July 12, 2021

The Management of Restless Legs Syndrome: An Updated Algorithm

Restless legs syndrome (RLS) is a common neurological disorder affecting up to 10% of the population in the United States, with nearly 3% experiencing severe symptoms that require daily medical treatment. An article in the Journal of Neural Transmission in 2007 reported that it takes nearly 13 years from the onset of symptoms to the initiation of a treatment plan for RLS.

Much has changed in RLS disease management in the last eight years, which has led to the update of the 2013 RLS treatment algorithm by the Scientific and Medical Advisory Board of the RLS Foundation. The updated algorithm was published in the July 2021 edition of Mayo Clinic Proceedings, a leading peer-reviewed clinical journal widely read by physicians and often cited in scientific papers. Publication in this journal will ensure the availability of this information to a broad group of clinicians, including primary care providers.

Scientific discoveries since 2013 have led to the better understanding of RLS and new approaches to disease management that include:

Clinical Advancements

• Untoward side effects of dopaminergic therapy; knowledge and understanding of the long-term risks of augmentation, impulse control disorders and rebound
• Consensus guidelines for the iron treatment of RLS
• Consensus guidelines for RLS diagnosis, treatment and management during pregnancy and lactation
• Appropriate use of opioid therapy in low total daily doses for refractory RLS
• Improved RLS diagnosis, treatment and management in children and adolescents

Research Advancements

• Clinical trials for pregabalin and oxycodone
• Adenosine and RLS relationship
• Identification and replication of 13 new RLS risk genes and confirmation of six previously identified RLS risk genes using GWAS (genome-wide association studies)

These advancements relate to ongoing research into the underlying causes of RLS and the search for durable treatments and potential cures for the disease.*

The 2021 RLS treatment algorithm is divided into sections that outline detailed guidance on clinical best practices in RLS disease management, including:

• General treatment considerations
• Alpha-2-delta ligands and iron treatment as first-line therapies
• Iron treatment guidelines for RLS
• Dopamine agonists as a second-line therapy
• Treatment for intermittent, chronic-persistent, and refractory RLS
• Special patient populations and potential future therapies

The new treatment algorithm describes medication selection, use, dose and side effects. Decision trees and tables provide visual guidance for treatment consideration. Nondrug therapies and other approaches are highlighted, which include activities to stimulate the mind and the avoidance of medications and substances known to worsen symptoms. For example, RLS specialists who practice at certified RLS Quality Care Centers report that augmentation from certain medications is the No. 1 reason that patients seek specialized care from a knowledgeable and experienced provider. The 2021 RLS treatment algorithm pays special attention to the use of combination therapies and the appropriate use of opioids in low total daily doses to treat refractory RLS – a common, yet manageable treatment challenge. For the first time, the new treatment algorithm also discusses RLS management in pregnancy, lactation and childhood.

The 2021 RLS treatment algorithm is a comprehensive approach to the management of RLS in the various stages of disease progression and across the life span. Michael Silber, M.B., Ch.B., lead author on the article and director of the Center for Sleep Medicine at Mayo Clinic, says, “This updated algorithm is based on current research, consensus documents and the combined practical experience of a team of practitioners highly experienced in the management of RLS. We hope it will provide practical guidelines for primary care providers and specialists who are needed to treat patients with this common and highly distressing disorder.”

The RLS Foundation has made this an open-access article, available for free download by patients, clinicians and researchers. The RLS Foundation encourages members to share this article with their healthcare providers at www.rls.org/21Algorithm. Executive Director Karla Dzienkowski says, “The publication of the 2021 RLS treatment algorithm is based on the latest scientific knowledge and clinical experience of RLS experts from around the globe who serve on our Scientific and Medical Advisory Board. I thank these members for their service to the Foundation and the RLS community and for their work on this seminal publication that furthers our mission and goals to educate and support RLS research leading to better treatments and a cure.”

*The RLS Foundation funds the only research grant program dedicated to RLS. Member support for the Foundation’s Research Grant Program has funded nearly $2 million for 47 grants to RLS researchers, whose research forms part of these key advancements. A revised RLS Research Grant Program protocol will be announced later this year to further the quest toward a cure.