Guidelines: Opioids for the Treatment of Refractory Restless Legs Syndrome

For patients with restless leg syndrome, opioids may be very beneficial if taken in low daily doses.

Opioids may be “life-transforming” for patients with refractory restless legs syndrome (RLS) when taken in relatively low total daily doses, according to a new guidance written by the Scientific and Medical Advisory Board of the Restless Legs Syndrome Foundation and published in Mayo Clinic Proceedings.

Opioids have been a mainstay of treatment in refractory RLS, but the worsening opioid epidemic in the US has made clinicians wary of prescribing them. “We have published this paper so that both specialists and primary care physicians can feel more comfortable prescribing opioids to RLS patients, not feel that they are at risk as physicians in treating these patients, and help relieve their suffering,” said first author Michael Silber, MD ChB, who is a neurologist at Mayo Clinic in Rochester, Minnesota.

For the 2 to 3% of patients in the US with severe RLS, symptoms can be debilitating and may include insomnia and suicidal depression. Although the researchers found opioids to have a favorable risk-benefit ratio, they recommend that other avenues of treatment be considered before initiating them, including addressing low iron stores and combination therapy with non-opioid agents. In addition, before patients are started on opioids, they should be assessed for opioid use disorder.

Effective opioid doses are considerably lower in refractory RLS compared to those prescribed for chronic pain. “Testing initial response with a short-acting opioid may be a reasonable initial option but in general, longer-acting and controlled-release drugs are preferred,” write the authors. Oxycodone (immediate or extended release, methadone, tramadol (immediate or extended release), codeine, morphine CR, and hydrocodone (immediate or extended release) may be considered treatment options, however, the authors note that the doses presented in the guidance are based on limited studies and anecdotal experience.

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The authors conclude by stating that future research should focus on the comparative effectiveness and side effects of various opioid treatments in refractory RLS, as well as how patients can be effectively converted from a dopamine agonist or alpha-2-delta ligand to an opioid.


Silber MH, Becker PM, Buchfuhrer MJ, et al. The appropriate use of opioids in the treatment of refractory restless leg syndrome. Mayo Clin Proc. 2018;93(1):59-67.

This article originally appeared on MPR