Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2025 Jan 1;21(1):153-199.
doi: 10.5664/jcsm.11392.

Treatment of restless legs syndrome and periodic limb movement disorder: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment

John W Winkelman  1   2 , J Andrew Berkowski  3 , Lourdes M DelRosso  4 , Brian B Koo  5   6 , Matthew T Scharf  7 , Denise Sharon  8   9 , Rochelle S Zak  10 , Uzma Kazmi  11 , Gerard Carandang  11 , Yngve Falck-Ytter  12   13 , Anita V Shelgikar  14 , Lynn Marie Trotti  15 , Arthur S Walters  16
Affiliations
Meta-Analysis

Treatment of restless legs syndrome and periodic limb movement disorder: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment

John W Winkelman et al. J Clin Sleep Med. .

Abstract

Introduction: This systematic review provides supporting evidence for the accompanying clinical practice guideline on the treatment of restless legs syndrome and periodic limb movement disorder.

Methods: The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine. A systematic review was conducted to identify studies that compared the use of pharmacological or nonpharmacological treatment to no treatment to improve patient-important outcomes. Statistical analyses were performed to determine the clinical significance of using various interventions to treat restless legs syndrome and periodic limb movement disorder in adults and children. The Grading of Recommendations Assessment, Development, and Evaluation process was used to assess the evidence for making recommendations.

Results: The literature search resulted in 3,631 studies out of which 148 studies provided data suitable for statistical analyses. The task force provided a detailed summary of the evidence along with the certainty of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations.

Citation: Winkelman JW, Berkowski JA, DelRosso LM, et al. Treatment of restless legs syndrome and periodic limb movement disorder: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med. 2025;21(1):153-199.

Keywords: Willis-Ekbom disease; periodic limb movement disorder; restless legs syndrome; sleep-related movement disorders.

PubMed Disclaimer

Conflict of interest statement

The development of this paper was funded by the American Academy of Sleep Medicine (AASM).

  1. Dr. Trotti serves on the AASM Board of Directors and is Chair of the Guidelines Advisory Panel (GAP), having been the GAP liaison from June 2023 to August 2024.

  2. Dr. Shelgikar also serves on the AASM Board of Directors and was the Board liaison for the Restless Legs Syndrome (RLS) Task Force.

  3. Dr. Zak was the former GAP liaison to the RLS Task Force (September 2021–June 2023) and is currently on the RLS Foundation’s Scientific and Medical Advisory Board (August 2024–present) while also serving on the Executive Board of the International RLS Study Group.

  4. Ms. Kazmi and Mr. Carandang are employed by the AASM.

  5. Dr. Falck-Ytter is a paid consultant for the AASM and an affiliated member of the United States Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Network and the Evidence Foundation.

  6. Dr. Winkelman has served on the Steering Committee for Luitpold Pharmaceuticals, investigating ferric carboxymaltose for RLS treatment. He was Secretary of the International RLS Study Group (2017–2019) and is its current Chair (2023–present). He also serves on the RLS Foundation’s Scientific and Medical Advisory Board (2013–present) and has consulted for companies including Emalex, Disc Medicine, Haleon, Alexza, Idorsia, and Noctrix Health. He has received research grants from American Regent, National Institute on Drug Abuse, the RLS Foundation, and Merck & Co., among others, for RLS treatment research.

  7. Dr. Sharon is a member of the International RLS Study Group’s executive committee, the RLS Foundation’s Scientific and Medical Advisory Board, and served on the Southern Sleep Foundation Board (2013–2019).

  8. Dr. Koo is a member of the RLS Foundation’s Scientific and Medical Advisory Board and the National Sleep Foundation’s Sleep Disorders Council.

  9. Dr. Berkowski is also on the RLS Foundation’s Scientific and Medical Advisory Board.

  10. Dr. Walters was a member of the International RLS Study Group executive committee (2015–2021) and the RLS Foundation’s Scientific and Medical Advisory Board. He has received research grants from Xenoport/Arbor and the National Institutes of Health for studies on RLS.

  11. Dr. DelRosso is the Treasurer of the International RLS Study Group (2022–present) and Secretary of the World Sleep Society’s Executive Committee (July 2023–present).

No other task force members have relevant conflicts of interest to disclose.

Similar articles

See all similar articles

Cited by

References

    1. Winkelman JW, Berkowski JA, DelRosso LM, et al. . Treatment of restless legs syndrome and periodic limb movement disorder: an American Academy of Sleep Medicine clinical practice guideline . J Clin Sleep Med. 2025. ; 21 ( 1 ): 137 – 152 . - PMC - PubMed
    1. Aurora RN, Kristo DA, Bista SR, et al. ; American Academy of Sleep Medicine . The treatment of restless legs syndrome and periodic limb movement disorder in adults–an update for 2012: practice parameters with an evidence-based systematic review and meta-analyses: an American Academy of Sleep Medicine clinical practice guideline . Sleep. 2012. ; 35 ( 8 ): 1039 – 1062 . - PMC - PubMed
    1. Allen RP, Picchietti DL, Garcia-Borreguero D, et al. ; International Restless Legs Syndrome Study Group . Restless legs syndrome/Willis-Ekbom disease diagnostic criteria: updated international restless legs syndrome study group (IRLSSG) consensus criteria–history, rationale, description, and significance . Sleep Med. 2014. ; 15 ( 8 ): 860 – 873 . - PubMed
    1. Picchietti D, Allen RP, Walters AS, Davidson JE, Myers A, Ferini-Strambi L . Restless legs syndrome: prevalence and impact in children and adolescents–the peds REST study . Pediatrics. 2007. ; 120 ( 2 ): 253 – 266 . - PubMed
    1. Yepes G, Guitart X, Rea W, et al. . Targeting hypersensitive corticostriatal terminals in restless legs syndrome . Ann Neurol. 2017. ; 82 ( 6 ): 951 – 960 . - PMC - PubMed

MeSH terms

LinkOut - more resources