Phyllis C. Zee, MD, PhD

Dr. Benca, could you just maybe take this angle of the importance of psychiatrists? Let's say that, just for the sake argument, this guy has a narcolepsy. How do you see the role of the psychiatrist in this picture working with a primary care doctor, who is trying to handle the narcolepsy?

 Well, this is a patient who has some other issues going on. Clearly, he has had a history of mood disorder. And depression is common in patients with narcolepsy, as is the general struggle they have because even when we treat narcoleptics, they may be totally normal in terms of their sleep propensity. They are having to deal with a lot of issues in their lives that can be increasing stress and exacerbating stress-related illnesses like depression. This is also a patient who clearly has predilection to substance use disorders and that would also be amenable to psychiatric treatment. And then we want to make sure that we keep his depression under control. Although he says his depression is better, I would be suspicious that he still may have insufficiently treated depression. Working with a psychiatrist to help manage the comorbid psychiatric illnesses and providing emotional support to these patients may be useful.

Yeah. Maybe you can go into that a little bit more about how would you treat his narcolepsy and this potential mood issue?

: This is not someone I’d be starting on amphetamines at step one. Again, it's not clear he's got cataplexy so we wouldn't be doing sodium oxybate probably on him. We'd probably want to make sure that he is in some substance abuse treatment, so he is not abusing other stuff, because you don't want to start him on a stimulant and then have him go out and start using cocaine. And he has in a lot of nicotine, so you want to manage his caffeine use, things like that. Then you might want to think about some of the newer agents that might be a little less likely to lead to abuse issues, like solriamfetol or pitolisant. I would defer to Dr. Zee to see what her thoughts would be on that, as well.

Yeah. Actually, Dr. Zee or Dr. Moawad, do you have other angles that you'd consider with this?

: I agree with Dr. Benca and her approach, but I think in addition to that, thinking about not just the patient support groups or narcolepsy support groups, but also the behavioral components of that. Again, he is in college and having a lot of difficulty dealing with the psychosocial aspects of excessive daytime sleepiness. I think that would be also helpful in addition to the medications. But again, I agree that being in college, having this history of substance abuse, it's tough with regards to what type of medication you would add. And I would probably still favor something like modafinil, for example, as probably my first line still here again, knowing that there are other options.

And when you say modafinil, we can sort of lump in armodafinil.

: Yeah. I would agree with that. And then if that is not sufficient to think about adding on some of the other ones, but pretty much stay away from amphetamines if at all possible.

 Yeah. I think to add to that, I would say because of the challenges with the drug use that he has had in the past, that definitely patient education will play a big role in this, so that he is actually very aware of that potential for addiction and negative aspects of using the medication and that can help prevent some of the adverse effects.

Dr. Moawad, you touched on something that I don't think we are really going to get to later on, but it's the role of psychologists in sleep clinic. And I am just curious, I think different clinics have different focuses and so forth. But I think we have been talking mainly about how the psychiatrist and so forth would manage this, but do you see a role for psychologist here?

: I do. I think that it's time-consuming and it can be something that some patients might not feel they want to invest the time and they just want to get that prescription and get better. But certainly long term, the outcome can be a lot better if patients understand how behavior modification, lifestyle modification can help their overall symptoms and can also be aware of potential adverse effects of medication so they can use them more responsibly. I think it's something that I can imagine a patient like this wanting to not spend the time, but certainly, it would pay off for him in the long run.

: Another issue I think to keep in mind is that given that he may need ongoing treatment for depression, be careful about which antidepressants we select, he's on fluoxetine now, which is probably one of the better ones in terms of not increasing excessive sleepiness, but again, some antidepressants can cause increased fatigue or sleepiness.

 One more thing to add perhaps is the nicotine use, that is pretty high and it may be self-medication to improve alertness during the day, but that could also potentially have an adverse effect on his sleep quality. Referral, perhaps, to a smoking cessation clinic would probably be important, as well.

When I was mentioning the role of a psychologist in this, I was thinking there is so much counseling needed here. It almost seems a little bit beyond what many doctors would be able to have the bandwidth for. Because who knows, maybe he is smoking a whole bunch before he goes to bed or he is drinking a lot of caffeine in the evening and they are contributing to insufficient sleep. As we have discussed there's lots of approaches to this patient and I think just simply putting them on a med will help, but more than that is necessary, there's a lot of behavioral work here.

Videos

Thought leaders discuss clinical considerations regarding the many intersecting and complicating conditions that individuals with narcolepsy may experience.

The Role of Multidisciplinary Teams and Treatment Options

Dr. Moawad, let's just turn to you for your overall impressions of this case and what stands out to you.

 Actually, this patient's history is, in many ways, so typical because he is attempting to explain his symptoms with the things that are going on in his life. He is not doing well in school. He is flunking his classes. And so he is describing the depression, the sleepiness, all of these things based on the events that are going on for him. Especially at this age, this is a normal way that a young person would describe what is going on with them. One thing that I do think that stands out is that he has been taking medication for a while and that can really have a lot of side effects and can change things that he doesn't seem to have been maybe warned about, what side effects to look for. I think that is coloring what's going on here. But the other thing that is really standing out is how persistent all of this is. A lot of times, when young people in particular try to explain symptoms with what is going on in their life, it shouldn't be so prolonged. In this case, we're talking about a 19-year-old, and he has been dealing with this since he was 16. It is definitely something to look at deeper.

He is problematically sleeping. How would you tease apart this question of depression and narcolepsy in this guy?

 Well, I think I actually do think that the scales would be helpful in this type of situation. One thing is that it opens up the discussion. It helps him to consider sleepiness in isolation from mood and to consider how much he's been sleeping, how much he falls asleep. Also, it allows for a discussion about the fact that this is not necessarily normal and that he really needs to start tracking this a little bit more. I think it is just an opening for sleep studies, which would be more definitive for him.

It sounds like just with this kind of history, after taking a good history, you would certainly move on to doing an overnight polysomnogram and multiple sleep latency test.

 Yeah. Given how long he has been dealing with this and that it seems that the conditions in his life that he is blaming all of this on are not getting—as probably things are fluctuating during summer vacation and things like that—it doesn't seem like his symptoms are getting better during those times.

: One thing that I notice is that we have this strong focus on excessive daytime sleepiness, daytime functioning, and there have been no questions about his nighttime sleep, being a college student, how regular sleep is. I think Dr. Benca brought up the issue of sleep deprivation being very common in this group. I think that's probably something I would be really interested in knowing about his sleep quality, the regularity as well, because that is important not to miss that in the history.

I think you're highlighting the fact that way more common than narcolepsy is insufficient sleep, circadian phase delay, things like this are really what it's most typically causing these kinds of problems in this stage group. Dr. Benca, were you going to say something?

 Yeah. Certainly, all of that is true, but it is also an age group where narcolepsy sometimes appears. We do have to keep that in mind, but I agree with Dr. Zee that particularly in young people like this, we do need to get a very careful sleep history. Does he have early morning classes and is staying up really late at night? Does he have an irregular pattern social jet lag, whatever that is contributing to his sleepiness? The other concern I have about him is his substance abuse history. Again, is he self-medicating because he is sleepy, or is he sleepy because he's addiction-prone in using stimulants that have their side effects when you withdraw excessive sleepiness, like the cocaine? And although he says he has not been using for a month or two, that's not really indicative of recovery from substance abuse, and he is smoking a pack a day. That also raises concerns about how we're going to treat him because he's clearly someone who does tend to abuse substances.

Yeah. I think it's obvious, but do you want to comment on the caffeine and the nicotine and his sleep patterns?

 I just have one other thing to add, which is that a young person at this age who's having trouble in school could potentially have undiagnosed ADHD or learning disorder and that can be contributing to his drug use as a way of coping with these difficulties.

Heidi Moawad, MD; Phyllis C. Zee, MD, PhD; and Ruth Benca, MD, PhD, share details about a patient case that may impact clinical considerations and therapeutic decision-making.

Clinical Impressions from Patient Case #1

Let’s transition to talking about an actual clinical case, so that we can put some of these thoughts in context. This is a 19-year-old man who presented to his psychiatrist with excessive daytime sleepiness. He has been seeing his primary care physician for the last 3 years for his condition. He says that he was diagnosed with depression at age 16 when he was in high school. For that, he is taking fluoxetine 20 mg each morning. He took it as prescribed, but he now takes it every other day because he feels that his depression has improved. He still has some days when he feels depressed, but he says that is mainly because he is failing his classes and he has been put on academic probation; he does not really see it as an intrinsic problem. He has been self-medicating for the last 3 months with caffeine and energy drinks and over the counter agents to try to improve his sleepiness, but he does not find them effective. There is no history of trauma or head injury. The past history is notable for the depression, and he does have a prior history of marijuana and cocaine abuse, but he has not been using it for the past couple of months. He is currently a full-time college student. He does smoke one pack of cigarettes a day, and, as I mentioned, he is on academic probation because he is not doing well academically, which he says is because he cannot stay awake and study properly. The only medication right now is fluoxetine 20 mg and his labs are all fine.

Thomas E. Scammell, MD, presents a case study for a college student with a history of sleepiness.

Patient Case #1: 19-Year-Old Man With Excessive Daytime Sleepiness

 Around the Practice program on the management of narcolepsy. I am Tom Scammell. I am a Professor of Neurology at Harvard Medical School Beth Israel Deaconess in Boston Children’s Hospital. I am joined by Dr Heidi Mowad, who is a clinical assistant professor of neurology at Case Western Reserve University School of Medicine in Cleveland, Dr Ruth Benca, who is a professor and chair of psychiatry at Wake Forest School of Medicine and Dr Phyllis Zee, who is a professor of neurology and director of the circadian and sleep program at Northwestern University School of Medicine. In addition to reviewing the diagnosis and management of narcolepsy, we will be presenting 2 hypothetical patient cases and will be talking through approaches to treatment. Let’s begin.

Let’s just start off generally talking about the challenges of diagnosing narcolepsy. How often is it underdiagnosed, or misdiagnosed? Why has it proven so difficult to properly diagnosis, and what is the differential diagnosis? Dr. Zee, do you want to start us off with that one?

 When you look at the data that has been published about the lag between presentation of symptoms of narcolepsy to diagnosis, it can lag up to about 3 to 8 years. Some of it is because it is misdiagnosed or underdiagnosed about 60% of the time, and that is a huge number. Of course, in addition to lack of awareness, or perhaps lack of familiarity with the disorder, probably what is driving this are common comorbidities that exist in patients with narcolepsy, such as depression and anxiety disorders. There are also other sleep disorders like sleep apnea, which is actually common in patients with narcolepsy, and even circadian rhythm sleep disorders. Excessive daytime sleepiness is so common; it is very nonspecific to many of the conditions that psychiatrists and neurologists take care of. Also, many patients are on medications that could mask some of the symptoms of narcolepsy. I think those are some of the common reasons for some of the missed or delayed diagnoses.

You mentioned that depression is often comorbid with narcolepsy. Dr. Benca, do you want to talk about how these symptoms can get blurred together?

One thing that a significant subset of patients with depression will complain about is excessive daytime sleepiness. Some of them are actually excessively sleepy and some of them are just really fatigued and don’t show objective evidence of excessive sleepiness, but they will report that they are sleepy. The other issue is that, like narcolepsy, mood disorders are sometimes characterized by early entrance into REM sleep. You can sometimes see shorter REM latency in patients with mood disorders, so there can be some overlap there.

In addition to narcolepsy often not being diagnosed in a timely manner, conditions often get diagnosed as narcolepsy inappropriately. One of the things I’ve seen more is people who are simply sleep deprived, such as those who are doing shift work, or physicians, who may be doing a lot of call and are not getting enough sleep and are falling asleep at work. These folks often get diagnosed with narcolepsy. Actually, they are just sleep deprived.

What kind of tools do you use to actually evaluate daytime sleepiness and separate it from, for instance, a more typical sense of fatigue and depression?

One thing is that you do a more careful clinical exam. One of the issues I see a lot in psychiatry is that patients report that they are tired. We assume they are sleepy. I always try to distinguish if they are tired and falling asleep inappropriately, or you just wish you were asleep and you’re exhausted.

Diagnosing narcolepsy, we generally do sleep testing. That is where it is really important to verify that patients are not sleep deprived and are sleeping adequately, and that they get sufficient sleep before we do their multiple sleep latency test.

Do you like the Epworth Sleepiness Scale?

The Epworth Sleepiness Scale just tells you whether the patient thinks they are excessively sleepy. It is not specific to any particular sleep disorder. Sometimes patients who are simply fatigued may report very high Epworth scores. I see that a lot in psychiatric patients. They sometimes have high Epworth scores but when we test them objectively, they are not actually sleepy.

One question I like to ask under those circumstances is: How many times do you actually fall asleep when you did not plan to in the last week? Because I agree with you. Sometimes there is a little inflation on the Epworth sleep score. People say, “I could fall asleep when I am watching TV.” Then I ask, “Did it really happen?” Usually the answer is no. Getting down to the nuts and bolts of falling asleep could be useful.

 One of the things I try to do is to see whether there is any cataplexy. It is quite amazing to me how oftentimes we miss that because we are asking about big things. Are you falling when you laugh hard? Do your knees buckle? Even if they say “No” to that, I try to probe deeper to see if I can get some of the milder symptoms, perhaps mild manifestations of cataplexy. Often times that can be helpful, especially to diagnose narcolepsy type 2. That can be more specific.

There is another screening tool if you are trying to determine whether someone has type 1 narcolepsy, and that is the Swiss narcolepsy scale. It is a 5-item scale that does elicit symptoms of cataplexy. It is a little bit more complicated to score, because you have to go through a formula. It doesn’t really help you with those patients who might have type 2 narcolepsy or narcolepsy without cataplexy, which are the group that tends to overlap a lot with other disorders that might present with hypersomnia, including mood disorders or even idiopathic hypersomnia.

A multidisciplinary panel of experts outline the difficulties of distinguishing narcolepsy frfom other sleep disorders and psychiatric comorbid conditions.

Phyllis C. Zee, MD, PhD

Articles

The Role of Multidisciplinary Teams and Treatment Options

Clinical Impressions from Patient Case #1

Patient Case #1: 19-Year-Old Man With Excessive Daytime Sleepiness

Challenges in the Diagnosis of Narcolepsy