Updated Guidelines for the Treatment of Restless Leg Syndrome: New Research Prompts a Significant Shift in Recommendations

December 3, 2024
Ruta Nonacs, MD PhD
This update from the American Academy of Sleep Medicine presents a significant change in recommendations for the treatment of RLS, discouraging the use of commonly prescribed dopamine agonists.
The American Academy of Sleep Medicine (AASM) has published new clinical practice guidelines for the treatment of restless leg syndrome (RLS).  The guidelines reflect the latest scientific evidence accumulated over the last decade, and recommend significant changes in the clinical management of RLS in adults.  

AASM’s previous guidelines were published in 2012.  In order to develop updated guidelines, the AASM commissioned a task force of sleep medicine clinicians with expertise in RLS. John Winkelman, MD, PhD, Chair of the AASM Task Force and Chief of the Sleep Disorders Clinical Research Program at Mass General notes, “This new clinical practice guideline from the AASM represents an important turning point in the treatment of RLS in adults.  Guided by the best evidence in the scientific literature, we’ve provided recommendations that will improve the ability of clinicians to provide patient-centered care for people who have RLS.”

According to the guidelines, the first step in the management of RLS should consist of identifying and managing exacerbating factors, including alcohol, caffeine, certain antidepressant and antihistamine medications, as well as untreated obstructive sleep apnea. They also note that RLS is common in pregnancy.

The updated guidelines include several important changes in the treatment of RLS:

Evaluation of Iron Studies:  Clinicians should regularly obtain serum iron studies, including ferritin and transferrin saturation (calculated from iron and total iron binding capacity, TIBC).  Depending on iron indices, iron supplementation is recommended.  The guidelines provide a strong recommendation for intravenous ferric carboxymaltose and conditional recommendations for IV low molecular weight (LMW) iron dextran, IV ferumoxytol, and oral ferrous sulfate. 

Avoidance of Dopamine Agonists:  The new guidelines recommend against the use of the dopamine agonists, pramipexole and ropinirole.  Although these treatments were included as strong recommendations in the 2012 guidelines, more recent research indicates that long-term treatment with dopamine agonists is often associated with the risk of “augmentation” or the gradual worsening of RLS symptom intensity and duration.

Use of Alpha-2-Delta Ligand Calcium Channel Blockers: New evidence supports the strong recommendation for the use of three alpha-2-delta ligand calcium channel blockers — gabapentin enacarbil, gabapentin, and pregabalin — for the treatment of RLS.   These medications are not associated with the augmentation of RLS symptoms.

Low-Dose Opioids: The use of low-dose, extended-release oxycodone and other low-dose opioids have demonstrated efficacy for RLS; however, opioids carry risks that require cautious use and clinical oversight.  Use of low-dose opioids have received conditional recommendations of support. The National RLS Opioid Registry based at Mass General is collecting longitudinal data to assess the long-term safety, dose stability, and efficacy of opioid medications for RLS.

Bilateral High-Frequency Peroneal Nerve Stimulation: This is an innovative treatment developed that has received a conditional recommendation of support for the treatment of RLS. Treatment involves the use of a wearable device to stimulate the nerves in the legs before bedtime.

Earlier this year, Winkelman and colleagues launched a website RLS Curbside to help clinicians optimize the medical management of complicated RLS patients.  Using this platform, licensed healthcare providers can present brief clinical histories of their patients with RLS and get specific, evidence-based information on treatment .  It is hoped that this tool will enable health care providers to confidently treat RLS with the most efficacious, evidenced-based, personalized treatments for their patients. 

Read More

Winkelman JW, Berkowski JA, DelRosso LM, Koo BB, Scharf MT, Sharon D, Zak RS, Kazmi U, Falck-Ytter Y, Shelgikar AV, Trotti LM, Walters AS. Treatment of restless legs syndrome and periodic limb movement disorder: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2024 Sep 26. 

Winkelman JW, Berkowski JA, DelRosso LM, Koo BB, Scharf MT, Sharon D, Zak RS, Kazmi U, Carandang G, Falck-Ytter Y, Shelgikar AV, Trotti LM, Walters AS. Treatment of restless legs syndrome and periodic limb movement disorder: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med. 2024 Sep 26. 

In The News

John Winkelman, MD PhD is the Chief of the Sleep Disorders Clinical Research Program in the Department of Psychiatry at Mass General and Professor of Psychiatry at Harvard Medical School.  Dr. Winkelman's research has primarily focused in two areas: 1) epidemiology, physiology, cardiovascular consequences and treatment of restless legs syndrome, and 2) neurobiology and treatment of insomnia.

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