RLS Guidelines Advise Against Dopamine Agonists, With John Winkelman, MD, PhD

Last fall, the American Academy of Sleep Medicine (AASM) updated the clinical practice guidelines for restless legs syndrome (RLS), advising against the standard use of dopamine agonists due to augmentation.1

Sleep experts recognized augmentation, the gradual expansion of symptoms, 30 years ago for individuals with RLS. In the past decade, growing evidence showed dopaminergic medications led to RLS augmentation, occurring in 7 to 10% of people per year.

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 said in a statement that 7 to 10% may not sound like a lot, but if you double that by 3 years, you get 20 to 30% of patients with RLS. In 5 years, that percentage will increase to 35 to 50% of individuals.

Moving away from dopamine agonists, the guidelines now recommend several iron treatments—intravenous iron and oral iron, as well as 3 alpha 2 delta calcium channel lignands that are gabapentin, gabapentin enacarbil, and pregabalin.

In December 2024, Winkelman published a piece on HCPLive about these new guidelines and shared the Home – RLS Curbside resource, a peer-to-peer HIPAA-compliant forum for healthcare providers to get advice from experts on the management of complex RLS cases.2

HCPLive sat down with Winkelman at SLEEP 2025, the 39th annual meeting of the Associated Professional Sleep Societies, in Seattle, to discuss these new guidelines and how clinicians can go about transitioning patients from dopamine agonists to newer recommended therapies. Sometimes, patients have been on dopamine agonists for 4 to 5 years, despite their symptoms worsening.

“At that point, you're going to describe the other approaches for restless legs [syndrome],” Winkelman said, “and there are other good approaches.”

The next step is looking for other things that could be making RLS worse, such as serotonergic antidepressants, sleep apnea, regularly taken antihistamines, the dopamine antagonists taken for either a psychiatric or GI indication, and alcohol consumption.

“First, we're going to look at all those things that make it worse,” Winkelman said. “We're going to try to modify them. If that doesn't make a difference, we're going to add one of these other medications or approaches. After we've started those other approaches and symptoms have [gotten] under better control, then we're going to extremely carefully and slowly reduce the dose of the dopamine agonist. It takes, generally, 6 to 12 months to get people off the dopamine agonist.”

Winkelman said that dropping a dopamine agonist dose is likely to lead to a week of worse RLS symptoms. A few weeks later, the dose will be dropped even more.

“I say to [patients], you're going to need to detox off of this medication, and it's going to be difficult,” he said. “At the end, you'll be much better, and you'll be very happy you're off this medication.”

References

1. Winkelman J, Berkowski J, DelRosso L, et al. Big Changes in the Updated AASM Clinical Practice Guidelines for RLS and PLMD. Presented at SLEEP 2025 the 39th annual meeting of the Associated Professional Sleep Societies, on Tuesday, June 10 in Seattle.

2. Derman, C. AASM Updates Clinical Guidelines for Restless Legs Syndrome. HCPLive. November 22, 2024. https://www.hcplive.com/view/aasm-updates-clinical-guidelines-restless-legs-syndrome. Accessed June 18, 2025.

3. Winkelman, J. Changes in Restless Legs Syndrome Treatment Recommendations. HCPLive. December 13, 2024. https://www.hcplive.com/view/changes-restless-legs-syndrome-treatment-recommendations. Accessed June 18, 2025.