AASM Updates Clinical Guidelines for Restless Legs Syndrome

The American Academy of Sleep Medicine (AASM) published new Clinical Practice Guidelines for treating restless legs syndrome (RLS), now recommending against the standard use of dopamine agonists due to augmentation.¹

Augmentation, characterized by the gradual expansion of symptoms both temporally and anatomically, was first recognized 30 years ago for individuals with RLS. In the past 10 years, more evidence suggested dopaminergic medications led to the incidence of RLS augmentation, with this occurring in 7 to 10% of people per year.²

“This may not sound like a lot, 7 to 10% but given that people with restless leg syndrome generally need long-term treatment, if you multiply that by just 3 years already, you've got 20 to 30% of people. In 5 years, you're looking more at 35 to 50% of people,” said John Winkelman, MD, PhD, chief of the sleep disorders clinical research program at Massachusetts General Hospital and chair of the AASM committee that revised the guideline.

The AASM committee weighed the efficacy of dopamine agonists with their adverse events. It concluded that while these medications work well for short periods, the complications in the long term outweighed the short-term benefits.¹

The updated guidelines include several first-line treatments that had yet to be approved at the time the previous guidelines were published in 2012. The new guidelines now recommend various iron treatments, including intravenous iron and oral iron, and 3 alpha 2 delta calcium channel ligands that are gabapentin, gabapentin enacarbil, and pregabalin. In the last 12 years, increasing evidence has shown these medications efficacy for people with RLS over long periods, and the committee strongly recommends them since the benefits of these medications outweigh the adverse events.

Although Winkleman said there is not a good method to access brain iron, clinical trials have shown keeping serum ferritin > 100 and serum transferrin saturation > 20% is effective for people with RLS.

“Even if somebody has a ferritin of 15 or 20 many providers would say, ‘Okay, it's a little bit low, but it's normal.’ We would say, ‘Absolutely, that's way too low for somebody with a restless leg syndrome,’ and we would push it up and try to get the ferritin above 100 similarly transference saturation,” Winkelman said.

He said clinicians should instruct patients to not have any iron vitamins or any red meat for 48 hours before getting iron levels checked. If a patient follows this, providers will get a better indication of their iron status.

Winkelman said gabapentin enacarbil, gabapentin, and pregabalin work for most patients.

“For those people who have neuropathy or many potentially another chronic pain syndrome, that they may be able to kill two birds with one stone, for individuals who are more sensitive to the side effects of these medications,” he said.

He recommends starting low and slow for patients who are more sensitive to adverse events of these medications—for instance, if they have instability of gait or are very sensitive to weight gain or dizziness. Although some patients may be more sensitive to these adverse events, clinical trials demonstrated the efficacy of these medications, hence why they are all first-line treatments for RLS.

“These are big changes for providers,” Winkelman said. “Every visit with somebody who you're prescribing a dopaminergic medication, you need to ask about the timing of symptoms to make sure that this augmentation process is not happening because it's very slow, generally steady, and increasing the dose, which is the reflexive thing to do when things aren't working, only accelerates the augmentation process.”

References

1. ^{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. doi: 10.5664/jcsm.11390. Epub ahead of print. PMID: 39324694.}
2. ^{Zeng P, Wang T, Zhang L, Guo F. Exploring the causes of augmentation in restless legs syndrome. Front Neurol. 2023 Sep 28;14:1160112. doi: 10.3389/fneur.2023.1160112. PMID: 37840917; PMCID: PMC10571710.}