Karl Doghramji, MD, on the Advances in Sleep Disorder Care in 2021

SAP Partner | <b>Vickie and Jack Farber Institute for Neuroscience</b>

The medical director of the Jefferson Sleep Disorders Center at the Vickie and Jack Farber Institute for Neuroscience of Jefferson Health offered his insight into the current state of care for sleep and the progress made this year.

Over the course of the last year, the awareness around the importance of sleep has become even more prevalent in the clinical setting. With the COVID-19 pandemic disrupting a number of facets of everyday life, the ability for individuals to get good, consistent sleep has been similarly affected.

At the same time, though, sleep science has continued to advance, with more research findings offering context on the role of sleep in the pathological processes of multiple diseases and literature suggesting major underlying effects of a lack of sleep on overall health. In that vein, organizations such as the American Academy of Sleep Medicine have put forth position statements reiterating this importance and calling for more attention to be given to the critical need for proper sleep for those with disease and those without.

Karl Doghramji, MD, FAASM, DFAPA, professor of psychiatry and human behavior; professor of neurology; and medical director, Jefferson Sleep Disorders Center, at the Vickie and Jack Farber Institute for Neuroscience of Jefferson Health, shared his perspective on the current state of care for sleep disorders and the advances made in 2021 with NeurologyLive® in an exclusive conversation.

NeurologyLive®: Looking back on 2021, what have been the major areas of focus for sleep disorder care?

Karl Doghramji, MD, FAASM, DFAPA: One of the biggest areas that we've been thinking about over the past few years has been the role of sleep in our emotional and physical lives, especially with the onset of the COVID-19 pandemic, many of us have been suffering from various disturbances of sleep, and so on and so forth. Some of the data that are emerging are indicating to us that a critical amount of sleep is important for all of us. For example, in the newborn ages, 14 to 17 hours of sleep seem to be relevant, and for toddlers and infants, something along the lines of 11 to 14 hours. But even for adults, a minimum of 8 hours or so of sleep on a regular basis seems to be important.

We're also discovering that diminishing the amount of sleep that we get is impactful in terms of all sorts of cognitive functioning. For example, response time diminishes, memory begins to decline, we are less efficient in learning new things, our ability to concentrate and focus diminishes, and even our emotional lives tend to experience decrement. Some of the physical consequences of poor sleep, or reduced amounts of sleep, are also becoming more and more clear to us. For example, we know that sleeplessness or lower levels of sleep increase sensitivity to pain stimuli. So, people suffering from pain disorders become more acutely impaired. And the opposite is true, nterestingly—that by sleeping more, we become less sensitive to pain to begin with, so they can sort of overcome pain more efficiently. Sleep disturbances also tend to aggravate lung disturbances and hypoxemia, increase blood pressure, and seem to be relevant in the development of obesity, interestingly, by changing the ghrelin-leptin ratio in the wrong direction.

One of the questions is always become how does this happen? How does it happen that sleep can result in some of these arrangements? Some fascinating research over the last couple of years has begun to show us that there is an intricate system, called the glymphatic system, within the central nervous system or brain that's responsible for the elimination of waste and poisons that accumulate inside the interstitial fluid of the brain, including beta-amyloid and tau proteins. This elimination process is most efficient and robust during sleep, and sleeplessness then seems to result in the accumulation of these poisonous compounds in the brain and may result in some of the decrements and performance issues that we were just talking about. Sleep seems to be such an important part of our lives, and this has been something which we're becoming much more aware of over the past few years.

From a clinician's perspective, how would you describe the overall awareness of how important sleep is in terms of the potentially detrimental effects of a lack of it?

I think we're getting better at it, but we are not where we need to be. We see this across the board. We have patients coming in with various disturbances—mood disorders, for example, or difficulties with functioning—who are not recognizing that sleeplessness or poor sleep may be a factor in the genesis of those abnormalities. One of the reasons, I think, is that the effects of sleeplessness are not necessarily things that we are consciously always aware of. Sleepiness, for example, is the tendency to fall asleep at inappropriate times, or excessive sleepiness is something that we may not be subjectively that aware of. Interestingly, we get used to it over longer periods of time—times of sleeplessness—and begin to be less sensitive to its effect consciously. One of the issues is that conscious awareness is not always there, even in cases of sickness or very high levels of sleepiness, where people are falling asleep while driving, operating machinery, and so on and so forth. So, awareness is still not there, not as acutely as it is, for example, with heart disease, and lung disease, and other conditions.

I think we have a lot more work to do here. I think this is especially true also in youngsters. The role of poor sleep in the production of obesity and metabolic disturbances in children is now beginning to emerge. Also, the role of sleeplessness in poor learning, or diminished learning ability, is beginning to emerge. I think we have more work to do, but I certainly think we have we've made some significant impact on awareness over the past decade or two.

Collecting data on sleep has been a challenge—do you believe that the data being collected are adequate, or are we still in the infancy collecting more rich data on sleep?

I think it's safe to say that we are in the infancy of this process. Right now, the tools that are available on a consumer level, unfortunately, have not yet crossed into the medical field in a way that we can say that the assessments are reliable and have a great deal of validity. But I do think that these tools, even though they're not necessarily accurate in the real medical sense of the word, do serve an important positive function: to increase awareness on the part of the public in terms of sleep. I see this every day, people look at their watches and their monitors and want to assess how well are they sleeping, if it’s enough and sufficient, and so on. And at least that sense of monitoring oneself from a sleep standpoint, which is so difficult to do subjectively, is enhanced with these types of devices. I have no doubt that in the future, possibly within the next decade or so, we'll see the transformation of many of the things that we do on a medical level.

Now, for example, in the sleep laboratory or in the context of the home sleep testing environment or medical sleep testing environment, we'll see the transformation of these technologies from this sort of complex process into the everyday monitoring with wristwatches possibly or with devices that are pasted on the skin so that people can, on an everyday level, measure how well they're sleeping, their levels of daytime sleepiness, and also other functions, such as blood pressure, heart rhythm, disturbances and so on. The future is exciting, but we're not there yet.

What's been the biggest step forward on the therapeutic side of things? Is there anything coming that you're excited about or are keeping an eye on?

Insomnia is such a common disturbance. We think that around half the population experiences this at some point within the course of their lives, and it has such great consequences in terms of how people’s everyday mental, emotional, as well as physical lives. One of the biggest areas of awareness for us in insomnia is the fact that non-medication strategies are so effective. Cognitive behavioral therapy, for example, is so helpful in alleviating insomnia on an acute level, but also in providing lasting benefits. Of course, one of the challenges we've had with this is that there's a paucity of therapists who are qualified to deliver this. A very nice and positive development over the past few years has been the transformation of cognitive behavioral therapy into the online realm. We have now a few programs that are available apps and so on, that provide predictable and proven benefits for patients who have insomnia in a non-medication fashion. This is a good day for insomnia.

In addition, from a pharmacologic standpoint, we've had hypnotics, or sleeping pills, there for many, many years. The challenge, though, has been that many of these are riddled with adverse effects for primarily daytime sleepiness, cognitive concerns, motor abnormalities; the risk of falls and hip fractures in the elderly is enhanced with some of these long-acting hypnotic medications. Respiratory disturbances seem to be a fomented with some of these agents as well. Over the past decade or so, we've seen the development of safer and safer medications—the GABA receptor agonists were so helpful, but in the past decade, we've seen the development of melatonin receptor agonists as well as histamine receptor antagonists. The most recent introduction is those of the orexin receptor antagonists. The orexin system is one that is responsible for wakefulness and coordinates the activity of other wake neurotransmitters throughout the central nervous system. Antagonizing the system, seemingly, is very helpful in the production of sleep, and these agents seem to have an index of safety that is unparalleled.

These are some exciting developments in the field of sleep medicine. I think the future probably will see the development of more of these orexin receptor antagonists, but I think also that we're going to be seeing some interesting devices being developed and introduced. In fact, one of them is on the market now, which has various mechanisms. One, for example, is involved in cooling the brain or cooling the head, and interestingly, when worn at nighttime, this seems to produce better sleep. There are other devices that are being developed that may help change the EEG spectrum of individuals during sleep and help them sleep better, possibly. Some other ones introduced auditory tones during sleep, and some, in fact, direct brain signals in a specific direction. So, the future is promising, and I think very exciting, in the area of insomnia.

What are some of the areas of need in terms of practical guidance? Are the general neurology community or the primary care community aware of these new agents and these new devices?

I do think that that awareness is always a challenge. More specifically, there's a need for education and awareness in the area of selection of a specific hypnotic agent for a particular use. We now are at the point where there are so many hypnotics available that we can actually be selective in tailoring the hypnotic to the specific clinical characteristics of the patient. For example, in sleep-onset insomnia, when patients have more difficulty falling asleep, a certain cadre of agents is more effective and indicated for that purpose, whereas other agents are more helpful and more productive for sleep maintenance.

Insomnia is when patients have more difficulty waking up repeatedly during the course of the day. When there are comorbid respiratory issues—for example, COPD, or obstructive sleep apnea—some agents have proven to be safer than others in this particular clinical realm. When patients have histories of substance use or abuse, some agents are nonscheduled, and maybe preferentially used in these areas. The age factor is an important one because as we age, the benzodiazepines receptor agonists seem to have more detrimental effects in terms of daytime motor functioning and memory, and so on. Some of the newer agents may be more desirable in these areas. I do think education is needed on the selection of the proper choice or selection of certain agents over others in the treatment of insomnia.

Transcript edited for clarity.