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Clinical Review State of the Art Review

New concepts in the management of restless legs syndrome

BMJ 2017; 356 doi: (Published 27 February 2017) Cite this as: BMJ 2017;356:j104
  1. Diego Garcia-Borreguero, neurologist and director,
  2. Irene Cano-Pumarega, head of pulmonology
  1. Sleep Research Institute, Madrid 28036, Spain
  1. Correspondence to: D Garcia-Borreguero dgb{at}


Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED) is a neurological condition with an overall prevalence in adults of 5-10% in Europe and North America. It is characterised by strong feelings of restlessness and distressing paraesthesia-like sensations in the lower legs, particularly when at rest. The symptoms vary considerably in severity and frequency. RLS/WED has a variable clinical expression influenced by genetic, environmental, and medical factors. Research into the pathophysiology of RLS/WED has found that various genetic markers and existing dysfunctions in dopaminergic mechanisms and iron mechanisms play a central role. Until recently, the first line treatment of RLS/WED was with low dose dopamine agonists, with three drugs having been approved by the US Food and Drug Administration and the European Medicines Agency. However, the occurrence of dopaminergic augmentation and an overall increase in severity of symptoms during long term treatment with dopamine agonists is leading to a shift towards non-dopaminergic alternatives as initial treatments, and particularly to α2δ ligands. Recent international guidelines recommend, whenever possible, to start treatment with these drugs (α2δ ligands) to avoid augmentation from the start. Other (eg, glutamatergic or adenosine) neurotransmitters might also play an important role in causing RLS/WED and might thus lead to new treatments.


  • We thank Anne-Marie Williams for her help with editing.

  • Contributors: DGB planned the review, searched and reviewed the literature, and wrote and revised the first draft. ICP reviewed the literature and critically reviewed the first draft and final version.

  • Competing interests: We have read and understood the BMJ policy on declaration of interests and declare the following interests: DGB has received research grants from UCB and Xenoport.

  • Provenance and peer review: Commissioned; externally peer reviewed.

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