Identification and treatment of augmentation in patients with restless legs syndrome: practical recommendations

ABSTRACT

Restless legs syndrome (RLS) is a chronic disorder causing clinically significant discomfort to approximately 3% of adults. Although RLS was first identified centuries ago, our understanding of this disorder, its causes, and its treatments is still evolving. In particular, our knowledge of the potential negative effects of RLS treatments, including dopaminergic augmentation, continues to expand. Augmentation, which refers to a paradoxical treatment-related increase in RLS symptoms, has been associated with all three dopamine agonists approved for the treatment of RLS – rotigotine, pramipexole, and ropinirole. This review presents key information on prevention and treatment of dopaminergic augmentation from the recently published consensus-based guidelines issued by the International RLS Study Group task force in conjunction with the European RLS Study Group and the RLS Foundation for first-line treatment of RLS/Willis-Ekbom disease. If dopamine agonists are used to treat RLS, it is recommended that the dosage should be kept as low as possible without exceeding the maximum dose recommended for RLS treatment. As the frequency of augmentation with the rotigotine patch may only be slightly lower than that associated with pramipexole or ropinirole, medications that are effective and have little risk of augmentation, such as alpha-2-delta ligands, may be considered for initial RLS treatment. In addition, we present our clinical experience with treating patients with dopaminergic augmentation by highlighting 2 case studies and practical considerations when treating different patient populations. Applying current RLS augmentation diagnosis and treatment guidelines, as well as collecting detailed histories of worsening RLS symptoms, is critical for patient safety and effective management of RLS augmentation.

KEYWORDS:

• Alpha-2-delta ligand
• augmentation
• dopamine
• gabapentin enacarbil
• restless legs syndrome
• treatment

Declaration of interest

J Geyer has served as a paid consultant for Arbor (formerly XenoPort). R Bogan has served as a consultant for Arbor (formerly XenoPort), GlaxoSmithKline and UCB, and on speakers’ bureaus for Arbor (formerly XenoPort), Merck, Jazz, and Cephalon. Medical writing assistance was provided by Sachi Yim Phd and Meghana Karnik-Henry Phd from CodonMedical and this was funded by Arbor Pharmaceuticals LLC. 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.

Additional information

Funding

This work was funded by Arbor Pharmaceuticals LLC.

Notes on contributors

James Geyer

J Geyer and R Bogan contributed to the drafting of this manuscript and revised it critically for intellectual content. Both authors approve the final version for publication and agree to be accountable for all aspects of the work.