Healthcare students in educational setting

Narcolepsy Type 1

Not actual patients.

Narcolepsy type 1 (NT1) is a chronic, rare neurological disorder of central hypersomnolence caused by the loss of orexin, a key regulator of sleep and wakefulness.1‑4

Narcolepsy, a chronic neurological disorder involving difficulty with maintaining continuous wake and sleep, is one of the most common causes of chronic sleepiness, affecting about 1 in 2000 people.1,5,6 There are two types of narcolepsy – Narcolepsy Type 1 (NT1) and Narcolepsy Type 2 (NT2), where NT1 is classified as narcolepsy with cataplexy and NT2 as narcolepsy without cataplexy.1 NT1 is caused by extensive loss of hypothalamic neurons that produce the neuropeptide orexin.1,6 While NT2 includes most of the same symptoms as NT1, with the exception of cataplexy, its pathophysiology remains unclear.1 NT1 symptoms usually manifest between the age of 10-20 years and its diagnosis takes an average of 15 years from the onset of symptoms.7

Medical illustration of brain showing central nervous system affected in narcolepsy type 1

Epidemiology

Estimating true incidence and prevalence of NT1 in the US is challenging. Epidemiological studies are limited and offer varying population estimates. Prevalence of NT1 is estimated at 14.0–35.8 per 100,000 individuals, while NT2 ranges from 25.1–65.4 per 100,000.

Incidence estimates for narcolepsy overall are 1.37–7.67 per 100,000 individuals.8‑10

Diagnosis

NT1 is diagnosed using clinical history together with objective sleep testing—primarily overnight polysomnography (PSG) followed by the Multiple Sleep Latency Test (MSLT)—and/or measurement of cerebrospinal fluid (CSF) orexin‑1 levels.11‑15 Clinicians follow two major diagnostic frameworks: the International Classification of Sleep Disorders, Third Edition (ICSD‑3 / ICSD‑3‑TR) and the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM‑5).11,14,15

ICSD-3/ICSD-3-TR diagnostic criteria for NT1:11

  • Daily periods of irrepressible need to sleep or daytime lapses into sleep for ≥3 months

Plus at least ONE of the following (ICSD‑3 Criterion B):

  • Cataplexy AND mean sleep latency ≤8 minutes AND ≥2 sleep-onset REM periods (SOREMP) on MSLT; OR one SOREMP on prior nocturnal PSG may substitute for one MSLT SOREMP
  • Low CSF orexin-1 (hypocretin-1) levels ≤110 pg/mL OR <1/3 of mean normal values using the same assay

Per the ICSD‑3, NT2 is distinguished from NT1 by the absence of cataplexy, and that CSF hypocretin-1 concentration has not been measured or is either >110 pg/mL or >1/3 of mean values obtained in normal subjects.11

DSM‑5 diagnostic criteria for narcolepsy:14,15

  • Recurrent periods of irrepressible need to sleep, lapsing into sleep, or napping within the same day ≥3 times/week for ≥3 months

Plus at least ONE of the following (DSM-5 Criterion B):

  • Cataplexy at least a few times per month
  • Hypocretin deficiency, defined as ≤1/3 of values obtained in healthy subjects or ≤110 pg/mL
  • Nocturnal PSG showing REM sleep latency ≤ 15 minutes OR mean latency on MSLT ≤ 8 minutes + ≥ 2 SOREMPs

Key Note
DSM‑5 does not distinguish NT1 from NT2.

Diagnostic Challenges

    • Diagnosis is often delayed. There is wide variability in the time between symptom onset and diagnosis, with a mean diagnostic delay of up to 15 years from symptom onset to correct diagnosis. Many patients are misdiagnosed with other neuropsychiatric or sleep disorders, and up to 50% of patients may be misdiagnosed7,16
    • Barriers to accurate diagnosis include:
      • Symptom overlap with other disorders (e.g., depression, sleep apnea, Attention-Deficit/Hyperactivity Disorder (ADHD))
        • Excessive Daytime Sleepiness (EDS)—often the first symptom to manifest—is associated with a variety of medical conditions17
      • Delayed or missed recognition of cataplexy often occurs because its presentation can be subtle or atypical. This challenge is compounded by differences in how clinicians and patients describe cataplexy symptoms, as well as the absence of objective tools to detect and measure cataplexy18,19
      • There is low awareness of NT1 among healthcare providers, especially physicians who are not board-certified in sleep medicine. These physicians are less likely to use ICSD criteria-based tests when evaluating patients16
      • Masking of NT1 symptoms by medications for comorbid conditions20
      • Although narcolepsy often begins in childhood or adolescence, its symptoms present differently in children than in adults, making early recognition challenging21

    Pathophysiology

    Narcolepsy type 1 (NT1) is caused by the loss of orexin. The core etiology of NT1 is a significant loss of orexin-producing neurons in the lateral hypothalamus, resulting in orexin deficiency—a defining feature of NT1. This loss is believed to be primarily immune-mediated, with several other contributing factors:1,5,6

    • Genetic Susceptibility: The HLA class II allele DQB1*06:02 is found in 86–98% of individuals with NT1 and increases the risk of disease 251-fold. DQB1*06:02 is thought to predispose individuals to NT1 through activation of T cell responses that result in the selective immune attack on and destruction of orexin neurons5,22‑25
    • Environmental and Triggering Factors: In genetically susceptible individuals with the DQB1*06:02 allele, NT1 may be initiated by inflammatory triggers, including bacterial ​and viral antigens from infections or vaccines5,26

    The loss of orexin-producing neurons in NT1 leads to low brain orexin levels and impaired orexin signaling. The orexin neuropeptides, Orexin A and Orexin B, are produced in the lateral hypothalamus and act via two receptors, Orexin Receptor 1 (OX1R) and Orexin Receptor 2 (OX2R). While both OX1R and OX2R are involved in the suppression of REM sleep, regulation of wakefulness/NREM sleep transitions is highly dependent on OX2R.1,27‑29

    Navigating NT1

    Burden of Disease in NT1

    Though the scope and severity of symptoms can vary, patients living with NT1 often experience a heavy burden of symptoms that affect daily life and overall well-being.14,18,20,30

    • NT1 is associated with a pentad of five main symptoms—EDS, cataplexy, sleep paralysis, hypnagogic/hypnopompic hallucinations, and disrupted nighttime sleep (DNS)14
    • Cognitive dysfunction is a prevalent and challenging aspect of NT1, contributing to disease burden. Impairments in attention, executive function, learning, and memory have been commonly reported in people living with NT1. Additionally, patients have reported fatigue and cognitive challenges associated with NT1 as well as impacts to work and activities of daily living27‑29
    • Comorbid conditions are common and complicate the care of people living with NT1. Individuals with NT1 can commonly experience sleep inertia and dysautonomia, along with increased prevalence of obesity, diabetes, headaches or migraines, mood and anxiety disorders, sleep apnea, periodic limb movements, REM behavior disorder, and restless legs syndrome compared to controls. These comorbidities contribute to a reduced health-related quality of life (HRQoL)31,34‑37
    • Mental health impacts of NT1 may add to the burden. People living with NT1 face increased risk of depressive symptoms. Increased suicidal ideation has been found in untreated people with NT1. These impacts were found to be influenced by factors such as low education, high Body Mass Index (BMI), severity of NT1 symptoms, and poor quality of life38
    • Healthcare utilization and costs are substantial. Annual direct medical costs for NT1 patients are approximately twice as high as for matched controls. Timely diagnosis can reduce healthcare utilization costs in the years following diagnosis39,40

    Navigating Narcolepsy Type 1 (NT1)

    There is currently no cure for NT1. Management focuses on symptom control using a combination of pharmacological and non-pharmacological strategies.41

    Comorbidity Management
    Comprehensive approaches for managing comorbidities is an important part of caring for people living with NT1.42

    Patient and Provider Education
    Improving awareness among HCPs about the full spectrum of NT1 symptoms and the importance of early, accurate diagnosis is critical. In a survey of 400 US healthcare providers, not all primary care physicians (n=300) and sleep specialists (n=100) could identify all five key symptoms, underscoring the need for ongoing education.43

    1. Scammell TE. Narcolepsy. N Engl J Med. 2015;373(27):2654-2662.
    2. Wang Q, et al. Front Aging Neurosci. 2021;13:713201.
    3. Sakurai T. Nat Rev Neurosci. 2007;8(3):171-181.
    4. Biscarini F, et al. J Sleep Res. 2025;34(2):e14277.
    5. Bassetti CLA, et al. Nat Rev Neurol. 2019;15(9):519-539.
    6. Nishino S, et al. Lancet. 2000;355:39-40.
    7. Thorpy MJ, et al. Sleep Med. 2014;15(5):502-507.
    8. Silber MH, et al. Sleep. 2002;25(2):197-202.
    9. Scheer D, et al. Sleep. 2019;42(7):zsz091.
    10. Ohayon MM, et al. Sleep Med X. 2023;6:100095.
    11. American Academy of Sleep Medicine. International Classification of Sleep Disorders. Third Edition. 2023 Text Revision (ICSD-3-TR). Available from: https://aasm.org/wp-content/uploads/2023/05/ICSD-3-Text-Revision-Refs.pdf. Accessed January 26, 2026.
    12. Khan Z, Trotti LM. Chest. 2015;148(1):262-273.
    13. Andlauer O, et al. Sleep. 2012;35(9):1247-1255.
    14. Ruoff C, Rye D. Curr Med Res Opin. 2016;32(10):1611-1622.
    15. Sleep-wake disorders. In: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). American Psychiatric Association; 2013:361-422.
    16. Carter LP, et al. Postgrad Med. 2014;126(3):216-224.
    17. Gandhi K, et al. Mayo Clin Proc. 2021;96(5):1288-1301.
    18. Ortiz LE, et al. CNS Drugs. 2025;39(suppl 1):S23-S36.
    19. Barateau L, et al. Sleep Med. 2024;124:510-521.
    20. Krahn LE, et al. Adv Ther. 2022;39(1):221-243.
    21. Plazzi G, et al. Pediatr Neurol. 2018;85:21-32.
    22. Xu W, et al. Int J Mol Sci. 2024;25(22):11914.
    23. Luo G, et al. Proc Natl Acad Sci U S A. 2018;115(52):E12323-E1233.
    24. Capittini C, et al. Sleep Med. 2018;52:150-157.
    25. Tafti M, et al. Sleep. 2014;37:19-25.
    26. Mahoney CE, et al. Nat Rev Neurosci. 2019;20:83-93.
    27. Stahl SM. CNS Spectr. 2016;21(3):215-218.
    28. Yamanaka A, et al. J Neurosci. 2010;30(38):12642-12652
    29. Mieda M, et al. J Neurosci. 2011;31(17):6518-6526.
    30. Bassi C, et al. J Sleep Res. 2024;33(3):e14087.
    31. Maski K, et al. J Clin Sleep Med. 2017;13(3):419-425.
    32. Maski K, et al. SLEEP. 2025. Seattle, WA. June 8-11, 2025. P329.
    33. Harel BT, et al. Sleep Adv. 2024;5(1):zpae043.
    34. Barateau L, et al. Sleep. 2019;42(12):zsz187.
    35. Mullington J, Broughton R. Sleep. 1994;17:69-76.
    36. Quaedackers L, et al. Nat Sci Sleep. 2021;13:1083-1096.
    37. Black J, et al. Sleep Med. 2017;33(suppl):13-18.
    38. Barateau L, et al. Neurology. 2020;95(20):e2755-e2768.
    39. Thorpy MJ, Hiller G. Am Health Drug Benefits. 2017;10(5):233-241.
    40. Villa KF, et al. Am Health Drug Benefits. 2018;11(3):137-145.
    41. Abad VC, Guilleminault C. Nat Sci Sleep. 2017;9:39-57.
    42. National Institute of Neurological Disorders and Stroke. Narcolepsy. U.S. Department of Health and Human Services, National Institutes of Health. Available from: https://www.ninds.nih.gov/health-information/disorders/narcolepsy. Accessed January 26, 2026.
    43. Rosenberg R, Kim AY. Postgrad Med. 2014;126(1):78-86.

    Videos

    Watch videos focused on Narcolepsy Type 1 (NT1).

    NT1 Pathophysiology animation

    Video animation of NT1 Pathophysiology.

     

    Additional Resources

    Find materials to help foster a deeper understanding of Narcolepsy Type 1 (NT1).

    pdf-icon1058378

    Burden of NT1 on Patients

    Burden of NT1 infographic.

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    NT1 Pathophysiology

    Pathophysiology of NT1.

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    pdf-icon1060946

    Impact of NT1

    Illustration showing the broad impacts of NT1, beyond the pentad.

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