title: Guidelines for the first-line treatment of restless legs syndrome/Willis-Ekbom disease, prevention and treatment of dopaminergic augmentation: a combined task force of the IRLSSG, EURLSSG, and the RLS-foundation.
abstract: A Task Force was established by the International Restless Legs Syndrome Study Group (IRLSSG) in conjunction with the European Restless Legs Syndrome Study Group (EURLSSG) and the RLS Foundation (RLS-F) to develop evidence-based and consensus-based recommendations for the prevention and treatment of long-term pharmacologic treatment of dopaminergic-induced augmentation in restless legs syndrome/Willis-Ekbom disease (RLS/WED). The Task Force made the following prevention and treatment recommendations: As a means to prevent augmentation, medications such as α2δ ligands may be considered for initial RLS/WED treatment; these drugs are effective and have little risk of augmentation. Alternatively, if dopaminergic drugs are elected as initial treatment, then the daily dose should be as low as possible and not exceed that recommended for RLS/WED treatment. However, the physician should be aware that even low dose dopaminergics can cause augmentation. Patients with low iron stores should be given appropriate iron supplementation. Daily treatment by either medication should start only when symptoms have a significant impact on quality of life in terms of frequency and severity; intermittent treatment might be considered in intermediate cases. Treatment of existing augmentation should be initiated, where possible, with the elimination/correction of extrinsic exacerbating factors (iron levels, antidepressants, antihistamines, etc.). In cases of mild augmentation, dopamine agonist therapy can be continued by dividing or advancing the dose, or increasing the dose if there are breakthrough night-time symptoms. Alternatively, the patient can be switched to an α2δ ligand or rotigotine. For severe augmentation the patient can be switched either to an α2δ ligand or rotigotine, noting that rotigotine may also produce augmentation at higher doses with long-term use. In more severe cases of augmentation an opioid may be considered, bypassing α2δ ligands and rotigotine.
authors.affiliation: Sleep Research Institute, Madrid, Spain. Electronic address: dgb@iis.es.
authors.forename: Diego
authors.initials: D
authors.lastname: Garcia-Borreguero
authors.affiliation: Center for Sleep Medicine and Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Silber
authors.affiliation: Harvard Medical School, Boston, MA, USA; Departments of Psychiatry and Neurology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Winkelman
authors.affiliation: Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Birgit
authors.initials: B
authors.lastname: Högl
authors.affiliation: Departments of Clinical Pharmacy and Neurology, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences and School of Medicine, Aurora, CO, USA.
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: Bainbridge
authors.affiliation: Stanford University School of Medicine, Stanford, CA, USA; Private Practice, Downey, CA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Buchfuhrer
authors.affiliation: Department of Neurology, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.
authors.forename: Georgios
authors.initials: G
authors.lastname: Hadjigeorgiou
authors.affiliation: Japan Somnology Center, Neuropsychiatric Research Institute, Tokyo, Japan; Department of Somnology, Tokyo Medical University, Tokyo, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Sleep and Epilepsy Center, Neurocenter of Southern Switzerland, Civic Hospital, Lugano, Switzerland.
authors.forename: Mauro
authors.initials: M
authors.lastname: Manconi
authors.affiliation: Department of Neurology, Philipps-Universität Marburg, Marburg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Oertel
authors.affiliation: Department of Neurology, Methodist Neuroscience Institute, Houston, TX, USA.
authors.forename: William
authors.initials: W
authors.lastname: Ondo
authors.affiliation: Helmholtz Zentrum München, Institute of Neurogenomics, Munich, Germany; Department of Neurology, Klinikum rechts der Isar, Technical University, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Winkelmann
authors.affiliation: Sleep Disorders Center, Johns Hopkins Bayview Medical Center, Baltimore, MD, USA; Department of Neurology, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Allen
mesh_terms: D032921:Consensus; D018491:Dopamine Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D004357:Drug Synergism; D019317:Evidence-Based Medicine; D006801:Humans; D017410:Practice Guidelines as Topic; D012148:Restless Legs Syndrome / Q000188:drug therapy*
chemical_list: D018491:Dopamine Agonists
keywords: Algorithm; Alpha 2 delta ligands; Augmentation; Dopamine agents; Prevention; Restless legs syndrome