National RLS Opioid Registry

Are You Interested in Supporting the National RLS Opioid Registry?

To donate to our research, please go to the Massachusetts General Hospital donations webpage and designate your gift to “Sleep Disorders Clinical Research Program (National RLS Registry)”. Alternatively, you can contact us at 617-643-6026 or RLSregistry@partners.org for more information.

Restless Legs Syndrome Overview

Restless Legs Syndrome (RLS) is a neurological disorder that causes an irresistible urge to move the legs accompanied by leg discomfort. Without adequate treatment, RLS symptoms can interfere with sleep and reduce quality of life.

Common Treatments for RLS

The FDA has approved four drugs for treating RLS:

• Ropinirole (Requip®)
• Pramipexole (Mirapex®)
• Rotigotine (Neupro®)
• Gabapentin enacarbil (Horizant®)

These non-opioid medications work for some people, but there are limitations to current treatments for RLS. For example, long-term use of certain medications can make RLS worse for some people.

Opioid Medications for RLS

Opioid medications have been used to successfully treat the symptoms in many patients with severe RLS or in patients who have found that conventional treatments have lost effectiveness.

However, the current climate of escalating opioid addiction and deaths from opioid overdose has resulted in increasingly strict regulation of these medications. Further regulations may make obtaining opioids for RLS more difficult, so both patients and physicians need more scientific evidence to assess the risks and benefits of treating RLS with opioids.

Learn more about the use of opioid medications for RLS: Opioids in the Treatment of RLS, Restless Legs Syndrome Foundation.

The RLS Opioid Registry

We have built an RLS Opioid Registry based at Massachusetts General Hospital with patients all around the country to assess the long-term safety and effectiveness of opioid medications for RLS. The registry is supported by a grant from the RLS Foundation, whose Executive Director Karla Dzienkowski recently noted, "This is the first study in which patients with RLS who use opioids are monitored over time to evaluate the effectiveness and tolerability of this treatment long-term."

A registry is an observational (non-intervention) study method that collects long-term data on a certain group of people. The RLS Opioid Registry collects data from people who have been diagnosed with RLS and are taking a prescribed opioid as treatment for RLS. This data will be used to evaluate specific treatments and outcomes for those living with RLS. Visit the Restless Legs Syndrome Foundation website to learn more about RLS symptoms, treatment and ongoing research.

Note: We do not provide any consultation, advice about clinical care or medication through this study.

Who Participates?

Interest in the RLS Registry has far surpassed expectations. After easily surpassing our original goal of 200 participants, we recently closed recruitment at 500.

Interest in the RLS Registry has far surpassed expectations. After easily surpassing our original goal of 200 participants, we recently closed recruitment at 500. Similar to the RLS population as a whole, the RLS Registry consists of slightly more women than men and is largely made up of individuals over the age of 60. Registry participants come from 44 US states and from 6 countries around the world.

What Have We Found So Far?

RLS Registry participants use 12 different kinds of opioids; whereas the majority of participants treat their RLS with a single opioid, a portion of participants use two. Methadone is the most common, with nearly half of participants using this medication. The average daily dose of methadone is 10 mg. Other commonly used opioids are oxycodone formulations, hydrocodone, and tramadol.

Many RLS Registry participants report that opioids are controlling their symptoms. At baseline, nearly all participants reported that their RLS symptoms were “very much improved” or “much improved” since starting an opioid. Over 20% of RLS Registry participants had experienced no RLS symptoms in the week before the baseline phone interview, and slightly more than 50% of participants reported just mild to moderate RLS symptoms in the past week.

Very few participants reported ever feeling “high” as a result of their opioid medication. However, a number of participants did report other side effects from their opioid treatments, with the most common being constipation, fatigue, and itching.

Brief data updates are periodically sent to RLS Registry participants. These can be accessed using the following links:

• February 2020: “What RLS Medications are Registry Participants Taking? (PDF)
• April 2020: “RLS Symptoms and Severity” (PDF)
• July 2020: “Opioid Doses” (PDF)
• December 2020: “RLS and Mental Health” (PDF)
• May 2021: "Anxiety and RLS Severity During the COVID-19 Pandemic" (PDF)
• January 2022: “Two-Year Data Update” (PDF)
• May 2022: “Stigma, Side Effects, and Symptoms" (PDF)
• January 2023: “Suicidal Thoughts in the RLS Opioid Registry" (PDF)
• July 2023: “Three-Year Registry Update" (PDF)
• December 2023: "What RLS Treatments are Registry Participants Using?" (PDF)
• June 2024: "Back to Basics: Medications and Dosages" (PDF)

In February 2021, we published our first full-length research article on RLS Registry data, titled “Baseline and 1-year longitudinal data from the National Restless Legs Syndrome Opioid Registry.”

• Baseline and 1-year longitudinal data
• Two-year longitudinal data (PDF)
• RLS severity in the National RLS Opioid Registry during the COVID-19 pandemic (PDF)
• Suicidality in Patients Using Opioid Medications to Treat Severe, Refractory RLS (PDF)
• Opioid Treatment of Patients with Painful Versus Painless RLS (PDF)
• National RLS Opioid Registry: Four-Year Dose Stability, Efficacy, and Tolerability (PDF)

Moving forward, there is much work to do. Among numerous research aims, we plan to assess whether opioid medications continue to control RLS symptoms over time, and whether or not dose escalation is needed for this to occur.

To learn more about Dr. Winkelman’s research grant, please visit the RLS Foundation Blog.

To learn more about RLS, visit the Restless Legs Syndrome Foundation website.