Opioids at low doses adequately control symptoms of refractory restless legs syndrome over two years: Study

More significant dose increases were seen in a minority of patients, which were invariably associated with a limited number of factors, most notably changes in non-opioid and opioid RLS medications and opioid use for a non-RLS condition.

"Continued longitudinal observations will provide insight into the long-term efficacy and safety of opioid treatment of severe, augmented RLS," the researchers wrote.

Restless legs syndrome (RLS), a sensory-motor neurological disorder, is a condition that leads to an uncontrollable urge to move the legs, usually due to uncomfortable sensations. For patients with augmented or refractory RLS, Low-dose opioids are prescribed. However, there is no clarity on these medications' long-term safety, efficacy, and dose stability for RLS treatment.

John Weyl Winkelman from Harvard Medical School in Boston, Massachusetts, and colleagues reported the 2-year longitudinal data in patients' samples treated with opioids for restless legs syndrome in the community.

The National RLS Opioid Registry, a longitudinal observational study, comprised of people taking a prescribed opioid for diagnosed and confirmed RLS, most of whom had augmented symptoms from dopamine agonists.

At the initial Registry entry and every six months after that, the authors collected information on opioid dosages, past and current RLS treatments, side effects, opioid abuse, psychiatric symptoms, and RLS severity.

The study revealed the following findings:

· Registry participants (n=448) with 2-year longitudinal data available were mostly white, female, over 60 years old, and, at Registry entry, had been on opioids for a median of 1-3 years at a mean morphine milligram equivalent (MME) of 38.4.

· Over the 2-year follow-up period, the authors did not observe any change in RLS severity in the overall cohorts.

· The median change in daily opioid dose from baseline to 2 years was 0 MME.

· While 41.1% of participants increased their dose during the follow-up period (median increase=10 MME), 58.9% decreased or saw no change.

· Only 8% and 4% saw increases of >25 MME and >50 MME respectively.

· Ninety-five percent of those who increased opioid dose >25 or >50 MME had one of the following features: discontinuation of non-opioid RLS treatment medications, switching opioids, at least mild insomnia, history of depression, age <45, male sex, and opioid use for comorbid pain.

"In the majority of participants, low-dose opioid medications continue to appropriately control symptoms of refractory restless legs syndrome over a follow-up of 2 years," the team wrote.

To conclude, the study provides Class IV evidence that opioid doses increase in about 40% of patients, primarily by small amounts, over two years when prescribed for adult refractory RLS.

Reference:

Long-term Safety, Dose Stability, and Efficacy of Opioids for Patients With Restless Legs Syndrome in the National RLS Opioid Registry John Weyl Winkelman, Benjamin Wipper, Jordana Zackon Neurology Jan 2023, 10.1212/WNL.0000000000206855; DOI: 10.1212/WNL.0000000000206855