Narcolepsy is a rare neurological disorder that impacts the brain’s ability to control sleep-wake cycles, leading to excessive daytime sleepiness with uncontrollable sleep attacks.

Some patients also experience sudden episodes of muscle weakness (known as cataplexy), sleep paralysis, fragmented sleep, and hallucinations. Affecting about 1 in 2,000 people, narcolepsy typically develops during the teen years and lasts for life. Despite its debilitating effects, the disorder goes undiagnosed or misdiagnosed approximately 50 percent of the time. Currently in the US, treatment is limited to behavioral modifications and medications aimed at mitigating some of the symptoms; no approved therapies address the underlying causes of the disease. And there is no cure.




  • Excessive daytime sleepiness (EDS) occurs even after a good night of sleep. The severity and frequency of sleepiness vary among individuals.

  • Cataplexy is often triggered by strong emotions and causes weakness of the face, limbs, and trunk, sometimes leading an individual to slump to the ground, awake but unable to talk or move for one to two minutes. An estimated 60–70% of individuals with narcolepsy also experience cataplexy. 
  • Vivid hallucinations occur upon falling asleep or waking up.
  • Sleep paralysis is a transient inability to move when an individual is drifting off to sleep or waking up.
  • Fragmented nighttime sleep can worsen daytime sleepiness.



Many doctors are unfamiliar with narcolepsy, so visiting a sleep-medicine specialist is often necessary for an accurate diagnosis. Patients typically participate in an overnight sleep study, followed by a series of planned naps the next day. The diagnosis is initially based on evaluation of drowsiness, measured using the Epworth Sleepiness Scale, and by the presence of cataplexy attacks.

Several tests can confirm a narcolepsy diagnosis: a polysomnography (electroencephalogram recording of a night’s sleep) reveals abnormal transitions from waking in REM sleep; a multiple sleep latency test (MSLT) measures how quickly patients fall asleep for naps (typically 3 to 4 minutes); and spinal fluid analysis will show very low hypocretin levels in patients with cataplexy.

Two types of narcolepsy are currently recognized according to the ICSD3 diagnostic criteria: type 1 is associated with cataplexy and low hypocretin-1 levels, while type 2 is not associated with cataplexy. 



For those diagnosed with narcolepsy, therapeutic options are currently limited to behavioral strategies and a combination of medications that mitigate some symptoms. While these therapies can greatly improve a patient’s quality of life, they have abuse, tolerability, and/or adherence issues

  • Sleep-hygiene strategies, like going to bed at the same time and napping frequently during the day, can reduce excessive daytime sleepiness
  • Psychostimulants (modafinil or amphetamines) stimulate certain parts of the brain, thereby preventing drowsiness
  • Antidepressants (off label) or sodium oxybate (GHB sodium salt) may reduce the frequency of cataplexy attacks



Research shows that narcolepsy with cataplexy is caused by a lack of hypocretins, key brain chemicals that help sustain alertness and also prevent rapid-eye-movement (REM) sleep from occurring at the wrong times. In people who have narcolepsy with cataplexy, most of the hypocretin-producing neurons have died off. Genetics, age, and triggering infections or inflammation play important roles in the development of narcolepsy.

Though much has been learned about narcolepsy with cataplexy, considerably less is known about the cause of narcolepsy without cataplexy. Some researchers suspect it is the result of less severe injury to the hypocretin-producing neurons, resulting in fewer and less severe symptoms. Both types of narcolepsy are associated with low levels of the wake-promoting neurotransmitter histamine.

A body of scientific evidence suggests that the destruction of hypocretin neurons is related to an autoimmune mechanism, encouraged by genetic susceptibility. In effect, 92% of people with narcolepsy (vs. around 20% of the general population) are carriers of a specific mutation of the human leukocyte antigen (HLA) system: HLA DQB1*0602. The HLA system is central to immunity and enables the immune system to differentiate self from non-self cells, that is to say foreign to the individual, that have to be destroyed. HLA typing contributes to the narcolepsy diagnosis by revealing an increased risk of developing the disease.