Progress Report on National RLS Opioid Registry

December 20th, 2023 Progress Report #12: National RLS Opioid Registry Relevance: This project continues to be relevant to the Res...

December 20th, 2023

Progress Report #12: National RLS Opioid Registry


This project continues to be relevant to the Restless Leg Syndrome Foundation’s mission to improve the quality of life for those living with RLS. The National RLS Opioid Registry is collecting much-needed data on the efficacy and safety of long-term opioid treatment for RLS. Opioids have been shown to successfully treat the symptoms in patients with severe RLS, even when current approved treatments lost effectiveness; however, there is a lack of concrete data to support opioids as a treatment option. Given the current overdose crisis, data on the efficacy and safety of opioids for the treatment of RLS is needed so that providers and patients can make informed treatment decisions, especially in the face of increasingly strict opioid regulations.

Research Goals and Methodology:

By asking questions about specific opioid dosages over time (including the first stable dose) and validated questions about RLS severity (IRLS, RLS-QLI), we aimed to assess the efficacy of opioid medications in the treatment of RLS. By asking questions about specific side effects over time, we aimed to assess the tolerability and safety of opioid medications. By obtaining a medical and psychiatric history, a list of concomitant medications, and information on habits, behaviors, and mood, we aimed to further understand how these factors may influence the efficacy and safety of opioid medications in this population.

We originally set a goal to enroll 200 subjects within 2 years. We surpassed that goal, having enrolled 502 subjects. Enrollment was closed in September 2019. Upon enrollment, participants completed a phone interview lasting approximately 45 minutes. Information about RLS symptoms, past and current medications, specific dosages, and opioid side effects was collected during this interview, in addition to more sensitive information related to psychiatric conditions and opioid risk factors.

After the phone interview, participants were sent an online survey that took approximately 15 minutes to complete and was completed within 7 days of the phone interview (extensions were given under certain circumstances). This online survey collected information on medical history, sleep behavior, habits, recreational drug use, and mood. A total of 500 of 502 enrolled subjects completed the baseline survey. Every 6 months following the initial enrollment interview, participants are sent a follow-up survey that takes approximately 20 minutes to complete. The follow-up survey consists of a combination of questions from the baseline phone interview and baseline online survey, and it should be completed within 7 days. The links to access both the baseline and follow-up online surveys are sent to personal email addresses.


We recruited participants from established RLSF Quality Care Centers around the country, and via RLSF circulated media. Designated and interested clinicians were provided with study brochures to give to potentially eligible patients. The brochure contained the necessary contact information to enroll in the Registry, and this contact information was also provided on the RLSF website and newsletter.


Enrollment was limited to individuals with: a diagnosis of RLS, confirmed by the Hening-Hopkins Telephone Interview at the start of the baseline phone interview; an opioid prescription, which may be confirmed by state prescription drug monitoring programs; and a past medication history that includes a positive response to dopamine agonists for RLS treatment, as confirmed by a question about past RLS treatments.

Longitudinal follow-up

We continue to send 6-month follow-up surveys to all remaining participants (excluding those who have discontinued opioids and those who are deceased). A total of 467 participants completed the 1-year follow-up survey (97.7% retention), 458 completed the 2-year follow-up survey (95.2% retention of eligible participants), 441 completed the 3-year follow-up survey (94.1% retention), 425 completed the 4-year follow-up survey (93.6% retention), and 288 completed the 5-year follow-up survey.

At this time (December 2023), 23 subjects are considered lost to follow-up, 9 subjects withdrew, 18 subjects are deceased, and 38 subjects discontinued their opioid treatment (see Figure 1). Retention is high as a result of participant commitment and our continuing efforts to encourage participation through vigilant follow-up with participants (emails, phone calls) as well as emailing quarterly analyses data updates.

Data analyses

As of this date, we have assessed baseline, 1-year, 2-year, 3-year, and 4-year longitudinal data from the RLS Registry. These analyses revealed that in refractory RLS, prescribed opioids are generally used at low doses with good efficacy. Longitudinally over 4 years, roughly one-half of participants increased their prescribed opioid dose, though generally by small amounts, with larger dose increases accounted for by predictable features. Our 1-year data has been published in Sleep. We have also analyzed data relating to the effects of COVID on the severity of RLS symptoms just prior to, and following, the national lockdown in March 2020. Our 2-year data was presented at the annual APSS meeting (June 2021) and published in Neurology. A poster on suicidality in the Registry using the 2-year data was presented at APSS Sleep 2023 in Indianapolis, and we are in the process of publishing a manuscript on the same subject. Findings from the 3-year data were presented at World Sleep 2023 in Rio de Janeiro, and we intend to present our 4-year findings at APSS Sleep 2024 in Houston, Texas.

Ten data updates using Registry data have been sent to participants. These include data summaries such as RLS and mental health, RLS severity during the COVID-19 pandemic, the stigma of opioid treatment for RLS, suicidality in the RLS Registry, and much more. All of the quarterly updates can be accessed on the RLS Registry webpage. We plan to continue sending updates to participants on a quarterly basis.

The Registry remains open to collaborators who desire to examine specific questions relating to RLS which can be addressed through its database. One such collaborator, Dr. Elias Karroum, has been assessing the effects of painful RLS on outcomes collected through the Registry and he has submitted an abstract describing his findings to APSS Sleep 2024 in Houston, Texas.


At this time, we are very pleased that the Registry is obtaining the data we had hoped, and participant commitment is high, as demonstrated by low rates of attrition. We aim to accurately answer questions about the efficacy and safety of opioid medications for the treatment of RLS, and in doing so, we are keeping with the RLSF’s mission to improve the lives of those living with RLS.

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