For US Healthcare Professionals
IT TAKES
understanding the science, symptoms, and impact
TO SUPPORT YOUR PATIENTS LIVING WITH NT1
Video library
An expert explains orexin
Dr Foldvary-Schaefer of the Cleveland Clinic talks about orexin and the role of orexin loss in NT1.
Watch Casey’s story
Casey takes cold plunges and washes his face with ice water during the day to help stay awake.
Watch Justice’s story
Justice has her own approaches to making her life with NT1 more manageable, such as taking a nap gap every day.
Watch Tara’s story
Tara breaks up tasks and tries not to do the same thing for too long to help herself feel more awake.
Patient stories reflect individual experiences, which may vary.
Find a sleep center near you
If you have patients that you may want to refer for a sleep evaluation, use this third-party link to access a directory of sleep centers in your area. The healthcare facilities in this directory are accredited by the American Academy of Sleep Medicine.
Third-party information is provided for reference only and does not imply Takeda endorsement.
Learn about key regulators of the sleep-wake cycle
Answers to frequently asked questions about narcolepsy type 1
NT1 is characterized by 5 symptoms1,6:
- Excessive daytime sleepiness (EDS): persistent sleepiness, tiredness, or fatigue that can return quickly after sleep or naps
- Cataplexy: the sudden and temporary loss of muscle tone
- Disrupted nighttime sleep: poor sleep quality due to a lack of sleep continuity
- Hallucinations: vivid, dreamlike states (auditory or visual) that happen when falling asleep or immediately when waking up
- Sleep paralysis: the inability to move when falling asleep or immediately after waking up, which is caused by the intrusion of rapid eye movement (REM) sleep into the wake state
The scope and severity of symptoms varies between individuals.
Cataplexy—the sudden and temporary loss of muscle tone—is a hallmark symptom of narcolepsy type 1 (NT1). It can happen any time that rapid eye movement (REM) sleep intrudes into the awake state and can be brought on by laughter or strong emotions, such as elation or anger. Cataplexy can be localized, such as to the limbs, head, or neck, or affect the entire body.6
Manifestations of cataplexy can be different in each person, with notable differences between children and adults. Some people with narcolepsy type 2 (NT2) will develop cataplexy later in their disease, making the identification of this symptom critical, but difficult.10
The hallmark symptoms of NT1—excessive daytime sleepiness (EDS), cataplexy, disrupted nighttime sleep, hallucinations, and sleep paralysis—have been shown to negatively affect patients’ quality of life. The effects of NT1 can extend across a range of normal daily functioning, including1,3,11,13:
- Not feeling well rested and refreshed
- Difficulty enjoying everyday activities, such as exercise
- Struggling to overcome the cognitive symptoms often associated with NT1 that can make work or school difficult
- Trouble building or maintaining relationships
- Difficulty managing everyday responsibilities, such as parenting, cooking, cleaning, and self-care
The scope and severity of symptoms vary between individuals.
Narcolepsy type 1 is thought to be caused by a disruption of orexin signaling, which regulates the sleep-wake cycle. Orexin, also known as hypocretin, is a neuropeptide released by orexinergic neurons located in the hypothalamus. It is responsible for stabilizing the sleep-wake cycle. Orexin neuropeptides project deep throughout the brain to regions involved in cognition and attention, mood, muscle tone, and energy.5-7
Orexin, also known as hypocretin, is a neuropeptide released by orexinergic neurons located in the hypothalamus. It is responsible for stabilizing the sleep-wake cycle. Orexin neuropeptides project deep throughout the brain to regions involved in cognition and attention, mood, muscle tone, and energy.5-7
Get NT1 news and resources
Sign up to have resources made available for you, your patients, and your office—sent right to your inbox.
Recommended for you
Follow us on social media
References
1. Krahn LE, Zee PC, Thorpy MJ. Current understanding of narcolepsy 1 and its comorbidities: what clinicians need to know. Adv Ther. 2022;39(1):221-243. doi:10.1007/s12325-021-01992-4 2. Maski K, Steinhart E, Williams D, et al. Listening to the patient voice in narcolepsy: diagnostic delay, disease burden, and treatment efficacy. J Clin Sleep Med. 2017;13(3):419-425. doi:10.5664/jcsm.6494 3. Maski K, Trotti LM, Kotagal S, et al. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2021;17(9):1881-1893. doi:10.5664/jcsm.9328 4. Scammell TE. Narcolepsy. N Engl J Med. 2015;373(27):2654-2662. doi:10.1056/NEJMra1500587 5. De Luca R, Nardone S, Grace KP, et al. Orexin neurons inhibit sleep to promote arousal. Nat Commun. 2022;13(1):4163. doi:10.1038/s41467-022-31591-y 6. Mahoney CE, Cogswell A, Koralnik IJ, Scammell TE. The neurobiological basis of narcolepsy. Nat Rev Neurosci. 2019;20(2):83-93. doi:10.1038/s41583-018-0097-x 7. Toor B, Ray LB, Pozzobon A, Fogel SM. Sleep, orexin and cognition. Front Neurol Neurosci. 2021;45:38-51. doi:10.1159/000514960 8. Sakurai T. The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness. Nat Rev Neurosci. 2007;8(3):171-181. doi:10.1038/nrn2092 9. Lipford MC, Ip W, Awasthi S, et al. Demographic characteristics and comorbidities of patients with narcolepsy: a propensity-matched cohort study. Sleep Adv. 2024;5(1):zpae067. doi:10.1093/sleepadvances/zpae067 10. Szabo ST, Thorpy MJ, Mayer G, Peever JH, Kilduff TS. Neurobiological and immunogenetic aspects of narcolepsy: Implications for pharmacotherapy. Sleep Med Rev. 2019;43:23-36. doi:10.1016/j.smrv.2018.09.006 11. Ortiz LE, Morse AM, Krahn L, et al. A survey of people living with narcolepsy in the USA: path to diagnosis, quality of life, and treatment landscape from the patient’s perspective. CNS Drugs. 2025;39(suppl 1):S23-S36. doi:10.1007/s40263-024-01142-8 12. Bassi C, Biscarini F, Zenesini C, et al. Work productivity and activity impairment in patients with narcolepsy type 1. J Sleep Res. 2024;33(3):e14087. doi:10.1111/jsr.14087 13. Davidson RD, Biddle K, Nassan M, Scammell TE, Zhou ES. The impact of narcolepsy on social relationships in young adults. J Clin Sleep Med. 2022;18(12):2751-2761. doi:10.5664/jcsm.10212 14. Quaedackers L, Pillen S, Overeem S. Recognizing the symptom spectrum of narcolepsy to improve timely diagnosis: a narrative review. Nat Sci Sleep. 2021;13:1083-1096. doi:10.2147/NSS.S278046 15. Bassetti CLA, Adamantidis A, Burdakov D, et al. Narcolepsy-clinical spectrum, aetiopathophysiology, diagnosis and treatment. Nat Rev Neurol. 2019;15(9):519-539. doi:10.1038/s41582-019-0226-9 16. Luca G, Haba-Rubio J, Dauvilliers Y, et al. Clinical, polysomnographic and genome-wide association analyses of narcolepsy with cataplexy: a European Narcolepsy Network study. J Sleep Res. 2013;22(5):482-495. doi:10.1111/jsr.12044 17. Black J, Reaven NL, Funk SE, et al. Medical comorbidity in narcolepsy: findings from the Burden of Narcolepsy Disease (BOND) study. Sleep Med. 2017;33:13-18. doi:10.1016/j.sleep.2016.04.004 18. Morse AM, Kim SY, Harris S, Gow M. Narcolepsy: beyond the classic pentad. CNS Drugs. 2025;39(suppl 1):S9-S22. doi:10.1007/s40263-024-01141-9 19. Yan Z, Li J, Yu Y, Qiu S, Wang B, Tang J. Comparative efficacy of new wake-promoting agents for narcolepsy–a network meta-analysis. BMC Neurol. 2025;25(1):466. doi:10.1186/s12883-025-04328-9 20. Dauvilliers Y, Mignot E, Del Río Villegas R, et al. Oral orexin receptor 2 agonist in narcolepsy type 1. N Engl J Med. 2023;389(4):309-321. doi:10.1056/NEJMoa2301940 21. Johns M. A new method for measuring daytime sleepiness: the Epworth Sleepiness Scale. Sleep. 1991;14(6):540-545. 22. Yu J, Zhou Y, Han X, Li Z, Chen F, Zhang L. Impaired vigilance in patients with narcolepsy type 1: a psychomotor vigilance task study. Nat Sci Sleep. 2024;16:2021-2028. doi:10.2147/NSS.S491893 23. Dauvilliers Y, Barateau L, Lopez R, et al. Narcolepsy Severity Scale: a reliable tool assessing symptom severity and consequences. Sleep. 2020;43(6):zsaa009. doi:10.1093/sleep/zsaa009 24. Brown RE, Basheer R, McKenna JT, Strecker RE, McCarley RW. Control of sleep and wakefulness. Physiol Rev. 2012;92(3):1087-1187. doi:10.1152/physrev.00032.2011
Hello, my name is Nancy Foldvary- Schaefer and I’m a neurologist and neurophysiologist at Cleveland Clinic in Cleveland, Ohio. I’ve been in practice since 1995 and I’ve been very active in the field of sleep medicine. My interest is in the area of central nervous system hypersomnia disorders in particular, and novel therapies to treat patients with these disorders.
Today, on behalf of Takeda, I’ll be discussing the role of orexin in narcolepsy type 1, or NT1, as well as differentiating between NT1 and narcolepsy type 2.
In terms of symptoms, narcolepsy type 1 is a central disorder of hypersomnolence that requires, at a high level, excessive daytime sleepiness and cataplexy for a diagnosis.
While narcolepsy type 2 also has excessive daytime sleepiness as part of its diagnostic criteria, there is an absence of cataplexy. In addition, there is no known biomarker for narcolepsy type 2.
Orexin is a neuropeptide that is produced from a specific group of neurons in the lateral hypothalamic area and posterior hypothalamus. Orexin is critically important in terms of the brain’s maintenance of sleep and wake, as well as muscle tone. We understand that many neurotransmitters are either turned on or turned off with sleep and wakefulness respectively, orexin is a key regulator of many of those neurotransmitters. Orexin is involved in a variety of biological functions beyond sleep and wakefulness, like appetite.
Sleep and wakefulness are intimately connected. When we wake, the neurotransmitters and systems within the brain that support wakefulness turn on, and technically those that manage sleep turn off or are suppressed.
In the evening, the opposite happens. Wake-promoting systems get dampened and sleep-promoting systems get activated. Orexin helps to stabilize that switch between sleep and wakefulness, and it does so by regulating communication and activity between those 2 systems. So during the day, orexin activates wake-promoting neurotransmitters that help us stay alert and awake, and in the evening, orexin activity naturally decreases and it helps coordinate that smooth transition to sleep. Sleep-promoting neurotransmitters become more active at night and cause the wake system to dampen or quiet down.
Orexin-producing neurons send widespread excitatory projections throughout the central nervous system to other known neurotransmitters that have very active roles in maintaining sleep and wakefulness.
These include:
- dopamine
- norepinephrine
- histamine
- serotonin
- and acetylcholine
Orexin has significant connections with so many other neurotransmitters in the brain, and signals to all of these downstream neurotransmitters help to stabilize the sleep-wake cycle but also can influence many other brain functions, including:
- alertness
- mood
- cognitive function
- and appetite
First and foremost, a loss of orexin causes the sleep-wake cycle to be dysregulated, and the boundaries between sleep states and wake states are destabilized. Instead of feeling awake or asleep, sleep and wakefulness become intermixed, with abrupt disruptions in wake from sleep, and vice versa, leading to many of the symptoms that we see in patients with narcolepsy type 1.
Without sufficient orexin in the brain, downstream neurotransmitters don’t receive consistent orexin signaling, and so this can lead to a disruption and dysregulation of a number of functions that are regulated within the central nervous system, including:
- alertness
- cognitive functioning, specifically memory and attention
- mood and emotion regulation
- as well as energy level and the maintenance of energy throughout the day
Narcolepsy type 1 is caused by a loss of orexin neurons. It’s a serious neurological condition that can cause ongoing challenges and significant impairments in the quality of life of those who are affected.
Narcolepsy type 1 requires both excessive daytime sleepiness and cataplexy for diagnosis.
Cataplexy differentiates narcolepsy type 1 from narcolepsy type 2. Cataplexy is a sudden, temporary loss of muscle tone that’s triggered by strong emotions, and this varies from individual to individual. It may be subtle or it may be more extreme. It can be partial with slurred speech or a droopy face, or it may be complete where the person may fall to the ground.
Another key symptom of NT1 is disrupted nighttime sleep: fragmented, poor-quality sleep with frequent, brief awakenings.
Next is sleep paralysis. People with narcolepsy may experience an inability to move when falling asleep or as they wake up. It’s usually a frightening experience because the person feels awake, but the muscles don’t move.
Finally, hypnopompic and hypnagogic hallucinations are thought of as dreamlike visions. Hypnopompic hallucinations occur upon awakening, whereas hypnagogic hallucinations occur at sleep onset. These are actually elements of REM sleep.
While the scope and severity of symptoms of NT1 can differ between individuals, most patients with NT1 struggle with a variety of challenges that really affect their ability to function optimally during the day. In my practice, I’ve seen patients struggle with:
- engaging in work, at school
- difficulty participating in social activities and then challenges in relationships
- depression, anxiety, and other mood complaints
- and cognitive complaints such as memory and attention
I have patients who have declined important events like weddings for fear of having a cataplexy event in public; I have patients who can no longer drive; who have lost their jobs because of performance issues. It can be really hard for my patients to live with and articulate these challenges.
So many of my patients with narcolepsy type 1 are unhappy, frustrated, or even depressed about their condition, their difficulties, and where they are in life. When I explain that orexin deficiency is the underlying cause, that there’s an underlying neurobiology of this disorder, that really helps them. It enables them to understand more about their symptoms and helps alleviate some of the guilt and shame they may feel.
I really beat myself up over dropping my phones and breaking them. So I call it the cataplexy tax. Every cell phone I’ve ever owned I have dropped. Narcolepsy type 1 is a rare neurological disorder that affects your wake and sleep cycles. My narcolepsy type 1 comes with something called brain fog. The way I would describe it would be like a hazy feeling. Not feeling totally awake. Not feeling 100% aware. Kind of living in a daze.
My name is Casey. I have narcolepsy type 1. If I had to guess when my symptoms of narcolepsy type 1 started, I would say I was probably 13 or 14. I was always tired or sleepy during the day. But I was always told it was just contributed to me being a teenager.
I was diagnosed when I was 17 years old, but I was never told that I was diagnosed. I finally found out about it when I was 32. I was putting together a medical record book for my doctors. I stumbled across the word narcolepsy. That was a pretty big surprise. At least now I had a word to describe my feelings.
So orexin is in charge of your sleep-wake cycles. It’s a neuropeptide. That’s what people with narcolepsy type 1 with cataplexy are deficient in. Even though I do take medications, I still experience excessive daytime sleepiness where most days I have to take a nap at some point. I still experience just that sleepiness feeling every day. It feels like somebody could tell me something, and unless I have it written down, I’m not going to remember what they said. Having a visual cue of being able to see what I need to do so I can stay on track.
I also take cold plunges and ice baths, cold water, washing my face during the day to kind of help wake me up. If I feel a migraine coming on, that’s usually my trigger and it tells me that I need to go take a nap.
I was accused of being an alcoholic. That’s why they thought I could not wake up in the mornings. I felt a lot of shame from all the jobs that I lost. My family shamed me about it. Everybody kept telling me, why can’t you just wake up in the mornings? But nobody actually knew how hard I was trying.
After I found my diagnosis of narcolepsy type 1 with cataplexy, I went online and I started attending these support group meetings.
“It’s good to see everybody again this week.”
I was listening to these stories and it felt like they were talking about my life. Really gave me a sense of belonging, and it finally felt like I found my community in a place that I actually belonged in.
“Being on my feet and being able to walk around and be outside and get some fresh air and the blood flowing always usually helps.”
Facilitating group meetings makes me very happy when people find our meetings, because it feels like we’re adding another family member. Because with narcolepsy type 1 with cataplexy, you absolutely need a support system. And having people that understand and have the same lived and shared experiences is an invaluable asset. Narcolepsy type 1 has taken everything from me and now I’m rebuilding.
I’ve been homeless. I’ve lived on the street. I’m currently on a friend’s couch right now. You know, my goals are to find a job or get back into school and gain my independence back. Giving up is not an option. Even though there’s been a lot of days where you think about it. Narcolepsy is incredibly difficult to live with. I was in a really deep, dark place for a long time, and taking the first step by going to the support group meetings was a huge step for me. It’s helped me find a great sense of support. I can’t imagine my life without it anymore.
Having narcolepsy type 1 for me feels a lot like being a deflated basketball. When the ball is deflated, can’t really use it. Just like when you’re feeling tired and you need a nap. So I literally live my life by a clock. I’m constantly just calculating how much time do I have to allocate before I become tired? I cannot stress enough that giving myself enough cushion time for a nap is imperative for me, just to ensure that I can enjoy the things that I want to enjoy without a fear of experiencing an episode in public.
My name is Justice. I have narcolepsy type 1. I definitely grew up as an athletic family, but I started noticing at specific times in the day I would pass out like a light bulb and definitely because I was a high-functioning human, a high achiever, excelled athletically.
People just chalked it up as “Justice is tired, enjoys a good nap” having narcolepsy type 1. For me, I just kind of just lose all control, honestly. So one of my symptoms that I deal with, regardless of the medication, definitely it’s going to be kind of like this balance between the dream state and reality. I call it sleepy talk, where my brain literally thinks that I am still awake, but I am technically asleep.
So there are certain things I try to incorporate in my life to make my life even easier in dealing with having narcolepsy type 1. I call them little tricks. One of the things are sunglasses. If I do feel myself getting tired, I put my sunglasses on and nobody even knows that I’m asleep in public. People just don’t get it and they don’t understand.
And then you feel like a spectacle.
I try to avoid my body shutting down and passing out by taking a nap gap. It’s 11 to 1. I’m going to be shut down.
If you do have narcolepsy type 1 and you are a collegiate athlete, you can do it. Just because you have narcolepsy type 1 doesn’t mean you can’t play sports at a high level and things of that nature. My teammates and my coaches have been a great support system. I have been incredibly lucky to be surrounded by people who can understand, who can advocate.
I don’t have a fear of missing out, so I still will participate and go out. It’s important to surround yourself with people who can advocate and protect you in those situations if you do experience an episode. I preach to people constantly how important communication is, how important it is to find a great support system when you can, but also just being open and honest about what you need in those moments, and not being fearful that somebody is going to misunderstand you.
TARA: My journey was a long journey. I always felt like something was off. I was misdiagnosed with a lot of things growing up. My parents just told me I had nightmares. But it ended up it was actually sleep paralysis and hallucinations. And, I then also had trouble sleeping. Lost a lot of friends, too, and missed out on a lot of things because of my sleepiness.
I was seeing a doctor and he was kind of concerned and then sent me to a sleep specialist, and that’s when I finally got diagnosed.
I’m Tara and I have narcolepsy type 1. I am a pediatric sleep coach, just started my own business. It is hard to do things with narcolepsy type 1, so I make sure to break tasks up and not do the same thing for too long. So like I’ll work for like an hour, but then I’ll go do laundry or clean, do another task to kind of help, like switch things up and like wake up.
I am taking medication right now. I take nighttime and daytime medication. They do help, but I still do have symptoms. Like, I’m still tired every day. And that doesn’t go away. I’ve always had cataplexy, but I was always told I was just clumsy because I drop things. It’s usually when I’m stressed, my hands give out. So I like to crochet and do pottery and painting because it helps relieve stress, which is a huge trigger for my symptoms.
And knowing about orexin, I mean like knowing there’s an underlying cause for NT1, I feel like, now, it isn’t my fault. And it was not just in my head.
JOEY: “If you could only eat one food and that’s all. What would it be and why?”
TARA: Joey and I, when we first met, he really impressed me. He said something along the lines like that must be difficult for you. He didn’t just be like, oh, you can fall asleep all the time, right?
JOEY: On a day to day basis, I help Tara in pretty much any way that I can think of. Mostly it’s a smaller task here and there that makes a world of difference to her.
TARA: To have a successful date night, we have to eat earlier rather than later just because I get tired.
TARA: “I’m gonna steal some of yours.”
JOEY: “I’m gonna steal some of yours.”
TARA: I need someone who is very empathetic and so, like, having Joey. He’s been great. There are people who care and are empathetic. It’s really nice because I never really thought that I would get that. Narcolepsy type 1—it definitely took things from me, but it also gave me a lot of things. Starting my own business has really helped me in a lot of ways.
Working in the medical field, I just really got tired of having to advocate for myself and being told I had to do it a certain way, when that way didn’t work for me. It was sucking the life out of me and now being my own boss, because I can take breaks when I need to, I can really manage my narcolepsy symptoms.
JOEY: Whether it’s making copies of her pamphlets, like I drive her to make those copies, any way that I can save her a little bit of energy, make her a little bit more comfortable. It’s little things like that. That’s important to communicate.
TARA: My life is going to be different than what I expected it to be, but I want to educate as much as possible, share my story, like talk about it as much as I can because most people don’t really know what it is. It’s not talked about enough and I just want others to know they’re not alone.