Beyond “Always Tired”: Recognizing Narcolepsy Type 1 and the Clinical Relevance of Orexin

Paid content from Takeda Pharmaceuticals intended for U.S. healthcare professionals.

You may recognize this patient: a young adult who spends more than 8 hours per night in bed, yet wakes unrefreshed and reports persistent excessive daytime sleepiness and an overwhelming urge to nap. They struggle to stay alert, may doze unintentionally, and may also experience cognitive “fog.” These symptoms are functionally impairing.¹

Casey*, now in his 30s, recalls that period clearly. As a high school senior, Casey ate dinner after sports practice, went straight to bed, and spent up to 12 hours each night trying to sleep. Despite these efforts, his sleep was fragmented and unrefreshing, and he was drowsy throughout the day, causing him to routinely miss early classes.

“For a long time, I struggled to accept that something might actually be wrong,” he says. “I believed that being exhausted all the time was normal.”

His symptoms, including cataplexy, were initially attributed to adolescence or mental health conditions. Clinicians considered ADHD, mood instability, depression, and anxiety. Casey was prescribed multiple medications without a unifying diagnosis. He eventually underwent overnight polysomnography (PSG) followed by a Multiple Sleep Latency Test (MSLT). The results provided the objective evidence needed to confirm a diagnosis of narcolepsy type 1 (NT1), a chronic neurological disorder.¹ However, it wasn't until years later when Casey was reviewing his medical records from the sleep tests that he saw mention of NT1. This led to Casey seeking a doctor for more information.

“NT1 is the classic phenotype of narcolepsy, caused by a loss of orexin neurons,” says Nancy Foldvary-Schaefer**, DO, MS, a professor of neurology and sleep medicine specialist at Cleveland Clinic. “It’s a serious neurological condition that can cause ongoing challenges and significant impairments in daily life.”

Looking back, Casey recognizes the signs were present. Signs and symptoms that not only impacted his physical and cognitive health but also had a psychosocial impact. “I carried a lot of embarrassment, especially after being told for years that I was just lazy or irresponsible,” he says.

Casey’s experience underscores the diagnostic complexity of NT1 and the importance of recognizing it as a serious, neurological disease. Clinicians can learn more about the multi-dimensional burden of NT1 from Casey and other patient perspectives by visiting Takeda’s What It Takes*** website.

The Hallmark Symptoms and Role of Orexin in NT1

NT1 is classified as a central disorder of hypersomnolence and is caused by a loss of orexin (also known as hypocretin).² Orexin is a neuropeptide produced in the lateral hypothalamus that stabilizes wakefulness and regulates transitions between wake and sleep, including REM and non-REM states.³

This pathophysiology explains the clinical features of NT1, including excessive daytime sleepiness, cataplexy, sleep paralysis, hypnagogic or hypnopompic hallucinations, and disrupted nighttime sleep.¹

Diagnostic criteria following the ICSD-3 criteria for NT1 includes excessive daytime sleepiness for at least three months plus either a) cataplexy with supportive sleep study findings (mean sleep latency ≤8 minutes and ≥2 sleep-onset REM periods), or b) low cerebrospinal fluid hypocretin-1 levels.² Cataplexy, which is a sudden, transient loss of muscle tone triggered by strong emotions, and/or low CSF orexin (hypocretin-1) levels distinguish NT1 from narcolepsy type 2.^1,4

“People with narcolepsy can also experience a host of symptoms beyond daytime sleepiness, including cognitive impairments, mood disturbances, low energy, and fatigue,” Dr. Foldvary-Schaefer notes. “Understanding the underlying neurobiology may support diagnostic clarity and inform patient counseling.”

Delayed Diagnosis Culprits

Correct diagnosis frequently takes eight to ten years, with multiple factors, including a patient’s age, potentially contributing to delay.⁵ Overlap of symptoms with other disorders contributes as well.^6,7 Excessive daytime sleepiness overlaps with conditions such as insufficient sleep, mood disorders, circadian rhythm disturbances, and obstructive sleep apnea, which may contribute to misdiagnosis.

“Patients with narcolepsy and other disorders of hypersomnolence are often misdiagnosed with more common sleep, psychiatric and even medical conditions,” Dr. Foldvary-Schaefer says. “Recognizing the patient with narcolepsy takes time, and busy providers who see common conditions like sleep apnea and insomnia may fail to appreciate the spectrum of sleep-wake complaints. Symptoms of NT1 vary in scope and severity, so it is important to take a comprehensive sleep history that includes both daytime and nighttime symptoms.”

Tools such as the Epworth Sleepiness Scale may help quantify subjective sleepiness but do not replace a comprehensive clinical assessment.⁸ Clinicians should ask about emotionally triggered muscle weakness, abrupt sleep attacks, sleep-related hallucinations, sleep paralysis, fragmented nighttime sleep, and the degree of functional impairment caused by daytime sleepiness. The severity and involuntary nature of sleepiness and symptoms of REM sleep dysfunction in NT1 are important for differentiating it from insufficient sleep or primary mood disorders.

For Casey, his symptoms affected his life in many ways. He was challenged academically and struggled to remain socially engaged. His doctors cycled through psychiatric explanations that did not fully account for his symptoms.

“People would ask me, ‘What’s wrong with you?’ and I didn’t have an answer,” he says. When he later understood his diagnosis, he describes feeling validated. “There was a sense of relief. Like, this is real, and it has a name.”

“Fully understanding their functional impairment, beyond just a sleepiness score, is essential to delivering optimal care,” adds Dr. Foldvary-Schaefer.

Management of NT1 should be individualized and may include pharmacologic and behavioral strategies to improve wakefulness and reduce REM-related symptoms, in accordance with established clinical guidelines.^1,9

Communicating the Biology

Explaining the role of orexin deficiency in NT1 may help patients contextualize their symptoms as neurological or neurobiological rather than behavioral. “It’s critical to understand that NT1 has a specific neurobiology that’s now recognized. It is an orexin deficiency,” Dr. Foldvary-Schaefer says. “Patients often experience relief knowing there is a definitive explanation for their symptoms.”

For clinicians, an important opportunity is earlier recognition of NT1 in patients with persistent, functionally impairing sleepiness. Asking specifically about cataplexy and REM-related symptoms, assessing functional impact, and clearly communicating the underlying biology may support appropriate evaluation and management.

As Casey reflects, what mattered most to him was being heard. “Feeling believed when patients describe what’s happening in their bodies goes a long way,” he says.

To learn more about NT1 and access educational resources for clinicians, visit WhatNT1Takes.com/hcp.

*Casey is a paid contributor for Takeda Pharmaceuticals. Last name is withheld to protect personal privacy. Individual patient experiences vary.

**In consideration of the time spent participating in the development of this article, Dr. Nancy Foldvary-Schaefer was paid honoraria by Takeda Pharmaceuticals.

***What It Takes is developed and brought to you by Takeda Pharmaceuticals and is intended for U.S. healthcare professionals.

©2026 Takeda Pharmaceuticals U.S.A., Inc. All rights reserved. Takeda and TAKEDA Logo are registered trademarks of Takeda Pharmaceutical Company Limited. US-NON-12688v1.0 05/26

References

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