It’s a very exciting time in narcolepsy research, particularly on two fronts: better understanding the complexities of the disorder and developing more targeted treatments. With so many advances underway, it can feel overwhelming to keep track of research developments and understand how the pieces fit together. This can be especially true for patients and caregivers who may be less familiar with scientific terminology.
For people with chronic conditions, the condition naturally becomes a large part of their life—yet its underlying science may be difficult to understand without a medical background, which can lead to frustration and feelings of isolation. As a health care provider, offering accessible and easily digestible information is a meaningful way to go the extra mile in caring for your patients.
Feeling educated about narcolepsy and its effects is empowering and validating for those living with the condition. Being equipped with the appropriate information can also foster informed conversations with other members of their health care team and lead to more participation and shared decision-making in their care.
Understanding Orexins and Their Role in Narcolepsy
Helping patients make sense of the science of narcolepsy begins with explaining the biology behind the disorder. In particular, the orexin system offers important insight into why symptoms occur and how emerging treatments may address them.
Orexins, also known as hypocretins, are molecules produced by specialized cells in a region of the brain called the hypothalamus. There are two similar peptides, orexin A and orexin B, that act as neurotransmitters at orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R). Orexin A binds both OX1R and OX2R with high affinity. Orexin B binds OX2R preferentially and has a much lower affinity for OX1R. Orexin signaling is required to maintain long durations of wakefulness and facilitate stable states of wake and sleep.
Narcolepsy type 1 (NT1) presents with excessive daytime sleepiness, cataplexy, fragmented sleep, and hallucinations around the time of wake or sleep onset. We now understand that these symptoms are a result of the loss of more than 90% of the orexin neuron population. In fact, orexin levels are low and sometimes even undetectable in the cerebrospinal fluid (CSF) of people with NT1. Narcolepsy type 2 (NT2) still has not been fully characterized; however, many people with NT2 have normal levels of orexin in their CSF, and the limited data that’s available they retain more orexin-producing neurons than people with NT1. People with NT2 experience all the symptoms of NT1 except for cataplexy.
A number of orexin receptor agonists are in development that can activate OX1R, OX2R, or both. It’s an exciting new chapter in the treatment of narcolepsy and idiopathic hypersomnia (IH), and it’s already begun. In August, the FDA approved oveporexton, a first-in-kind OX2R agonist to treat narcolepsy and IH, which makes these conversations with patients all the more pertinent.
Validating Experiences with Facts
With a rare disorder like narcolepsy, it’s not unusual for patients to feel like it’s all in their head—especially because it’s a societal norm to treat lack of sleep as a necessary evil or even a badge of honor. Tiredness affects everyone and because it’s discussed frequently and extensively in social situations, sometimes it might feel like people are reducing the challenging experience of someone with narcolepsy to a common occurrence.
Compounding that is the widespread psychological phenomenon of competitive suffering, which often comes up in schools, workplaces, and even at the family dinner table. Let’s use the example of a student telling their classmates they’re exhausted because they stayed up to finish a project last night and only slept for six hours. A friend chimes in, saying, “You’re lucky you even got six because I had two projects to finish, so I only got three hours of sleep, and I’m really exhausted.” This reinforces the already rampant push for maximizing productivity as much as possible each day. Rest takes a backseat, and tiredness becomes a sign we’re working hard.
Now apply this to someone with narcolepsy, a student who consistently prioritizes eight hours of sleep because of their strict treatment regimen. They have to sacrifice other things to maintain that. They may feel like they aren’t working hard enough or worry they’re perceived as lazy, especially when hearing their peers talk about how they’re sacrificing sleep. They may feel invalidated in their ongoing sleepiness, thinking that if someone else can survive on three hours of sleep, they shouldn’t have to nap after eight hours.
Understanding the biological basis of narcolepsy can help people recognize that excessive daytime sleepiness is not a matter of willpower or motivation. Someone with narcolepsy can do everything “right”—maintain a consistent sleep schedule and prioritize enough time for sleep—and still experience overwhelming daytime sleepiness. Comparing themselves to people without narcolepsy, who may function after not getting an ideal amount of sleep, isn’t a fair comparison because the quality and regulation of their sleep are fundamentally different. Recognizing these differences can help people set realistic expectations for themselves and appreciate that prioritizing sleep and rest is an essential part of managing their health, not a sign of weakness or a lack of effort.
Narcolepsy can often be dismissed, especially in youth, as the result of a poor sleep schedule. Because many teens stay up late, someone with narcolepsy may blame their tiredness on that alone. While routine has an impact, understanding the actual cause and effects of the disorder can reassure them it’s not their own doing.
Understanding how treatments
work can also empower patients to take a more active role in managing their narcolepsy. Experiencing symptom relief is important, but knowing what each treatment is designed to target can help patients recognize its benefits, monitor how well it’s working, and identify changes when doses are missed or medications are adjusted. This knowledge also helps patients make informed decisions with their health care providers about which therapies best fit their needs and lifestyle. As new treatments continue to emerge, they offer increasingly targeted approaches, giving patients more options to find a regimen that works best for their individual symptoms and goals.
The Provider Role
Symptoms of narcolepsy can show up in similar ways for individuals yet also be very personal, which might lead to diagnostic delays among providers. Take cataplexy, for example. If someone only hears it described as knees buckling, they may overlook their jaw drooping. Knowing how to interpret a patient’s descriptions of their symptoms can streamline diagnosis.
(See sidebar, “Don’t Let Symptoms Get Lost in Translation” on page 14.)
Recognizing and naming symptoms is only the first step; patients may also need help establishing a baseline and identifying changes over time. Efficiently tracking how symptoms change based on a variety of factors and a treatment regimen can lead to continued improvements in care. When someone has experienced excessive daytime sleepiness for as long as they can remember, it may be difficult for them to imagine what being fully awake feels like. The tendency to compare levels of tiredness can make that distinction even harder. As a result, patients may have difficulty determining if a treatment is working and identifying which factors improve or worsen their symptoms.
When first starting medication, any improvement in energy seems drastic. This can prevent patients from reporting any persisting exhaustion to their doctor, brushing it off as the normal levels they just have to deal with.
A strategy used by Alicia Roth, MD, is asking patients what they aren’t doing rather than what they are doing. This gives them the chance to reflect on things they used to be able to do or would like to start doing but don’t have the energy for. These conversations help patients identify what matters most to them and guide the development of a treatment plan that aligns with their priorities. Some patients may prefer a single medication combined with scheduled naps, while others may choose a combination of therapies if it allows them to stay awake throughout the day without needing to nap. Still others may require multiple medications and scheduled naps to achieve their best level of functioning. Narcolepsy is incredibly personal and should be treated as such to maximize the quality of life for patients.
Providers can also be incredibly helpful in keeping patients updated on research developments. Updates don’t need to be given every time, especially with how fast advances are happening nowadays, but being a trusted source pointing them to the right places to learn more is a huge weight off their shoulders. For example, providers could direct patients to clinical trials if they’re a good fit. Patients also often have questions about insurance coverage and access to new medications. A provider can help the individual be realistic about timelines, side effects, complications, and unknowns when it comes to starting a new therapy.
Another great resource for patients is plain language summaries. Many research studies now include these easy-to-understand synopses that explain the findings without technical jargon. Just making patients aware of these so they can look for them when they see an article they’re struggling to understand can make an impact.
Moving the Field Forward
Although this article primarily focused on narcolepsy, these sentiments typically apply to any disorder that makes patients feel misunderstood, isolated, or judged, especially rare ones. Without the proper knowledge, they may blame themselves or think they are alone. Providing understandable resources benefits everyone and helps move the field forward, especially during this exciting time of discovery and innovation. It is a shared responsibility among researchers, clinicians, and patient communities to continue improving how we communicate science by offering information that is accurate, accessible, and meaningful to people at all levels of understanding. Together, we can make a greater impact and dedicate ourselves to improving the quality of life for patients.
By Carrie E. Mahoney, PhD, and Cara Weaver
Source: SleepWorld Magazine Sept/Oct 2026
Carrie E. Mahoney, PhD, is a staff scientist at Beth Israel Deaconess Medical Center in Boston whose research focuses on the neural mechanisms regulating sleep and wakefulness, with an emphasis on narcolepsy and orexin biology. Cara Weaver is the manager of PR &public relations and communications at Wake Up Narcolepsy and is also a person with narcolepsy type 2.
Cara Weaver is the manager of public relations and communications at Wake Up Narcolepsy and is also a person with narcolepsy type 2.
