Augmentation of restless leg syndrome (Willis-Ekbom disease) during long-term dopaminergic treatment

Abstract

Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), is a common sensorimotor disorder that can generally be effectively managed in the primary care clinic. However, some treatment complications may arise. According to the recommendations of the International Restless Legs Syndrome Study Group, non-ergot dopamine-receptor agonists have over the past years been one of the first-line treatments for patients with RLS/WED requiring pharmacological therapy. Augmentation is the main complication of long-term dopaminergic treatment of RLS/WED and is defined as an overall worsening of symptoms beyond pretreatment levels in patients who experienced an initial positive therapeutic response. Once identified on the basis of its characteristic clinical features, augmentation requires careful management. In order to provide clinicians with a comprehensive understanding of this common treatment complication, this review discusses the clinical features of augmentation, and its differentiation from morning rebound, symptom fluctuations and natural disease progression. Reported incidences of augmentation in clinical trials of dopaminergic RLS/WED therapies are summarized. Finally, the hypothetical pathophysiology of augmentation and the current recommendations for management of patients with augmented RLS/WED symptoms are discussed.

Keywords:

• Augmentation
• dopamine agonist
• restless legs syndrome
• Willis-Ekbom disease

Acknowledgements

The authors acknowledge medical writing assistance provided by Hannah Carney, PhD, CMPP, Evidence Scientific Solutions, Horsham, UK, and Richard Fay, PhD CMPP, Evidence Scientific Solutions, Philadelphia, PA, USA.

Declaration of interest

Writing and editorial assistance was funded by UCB Pharma, Smyrna, GA, USA. The sponsor was given the opportunity to review the manuscript for scientific and medical accuracy. D Garcia-Borreguero has served as a consultant for Xenoport, UCB Pharma and Merck, and has received grants from Pfizer and UCB Pharma. A Benitez is an employee of UCB Pharma. R Allen has served as board member for GlaxoSmithKline, Pfizer, UCB Pharma, Jazz Pharma, and Boehringer Ingelheim, and as a consultant for Pfizer, GlaxoSmithKline, Xenoport, Luitpold Pharma, and Neurogen. He has received grants from Pharmacosmos and GlaxoSmithKline, and speakers fees from UCB Pharma, EMD Serono, Pharmacosmos and Boehringer Ingelheim. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes