Hypersomnolence in Individuals With Mental Illness

In this video taken at the 2024 Psych Congress NP Institute, Craig Chepke, Scientific Director for Psych Congress, discusses hypersomnolence disorders in people with psychiatric conditions. Dr Chepke first describes the bi-directional relationship between sleep and mental health, emphasizing that a disruption in one dimension can worsen the condition of the other. Dr Chepke then talks about novel treatments available for excessive daytime sleepiness due to hypersomnolence disorders, highlighting innovations in sodium oxybate as well as pitolisant as an option.

For more expert insights, visit the Sleep Disorder Excellence Forum here on Psych Congress Network.

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Read the Transcript

Craig Chepke, MD, DFAPA: Hi, I am Dr. Craig Chepke. I'm a psychiatrist and the medical director of Excel Psychiatric Associates in Huntersville, North Carolina. I'm an adjunct associate professor of psychiatry at Atrium Health, and I'm also the Scientific Director of Psych Congress. Today I'm going to be talking about hypersomnolence disorders in people with psychiatric conditions.

Psych Congress Network (PCN): In what ways do sleep disorders and mental health conditions reinforce each other? How does understand this interplay improve clinical practice?

Dr Chepke: One of the things that's really challenging about managing people with psychiatric conditions that have hypersomnolence or other sleep disorders is that it's a bi-directional relationship. One can make the other worse. Let me give you a couple examples. First, if someone has a psychiatric condition, many times that causes problems with sleep as one of the cardinal symptoms, and that could be insomnia or it could be hypersomnia. There's about a 25% prevalence overall of people with psychiatric disorders having a condition that has hypersomnolence as part of this symptomatology. But then it's even worse that the treatments for many psychiatric conditions will cause other sleep disruptions as well. For instance, many antidepressants will disrupt sleep architecture. They can cause insomnia or, on the other side of things, many medications for psychiatric conditions are very sedating, and those can also disrupt the sleep architecture. That can make detection of the primary sleep issue very difficult.

On the other side, if someone has a primary sleep disorder with a comorbid psychiatric condition, well that sleep disorder can make things worse as well, because the sleep disorder—if they're not sleeping well at night—well, poor sleep will exacerbate literally any psychiatric condition. Also, it'll contribute potentially to next time daytime sedation because if someone is not sleeping well at night and they can't function well the next day because they're not thinking clearly, they have some cognitive deficits, maybe some brain fog is how patients put it, they're not going to be able to perform and function as well at work, at home, in their hobbies and activities. It may come across looking like a lack of motivation or even depression. Then treatments for certain hypersomnolence conditions or for other sleep disorders, even insomnia disorder, someone takes sedative medications to help them sleep, well that could bleed over the next day and cause sedation. So it's really important to tease out where does the psychiatric condition begin and end, and where does the sleep disorder begin and end, because we really want to treat both efficaciously. Sometimes treating one in the right way can help the other, but sometimes they need their own specific treatments concomitantly.

PCN: What are some of the novel treatments available for excessive daytime sleepiness due to hypersomnolence disorders in individuals with mental illness? What are you most excited about?

Dr Chepke: So, there have been some exciting developments in managing the hypersomnolence conditions, and there's a couple of them, I have to take you through which ones are for which. But hypersomnolence conditions, and this includes people who do have comorbid psychiatric conditions. Just to let you know, I've prescribed all of these medications to people in my practice, so they are something that is within the scope of a psychiatric clinician with the right study and training.

So we have to break it down into what diagnoses are we talking about. There's EDS, excessive daytime sleepiness due to sleep apnea. I'm going to leave that one aside for today and focus on idiopathic hypersomnia and narcolepsy.

Some of the treatments that we've had for a while for narcolepsy have been focused on sodium oxybate. One thing about sodium oxybate though (the original one) is that it's got a very high sodium content. Just like people with other psychiatric conditions like schizophrenia and bipolar disorder, people with narcolepsy have higher rates of medical comorbidities like obesity, heart disease, and the risk for things like congestive heart failure, coronary artery disease, at baseline unmedicated. Then if they also have a bipolar disorder, MDD, something like that, that risk could potentially be additive. So we don't want to pour fuel on the fire either with the psychiatric medications or in many cases with the treatment for the hypersomnolence condition.

But up until recently, there was no other game in town for oxybate than the high sodium, regular sodium oxybate. But a few years ago, there was a low sodium oxybate that was introduced. They used different salts other than just sodium to reduce the sodium burden by about 80%. So, whereas before just the maximum daily dosage of sodium oxybate hit about the recommended daily intake of sodium for that individual, if they didn't have any other sodium intake in their diet, even this low sodium oxybate has 80% less. So, it can really help to reduce the sodium burden, which can have a downstream effect on reducing cardiovascular burden and risk factors for that individual going forward. That's a really important one because we have to treat the psychiatric conditions, the hypersomnolence conditions, but first, we have to keep our patients alive. We have to protect their physical health first and foremost of all things.

The same low sodium oxybate that's approved for narcolepsy type 1 and type 2 also is approved in idiopathic hypersomnia. That is actually the first FDA approved treatment for idiopathic hypersomnia and the only approved option for idiopathic hypersomnia. These people unfortunately had to suffer with no approved options, and we just use things like stimulants and other medications that were off label and often had some fairly significant side effect issues because we had no approved option. Really exciting for those folks.

Moving over to another treatment for narcolepsy that has come out in recent years is pitolisant. Now, oxybate is a schedule three controlled substance. Pitolisant is not. It's an unscheduled medication and it's an inverse agonist of the histamine H3 receptor. Now, you might be thinking, well, an antihistamine that's going to make people sleepier, but not the H3 receptor. The H3 receptor is found pretty much only in the central nervous system, and it is a presynaptic auto receptor. So that means it puts the brakes on the release of histamine, and histamine itself is wake-promoting. So if you block as an antagonist or an inverse agonist even more strongly, the H3 receptor, you're going to get an increase in the release of histamine, and that is wake-promoting, vigilance-promoting and will benefit people with narcolepsy. You might think what it will only help with the excessive daytime sleepiness, but pitolisant is actually also approved for cataplexy in type 1 narcolepsy as well. So, it's helpful for both EDS and for the cataplexy of type 1 narcolepsy.

The final option that has come out recently is a once-nightly sodium oxybate, and this is for type 1 and type 2 narcolepsy. So I did mention that the higher sodium oxybates do have cardiovascular risks and the once-nightly oxybate does carry that same amount of sodium burden. But some patients really strongly prefer a once-nightly oxybate as opposed to the twice-nightly. There can be some benefits in certain terms of safety and tolerability with once-nightly approach because pharmacokinetically, you're not getting that second peak after the second dose that is actually quite high for some patients and for some patients may bleed over into the next day. The once-nightly oxybate has a smoother pharmacokinetic curve, and some people may tolerate that better. There's actually some language in the label that says that it may have a superior tolerability profile. So as I like to practice shared decision-making, I'm offering that option of once-nightly oxybate, but with the caveat that it has a higher sodium burden and the twice-nightly oxybate that has the lower sodium option for them, and let them go over the risks and benefits with me, decide what's going to be the right option for them. Also we can trial both in an individual patient. Beyond just academically discussing which one might be right for them, it is possible to try both, and then having tried both, see which one they felt worked best for them, and that is something that they would want to continue over the long term of their disease.

Thanks again for joining me today. I really hope this was helpful for you in managing patients with hypersomnolence disorders because these patients do suffer really tremendously. Unfortunately, the hypersomnolence conditions often go misdiagnosed or undiagnosed altogether, so it's really critical we as both psychiatric clinicians, neurology clinicians, anyone who is watching this video, be on the look for these conditions and make sure they're getting appropriately treated because you can make a tremendous difference in their quality of life. I'm Dr Craig Chepke. Thanks for joining me.

Craig Chepke, MD, DFAPA, is a board-certified psychiatrist in clinical practice as the medical director of Excel Psychiatric Associates in Huntersville, NC, and is an Adjunct Associate Professor of Psychiatry for the Sandra and Leon Levine Psychiatry Residency Program at Atrium Health. Dr Chepke is the scientific director for the Psych Congress portfolio of CME conferences, and he has been recognized as a Distinguished Fellow of the American Psychiatric Association.

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