)
To serve as a guide for the appropriate use of dopaminergic agents in the treatment of restless legs syndrome (RLS) and periodic limb movement disorder (PLMD)
Target Population
Patients with restless legs syndrome (RLS) and periodic limb movement disorder (PLMD)
Interventions and Practices Considered
- Levodopa with decarboxylase inhibitor
- Pergolide*
- Pramipexole
- Ropinirole
- Other dopamine agonists including talipexole cabergoline piribedil and alpha-dihydroergocryptine
- Amantadine and selegiline
*Note from the National Guideline Clearinghouse (NGC): On March 29 2007 Permax (pergolide) was withdrawn from the market in the U.S. and worldwide due to safety concerns of an increased risk of cardiovascular events. See the U.S. Food and Drug Administration (FDA) Web site for more information.
Major Outcomes Considered
- Therapeutic efficacy of dopaminergic agents for treatment of RLS and PLMD
- Sleep parameters (total sleep time sleep efficiency)
- Restless legs syndrome (RLS) and periodic leg movement disorder (PLMD) symptoms
- Adverse effects
- Quality of life
Methods Used to Collect/Select Evidence
Hand-searches of Published Literature (Primary Sources)
Searches of Electronic Databases
Description of Methods used to Collect/Select the Evidence
Literature searches were first conducted in January 2001 and then updated in August 2001 and finally April 2002. The search was performed through Medline using the search terms: restless legs periodic leg movement periodic limb movement and nocturnal myoclonus. A PubMed search was also done. Search terms were applied both to the keyword field and as a text search. A total of 227 papers were derived from the searches and reviewed for relevance to the therapeutic literature based on their abstracts. 56 papers were selected for detailed consideration and four were added by task force member recommendation from other search resources. Of these 27 met the criteria of having a focus on restless legs syndrome (RLS) treatment with a minimum of 5 patients studied a clear indication of restless legs syndrome or periodic limb movement disorder (PLMD) diagnosis for study entry and use of a pharmaceutical agent which was primarily active on the dopamine system.
Number of Source Documents
27 articles were identified
Methods Used to Assess the Quality and Strength of the Evidence
Weighting According to a Rating Scheme (Scheme Given)
Rating Scheme for the Strength of the Evidence
Level I (Grade A Recommendation): Large well-designed randomized and blinded controlled study with statistically significant conclusions on relevant variables
Level II (Grade B Recommendation): Smaller well-designed randomized and blinded controlled study with statistically significant conclusions on relevant variables
Level III (Grade C Recommendation): Well-designed non-randomized prospective study with control group
Level IV (Grade C Recommendation): Well-designed large prospective study with historical controls or careful attention to confounding effects or small prospective study with control group
Level V (Grade C Recommendation): Small prospective study or case series without control groups
Methods Used to Analyze the Evidence
Systematic Review with Evidence Tables
Description of the Methods Used to Analyze the Evidence
Not stated
Methods Used to Formulate the Recommendations
Expert Consensus
Description of Methods Used to Formulate the Recommendations
In most cases the conclusions are based on evidence from studies published in peer-reviewed journals that were evaluated as noted in the evidence tables of the companion review paper in the original guideline document. When scientific data are absent insufficient or inconclusive the recommendations are based upon consensus opinion.
Rating Scheme for the Strength of the Recommendations
Standard: This is a generally accepted patient-care strategy which reflects a high degree of clinical certainty. The term standard generally implies the use of Level I Evidence which directly addresses the clinical issue or overwhelming Level II Evidence.
Guideline: This is a patient-care strategy which reflects a moderate degree of clinical certainty. The term guideline implies the use of Level II Evidence or a consensus of Level III Evidence.
Option: This is a patient-care strategy which reflects uncertain clinical use. The term option implies either inconclusive or conflicting evidence or conflicting expert opinion.
Cost Analysis
A formal cost analysis was not performed and published cost analyses were not reviewed.
Method of Guideline Validation
Internal Peer Review
Description of Method of Guideline Validation
These recommendations were developed by the Standards of Practice Committee and reviewed and approved by the Board of Directors of the American Academy of Sleep Medicine.
Major Recommendations
Levels of recommendation (Standard Guideline and Option) and levels of evidence (I-V) are defined at the end of the "Major Recommendations" field.
- Levodopa with decarboxylase inhibitor is effective in the treatment of restless legs syndrome (RLS) and periodic limb movement disorder (PLMD). (Hening et al. 2004; 4.b; Table 3) (Standard)
- The dopamine agonist pergolide* is effective in the treatment of RLS and PLMD. (Hening et al. 2004; 4.c.ii; Table 4) (Standard)
- The dopamine agonist pramipexole is effective in the treatment of RLS and PLMD. (Hening et al. 2004; 4.c.iii; Table 4) (Guideline)
- The dopamine agonist ropinirole is effective in the treatment of RLS and PLMD. (Hening et al. 2004; 4.c.iv; Table 4) (Option)
- Other dopamine agonists (talipexole cabergoline piribedil and alpha-dihydroergocryptine) may be effective in the treatment of RLS or PLMD but the level of effectiveness of these agonists is not currently established. (Hening et al. 2004; 4.c.v; Table 4) (Option)
- The dopaminergic agents amantadine and selegiline may be effective in the treatment of RLS and PLMD but the level of effectiveness of these agents is not currently established. (Hening et al. 2004; 4.d; Table 5) (Option)
- No specific recommendations can be made regarding dopaminergic treatment of children or pregnant women with RLS or PLMD. (Hening et al. 2004; 5.b)
*Note from the National Guideline Clearinghouse (NGC): On March 29 2007 Permax (pergolide) was withdrawn from the market in the U.S. and worldwide due to safety concerns of an increased risk of cardiovascular events. See the U.S. Food and Drug Administration (FDA) Web site for more information.
Definitions:
Levels of Recommendation
Standard: This is a generally accepted patient-care strategy which reflects a high degree of clinical certainty. The term standard generally implies the use of Level I Evidence which directly addresses the clinical issue or overwhelming Level II Evidence.
Guideline: This is a patient-care strategy which reflects a moderate degree of clinical certainty. The term guideline implies the use of Level II Evidence or a consensus of Level III Evidence.
Option: This is a patient-care strategy which reflects uncertain clinical use. The term option implies either inconclusive or conflicting evidence or conflicting expert opinion.
Levels of Evidence
Level I (Grade A Recommendation): Large well-designed randomized and blinded controlled study with statistically significant conclusions on relevant variables
Level II (Grade B Recommendation): Smaller well-designed randomized and blinded controlled study with statistically significant conclusions on relevant variables
Level III (Grade C Recommendation): Well-designed non-randomized prospective study with control group
Level IV (Grade C Recommendation): Well-designed large prospective study with historical controls or careful attention to confounding effects or small prospective study with control group
Level V (Grade C Recommendation): Small prospective study or case series without control groups
Clinical Algorithm(s)
None provided
References Supporting the Recommendations
- Hening WA Allen RP Earley CJ Picchietti DL Silber MH. An update on the dopaminergic treatment of restless legs syndrome and periodic limb movement disorder. Sleep 2004 May 1;27(3):560-83. [88 references] PubMed
Type of Evidence supporting the Recommendations
The type of evidence is specifically stated for each recommendation (See "Major Recommendations" field).
Potential Benefits
- Appropriate use of dopaminergic agents in the treatment of restless legs syndrome (RLS) and periodic limb movement disorder (PLMD)
- Relief of RLS and PLMD symptoms
- Reduction of PLMS and PLMS-Waking Index
- Improvement in sleep parameters
Potential Harms
Levodopa with Decarboxylase Inhibitor
The main side effects complicating the use of this agent in clinical series are the high frequencies of restless legs syndrome (RLS) daytime augmentation (i.e. occurrence or worsening of daytime RLS symptoms with long-term medication usage typically increased by higher doses) and early morning rebound of RLS symptoms especially at higher dose levels.
Pergolide
Adverse effects include nausea congestion and mild augmentation. In most cases these adverse effects were either minor or could be adequately controlled; however the development of pleuropulmonary fibrosis or cardiac valvulopathy has been reported in isolated case reports.
Pramipexole
The most common reported side effects in these studies were fluid retention/edema daytime fatigue/sleepiness gastrointestinal distress insomnia/alertness dizziness and occasional augmentation of RLS.
Amantadine
In one study side effects of drowsiness and fatigue were reported.
Qualifying Statements
- These practice parameters define principles of practice that should meet the needs of most patients in most situations. These guidelines should not however be considered inclusive of all proper methods of care or exclusive of other methods of care reasonably directed toward obtaining the same results. The ultimate judgment regarding the propriety of any specific care must be made by the physician in light of the individual circumstances presented by the patient and the available diagnostic and treatment options.
- These practice parameters reflect the state of knowledge at the time of development and will be reviewed updated and revised as new information becomes available.
Description of Implementation Strategy
An implementation strategy was not provided.
IOM Care Need
Getting Better
Living with Illness
IOM Domain
Effectiveness
Bibliographic Source(s)
- Littner MR Kushida C Anderson WM Bailey D Berry RB Hirshkowitz M Kapen S Kramer M Lee-Chiong T Li KK Loube DL Morgenthaler T Wise M. Practice parameters for the dopaminergic treatment of restless legs syndrome and periodic limb movement disorder. Sleep 2004 May 1;27(3):557-9. [4 references] PubMed
Adaptation
Not applicable: The guideline was not adapted from another source.
Source(s) of Funding
American Academy of Sleep Medicine
Guideline Committee
Standards of Practice Committee
Composition of Group that Authored the Guideline
Committee Members: Michael R. Littner MD VA Greater Los Angeles Healthcare System and David Geffen School of Medicine at UCLA Sepulveda CA; Clete Kushida MD PhD Stanford University Center of Excellence for Sleep Disorders Stanford CA; W. McDowell Anderson MD College of Medicine University of South Florida Tampa FL; Dennis Bailey DDS Englewood Colorado; Richard B. Berry MD Malcom Randall VAMC/Univ. of Florida-GainesvilleFla; Max Hirshkowitz PhD Baylor College of Medicine and VA Medical Center Houston TX; Sheldon Kapen MD VA Medical Center and Wayne State University Detroit MI; Milton Kramer MD Maimoides Medical Center Psychiatry Department Brooklyn NY and New York University School of Medicine New York NY; Teofilo Lee-Chiong MD National Jewish Medical and Research Center Sleep Clinic Denver CO; Kasey K. Li DDS MD Stanford Sleep Disorders Clinic and Research Center; Daniel L. Loube MD Sleep Medicine Institute Swedish Medical Center Seattle WA; Timothy Morgenthaler MD Mayo Sleep Disorders Center Mayo Clinic Rochester MN; Merrill Wise MD Departments of Pediatrics and Neurology Baylor College of Medicine Houston TX
Financial Disclosures/Conflicts of Interest
All authors of the accompanying review paper members of the Standards of Practice Committee and the American Academy of Sleep Medicine (AASM) Board of Directors completed detailed conflict-of-interest statements and were found to have none with regard to this subject.
Guideline Status
This is the current release of the guideline.
Guideline Availability
Electronic copies: Available in Portable Document Format (PDF) from the American Academy of Sleep Medicine (AASM) Web site.
Print copies: Available from the Standards of Practice Committee American Academy of Sleep Medicine One Westbrook Corporate Center Suite 920 Westchester IL 60154. Web site: www.aasmnet.org.
Availability of Companion Documents
The following is available:
- Hening WA Allen RP Earley CJ Picchietti DL Silber MH; Restless Legs Syndrome Task Force of the Standards of Practice Committee of the American Academy of Sleep Medicine. An update on the dopaminergic treatment of restless legs syndrome and periodic limb movement disorder. Sleep 2004 May;27(3):560-83.
Electronic copies: Available in Portable Document Format (PDF) from the American Academy of Sleep Medicine Web site.
Print copies: Available from the Standards of Practice Committee American Academy of Sleep Medicine One Westbrook Corporate Center Suite 920 Westchester IL 60154. Web site: www.aasmnet.org.
Patient Resources
None available
NGC STATUS
This NGC summary was completed by ECRI on May 2 2005. The information was verified by the guideline developer on June 2 2005. This summary was updated by ECRI Institute on May 8 2007 following the U.S. Food and Drug Administration market withdrawal of Permax (pergolide).
COPYRIGHT STATEMENT
This NGC summary is based on the original guideline which is subject to the guideline developer's copyright restrictions. Please contact the American Academy of Sleep Medicine (AASM) for information regarding reproduction of AASM guidelines.
NGC Disclaimer
The National Guideline Clearinghouse™ (NGC) does not develop produce approve or endorse the guidelines represented on this site.
All guidelines summarized by NGC and hosted on our site are produced under the auspices of medical specialty societies relevant professional associations public or private organizations other government agencies health care organizations or plans and similar entities.
Guidelines represented on the NGC Web site are submitted by guideline developers and are screened solely to determine that they meet the NGC Inclusion Criteria which may be found at http://www.guideline.gov/about/inclusion.aspx .
NGC AHRQ and its contractor ECRI Institute make no warranties concerning the content or clinical efficacy or effectiveness of the clinical practice guidelines and related materials represented on this site. Moreover the views and opinions of developers or authors of guidelines represented on this site do not necessarily state or reflect those of NGC AHRQ or its contractor ECRI Institute and inclusion or hosting of guidelines in NGC may not be used for advertising or commercial endorsement purposes.
Readers with questions regarding guideline content are directed to contact the guideline developer.
Tools
No Quick Reference tools have been developed.