A ReLACSing Blog #18: 5 Notes from MASM 2022
The Michigan Academy of Sleep Medicine returned to an in-person Annual Fall Conference this year, and I had the pleasure of presenting “More Opioids?! Yes, for RLS” on Friday, October 21, 2022. In this presentation, the three learning objectives were for clinicians treating restless legs syndrome (RLS) to recognize the symptoms of augmentation in patients on dopamine agonists (see blog #4 for more details) and how to reverse the phenomenon by slowly tapering off the medications. The second objective was to provide a deeper understanding of the importance of testing iron levels on everyone with RLS, including what the desired ranges are for the blood tests and how to use both oral supplements and IV iron infusion to bring levels up aggressively. The last section addressed the title of the talk in that for patients with moderate to severe RLS, patients often require opioids for control of symptoms. Despite the War on Drugs and the current opioid epidemic in the United States, opioids have been used since the 17th century and are possibly the oldest known treatment for the condition by Sir Thomas Willis. This class of drugs can and should be used safely and effectively for those suffering with symptoms and where the first-line agents have already been unsuccessful. I included some initial data from an ongoing project looking at 55 patients who have taken buprenorphine for RLS and had excellent results. Hopefully, these data can be published in the next year with the help of some colleagues working on this project from the Cleveland Clinic. Buprenorphine is a partial opioid agonist used most notably for opioid use disorder but also pain conditions. It appears to have excellent effects on RLS symptoms equal to that of common full agonist opioids for RLS like methadone and oxycodone. However, buprenorphine does not generally cause euphoria (or getting the feeling of a “high”) making it less likely to be abused or lead to addiction. Most importantly it does not cause effects on the centers of the brain that control breathing, even at high doses, which is the most concerning side effect of full agonist opioids and why there are so many opioid-related deaths. Buprenorphine is a schedule III controlled substance by the DEA and thus less highly regulated than most other opioids because of its relative safety. This drug can be a great tool in the armamentarium of medication treatments for RLS, and will become increasingly necessary to combat the epidemic of augmentation from continued over-prescribing of dopamine agonists for this condition.
As I will try to do after each conference, here is the summary of five interesting things learned at this year’s MASM Annual Fall Conference:
Marijuana is a hot topic in medicine across all areas, but it remains a rare case in which a drug has rapidly come to market with significant momentum, popularity, and availability before it has been well-studied and thoroughly vetted by scientific studies. It appears there will be important uses for this in multiple areas of allopathic medicine, but we first have to figure out the effects, side effects, dosage, interactions, route of administration, etc. just like all other drugs before we can use this group of compounds for medical purposes most effectively. A former sleep psychology colleague at the University of Michigan, Deirdre Conroy, PhD gave a very interesting and topical lecture on “Marijuana Use & Sleep”. Her group’s research revealed that 80% of medical marijuana users are trying to get help, in part, with sleep symptoms. The results related to insomnia and sleep are mixed and significantly more sleep research is needed, but marijuana can cause tolerance (needing more of the drug to produce the same effect) and dependence (body becoming reliant on the drug and going through withdrawal if not getting it). She and her colleagues demonstrated that cognitive and behavioral therapy for insomnia (CBT-I), which is the first-line, but challenging to find, treatment for chronic insomnia can improve sleep and reduce cannabis use.
Maximiliano Tamae Kakazu, MD, FCCP from the Michigan State University College of Medicine presented on relationships of cancer to sleep disorders. In mouse studies, intermittent drops in oxygen levels similar to what would be seen in obstructive sleep apnea (OSA) were associated with the increased risk of cancer and faster growth of tumors. The severity of OSA in humans was also associated with increased risk of developing cancer and the severity of the cancer. There is no evidence to support causality, in other words, that untreated OSA causes cancer, but there is a strong association. [Switching to my commentary] These associations are unsurprising as the risk factors for cancer–obesity in particular–overlap with the risk factors for OSA. Generally, obesity, high levels of inflammation, poor lifestyle choices, hyperinsulinemia (high levels of insulin in response to excess sugar including prediabetes/diabetes), etc. lead to obstructive sleep apnea, and so too cancer, so it hard to separate if the OSA came first and contributed to the cancer directly or just came for the ride. It would be interesting to see a series of patients with severe OSA due to a naturally narrow breathing airway inherited from parents who lacked all these other metabolic features to see if they were also at increased risk of cancer. Maybe such a study is out there already.
Another former colleague from University of Michigan, Cathy Goldstein, MD, MS gave the keynote address on the use of artificial intelligence (AI) in the understanding of sleep. It is extremely exciting to think that AI technology may someday aid in the diagnosis and treatment of sleep conditions, and even that tons of data obtained from consumer sleep trackers, for example, could be used to identify and treat patients with sleep disorders and improve sleep health overall. To pluck out one exciting area in which analysis of sleep studies and other data could be helpful in the clinic is in classifying various forms of OSA. Right now, we largely determine OSA severity by the number of breathing episodes per hour (AHI) and pretty much everyone is treated with a CPAP (continuous positive airway pressure) machine. However, there are so many different causes and flavors of sleep apnea that include those with anatomical causes, throat muscle dysfunction, instability of the breathing systems, low arousal threshold (i.e. those with brains more easily awakened from sleep), and many others. AI may be able to separate individuals to allow personalized treatment as CPAP is not always the best for everyone and works better for some flavors of sleep apnea than others. I personally am hoping that AI can help us identify true causes of excessive sleepiness beyond narcolepsy type 1 and the dubious diagnostic categories of periodic limb movement disorder, narcolepsy type 2, and idiopathic hypersomnia about which I have written in previous blogs and discussed in videos.
A current pediatric pulmonary fellow and T32 funded sleep researcher, Gita Gupta, MD, with whom I had supervised as both a medical student and sleep medicine fellow, presented her research on “Sleep in Children with Genetic Epilepsies”. Sleep disturbance symptoms are present in about 50% of these children, and the epilepsy syndromes can lead to sleep disruptors including increased brain awakenings during sleep (arousals), circadian rhythm/biological clock disturbance, impaired ability to clear throat and air passages from fluids, breathing muscle weakness, behavioral issues that make it hard to sleep, and of course medications whose side effects can cause sleepiness during the day or difficulty sleeping. This is amazing work by Dr. Gupta, and the challenges facing parents and caregivers with children enduring these conditions are monumental just from the epilepsy alone, not to mention all of the effects on other aspects of health including sleep. Our thoughts, prayers, and support go out to them.
As a final but equally important topic to mention, a former mentor of mine, M. Safwan Badr, MD, MBA, FAASM at the Detroit Medical Center gave a presentation on sleep and cardiovascular disease. Unfortunately, right now, though the associations of OSA and cardiovascular disease are numerous, the field does not have a lot of studies showing that treatment of OSA, particularly with CPAP, leads to improved cardiovascular outcomes for the conditions with which it is associated, other than some evidence showing positive effects on high blood pressure. Without “proof”, particularly the financial benefit of showing treatment of OSA will lead to improvement in specific cardiovascular conditions, the testing, treatment, and management of OSA could become marginalized by third-party payers. (Switching to my commentary again) The benefits to sleep, alertness, mood, daytime function, quality of life etc. with OSA treatment may not be enough as these are qualitative benefits for patients and not financial benefits to the purse-holders. (Again, who is serving whom here?) Two issues I see with many of these large studies is that the treatment group often has suboptimal treatment and looks a lot like the untreated comparison groups. This is mainly because PAP therapy involves using a blowing machine with a mask over the nose all night to treat OSA rather than just swallowing a pill, which works more easily for many other conditions. The second issue is that these studies cannot use very sleepy people and withhold treatment to create a comparison group. Excessively sleepy people–the ones more often using CPAP most effectively because they feel the effects and consequences the most–are a risk to themselves and others including in events like auto accidents or work-related injuries so they cannot ethically be left without treatment to study. This group usually gets treatment regardless so the positive benefits to cardiovascular disease in this group cannot easily be studied in trials comparing two groups, including randomized trials which are the gold-standard for medical evidence currently. Though unfortunate that quality of life is not enough to justify treatment, we do need more high quality studies and positive outcomes in other areas of health and Dr. Badr’s message here is a call to action.
As with AAN 2022 and AASM 2022, it was fantastic to be at an in-person conference again, this time with masks and black-tie optional, and it was great to see old friends and colleagues after so long.
-Andy Berkowski, MD of ReLACS Health, who learned a lot about–but did not catch up on–sleep last weekend at MASM 2022!
