Restless Legs Syndrome Foundation Blog

May 17, 2023

The ‘Opioid Issue’ Still Needs Your Attention

By Lewis Phelps, Former Chair, RLS Foundation Board of Directors

Five years ago, we wrote in NightWalkers about the challenges that people with RLS and their doctors face in getting opioid prescriptions filled. In recognition of the seriousness of the problem experienced by many of our members, we retained the services of a public affairs firm in Washington that specializes in healthcare issues to help us alert policymakers about the problem and to craft sensible federal policies that recognize the unique role these medications play in providing relief for many among us.

In response to concerns about opioid addiction, the Foundation has funded groundbreaking research that documents the long-term safety and efficacy of opioids as a treatment for severe RLS.

Over the intervening years, we have deployed Foundation staff, members of our Scientific and Medical Advisory Board, and individual Foundation members to visit members of Congress, federal agencies, and others making or influencing policy, legislation or regulation on this topic.

Nevertheless, those who write the guidelines and rules about dispensing opioids continue to get it wrong: They craft guidelines appropriate for treatment of chronic pain that lack recognition of the unique neuropathology of RLS and the specialized consideration required in treating RLS, but rather include RLS in the category of generalized pain issues.

Documentation can be found in medical literature as far back as four centuries ago about the safety and efficacy of low total daily doses of opioids to treat people with severe RLS that has failed to respond to other treatments. This so-called “off-label” use is relatively common when physicians discover that drugs can alleviate conditions beyond those specifically approved by the government. (For example, a medication approved for high blood pressure is frequently prescribed to musicians to prevent performance anxiety.) To obtain approval “on label,” the government requires extensive, costly years of testing.

Pharmaceutical companies are unwilling to invest in such lengthy trials, particularly in the case of drugs like common opioids that cannot be patented. With no hope of recapturing the costs of testing a drug, no company will undertake the licensing process.

To be sure, there are approved drugs that are useful in treating RLS symptoms. These include alpha-2-delta ligands (gabapentin-type drugs, originally developed to treat seizure disorders and nerve pain), iron infusion, and dopaminergic drugs such as pramipexole, ropinirole, rotigotine and levodopa/carbidopa.

Unfortunately, experience has shown that while dopamine agents improve symptoms over the short term, over time, they can make RLS worse. This is an untoward effect of dopamine therapy known as augmentation, in which the medication prescribed to treat RLS symptoms actually makes the disease worse over months or years. Thus, dopamine drugs are no longer favored for long-term use.

When all other options have failed, as they do for many people with RLS, there is only one remaining treatment available: opioids.

The Centers for Disease Control and Prevention (CDC) has recently published a revised guideline for the use of opioids to treat chronic pain. The new rules are similar in many respects to prior versions, except that they reduce the maximum recommended daily dose of opioids to an even lower level than before.

Available information indicates that three-fourths of RLS patients using opioids are prescribed doses below these new CDC guidance levels. Alarmingly, this means that about one-fourth of patients receiving opioids are at risk of losing access to the only effective treatment for their disease.

It appears that the new guidelines ignore well-established scientific evidence that RLS is different from chronic pain and needs to be treated differently. Consider the following facts:

• In contrast to chronic pain, where opioids lose their effectiveness over time, when used to treat RLS, the drugs continue to provide relief from RLS symptoms for years, even decades.
• When prescribed for chronic pain, patients must increase doses over time to achieve relief. In contrast, The RLS Opioid Registry, a longitudinal study conducted at Massachusetts General Hospital, has found RLS patients remain at low total daily doses for decades; no increases are required to sustain relief.
• RLS patients typically do not develop opioid use disorder or develop issues of tolerance or dependence. Research and expert opinion have found that the low total daily doses used to manage severe RLS do not lead to tolerance or dependency issues, which are hallmarks of opioid use disorder.

To be fair, the revised CDC guideline recognizes that it is only advisory, not mandatory. “This clinical practice guideline provides recommendations but does not replace clinical judgment and individualized, patient-centered decision-making.”

Unfortunately, experience demonstrates that such language is widely ignored. Suggestions are transmuted into hard and fast rules. The Foundation receives reports from members and physicians that state regulators have converted this guideline into rigid regulations, insurance companies have refused to provide coverage for opioids even when within the recommended limits, pharmacies have refused to fill legal and proper prescriptions for opioids for RLS, hospital emergency rooms have treated patients using opioids for RLS control as if they were addicts and criminal drug dealers, and some doctors, clinical practices and medical centers have stopped prescribing opioids at all treat RLS. Even worse is the letter patients receive that their physician no longer treats RLS and they will need to find a new provider. These reactions are driven by fear, not science.

It is notable that the new guideline acknowledges that the general advice the CDC provides on opioids specifically does not apply to three situations: patients with sickle cell anemia, cancer patients with pain, and palliative care (end-of-life) treatments. We believe that the CDC needs to add RLS to the list of medical conditions that lie outside of its recommendations for the treatment of chronic pain.

How is the Foundation responding to this challenge facing its members? We have already held conversations with the leadership at the CDC. We note that:

• RLS is a distinct neurological condition that responds differently to opioids than chronic pain.
• RLS is a very significant disorder with a greater disruption in health-related quality of life than many other recognized medical conditions.
• There is a four times greater risk of suicide among those with severe RLS than in the general population, and twice the risk than that of people with severe chronic pain.
• There is strong evidence that using opioids to treat RLS does not lead to tolerance or dependence on opioids.
• Most of the drugs approved by the Food and Drug Administration to treat RLS (Requip, Mirapex and Neupro) actually make the condition worse over time, and the remaining approved drug (Horizant) is either not tolerated or is not fully effective in a large percentage of people with severe RLS.
• The CDC should specifically exempt RLS from the guideline for opioid prescribing in the same way that it has exempted sickle cell disease. Like sickle cell disease, RLS is a disease with a genetic predisposition.

The RLS Foundation hopes that the CDC will respond to these arguments. If it does not, we expect that we will need to carry the same discussion to other venues that are involved in the process, up to and including the United States Congress.

We will keep members of the RLS Foundation advised of our progress. It is possible that we will ask members to add their voices to the more than 500 members of the Foundation who have already submitted comments to the CDC during the public comment period preceding the issuance of the new opioid guideline (more than 10% of all comments listed). Although we did not achieve the hoped-for goal in that process, it is clear that there is more work to be done. Please be alert to calls for action.

Our efforts to fight for the rights of those with RLS to obtain the medical treatment they need and deserve, without undue restrictions, are ongoing. The RLS Foundation is a volunteer-driven organization, and we appreciate your continued financial support to increase our advocacy efforts. For more information on how you can get involved, go to www.rls.org/advocacy.