John Winkelman, MD, PhD: When to Use Low-Dose Opioids for Restless Legs Syndrome


The first line treatment for restless legs syndrome—dopamine agonists—may be making a patient’s condition worse in the long-term, Winkelman told HCPLive at SLEEP 2024.

Sometimes, treatments for restless legs syndrome may lack efficacy or exacerbate the condition—hence why patients might need to turn to low-dose opioids as another treatment option.

John Winkelman, MD, PhD, from Massachusetts General Hospital, presented a session called “Low-Dose Opioids for Restless Legs Syndrome: When, Who, What and How,” at SLEEP 2024, the 38th annual meeting of the Associated Professional Sleep Societies, in Houston. HCPLive sat down with Winkelman to discuss his presentation who shared when it is appropriate for doctors to consider low-dose opioids for treating restless legs syndrome.

About 2 to 3 percent of US adults have restless leg syndrome. For the past 20 years, the first line treatment for this condition has been dopamine agonists, which are effective for treating restless leg syndrome. Except, only in the short term—over time, the medication not only loses its efficacy but makes the restless legs syndrome worse.

“This is a phenomenon we call augmentation where symptoms increase in temporally. In the…number of hours per day that people will have symptoms, they can also increase, expand anatomically, going from the legs to the upper extremities,” Winkelman said. “This is an insidious process that happens over years, not months. Unfortunately, the majority of people who are treated for restless leg syndrome in the US are treated with these medications because they're so good in the short term, and the long-term worsening that's associated with them is not recognized for that reason.”

To avoid dopamine agonists, patients can take other, better options to reduce iron deficiency—alpha-2 delta calcium channel ligands, such as gabapentin, pregabalin, and acarbose.

Another option is low dose opioids, which have been used for restless legs syndrome for 350 years but called another name. Many people who use opioids for restless leg syndrome use long-acting opioids since they experience symptoms for at least half the day.

“Rather than using multiple doses of short-acting opioids, we prescribe long-acting opioids,” Winkelman said.

Winkelman’s relevant disclosures include Idorsia Pharmaceuticals and Azurity Pharmaceuticals.


Winkelman, J. Low-Dose Opioids for Restless Legs Syndrome: When, Who, What and How. Session presented at SLEEP 2024. Houston, TX. June 3, 2024.

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