Will I Get Addicted to Opioids from My Restless Legs Syndrome (RLS) Treatment?: Part III; A ReLACSing Blog #33
(Note: Though I could have squeezed out four parts, they say a trilogy is better. Be sure to read Part I and Part II first, or watch the full video summary on the @andyberkowskimd YouTube channel)
In Part I, we reviewed the aspects of opioid use disorder as it pertains to restless legs syndrome (RLS). In Part II, we looked at the data and the clinical experience supporting the prevailing belief that low-dose opioids are safe and effective in treating RLS and the risks of opioid use disorder are much lower than assumed based on the impact on chronic pain and recreational use. In Part III, we address why opioids are lower risk, in particular, for RLS over other uses.
Photo by janilson furtado on Unsplash
First, the biology of RLS is different than for chronic pain, and certainly for recreational use. There may be defects in the opioid system of the brain that are related to how the brain processes sensations including pain and RLS. This study looking at the brains from the deceased with RLS showed deficiency in several chemicals that are involved in the opioid system. This more recent study on mice was one of several that have shown connections between low iron levels of the brain and the opioid system not working correctly. Hot off the presses is the work from Dr. Brian Koo and colleagues showing deficiencies in opioid system chemicals in those with RLS compared to controls. To over-simplify the implications of some of these studies, what if those with RLS are deficient in opioids and the treatment is supplementing the low levels of opioids in the body? The effect of correcting a deficiency may be different than giving extra to something that is already normal. As an analogy, a football player with normal growth hormone levels, who is taking human growth hormone (hGH) to build muscle or recover from injury faster may have a different outcome than someone who had growth hormone deficiency and got treated with hGH.
Another big factor is the different demographics of those with RLS who need opioids. RLS does not necessarily get worse with age, but the condition does not peak in young adulthood. Conversely, opioid use disorder decreases with age. RLS may occur more severely in an older population, in part due to health problems that develop over time that may worsen RLS. The more health problems, the more medications and treatments for the health problems as well. For example, one may develop acid reflux and then need an acid blocker to prevent the reflux symptoms. The acid blocker lowers iron absorption, iron levels decrease, and the RLS gets a little worse. A person develops an autoimmune condition that increases inflammation. The inflammation causes the RLS to get worse. There could be countless examples but these triggers for RLS are not happening in 18 or 25 year-olds who are more likely to abuse anything than a 65 year-old. The opioid prescriptions for RLS are usually going to the 65 year-old, not the teenager.
Another age factor is exposure to dopamine agonists and risk of augmentation. You can’t be stuck on pramipexole for 15 years with augmentation if you were 5 years old in 2010. You would not have been on the drug. Middle-aged and senior individuals with RLS may have been prescribed dopamine agonists as far back as 25 years ago, giving them more time and opportunity to be prescribed more of the drug and get worse on the drug. Hopefully, young adults right now are rarely prescribed these drugs with what is known about them now.
Those with RLS are not generally looking for opioids. Most patients with RLS I have treated do not want to take opioids, and I have to convince them that they are safe and highly effective even for severe RLS. There is understandably quite a bit of hesitancy and many decline to try the treatment. The ones who do ask for opioids are generally very knowledgeable about RLS and have read far more about the condition than their clinicians who never knew they were a treatment. They know they are at the end of the rope and this is a powerful treatment option that rarely fails due to ineffectiveness, only adverse effects. Though most with chronic pain are not seeking opioids, there are some that use it as a conduit to get opioids whether they have chronic pain or not. Those who want to get opioids to use recreationally or to get high, are by definition seeking opioids for these intrinsic reasons. The RLS group is lower risk of something bad happening to them.
In RLS, long-acting opioids seem to be prescribed more commonly than short-acting opioids. This further reduces the risks of abuse or adverse effects. Buprenorphine, which I continue to argue should be considered as the first opioid used in most with RLS, typically does not get people high, is a long-acting, stable drug, and most importantly, does not cause respiratory depression (slowing of breathing) even at very high doses, i.e. minimal risk of death from overdose/poisoning. This is why buprenorphine is less highly regulated by the DEA than most opioids (Schedule III) and why most addiction specialists are using this drug to get people with opioid use disorder or dependence off other opioids including the illicit fentanyl and heroin. It is safer and less risky, even for those at highest risk. In the abstract my group published on 55 patients prescribed buprenorphine for severe RLS (one day to see full journal publication), the patients were followed for as much as 1.5 years and did not need more than low doses of this drug and had significant long-term improvement to their RLS, sleep, mental health, and quality of life.
Similarly, methadone, as mentioned in Part II, has been the go-to opioid for RLS for years and is another long-acting, stable drug, which is less likely to invoke a drug high or be abused. Short- or intermediate-acting opioids can be used and may be necessary for RLS but may come with slightly increased risks. Thus, the high frequency of slow in, slow out, long-lasting opioids used in RLS may further reduce the risks over other conditions in which these may not be used as commonly or as effectively.
The final major area to discuss is what patients and clinicians do proactively to prevent any, even low risk of opioid use disorder from RLS treatment with opioids. First, patient selection is essential. Studies show that substance use disorder is less about the drug than the circumstances and experiences of the person taking the drug. Those who want to legalize most recreational drugs use this as a key argument. Some people can use drugs recreationally and not develop a use disorder. In fact, some of the common legal substances–alcohol, nicotine, and more recently cannabis–are used recreationally all the time, and most do not abuse these or develop a dependence. However, they are not without these risks and people of certain experiences and demographics are more at risk.
The Opioid Risk Tool is a great resource for patients and clinicians to measure their individual risk of opioid use disorder. It is based on epidemiological research highlighting those factors that make the most difference. These include personal history and family history of alcohol, illicit drug, and prescription drug abuse, as well as the aforementioned age with 45 years as the cut point, and a special category for women who are more at risk than men of substance use disorder if they have experienced preadolescent sexual abuse. Most clinicians treating restless legs will not refuse to prescribe opioids to those who score as medium or high risk, but the results will warn both clinicians and patients to be more vigilant.
Vigilance, specifically prescription drug monitoring, can and should be done in many ways. Up front, a clinician should have a lengthy discussion with the patient about the risks and benefits of opioid prescribing. The potential benefits should outweigh the risks of using opioids, particularly if other less risky options have not been effective. After the discussion, both parties should sign an opioid agreement or contract. This gives the patient written rules for taking their prescription medications, ordering refills, reporting unwanted side effects, etc. In turn, it tells the patients that the doctor will be monitoring them, including for signs of opioid use disorder, and do their best to look out for their safety. The patient does not have all the burden, and it is shared equally as part of a personal doctor-patient relationship. The contract gives both parties the added commitment to the process in writing that they must live up to.
Photo by National Cancer Institute on Unsplash
Regular communication and evaluation between the doctor and patient should occur, whether in person, through telemedicine, by phone, or messaging. A patient is never making decisions about their opioid on their own without discussing it with the licensed professional first. Some states require in person visits as a requirement to some opioid-prescribing, but with the measures discussed above and below here, this in-person policy adds little to safety other than creating an additional obstacle for the patient to have opioids prescribed in the first place. If the goal is to reduce opioid prescribing as a whole, this draconian policy, particularly to those in rural communities, ones with social barriers (e.g. can’t get time off work), transportation issues, etc. creates a barrier of access to this needed treatment, particularly for those with severe RLS. This was discussed in a previous blog on the DEA’s proposed telemedicine and controlled-substance prescribing policy that currently is on hold.
A baseline urine drug screen can be done to show the clinician that the patient is not taking any legal or illicit drugs that they should not be. Annual and random urine drug screens affirm that the patient is taking the opioid they are supposed to and not taking other risky drugs they shouldn’t be. Rather than being a nanny, the provider is telling the patient that they are alongside the patient, continuing to guide their care and look out for their safety.
The last monitoring technique is each state’s controlled substance pharmacy databases. These databases track the drug, prescriber, amount, dosage, and pharmacy for every controlled or monitored substance that comes from a pharmacy in each state. It is very hard to evade this database while obtaining drugs legally (the urine drug screen is an effort to identify drugs obtained illegally that won’t show up in the pharmacy database). A clinician or pharmacist can instantly tell if a person is going around to different clinicians and pharmacies or different states, getting legal controlled substances to use personally or to divert to others. Most states now require the physician to review the database prior to submitting any controlled prescription. It is a hassle, but it is a great intervention in my view, unlike mandated in-person visits.
Unfortunately, the inconvenience of all of the above and the perceived legal risk of prescribing opioids leads some clinics, medical centers, and doctors to say they “can’t” or “don’t” prescribe opioids, full stop. The culture in the medical field has swung to the very anti-opioid side currently, something I discussed here in greater detail. The fact is that, if you have a Schedule II DEA license–regardless of whether you are a doctor, nurse practitioner, physician assistant, dentist, etc., you can prescribe a Schedule II opioid. It is disingenuous to say “I am not allowed to prescribe opioids.” From my experience working with providers in other states, this is a phrase I am hearing frequently to RLS patients desperate for an effective treatment.
The question for you, the reader, as well as the medical field as whole: Is it truly ethical to have a blanket stance or even policy that a clinician will not prescribe opioids under any circumstances, thus denying those suffering with RLS one of the most valuable, and not all that high risk, treatment options?
The bottom line with concerns of opioid use disorder in RLS is whether the benefits outweigh the risks, as I say about a lot of treatments. The vast majority of individuals with RLS do not need and should not be offered opioids. But for those that could benefit from opioids quite strongly, what is the risk to sleep, quality of life, mental health, and overall well being of continuing to endure severe RLS and be denied opioids as treatment?
-Andy Berkowski, MD of ReLACS Health, whose medical director thankfully allows him to prescribe opioids for RLS
