Perspectives on the Management of Narcolepsy and Excessive Daytime Sleepiness

NeurologyLive, February 2022, Volume 5, Issue 1

Expert neurologist and sleep specialist Chris Winter, MD, provides a practical outlook on the identification and management of narcolepsy and excessive daytime sleepiness.

NARCOLEPSY HAS BEEN A challenging condition for physicians to treat, although advances in clinical care have allowed for a great understanding of the condition and its features. Among the biggest challenges, though, has been the identification of patients. The symptoms of narcolepsy can be easy to recognize once they are noticed, but often, even the cardinal feature—excessive daytime sleepiness—can be difficult to see.

Fortunately, there have been several therapeutic and clinical developments that have made intervening much easier. In a recent NeurologyLive® Insights series, Chris Winter, MD, owner of Charlottesville Neurology and Sleep Medicine (CNSM) Clinic and CNSM Consulting, offered up his experience with treating and assessing the sleep disorder, highlighting ways the physician community can address the unmet needs and the current therapeutic options for patients.

Challenges With Differential Diagnosis

The formal diagnosis of narcolepsy can be difficult to reach. Often, it can require an overnight stay at a sleep center for an in-depth sleep analysis by a sleep specialist, with patients providing sleep history and records, and undergoing polysomnography and the multiple sleep latency test. Much of this is in an attempt to rule out other similarly presenting disorders.

“Narcolepsy has been referred to as the ‘great pretender’ because its symptoms often look like different diagnoses, and that’s especially true when you start to divide out the excessive sleepiness that patients with narcolepsy have,” Winter said, adding that there are several other symptoms that can add to the challenge, such as hallucinations and cataplexy. However, there are also symptoms that can introduce difficulty in differentiation because of their broad nature. One such example, Winter said, is depression.

“If you just look at excessive daytime sleepiness and imagine a patient going to a doctor, saying, ‘I’m tired all the time. I don’t want to get out of bed. I fall asleep at work. On weekends I ignore my friends. I ignore my hobbies. I ignore the things that I like to do. All I want do is spend time in bed sleeping.’ You can imagine that a primary care provider might look at those symptoms and think, ‘Wow, you sound pretty depressed because it’s so difficult for you to really get out of bed and engage in life,’” he said. “There certainly can be depressive elements to that, but what we’re really describing is a person with excessive sleepiness, so depression is high on that list. Individuals who are excessively sleepy often have tremendous difficulties with concentration and focus, so ADHD [attention-deficit/hyperactivity disorder] can jump in there as well, because people can have tremendous difficulty with attention.”

Winter explained that another common symptom is anxiety, as those with excessive daytime sleepiness may rely on anxiety as a tool to stay awake. In these instances, these patients are often disguised as busy people because they avoid sitting still for too long. These symptoms can muddy the diagnostic waters because they hide the underlying symptom of excessive sleepiness, but the challenge does not stop there. Even the more traditional symptoms can cause confusion.

“When you start looking at the hallucinations that people have, when you look at the cataplexy, somebody, when they’re laughing, actually kind of falls over and can’t move for a short period. Now we start getting into the confusion with seizures, confusion with syncopal events or passing out, [and] psychiatric conversion disorders. He’s pretending to have a seizure. He’s pretending to pass out,” Winter said. “Then the hallucinations, hearing things before you go to bed or seeing things, could often be confused for a frank psychosis or a bipolar kind of disorder, where individuals are very depressed or having manic episodes.”

Because of this, patients with narcolepsy often run through the gamut of misdiagnoses before getting the proper one. That delay in diagnosis can last as long as 15 years for some individuals, Winter said, which can ultimately result in worse outcomes. But for Winter, the biggest issue with the misdiagnosis—besides unnecessary medication use—is the great disruption to the quality of life.

“I talked to a patient one time who said, ‘You’re the 13th doctor that I’ve seen for my problem, and if you can’t figure out what’s wrong with me, I’m going to stop seeing doctors,’” he said. “She told me that her problem was that she melted every day, and the melting was cataplexy.

Thus, she was diagnosed with all kinds of problems. To me, the biggest problem is this wasted time or wasted opportunity.” “That in and of itself is really sad to me. I want people to lead their fullest lives, and this disorder prevents that from happening,” he said.

Selecting Optimal Therapy for Narcolepsy

In recent years, a number of therapies have made their way through clinical development into the therapeutic arsenal. Each new option offers more possibilities for patients, making the process of determining which is best for a given individual extremely important. One such factor for deciding on therapy is age, Winter explained.

“We know that oxybates are approved for kids who are quite young. That’s a factor,” he said. “Pregnancy is always a factor with any medication, so we want to make sure individuals who could become pregnant or are pregnant understand the different mechanisms of actions of the drugs and the relative risks they carry. Some medications, like oxybate, don’t play well with alcohol, so if an individual is known to drink significantly, particularly in the evening—maybe a young grad student who might be prone to more drinking—we want to talk about that as well.”

Another facet for consideration is drug-drug interactions, as some of the available narcolepsy agents interact with other drugs. One such example Winter offered was birth control, as its metabolism can be affected by agents, such as modafinil (Provigil; Cephalon), armodafinil (Nuvigil; Teva), and pitolisant (Wakix; Harmony Biosciences). “We’re looking at concurrent psychiatric conditions and the other medications that the patient might be taking for those or other disorders, including depression and anxiety. All those things may predispose the clinician to choose one drug over another,” Winter said.

As Winter put it, one of the “balancing points” with the medications used to treat narcolepsy is that they can occasionally create anxious feelings, jitteriness, or heart rate elevations for patients. These symptoms can be minimal with solriamfetol (Sunosi; Jazz Pharmaceuticals) use, Winter said, making it “another great option in line with drugs like modafinil and armodafinil for individuals to take when they’re awake to help them improve or stabilize wakefulness during the day.”

“The final thing I would say is: Do you have a patient who’s predominantly type 2 excessively sleepy, or do you have a patient who struggles with sleepiness and cataplexy? If cataplexy is a big feature in a patient’s life, we may want to consider a drug like oxybate or pitolisant earlier in the process to get that cataplexy under control,” he said.

Practical Insight for Community-Based Physicians

Winter closed the series by providing some advice for community-based physicians on how to address and identify patients with narcolepsy. He began by pointing out some of the current unmet needs and challenges in clinical care, namely, education.

“Challenge No. 1 is getting good information out there to primary care doctors, parents, teachers, school administrators, and school nurses about what narcolepsy looks like and how can we better identify it,” he said. “In other words, if a child always falls asleep during world history class, maybe punishing them isn’t what we need to do. Rather, ask some questions, and don’t automatically assume it’s because the kid is staying up too late playing video games. The same thing could be said for employers. If you’ve got an individual who’s falling asleep a lot at work, rather than firing them or blaming them for some personality fault, sit down with them and say, ‘Listen, your coworkers say you’re falling asleep at your computer every day. Is everything OK? What’s going on?’ Point them in the direction of a resource that could help them.”

Once individuals receive a diagnosis, though, the challenge is not immediately resolved. Winter explained that some estimates suggest that the majority of sleep doctors do not feel comfortable diagnosing or treating narcolepsy, and his personal clinical experience has been in line with that. Unfortunately, this can often lead to patients getting diminished or forgotten because of a lack of interest or uncertainty about treatment.

“Misdiagnosis is a big problem, too. It’s just a matter of spending the time with the patient to figure out what medication or medication combination is going to work best. That does take some effort, enthusiasm, and time, but from my personal viewpoint, there’s nothing more satisfying than discovering and diagnosing a patient with narcolepsy and getting them the wakefulness they need to lead a much more fulfilled and happy life. These are some of the most appreciative patients in my clinic,” Winter said.

Winter offered up 2 main points of advice for community-based providers who see patients with narcolepsy. The first is to always perform a sleepiness evaluation every visit, even for those with an existing diagnosis of narcolepsy. The Epworth Sleepiness Scale “does a great job of it,” he said, adding that it is a valuable tool in discovering those with sleepiness issues.

“Patients with narcolepsy are not great at describing their symptoms, so they tend to underestimate and minimize their symptoms,” he said. “Never trust a patient who has narcolepsy’s ability to determine whether they’re normal. They’re good at telling you they’re better or worse, but their great day may be your worst day. Thus, it’s very important for us to always screen for excessive sleepiness in all our patients.”

The second main point of advice Winter offered was to refrain from automatically assuming the first-choice medication is going to be the best choice, even if a patient reports feeling better. Again, he advised referring to the Epworth Sleepiness Scale for guidance.

“All medications that we use to treat narcolepsy have a role with a patient, so if you’re a provider who said, ‘You know what, I only use drugs A and B for narcolepsy. Drugs C, D, E, and F, I don’t even bother with,’ then you’re probably making a bad choice. Drugs C, D, E, and F may not be perfect for everyone, but for individuals who treat a lot of narcolepsy, we find that every one of these medications is meaningful and helpful to somebody. That’s really important,” he said.