Awareness, Diagnosis, and Novel Treatment of Excessive Daytime Sleepiness in Patients with Psychiatric Disorders
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Saundra Jain, PsyD:
Hi everyone. My name is Saundra Jain and it is my pleasure to welcome you to this session titled, ADT of EDS: Awareness, Diagnosis, and Novel Treatment of Excessive Daytime Sleepiness in Patients with Psychiatric Disorders. This activity has been supported through an independent educational grant from Jazz Pharmaceuticals, Inc. While I introduce the speakers for this morning's session, please take just a moment to answer the polling questions. You should see them on your screen.
Now, depending on the device you're using, the questions will either appear to the right of the live stream or just below. These questions will be asked again at the end of the program. Thanks so much for answering the polling questions. Now, it's my pleasure to introduce our two speakers for this session. Dr. Karl Doghramji and Saoirse Owens Dr. Doghramji is Professor of Psychiatry, Neurology and Medicine at Sidney Kimmel Medical College of Thomas Jefferson University in Philadelphia, Pennsylvania, and Medical Director of the Jefferson Sleep Disorder Center at Thomas Jefferson University Hospital, also in Philadelphia. Dr. Doghramji is also Program Director of the Fellowship in Sleep Medicine.
Saoirse Owens is a sleep medicine nurse practitioner, also at Thomas Jefferson University's Sleep Disorder Center. Please type your questions for the presenters in the Q&A box. During the presentation, you'll find that to the right side of the screen, or if you prefer, just upvote the questions that you like the most. The presenters will try to answer all of the most popular questions with the time remaining at the end of the presentation. So without further delay, let's get started.
Saoirse Owens, CRNP:
Hi, thanks for having me. We're here today to discuss the awareness, diagnosis and novel treatment of excessive daytime sleepiness in patients with psychiatric disorders. And these are our disclosures, I'm not going to go through these myself to save time. And these are learning objectives. And again, in the interest of saving time, I'm not going to read through these, but we will cover these throughout our presentation.
So when we talk about excessive daytime sleepiness, there are multiple terms that are used and sometimes used interchangeably, but it's important to understand the distinction between each of them. Fatigue is the sensation of weariness, tiredness, exhaustion, loss of energy: it is not the desire to sleep. Whereas sleepiness is the desire to sleep, and is a natural phenomenon that we all experience every day. We require sleep and our circadian rhythm and our homeostatic sleep drive dictates when we should and should not be asleep, and when we should be awake. The hypersomnia refers to prolonged sleep times, though is used in the naming of many disorders of excessive daytime sleepiness. Excessive daytime sleepiness itself is simply, by its title, excessive sleepiness that occurs when we should be awake and alert, and we should not have any difficulties fighting to stay awake.
The impact of daytime sleepiness, I'm sure we're all familiar to some extent with these symptoms as this is such a common symptom, but it includes slower response time, reduced retention, deterioration of performance, poor recall of information, decreased motivation, it can also affect our immune system and our insulin resistance, and depression is often a symptom of excessive daytime sleepiness as well.
What causes excessive daytime sleepiness? This can be multifold, manyfold, but as we see here the categories of sleep disorders, neurological disorders, and psychiatric disorders can all have symptoms of excessive daytime sleepiness. Insufficient sleep syndrome is probably the most common cause of excessive daytime sleepiness, and the World Health Organization has declared sleep deprivation to be a global health epidemic. Circadian rhythm disorders can also influence our daytime sleepiness, obstructive sleep apnea is an increasingly common cause of excessive daytime sleepiness, and we have central disorders of hypersomnia such as narcolepsy, which can also present with symptoms of excessive daytime sleepiness. Neurological disorders that in which we see daytime sleepiness include epilepsy, dementia, Parkinson's disease, multiple sclerosis, myotonic dystrophies, and fibromyalgia. Psychiatric disorders also lead to excessive daytime sleepiness, or vice versa: there's a bidirectional relationship here between sleep difficulties and psychiatric disorders. These include depression, bipolar disorders and sleep disorders, anxiety, PTSD, schizophrenia, and alcoholism.
In patients with major depressive disorder, we frequently see sleep difficulties. These patients can experience insomnia and hypersomnia, but hypersomnia occurs in about 30% of these patients. And in patients with seasonal affective disorder, we can see hypersomnia in up to 50% of these patients bipolar disorder. During the manic phase and the hypomanic phase, we see decreased need for sleep. However, this decreased need for sleep does not seem to affect their functionality or their quality of life. But during the depressed phase, we see hypersomnia commonly. Anxiety is also a major factor affecting sleep, and in patients with general anxiety disorder, 50% experience sleep difficulties and daytime fatigue. Patients who experience panic attacks, particularly nocturnal panic attacks, can experience disruptions in their sleep, and also develop as a result of these attacks fear of sleeping, called sleep phobia.
PTSD similarly affects sleep: the nightmares and the distressing dreams that are associated with this disorder disrupt sleep and lead to daytime sleepiness, and can also lead to sleep avoidance for fear of experiencing or having these dreams and nightmares. Schizophrenia disrupts sleep. We oftentimes see shifts in circadian rhythm with these patients, with them being awake at night and asleep during the day. The cause for this is not readily known, but we do see this. We also see that when we see extreme changes in their sleep habits is usually an indicator that they may be having an acute psychotic decompensation. And in this particular population, sleep-disordered breathing is prevalent in about 15%. Alcohol also affects sleep quality, though a lot of patients will use it as a sleep aid to help with sleep, but while it does help them fall asleep, it often disrupts their sleep overall, and leads to poor quality sleep, and excessive daytime sleepiness.
So the ICSD-3 criteria for hypersomnia associated with psychiatric disorder includes daytime sleepiness for at least three months, and must occur in the presence of another psychiatric disorder. It accounts for 5% to 7% of hypersomnia cases, it's more common in women and occurs typically between the ages of 20 and 50 years of age. As we see here also, those with hypersomnia and insomnia are 10 times more likely to experience major depressive disorder. Key learning point: sleep difficulties are encountered in up to 90% of patients with major depressive disorder and 30% of patients with major depressive disorder have hypersomnia.
So, when we're evaluating patients with complaints of excessive daytime sleepiness, we want to be extremely thorough, we want to explore their entire health history, and then when it comes to their sleep, we want to get a detailed sleep history: sleep logs can be helpful in achieving this. We also like to use the sleepiness scales to gauge an objective measure of the severity of their sleepiness. The Epworth and the Stanford Sleepiness Scales are typically used, and we'll discuss those momentarily. The STOP-BANG survey is also used to screen for patients at risk for obstructive sleep apnea.
And in the management of these patients, we always try to employ good sleep hygiene measures, behavioral strategies to improve their sleep quality, and reduce their complaints of excessive daytime and sleepiness. If those alone don't suffice, then we often do need to consider pharmacotherapy. This Epworth Sleepiness Scale and the Stanford Sleepiness Scale as we see here are common tools used to assess for sleepiness. The Epworth Sleepiness Scale evaluates sleepiness in certain contexts and situations, whether it be watching TV, as a passenger in a car, or simply talking with someone. On a scale of 0 to 3, they rate their likelihood of dozing, 0 being low likelihood, and 3 being a high likelihood of dozing. A score greater than 10 is indicative of excessive daytime sleepiness.
The Stanford Sleepiness Scale on the other hand evaluates the subjective feelings of sleepiness on a scale of 1 to 7, with one being alert, awake, no problems with sleepiness, and 7 being extreme difficulties maintaining wakefulness. The STOP-BANG survey, as mentioned, is used to survey patients or screen patients who might be at risk for obstructive sleep apnea. And it's an acronym, and this the S stands for snoring, T for tiredness, fatigue, sleepiness, witnessed apneas are often seen in these patients where they begin waking up, choking, trying to catch their breath. We see patients with OSA are at increased risk for high blood pressure, so high blood pressure can be a risk factor or indicator for OSA. These patients tend to be overweight, not always, but certainly we do see a correlation with weight as well.
Age, it occurs in typically in adults, older adults rather than younger adults, and we often measure their neck circumference as well as a screen. The next circumference greater than 16 in men and 15 inches in women is a risk factor for OSA. And we see this typically more in men than women, though postmenopausal that discrepancy can equal out. A low score on the STOP-BANG is not highly indicative of OSA, but a high score is not surprisingly concerning for OSA.
We have a case study here: we have 23-year-old Emily who presents to her mental health provider with complaints of excessive daytime sleepiness ongoing since high school, she's now medical school and the sleepiness is becoming an increasing problem for her. She is told that she snores and she's an active sleeper, no matter how many hours of sleep she gets, she never feels fully refreshed, and she can average about 8 to 12 hours of sleep at night, she often takes naps during the day, the naps are the only type of sleep she experiences that where she feels some degree of refreshingness with restoration.
And she'll also report that she'll vivid dreams with these naps. She's seen weight gain. Her BMI has risen to 30. She does report an increased appetite. Her motivation and energy has decreased, and she's found to get harder to perform well in school. She denies any history of cataplexy, witnessed apneas, morning headaches, parasomnias, such as sleepwalking and restless legs syndrome. No history of anemia or thyroid disorder as well. She has been on sertraline, 100 milligrams, but this has only helped minimally at best. She drinks several cups of coffee a day with some help, but the effects of these seem to be waning. She does admit to drinking about one to two cups glasses of wine with dinner each night. As we can see from her sleep routine here, her schedule is quite inconsistent. She does spend a fair bit of time in bed.
No difficulties falling asleep, but her sleep is frequently disrupted with awakenings up to three to five brief awakenings a night. These can typically last less than 15 minutes each. On weekdays, she has to be out of bed and up by 6:00 AM, and on weekends, however, she'll often find herself sleeping late until around noon. Again, she naps when she can and these are quite refreshing as well. Her Epworth sleepiness score and her Stanford sleepiness score are high. Her STOP-Bang score is low. As we see, she's on the sertraline and we see some psychomotor retardation. Her mood is very low and she reports feeling low essentially all the time. The differential diagnoses for Emily could include excessive daytime sleepiness associated with depression, obstructive sleep apnea, narcolepsy, idiopathic hypersomnia, impaired sleep hygiene, and hypersomnia related to medication use.
The plan upon her initial assessment is to continue the sertraline, potentially adjust the dosaging there. She's asked to limit caffeine intake and avoid it past 1:00 P.M. She should limit, if not avoid, alcohol. She's advised to keep a strict sleep-wake routine and allow for sufficient sleep opportunity. She should avoid electronics in the bedroom, and she is encouraged to nap as able throughout the day but asked to avoid longer naps as these are unrefreshing and could potentially affect her ability to sleep well at night.
Emily:
Where to start? Since high school, my mom always had to bang on my bedroom door and yell at me every day to get me to wake in time for school. I thought I just wasn't a morning person, but it just got worse in college. I was tired all day, even during the weekends when I did nothing. I had to take a nap after each class. My junior year, I made sure I had enough time between classes to nap, but I was still falling asleep during my lectures. I somehow made it through college with decent enough grades to get into medical school. I knew I had to change things though before I started medical school, so I talked to my doctor and he prescribed me Zoloft for depression and sleep problems. I was taking it for three months and it didn't help me at all. Still exhausted all day.
It's not like I'm up all night either. I sleep for like 10 hours a night and it's still not enough. I don't have the energy to go to my Zumba classes, so I've gained even more weight. I can't even rely on coffee to keep me up. I'm only three months into medical school and my professors are giving me warnings that I need to do better or they'll fail me, so I went back to my psychiatrist because this is getting out of control. He gave me a list of things that I should try to improve my sleep. He calls it sleep hygiene. I'm going to stick with it, but I honestly don't know if it'll actually work.
Saoirse Owens, CRNP:
We'll talk about narcolepsy and its relation to patients with psychiatric disorders. Narcolepsy is experienced as recurrent, irrepressible desire to sleep greater than three times a week over three months or for time greater than three months. There are two types of narcolepsy, type 1, type 2. Type one, in those patients' wheels, it's known as narcolepsy with cataplexy. In these patients, we'll also see a hypocretin deficiency. In narcolepsy type 2, there's no history of cataplexy and typically no association with hypocretin deficiency. A orexin level can be requested to officially diagnose narcolepsy, but this is expensive and difficult to do. Very few places provide that service, so the main way of obtaining objective data to support the suspicion for and the diagnosis of narcolepsy is through sleep studies, particularly PSG followed by an MSLT, so polysomnogram and sleep study.
MSLT stands for mean sleep latency test, where we give a patient... During this daytime study, we give them five nap opportunities. What we're looking for, particularly using the EEG, we're looking to see how fast they fall asleep and how fast they go into REM sleep. To meet the criteria for narcolepsy, these patients, their mean sleep latency should be--or mean sleep latency would be less than eight minutes and their REM latency of less than 15 minutes on at least two of the naps or the nocturnal study meets the criteria for narcolepsy. This is simply a picture emphasizing the hypocretin and orexin loss that we see in patients with narcolepsy type 1. This slide simply shows a patient undergoing a sleep study, whether it be PSG, or the following days, MSLT. We see, again, short sleep latency and sleep onset REM periods.
For patients with narcolepsy, they experience, obviously, excessive daytime sleepiness, prolonged daytime sleepiness. They'll take voluntary naps, as we saw Emily would do. Involuntary sleep episodes are also seen, these are known as sleep attacks. We may also see automatic behavior and microsleeps. Cataplexy is actually a narcoleptic specific symptom. If patient has a cataplexy, it's essentially guaranteed that they have narcolepsy. We see this in about 60% who have narcolepsy. Sleep-related hallucinations are also seen in about 67% of narcoleptics, and these tend to occur at sleep onset, so hypnagogic, and the patient usually experiences these as an animal or person being in the room with them. This can be quite a scary or frightening experience.
Sleep paralysis occurs in about 64% of patients with narcolepsy. This is where the body remains in a paralyzed state for a short period of time outside of their diaphragm and their extraocular muscles but they're unable to move for a period of time. That, too, can be quite scary as well. Sometimes we'll see the hallucinations on the paralysis occur simultaneously. These patients have, due to their disrupted sleep-wake neurochemistry, they actually, although have experienced daytime sleepiness and a desire to sleep during the day, will often experience difficulty sleeping at night. It's quite a cruel combination there. Given these common symptoms or associated symptoms with narcolepsy, they can oftentimes be misconstrued or misinterpreted to be other conditions. As we see here, cataplexy could be misinterpreted as syncope or a transient ischemic attack. Hypnagogic hallucinations could be simply interpreted as dreaming or as a psychotic hallucination. Sleep paralysis, again, could also be thought of or interpreted as a stroke.
But also, people can have independent sleep paralysis where they simply have these moments, these events. They're not really concerning, but they have them. They may be concerned by them, but they're not in and of themselves concerning and are not a symptom in this particular patient population of narcolepsy. Again, given their altered neurochemistries and the complaints of difficulty sleeping at nighttime or disrupted nighttime sleep and daytime sleepiness, sometimes this can be initially misdiagnosed as insomnia. In this 2017 study, we see that psychiatric comorbidities are highly prevalent in patients with narcolepsy. 25% of the patients in this study who had narcolepsy were also found to have anxiety disorder and 37.9% were seen to have mood disorders, so definitely an interesting correlation there or association there to keep in mind. Now, I'm going to hand over to Dr. Doghramji who will talk more in depth about the treatment of this complaint and these conditions associated with it, but thank you for listening.
Karl Doghramji, MD:
Well, thank you, Saoirse. Saoirse talked about daytime sleepiness in the context of psychiatric disease and also discussed primary sleep disorders such as narcolepsy and sleep apnea. I'd like to focus on the treatment aspect of daytime sleepiness in narcolepsy and other sleep disorders. Of course, there are many behavioral methods that we use for managing sleepiness in these various disorders, sleep hygiene and so on, but I'd like to focus in this first slide on pharmacology of alerting medications, which are used to control daytime sleepiness. On left-hand column are the medications, middle column are their mechanisms of action, and the right-hand column are FDA indications. You'll quickly see that the FDA indications are also they're not just for daytime sleepiness, but also for cataplexy in many of these medications. Cataplexy is a very important target symptom in narcoleptics. It can be as troublesome, if not more troublesome, than sleepiness itself.
Cataplexy is the tendency to lose control of one's muscles and sometimes to fall, but also sometimes just to simply lose control of various muscles leads to clumsiness, difficulty speaking. Sometimes dysarthria can be extraordinarily embarrassing, especially when narcoleptics laugh, and to have anger outbursts, to have the sudden inability to function. These are the medications. You'll see, on the very top, caffeine, one of the most commonly utilized stimulants in the world. Certainly not indicated, but many narcoleptics do use this for maintaining alertness. Methylphenidate, amphetamines, these are very commonly used in psychiatry for attention deficit disorder and so on. Also used in control of sleepiness and narcolepsy.
But over the past decade or so, we've seen the introduction of safer agents, agents which are highly scheduled, less addictive, less controlled than the methylphenidates, amphetamines, and so on, such as modafinil, armodafinil: these are dopamine reuptake inhibitors used for the control of daytime sleepiness in narcolepsy, sleep apnea, and shift work disorder. Sodium oxybate, as well as its new cousin, low-sodium oxybate, we'll talk about those in a couple of minutes: these are GABA-B agonists, fascinating agents, which are given at nighttime to control cataplexy and daytime sleepiness in patients with narcolepsy. Solriamfetol, one of the most recently introduced agents, given in the morning, a dopamine and norepinephrine reuptake inhibitor, controlling daytime sleepiness in patients with narcolepsy and sleep apnea.
Pitolisant, a histamine H-3 antagonist, essentially increases histamine neurotransmission. Again, recall that histamine is an activating, alerting neurotransmitter. It's a histamine inverse agonist, increasing wakefulness, decreasing daytime sleepiness. But this medication is also indicated for cataplexy and an investigational agent TAC 925. Interesting agent meant to replace what is missing in narcolepsy. Hypocretin neurotransmission is deficient in narcolepsy. That's its key etiology, and this medication may come close to replacing that neurotransmission. It's investigational, not currently available commercially.
Now let's just talk about some of these medications. Sodium Oxybate, the medications, I should say that are indicated not just for daytime sleepiness, but also for cataplexy. Sodium oxybate, low sodium oxybate, pitolisant, and some antidepressants which we're very familiar with in psychiatry, tricyclics, SSRIs, norepinephrine reuptake inhibitors. These are inhibitors of REM sleep. And recall again that in narcolepsy, the main deficit problem is that there's a disintegration of REM. REM sleep expresses itself indiscriminately during the day and at nighttime, so that if it expresses itself during the day, there's cataplexy. And by inhibiting REM, these agents can actually decrease cataplectic episodes and treat some depressive phenomena that are very common in narcolepsy.
Now in terms of low sodium oxybate, this agent was just introduced, it basically is sodium oxybate with much less sodium. Why is that important? Well, we know that sodium loading can be problematic for patients over the long term. It can increase the risk of high blood pressure, cardiovascular problems, and certainly the amount of sodium in sodium oxybate is between 1100 and 1640 milligrams, very high, almost as high as the daily recommendations by the American Heart Association. So low sodium oxybate is important to consider as a replacement for patients if they're going to be on this agent for long periods of time. It's schedule three, approved for cataplexy and daytime sleepiness. Dosage, it's an interesting dosing strategy, you start out by 2.25 grams twice per night. So patients take it at the beginning of the night, wake up three or four hours later, take it again, and then go back to sleep.
And then they have to make sure they have three or four hours ahead of them in bed so that the drug does not stay in their system too long, cause daytime sleepiness. And so it's administered twice during the course of each night and the maximum dose is nine grams, although many patients do very well on a six gram nightly dosage.
It's a novel product and of course it has much less sodium than sodium oxybate, which is where it excels. One of the newer agents also to be introduced is pitolisant. Pitolisant is the only non-scheduled or only agent not scheduled as a controlled substance by the DEA, so it's not an addictive substance. It's a histamine antagonist or inverse agonist, essentially increasing histamine neurotransmission. It's approved not only for the treatment of daytime sleepiness, but also for cataplexy. And its dosing is on the order of 8.9 grams once during the day, up to, all the way up to 35.6 milligrams, I should say, administered in the morning.
Two things about this drug, it might increase the QT interval, so you have to be careful when co-administering with other drugs that may do the same thing. I usually get an EKG after a few doses of administration if in fact there is another QT-sensitive drug on board. And it also may decrease the effectiveness of other substances which have a 3A4 metabolism, for example, non-hormonal contraceptives. So women who are taking oral contraceptives need to be aware of this and possibly even use alternative methods of birth control.
Solriamfetol, it's a dopamine norepinephrine reuptake inhibitor. It is a schedule four agent. Its doses are 75 to 150 milligrams. I generally start out with half of the 75 milligram dose, 37.5 milligrams, administered once in the morning and gradually go up to the maximum desired dosage, which is the maximum allowed dosage is 150 milligrams. It's contraindicated with monoamine oxidase inhibitors as most of these agents are. It can increase blood pressure, so it's a good idea to monitor blood pressure for a few days, if not a few weeks when patients are initially taking this medication. It has no effect on the QTC interval. It has no effect on oral contraceptives and there are no data available on breast milk. And of course, it is not an agent that can be used for cataplexy. So if administered for daytime sleepiness, some other drug has to be used in conjunction with this drug for the treatment of cataplexy. The next drug to discuss ... Oh yeah, I wanted to also mention a couple words about the studies that went into approving these drugs and post-approval. The top line is that of solriamfetol. This is a 12-week randomized controlled study, again showing significant reduction in daytime sleepiness in participants with narcolepsy. The second one is an open-label study on pitolisant, which was administered over many, many months, up to one year. And in this particular study compared to baseline, there was a reduction in cataplexy attacks as well as daytime sleepiness. And finally, low sodium oxybate on the very bottom. This was a withdrawal study, so patients who were taking other agents were then switched to low sodium oxybate and then the drug was withdrawn or kept on board. And compared to the situation where the drug was withdrawn, when it was kept on board, there was a significant increase in the level of effectiveness in terms of daytime sleepiness and with cataplexy.
So let's just review the key learning points up to this point in time, there are many novel wake promoting agents that are available for the treatment of daytime sleepiness, including low sodium oxybate, which is a GABA-B agonist, pitolisant, which is a histamine antagonist, inverse agonist, and solriamfetol, which is a dopamine norepinephrine reuptake inhibitor. Now let's discuss Emily. You all recall that Emily was a sleepy woman, young woman, who was [inaudible 00:33:41] sleepy, and we basically began managing sleep hygiene aspects with Emily to be able to see if we could improve on her behavior to improve daytime sleepiness. She comes back in four weeks and she's adhered to our recommendations, but unfortunately sleepiness has not improved. It's been steadily worsening and she's on a medication, but she's feeling more depressed, so mood has not improved either. Now interestingly, she reports episodes of sleep paralysis, this phenomenon of lying in bed and just feeling as though she can't move during which she experiences very frightening dream content.
You can't move in face of very frightening dreams which want to make you move. This is of course ... These are hypnogogic hallucinations in the context of sleep paralysis. Very common in narcolepsy. So you see these symptoms were not there before at baseline, but she now has developed them. And it's not uncommon for people who have narcolepsy to develop these symptoms that are characteristic of narcolepsy over the course of time. She undergoes a sleep study, A PSG or a nighttime study and an MSLT or daytime multiple nap study. And the bottom line, the MSLT reveals a mean sleep latency of 4.5 minutes. Anything below eight minutes is very, very low, meaning she's very, very, very sleepy, and she has three sleep onset REM episodes. Normal individuals who sleep during the day do not have REM sleep. Narcoleptics do. These two findings are highly diagnostic of narcolepsy, and of course this is type two because she does not have cataplexy.
The finding is narcolepsy but no cataplexy, and she's treated with a awake promoting agent and she ends up doing very, very well. Focus, concentration have improved, she's able to stay awake all day long, she is napping only once per day now. So what looked like a depression, now you see turns out to be narcolepsy because sleepiness can often mimic affective instability and affective decline. Very difficult to separate these two from one another, but important to do so because we need to treat these patients for the proper disorder. Treating what looked like a depression, but turned out to be narcolepsy with the proper medication, that really helped the patient improve. Let's now go on to next the video about this patient.
Emily:
Okay, so I actually did everything my psychiatrist told me to do. I had a strict sleep routine that I even kept during the weekends. I put my phone and my computer away two hours before bedtime, stopped drinking, and I even stopped drinking coffee after 1:00 PM. But guess what? It didn't make a single difference. After a month of this, I went back to my psychiatrist and he made me do a couple of different tests and diagnosed me with narcolepsy, type two. Narcolepsy, I was shocked. All I knew about narcolepsy was from that character in Spaceballs, but my doctor explained everything to me and then prescribed me a new medication.
I've been taking that for about two months now, and I can't even begin to describe how much better my life is now. I can stay awake during my lectures and actually stay focused while doing my assignments. My friends noticed the difference too. They said I was like a zombie before my diagnosis. I'm only napping once a day, but I still feel awake throughout the day for the first time in years. I'm actually in the moment now and I'm loving my life again.
Karl Doghramji, MD:
Okay, let's now go on to our second case, that of Charles. Charles is a 56-year-old man who complains of decreased motivation, energy. He's been at home, anhedonia, low desire for all sorts of pleasurable activities, lies on the couch, sleeping for long periods of time, 10 hours or more. His performance is lower, admits to working less. He's been berated as being lazy, unfortunately no longer exercising, putting on weight, ashamed of his weight gain. His wife says he snores a lot.
He's been reluctant to leave the house even to get vaccinated. He's been seeing a psychiatrist and has been placed on bupropion for what looks like it might've been anhedonic depression. He's also been given melatonin to improve his sleep, but he still says he's very tired during the day. Denies self-harm, suicidal ideation. Denies some classic other symptoms, but on the sleep logs, we can see that he's not good with sleep hygiene. He's going to bed early. Looks like he's going to bed at dinnertime and waking up early in the morning, dozing off during the day. So he doesn't really keep a strict bedtime schedule, which is not that great. On mental status, poor eye contact, psychomotor retardation, looks classically depressed. But again, one of the questions is, is he depressed or is he sleepy? Is this a fatigued person or sleepy person or is this a depressed person?
And assessment on visit two, is that bupropion should be continued? Encouraging proper behaviors, sleep hygiene, better scheduling of sleep, eliminating napping, eliminating alcohol, caffeine avoidance, so on and so forth. And here we should be considering an HST or home sleep study because he snores. Snoring in the context of sleepiness in a man who is overweight, Saoirse has mentioned this before, raises the possibility of sleep apnea. And in that context, we should really consider CPAP or PAP therapy.
Now a couple of things about apnea. Saoirse mentioned a number of the symptoms that are characteristic, but these patients present with some of these things we're seeing with Charles, excessive sleepiness, fatigue, snoring, restlessness, and they look like they're depressed, but they really have sleep apnea. They can also, as Saoirse mentioned, have memory impairment, decreased libido, refractory hypertension, and other physiologic findings, but some of the very classic findings which we find in depression.
The management of sleep apnea of course relies on management of the sleep disorder itself with CPAP machines, upper airway surgery, oral appliances, sometimes devices which stimulate the airway musculature such as hypoglossal and nerve stimulation, therapy, weight reduction. Of course, the treatment of sleep apnea is important, but sometimes these patients remain sleepy. So we need to also treat comorbid disorders that may cause sleepiness. Not uncommon for sleep apnea patients to have comorbid problems such as low levels of sleep at night or so on and so forth. The patients who have been properly managed for sleep apnea with CPAP and other measures, but who still remain sleepy without any other comorbidities that could cause it are appropriate patients for pharmacologic management for modafinil, armodafinil or solriamfetol. So Charles, if he does satisfy these criteria, might be somebody with who we could manage with those agents.
These agents, by the way, have been studied with sleep apnea. The top line refers to patients who were studied with modafinil, armodafinil, the second line with solriamfetol. And the last line is a meta-analysis of patients studied with solriamfetol, again, for the treatment of sleepiness in patients with sleep apnea. One interesting finding that jumps out at us is that most of the studies with their agents before solriamfetol produced changes in physiologic sleepiness measures on the order of two points or three points or so. For example, modafinil, armodafinil produced about 2.7 point changes in the MWT or the maintenance of wakefulness test, which is a very sensitive physiologic test for the assessment of sleepiness. That's a meaningful change. That is a very meaningful clinical change. When you go to solriamfetol, the change was on the order of nine or 10 points. Again, these two are not directly comparative, not the same studies, but this is an impressive change in the degree of daytime sleepiness in patients with sleep apnea who have been treated for apnea with other measures.
Charles, going back to Charles, again, patient's very sleepy, looks depressed, may have sleep apnea. What do we do? We get a home sleep study, HST, reveals an apnea index of 23, apnea index of 23, meaning that he has 23 breathing stoppages every hour of sleep, that's high. And anything above five is considered diagnostic for sleep apnea, between five and 15 is considered moderate... I apologize, mild. 15 to 30 is moderate, so he's in the moderate range for sleep apnea and this certainly could be a cause of his sleepiness. He's treated with CPAP management by a psychiatrist who's also sleep specialist who feels comfortable with his treatment. And if we in the field do not feel comfortable, certainly referral to a sleep specialist for CPAP management is very appropriate.
Unfortunately, Charles returns after appropriate management with CPAP revealing that he's still sleepy. You can see that his CPAP machine indicates he's very compliant, 90% compliance. Apnea index is now two. He's reduced 23 down to two, which is normal, but he's still sleepy. And this happens in about 10% to 20% of patients who have apnea who are under proper management for the sleep apnea, they still remain sleepy. And in those patients we can treat these people with these wake promoting agents that we mentioned before. That's their FDA indication.
So to summarize, excessive sleepiness, hypersomnia and fatigue are commonly encountered in psychiatric disorders. They're associated with significant impairment. A systematic evaluation of sleepiness is important, especially for us in the mental health field to uncover other disorders that may be causing sleepiness in the context of our psychiatrically disordered patients. Patients who are, for example, depressed and who are fatigued and sleepy may have another comorbid sleep disorder, which may need to be identified and treated in its own right. Novel wake promoting agents for the treatment of sleepiness are available for narcolepsy as well as sleep apnea. And mental health professionals have an opportunity, I think here, to uncover and address sleepiness within narcolepsy and obstructive sleep apnea in their patients.
Thank you very much for your attention. We'd like now to pause for questions.
Saundra Jain, PsyD:
Welcome back everyone. Now, before we jump into Q&A, please be sure to answer the post activity questions to the right side of your screen. Please remember to click the submit button after the last question so you know that you'll successfully have submitted your answers. And as always, thanks for answering the polling questions.
Hey Karl, hi Saoirse, it's so nice to see both of you.
Karl Doghramji, MD:
Hi, Saundra.
Saundra Jain, PsyD:
Great. And thanks so much. Really an informative presentation. We have so many questions, but unfortunately the bad news is we only have time for one. We'll have to keep our answers right at about a minute. But I'd like to pose the most popular question to both of you. Let me start with you, Karl. What is your number one recommendation to all of us as mental healthcare practitioners? How can we go about upping our game when it comes to identifying sleep challenges?
Karl Doghramji, MD:
Well, Saundra, we spoke about sleepiness in particular in this lecture, and we presented a few scales. In psychiatry we often don't use scales in psychiatric practice, but I'd like to just make a pitch towards using some of these scales such as the Epworth sleepiness scale, which we talked about, which measures the quantity of daytime sleepiness, so the predilection of people to fall asleep. Very easy, patients can fill this out in 15 seconds in the office and it can give us a number. Anything greater than 10 is significant. And the STOP-Bang inventory, we also mentioned that as a way of identifying potential risk for sleep apnea, a condition which often causes a daytime sleepiness, very easy to use in psychiatric practice. So use scales. We're busy professionals, we don't have time in a lot of cases to ask these questions. Scales can really help us out.
Saundra Jain, PsyD:
Absolutely love that recommendation, Karl. Saoirse, what about you? What's your number one recommendation to our viewers?
Saoirse Owens, CRNP:
I mean, I definitely agree. Scales are an awesome tool to use. But for me, I think the number one question, I always like to start with an open-ended question or a general question to get them thinking, are you satisfied with your sleep? Do you find your sleep refreshing? And just simply asking that begins the conversation. And I think that's hugely important. Obviously when they're coming in with multiple complaints, sometimes that question isn't asked. So I'd say that's the number one thing to do. And then maybe following that up with, "Do you have enough energy to get through the day? Are you able to get what you want to accomplish throughout the day done?" And assessing it through those questions. I think a lot of us somehow think that we've gotten accustomed to maybe being a little more tired than we ought to be, and so we're not aware of it ourselves. So maybe some probing questions help to identify that for the patient themselves and for ourselves as the provider and maybe helping them live their best lives.
Saundra Jain, PsyD:
Well, let me say thank you so much for that additional recommendation, so on target. Well, as you might guess, the clock tells me that we are out of time. I want to thank everyone again for joining us. Be sure to check out the Innovation Theaters that are coming up next. Visit the live agenda page to see full session details. And remember attending Innovation Theaters earns you extra points towards the Earn While You Learn Competition. Enjoy the rest of the conference and we'll see you later.