Excessive Daytime Sleepiness

Sleep is a fundamental part of maintaining a healthy lifestyle. Yet, one of the most prevailing concerns amongst students at Emory is the amount of sleep we get on a daily basis. To combat the effects of sleepiness, many students opt for caffeine as a quick fix. However, caffeine is not a substitute for the performance-enhancing effects of a good night’s rest – it merely prolongs wakefulness until sleep is restored (Roehrs & Roth, 2008). 

Sleep deficiency can cause issues such as daytime drowsiness, but chronic daytime sleepiness could be indicative of something more serious such as narcolepsy or other hypersomniac conditions. Narcolepsy is a lesser-known sleep disorder that results in constant sleep deprivation and is the second leading cause of excessive daytime sleepiness (“About Narcolepsy”, 2019). It can manifest before puberty, but the most frequent age of onset is in the range of 15-40 years old. Under normal conditions, the body is able to regulate itself through a circadian rhythm, while the brain, at night, experiences the REM (rapid eye movement) stage of sleep — both of which are crucial to biological function. However, in patients with narcolepsy, the REM stage is foregone and replaced with other substitutes that manifest as symptoms of the disorder (“FAQs”, 2019). But what exactly causes these symptoms and how are they expressed in daily life?

This is the distribution of how many hours subjects in one experiment slept over a 24-hour period, and how much of that time was during the night.

Narcolepsy is accompanied by symptoms of sleep paralysis, dream-like hallucinations, and a condition unique to narcolepsy known as cataplexy. Cataplexy is a sudden episode of muscle weakness stirred by emotions. For example, a person may go limp after expressing strong laughter or anger. One in two thousand Americans suffer from narcolepsy (“About Narcolepsy”), but often go undiagnosed for years. In cases of narcolepsy with cataplexy, the brain lacks two chemicals, orexin A and orexin B (also known as hypocretin), which are located in the hypothalamus and responsible for regulating sleep (Overeem et al., 2008). Narcolepsy without cataplexy is often much harder to diagnose. 

Scans of potential areas of the brain affected solely by idiopathic hypersomnia.

Preliminary studies regarding narcolepsy and idiopathic hypersomnia in test populations have been conducted and scientists have looked for specific markers. The DQB1*0602/DQA1*0102 heterodimer, which has been identified as significant indicator for narcolepsy, was used in one study to compare carrier frequency across populations throughout several countries. On average, countries with higher frequencies of narcolepsy were correlated with a higher proportion of people who were carriers of DQB1*0602. As a disclaimer, excessive sleep can be difficult to attribute to cases of narcolepsy. Hypersomnia accompanied by depression, for example, has confounding factors that may have led to the outliers in the Japanese population, which had low numbers of carriers, but high rates of “narcolepsy” (Mignon, 2008).

Luckily, there are several temporary and long-term prescription treatments for narcolepsy. Caffeine is known to be a temporary treatment for narcolepsy and sleepiness. It works by blocking adenosine receptors, which regulate the body’s homeostasis and sleep patterns (Roehrs & Roth, 2008). Of course, small naps can also be taken throughout the day to restore energy (Mignon, 2008). These are only temporary fixes, however. Stanford University’s Narcolepsy Center, a world leader in narcolepsy research, has several compounds listed on its site that can be used as medication. Among those are amphetamines and antidepressants. The primary function of the amphetamines are to treat sleepiness, and antidepressants are used to treat the symptoms of narcolepsy. However, all the medications produce negative side-effects, which can be minimized by taking small doses of the pharmaceutical drugs and napping.

Luckily, research is conducted and significant new medications are being developed. Among these treatments is pitolisant, a first-in-its-class H3-receptor agonist for both types of narcolepsy, recently approved by the FDA in August of 2019. Pitolisant works by improving wakefulness and decreasing the chance of cataplexy attacks. It primarily “increases histaminergic signaling in the brain”, and a new study has shown that it has minimal side effects in patients (Setnik et al., 2019). New advancements like this serve as a beacon of hope for both healthcare professionals and people experiencing narcolepsy.

Edited by Lauren Flamenbaum

References

Setnik et al. (2019). Evaluation of the abuse potential of pitolisant, a selective H3-receptor antagonist/inverse agonist, for the treatment of adult patients with narcolepsy with or without cataplexy. Sleep, 21–22. doi: https://doi.org/10.1093/sleep/zsz252

Center for Narcolepsy. “About Narcolepsy.” Center for Narcolepsy, med.stanford.edu/narcolepsy/symptoms.html.

Center for Narcolepsy. “FAQs.” Center for Narcolepsy, med.stanford.edu/narcolepsy/faq1.html.

Hackney, J. E., Weaver, T. E., & Pack, A. I. (2008). Health literacy and sleep disorders: A review. Sleep Medicine Reviews, 12(2), 141–151. doi: https://doi.org/10.1016/j.smrv.2007.07.002

Mignon, E. (2008). Excessive daytime sleepiness: Population and etiology versus nosology. Sleep Medicine Reviews, 12(2), 87–94. doi: https://doi.org/10.1016/j.smrv.2007.12.006

Ohayon, M. M. (2008). From wakefulness to excessive sleepiness: What we know and still need to know. Sleep Medicine Reviews, 12(2), 129–141. doi: https://doi.org/10.1016/j.smrv.2008.01.001

Overeem, S., Black J. L. III., & Lammers, G. J. (2008). Narcolepsy: Immunological aspects. Sleep Medicine Reviews, 12(2), 95–107. doi: https://doi.org/10.1016/j.smrv.2007.07.010

Plante, D. T. (2015). Hypersomnia in Mood Disorders: a Rapidly Changing Landscape. Current Sleep Medicine Reports, 1(2), 122–130. doi: https://doi.org/10.1007/s40675-015-0017-9

Roehrs, T., & Roth, T. (2008). Caffeine: Sleep and daytime sleepiness. Sleep Medicine Reviews, 12(2), 153–162. doi: https://doi.org/10.1016/j.smrv.2007.07.004

Image citations

Boucetta et al. (2017). Scans of potential areas of the brain affected solely by idiopathic hypersomnia. Retrieved October 27, 2019. From https://doi.org/10.1093/sleep/zsx140. 

Ohayon, M. M. (2008). Distribution of subjects sleeping too much by nighttime and 24-h sleep duration. Retrieved October 27, 2019. from https://doi.org/10.1016/j.smrv.2008.01.001.

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