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December 13, 2016; 87 (24) Special Article

Practice guideline summary: Treatment of restless legs syndrome in adults

Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology

John W. Winkelman, Melissa J. Armstrong, Richard P. Allen, K. Ray Chaudhuri, William Ondo, Claudia Trenkwalder, Phyllis C. Zee, Gary S. Gronseth, David Gloss, Theresa Zesiewicz
First published November 16, 2016, DOI: https://doi.org/10.1212/WNL.0000000000003388
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Article Information

vol. 87 no. 24 2585-2593
DOI: 
https://doi.org/10.1212/WNL.0000000000003388
PubMed: 
27856776
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Print ISSN: 
0028-3878
Online ISSN: 
1526-632X
History: 
  • Received March 22, 2016
  • Accepted in final form August 2, 2016
  • First Published November 16, 2016.

Article Versions

Copyright & Usage: 
© 2016 American Academy of Neurology

Author Disclosures

    1. John W. Winkelman, MD, PhD,
    2. Melissa J. Armstrong, MD, MSc,
    3. Richard P. Allen, PhD,
    4. K. Ray Chaudhuri, MD, FRCP, DSc,
    5. William Ondo, MD,
    6. Claudia Trenkwalder, MD,
    7. Phyllis C. Zee, MD, PhD,
    8. Gary S. Gronseth, MD,
    9. David Gloss, MD, MPH&TM and
    10. Theresa Zesiewicz, MD
  1. John W. Winkelman, MD, PhD,
    2. Scientific Advisory Boards:

    1. (1) Merck (2) Flex Pharma (3) UCB (4) Impax (5) Pfizer (6) Lacrima (7) Luitpold Pharmaceuticals (8) GlaxoSmithKline (9) Boehringer-Ingelheim (10) Xenoport (11) Zeo Inc. (12) Sunovion (13) Insys (14) Takeda (15) Jazz (16) Neurogen

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. (1) Boehringer-Ingelheim (2) GlaxoSmithKline (3) Pfizer (4) Sepracor (5) Takeda (6) Luitpold Pharmaceuticals (7) Novartis (8) Neurogen (9) Otsuka (10) UCB (Schwarz Pharma)

    Editorial Boards:

    1. (1) Sleep, Associate Editor, 2007- (2) Sleep Medicine, Editorial Board, 2005- (3) CNS Drugs, Editorial Board, 2006-

    Patents:

    1. NONE

    Publishing Royalties:

    1. (1) Foundations of Psychiatric Sleep Medicine, Cambridge University Press, 2012- (2) Nocturnal Leg Cramps, UpToDate, 2012-

    Employment, Commercial Entity:

    1. (1) Massachusetts General Hospital, physician, 2013- present

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. (1) Xenoport (2) GlaxoSmithKline (3) UCB (Schwarz Pharma) (4) Sepracor (5) Pfizer (6) Impax Pharmaceuticals (7) Purdue (8) Neurometrix

    Research Support, Government Entities:

    1. (1) National Institute of Mental Health, 1RO1MH095792- 01A1, PI, 2012-2017

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. (1) Flex Pharma

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. Expert witness work for: ArentFox, 2015-2016 CantorColburn 2012-2014

  2. Melissa J. Armstrong, MD, MSc,
    3. Scientific Advisory Boards:

    1. (1) Eli Lilly (April 2013 - unrelated but within time course of guideline development)

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. (1) International Parkinson and Movement Disorder Society, speaker honoraria for the 17th and 18th International Congresses (2013, 2014) (2) American Academy of Neurology, faculty honoraria for the 2014, 2015, and 2016 annual meetings

    Editorial Boards:

    1. (1) Neurology, Level of Evidence Editorial Board, 2012- current

    Patents:

    1. NONE

    Publishing Royalties:

    1. (1) Parkinson's Disease: Improving Patient Care, Oxford University Press, 2014

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. (1) American Academy of Neurology Evidence-Based Medicine Methodology Consultant

    Speakers' Bureaus:

    1. NONE

    Other activities:

    1. (1) Medscape CME (writing, speaking honoraria)

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. (1) Abbvie (2012-2015) (2) Insightec (2014-2015)

    Research Support, Government Entities:

    1. (1) ARHQ, K08HS024159, PI, 2015-2020 (2) NIH U01 AR057967-01, sub-investigator, 2014-2015

    Research Support, Academic Entities:

    1. (1) University of Maryland School of Medicine (2012-2015) (2) TBI Endpoints Development Initiative

    Research Support, Foundations and Societies:

    1. (1) Parkinson Study Group (2) Huntington Study Group (3) CHDI Foundation

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  3. Richard P. Allen, PhD,
    4. Scientific Advisory Boards:

    1. UCB pharma, Luitpold Pharmaceutical

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. honoraria and travel , commercial: UCB pharma, Luitpold Pharmaceutical honoraria and travel, non-commercial: NIH Travel: WASM, IRLSSG, EU-RLSSG

    Editorial Boards:

    1. editorial board - Sleep, Movement disorders Field editor - Sleep Medicine

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. Pfizer - commercialUCB - commercial (through Johns Hopkins) Luitpold - commercial

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NIH grants R01 NS075184 PI 20012-2017 P01-AG21190 Co-Inv 2006-20012 MII grant phase 1 and 3 2016-MII-2984

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  4. K. Ray Chaudhuri, MD, FRCP, DSc,
    5. Scientific Advisory Boards:

    1. Scientific advisory board for Abbott, Boehringer- Ingelheim, GSK, Serrono, Teva, UCB, Britannia pharmaceuticals between 2007-2012 and received honorarium for scientific advise.

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. Editor in Chief Nature Parkinson's Journal Parkinson's disease and related disorder. Editorial board 2009-2014 European Editor Basal ganglia Editorial board: Journal of Parkinson's Disease Editorial Board: JPD

    Patents:

    1. NONE

    Publishing Royalties:

    1. Book : Non motor symptoms of Parkinson's disease (Oxford University Press) 1st ed 2010 2nd ed 2014

    Employment, Commercial Entity:

    1. Honoraria for advisor in scientific advisory boards as listed above. Honoraria for lectures in international scientific meetings (EFNS, Swedish Movement Disorders Society, LIMPE Italy 2007-2009, MDS (Paris)) MDS 2010,2011,2013, 2014, 2015 EFNS 2011, WPD 2010, WFN PRD 2011

    Consultancies:

    1. 1: PDNMG 2: Mundipharma 3: AbbVie 4: Britannia

    Speakers' Bureaus:

    1. NONE

    Other activities:

    1. Academic grants from Parkinson's UK, NIHR, EU FP-7 and Horizon 2020 programme

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. 2015-2017: Development of intrajejunal levodopa infusion programme at Kings. AbbVie Pharmaceuticals K Ray Chaudhuri ?46, 304. ((AXDUO131858.) 2011-2015: PDNMG and UCB Pharma: An international cross sectional longitudinal study investigating natural history of non motor symptoms of PD (NILS) and dopaminergic treatment effect, tolerability in young and old subjects. K Ray Chaudhuri and Pablo Martinez-Martin ?508,339 (Adopted in Department of Health UK Portfolio by DenDron) UKCRN No : 10084 Research support for a clinical research nurse from UCB Pharma (2008-2009). Solvay (clinical fellow) Educational grant from UCB, Abbott, Boehringer for EUROPAR - an European Multicentre PD non motor studies programme

    Research Support, Government Entities:

    1. 2014-2016 NIHR: HS&DR Project ref: 12/130/47: Evaluation of the clinical and cost-effectiveness of Short-term Integrated Palliative Care Services (SIPC) to OPTimise CARE for people with advanced longterm Neurological conditions (OPTCARE Neuro). A randomised fast-track trial of the clinical and cost effectiveness of Short-term Integrated Palliative Care (SIPC) for people with advanced long term neurological conditions (LTNCs) I Higginson, G Wei, F Mirtagh, C Evans, A Byrne, A Pickles, E Silber, P McCrone, V Crosby, A Wilcock, A Al- Chalabi, K Ray Chaudhuri, P N Leigh, R Burman ?1,179,977.80 NIHR. 2015-2016: CRN South London contingency funding. Europar European research programme and recruitment. K Ray Chaudhuri ?26,550

    Research Support, Academic Entities:

    1. 2016-2018: The Kirby Laing Foundation. Ethnicity and non motor symptoms in Parinson?s disease. K Ray Chaudhuri. ?100,000

    Research Support, Foundations and Societies:

    1. 2014-2016 International Parkinson?s and Movenet Disorders Society. Field Validation of the MDS-NMS Scale ? International Parkinson?s Disease and Movement Disorders Society Non-Motor Symptoms Scale for Parkinson?s Disease K Ray Chaudhuri, Dan Weintraub, Anette Schrag, Pabo Martinez-Martin $ 100,000 2014-2016: Parkinson?s UK: K-1406: Non-motor symptoms of people with Parkinson?s in black African/Caribbean and South Asian population in London: case control study and biomarkers and non-motor subtypes evaluation. K Ray Chaudhuri, A Schrag, A Sauerbier, C Ballard. ?34,000 2013-2017: Parkinson?s UK :K-1301 Biomarkers of pain in Parkinson's Disease Monty Silverdale, Donald Grosset, Christopher Kobylecki, Rayaz Malik, Huw Morris, K Ray Chaudhuri, Nigel Williams. ?16,060.00 2013-2016 Parkinson?s UK: Tracking Parkinson's with Proteomic Biomarkers. S Lovestone, D Burn, D Grosset, N Wood, R barker, S Gentleman, M Ward, C Ballard, K Ray Chaudhuri, R Dobson, ?749,887.91 2014-2017: Parkinson?s UK: RAP-12: Project grant: G- 1306: PD-HELP - Development of an intervention to increase helpseeking for non-motor symptoms in people with Parkinson?s disease. C Hurt, R Brown, K Ray Chaudhuri, M Samuel, R Moss- Morris. ?116,589.32 2012-2014: Parkinson?s UK. : Pilot clinical validation of a novel pain scale in Parkinson?s. K-1210. Adopted to DeNDroN portfolio. K Ray Chaudhuri, S Pal, P Martinez-Martin ?35,000 2012-2015: Biomedical Research Centre and BRU , KCL.: Non motor symptoms in Parkinson?s clinical programme in translational research. K Ray Chaudhuri ?258,600 Biobanking and phenotype-genotype collaboration/database ?20,000 2011-2013: Parkinson?s UK: Testing a mobile phone software application being developed that encourages louder speech in Parkinson's patients with dysarthria / speech impairments; IRAS: 75895. Portfolio ID: 10753 P UK: K 1102 R Eglin, J Johnson, K Ray Chaudhuri ?35,000

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. Kings Parkinson's Pain Scale

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  5. William Ondo, MD,
    6. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. Consultant ACADIA, Lundbeck

    Speakers' Bureaus:

    1. TEVA UCBPharma Lundbeck ACADIA Xenoport Avanir

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. Cynapsus

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. Huntington Study Group Tremor Research Group

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  6. Claudia Trenkwalder, MD,
    7. Scientific Advisory Boards:

    1. UCB Pharma, Britannia, Mundipharma,Vifor

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. Mundipharma, UCB Pharma, Desitin, Abbvie.

    Editorial Boards:

    1. Sleep Medicine, Editorial Board CNS Drugs, Editorial Board

    Patents:

    1. Treatment with oxycodone/naloxone for Dyskinesias in PD

    Publishing Royalties:

    1. Parkinson - Schattauer Verlag, Germany, 2015

    Employment, Commercial Entity:

    1. Paracelsus-Elena-Klinik Kassel, 2003-2016

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. TEVA research grant for 2 years Michel J.Fox Grant Mundipharma unrestricted research grant

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  7. Phyllis C. Zee, MD, PhD,
    8. Scientific Advisory Boards:

    1. (1) Merck (advisory board) (2) Eisai (advisory board) (3) Philips (advisory board)

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. (1) Merck (travel to advisory board meeting)

    Editorial Boards:

    1. Sleep (Deputy editor; 2010-2015)

    Patents:

    1. (1) Software code for phase locked loop stimulation of acoustic signal to improve slow wave sleep (pending)

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. (1) Merck (2) AARP (3) Philips (4) Eisai

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. (1) Philips (2) Technogel (3) Jazz

    Research Support, Government Entities:

    1. (1) NIH/NHLBI, UM1HL112856, PI, May 2012-June 30, 2016 (2) NIH/ NIA, P01 AG11412, PI, 2009-April 30, 2016 (3) DARPA, D15AP00027, Co-Investigator, June 2015-present (4) DARPA, W911NF-16-2-0021, site PI, January 2016-present (5) NIH/NHLBI, 1U10 HL119992, Co-I, August 2013 - Present (6) NIH/NHLBI, R01HL105549, PI, June 2011 - Present (7) NIH/NIDDK, 5U01DK097779-03, Co-I, September 2012 - Present (8) Transportation Research Board, Co-I, October 2013 - June 2015 (9) NIH, R01HL098433, Co-I, July 2010 - April 2015 (10) NIH/NICHD, U10 HD063036, Site Co-I, December 2010 - December 2014

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. Northwestern Memorial Foundation

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. (1)Teva (2)Express Scripts

    Legal Proceedings:

    1. NONE

  8. Gary S. Gronseth, MD,
    9. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. (1) Neurology Now, Editorial advisory board, Inception- Present (2) Neurology, Associate Editor, 2013-Present

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. American Academy of Neurology

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  9. David Gloss, MD, MPH&TM and
    10. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. Neurology, LOE Review Team

    Patents:

    1. NONE

    Publishing Royalties:

    1. (1) Neurology for the Specialty Boards, Lippincott Williams and Wilkins, 2006

    Employment, Commercial Entity:

    1. (1) Charleston Area Medical Center, Charleston, WV 25311

    Consultancies:

    1. (1) I am an Evidence-based medicine consultant for the American Academy of Neurology

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  10. Theresa Zesiewicz, MD
    11. Scientific Advisory Boards:

    1. Steniment

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. (1) TEVA- speaking engagements (2) UCB Speakers Bureau (3) GE Healthcare Speaker Program

    Editorial Boards:

    1. Tremor and Other Hyperkinetic Movement Disorders, Editorial Board 2011

    Patents:

    1. Patent Pending Varenicline in the treatment of ataxia

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. (1) TEVA- speaking engagements (2) UCB Speakers Bureau (3) GE Healthcare Speaker Program

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. (1) TEVA (2) UCB (3) GE Healthcare

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. (1) GlaxoSmithKline (2) UCB Pharmaceuticals (3) Edison Pharmaceuticals

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. (1) National Ataxia Foundation, grant support (2) Friedreich's Ataxia Research Association, grant support (3) Bobby Allison Ataxia Research Center, grant support

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  1. From Harvard Medical School and Massachusetts General Hospital (J.W.W.), Boston; Department of Neurology (M.J.A.), University of Florida College of Medicine, Gainesville; Department of Neurology (R.P.A.), Johns Hopkins University, Baltimore, MD; King's College and King's College Hospital (K.R.C.), London; Methodist Neurological Institute (W.O.), Houston, TX; Department of Neurology (C.T.), University Medical Center, Göttingen, Germany; Northwestern University Feinberg School of Medicine (P.C.Z.), Chicago, IL; University of Kansas Medical Center (G.S.G.), Kansas City; CAMC Neurology Section (D.G.), Charleston, WV; and Department of Neurology (T.Z.), University of South Florida, James A Haley Veterans Administration Hospital, Tampa.
  1. Correspondence to American Academy of Neurology: guidelines{at}aan.com

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Letters: Rapid online correspondence

  • Authors' response to Dr. Sethi
    • Richard P. Allen, Psychologist, Johns Hopkins University
    • Richard P. Allen, PhD, Baltimore, MD; Melissa J. Armstrong, MD, MSc, Gainesville, FL; Claudia Trenkwalder, MD, Goettingen, Germany;Phyllis C. Zee, MD, PhD, Chicago, IL; John W. Winkelman, MD, PhD, Boston, MA
    Submitted January 17, 2017
  • RLS treatment Practice Guideline Summary
    • Nitin K. Sethi, Associate Professor of Neurology, New York-Presbyterian Hospital, Weill Cornell Medical Center, New York, NY
    Submitted January 03, 2017
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