title: The long-term treatment of restless legs syndrome/Willis-Ekbom disease: evidence-based guidelines and clinical consensus best practice guidance: a report from the International Restless Legs Syndrome Study Group.
abstract: A Task Force was established by the International Restless Legs Syndrome Study Group (IRLSSG) to develop evidence-based and consensus-based recommendations for the long-term pharmacologic treatment of restless legs syndrome/Willis-Ekbom disease (RLS/WED). The Task Force reviewed the results of all studies of RLS/WED treatments with durations of 6 months or longer presented at meetings over the past 2 years, posted on Web sites of pharmaceutical companies, or published in peer-reviewed journals, asking the questions, "What is the efficacy of this treatment in patients with RLS/WED?" and "What is the safety of this treatment in patients with RLS/WED?" The Task Force developed guidelines based on their review of 61 papers meeting inclusion criteria, and using a modified evidence-grading scheme. Pregabalin has been established as effective for up to 1 year in treating RLS/WED (Level A evidence). Pramipexole, ropinirole, and rotigotine have been established as effective for up to 6 months in treating RLS/WED (Level A). The following drugs have been established as probably effective (Level B) in treating RLS/WED for durations ranging from 1 to 5 years: gabapentin enacarbil, pramipexole, and ropinirole (1 year); levodopa (2 years); and rotigotine (5 years). Because of associated safety concerns, pergolide and cabergoline should not be used in the treatment of RLS/WED unless the benefits clearly outweigh the risks. Other pharmacologic therapies have insufficient evidence to support their long-term use in treating RLS/WED. The IRLSSG Task Force also developed consensus-based strategies for the prevention and treatment of complications (such as augmentation, loss of efficacy, excessive daytime sleepiness, and impulse control disorders) that may develop with the long-term pharmacologic treatment of RLS/WED. The use of either a dopamine-receptor agonist or α2δ calcium-channel ligand is recommended as the first-line treatment of RLS/WED for most patients, with the choice of agent dependent on the patient's severity of RLS/WED symptoms, cognitive status, history, and comorbid conditions.
authors.affiliation: Sleep Research Institute, Madrid, Spain. dgb@iis.es
authors.forename: Diego
authors.initials: D
authors.lastname: Garcia-Borreguero
authors.forename: Ralf
authors.initials: R
authors.lastname: Kohnen
authors.forename: Michael H
authors.initials: MH
authors.lastname: Silber
authors.forename: John W
authors.initials: JW
authors.lastname: Winkelman
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Earley
authors.forename: Birgit
authors.initials: B
authors.lastname: Högl
authors.forename: Mauro
authors.initials: M
authors.lastname: Manconi
authors.forename: Jacques
authors.initials: J
authors.lastname: Montplaisir
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Inoue
authors.forename: Richard P
authors.initials: RP
authors.lastname: Allen
mesh_terms: D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D032921:Consensus; D018491:Dopamine Agonists / Q000627:therapeutic use*; D019317:Evidence-Based Medicine / Q000592:standards*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000627:therapeutic use*; D038622:Internationality; D017410:Practice Guidelines as Topic; D012148:Restless Legs Syndrome / Q000188:drug therapy*
chemical_list: D002121:Calcium Channel Blockers; D018491:Dopamine Agonists; D006993:Hypnotics and Sedatives
keywords: Calcium channel alpha 2 delta ligands; Dopamine agents; Hypnotics and sedatives; Opioids; Periodic limb movements of sleep; Pharmacologic therapy; Restless legs syndrome; Willis–Ekbom disease