One-year longitudinal data from the National Restless Legs Syndrome Opioid Registry

Benjamin Wipper, BA

Massachusetts General Hospital
One-year longitudinal data from the National Restless Legs Syndrome Opioid Registry

Scientific Abstract

Background: Restless Legs Syndrome (RLS) is a sensory-motor neurological disorder. Low-dose opioid medications are frequently used in patients who have become refractory to first-line RLS treatments, particularly dopamine agonists (e.g. ropinirole). In the present work, we aim to collect observational longitudinal data on the RLS treatment efficacy, dosage changes, and tolerability of opioid medications in this population.

Methods: Individuals currently taking a prescribed opioid for diagnosed RLS are included in the registry. Information on initial and current opioid dosages, side effects, past and current concomitant RLS treatments, RLS severity, psychiatric history, and opioid abuse risk factors was collected at baseline. Follow-up online surveys were performed at 6 months and 1-year.

Results: Participants (n=500) are primarily white, elderly, educated, and retired. Nearly 50% of all subjects are taking methadone, and one-quarter are taking oxycodone formulations. Median opioid dose at baseline was 30.0 morphine milligram equivalents (MME). Three-quarters of registry participants had been taking a prescribed opioid for RLS for more than one year and one-third for more than five years. At 1-year follow-up, 31.2% increased dose (median=10 MME) and 16.0% decreased dose of their opioid. An MME increase ≥25 (n=24) was associated with opioid use for non-RLS pain, <1 year of opioid use, opioid switch to methadone, and discontinuation of non-opioid RLS medications which, combined, accounted for 91.7% of those with 1-year follow-up increases ≥25 MME.

Conclusions: In this population, opioids are generally used at low doses with good efficacy. Longitudinally over one year, roughly one-third of participants increased their prescribed opioid dose, with larger dose increases accounted for by predictable features. Longitudinal data collected in the coming years will continue to grow knowledge on the safety and tolerability of opioids for RLS.

SoundCloud Transcript

Restless Legs Syndrome, or RLS, is a sensory-motor neurological disorder characterized by an irresistible urge to move the legs. Although dopamine agonists and alpha-2-delta calcium channel ligands are effective treatments for this disorder, low dose opioid medications are prescribed for patients with treatment-refractory RLS. The RLS National Opioid Registry is a longitudinal observational study that will provide important information about long-term symptom control, dose escalation and complications in patients using prescribed opioids for RLS. Baseline interviews and recurring 6-month surveys on REDCap collect data on opioid type and dose, side effects, psychiatric symptoms and RLS severity. 


At baseline assessment of the 500 enrolled participants nearly half were taking methadone, and roughly one-quarter were taking oxycodone formulations. The prescribed opioids were generally used at low doses with good efficacy. At 1-year follow-up, 98% remained enrolled and the majority remained on the same opioid dose. Just under a third of participants increased opioid dose, and about 15 percent decreased their dose. Larger dose increases were associated with a number of predictable factors: use of opioid medications for pain in addition to RLS, discontinuation of other RLS medications since baseline assessment, and under 1 year of opioid use at baseline. Continued longitudinal data will grow knowledge on treatment efficacy and tolerability of opioids for RLS which will better inform clinical decisions.

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research Areas


Benjamin Wipper, BA, Julia Purks, BS, John Winkelman, MD, PhD

Principal Investigator

John Winkelman, MD, PhD

Affiliated Website