All people run on their own biological clock, known as the circadian rhythm. For sighted individuals, this internal clock resets to an approximately 24-hour day with exposure to light. The circadian rhythm is essential to guiding daily activities, including sleep patterns, body temperature, blood pressure, and appetite. In non–24-hour sleep-wake rhythm disorder (N24SWD or Non-24), the circadian rhythm is disrupted, which leads to irregularities in the normal 24-hour day-night cycle. This disruption is most commonly seen in people who are completely blind and unable to perceive light. When there is no light signal or intrinsic way to reset their internal clock to a 24-hour day, the result is a gradual drift in the timing of the individual’s daily activities over time. This is because the inherent internal clock (circadian rhythm) is not exactly 24-hours, but ranges from 23.8 to 25 hours. This occurs in about 55-70% of totally blind people. N24SWD can also occur in sighted individuals, though the cause is unclear.
Rare Disorders
HETLIOZ (tasimelteon)
HETLIOZ (tasimelteon) is the first and only FDA-approved treatment for Non-24-Hour Sleep-Wake Disorder (Non-24).
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Vanda Pharmaceuticals
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Symptoms
N24SWD initially presents as periodic nighttime insomnia and excessive daytime sleepiness. Due to the cyclical nature of the disorder, these episodes can alternate with periods of a relatively normal sleep schedule. When the patient’s body becomes out of sync with that cycle, the symptoms begin to return. Other symptoms can include:
- Fatigue
- Sleep deprivation
- Depression
- Anxiety
- Memory impairment
- Malaise
- Disrupted sleep
- Isolation
- Occupational disability
Diagnosis
A sleep log or sleep activity monitor, known as an actigraph, is used in the diagnosis of N24SWD since the hallmark of N24SWD is an inability to sleep and wake according to the standard 24-hour circadian rhythm. A person with N24SWD would see a slow drift to their sleep and wake times on the actigraph. Monitoring is usually conducted for a period of fourteen days to observe the variations in the individual’s biological clock. Sometimes, markers of sleep onset, such as the timing of melatonin onset in dim lighting or the rhythm of certain melatonin urinary metabolites, are also tested.
Treatment
Tasimelteon is currently the first and only FDA approved prescription medication for the treatment of Non-24-Hour Sleep-Wake Disorder. This medication is a melatonin receptor agonist that has been shown to improve nighttime sleep as well as decrease daytime sleepiness. Because every patient with N24SWD has their own unique sleep cycle, it might take longer for some patients to notice improvements while taking tasimelteon. Supplementation with melatonin is another possible treatment avenue. Other treatment options for sighted people include the use of specific exposure to light, known as phototherapy.
References
- 1.Abbott SM. Non-24-hour Sleep-Wake Rhythm Disorder. Neurol Clin. 2019;37(3):545‐552. doi:10.1016/j.ncl.2019.03.002
- 2. Non-24-Hour Sleep-Wake Disorder. National Organization for Rare Disorders. https://rarediseases.org/rare-diseases/non-24-hour-sleep-wake-disorder. Accessed Accessed February 20, 2023.
- 3. Non-24-Hour Sleep-Wake Rhythm – Overview & Risk Factors. American Academy of Sleep Medicine. http://sleepeducation.org/sleep-disorders-by-category/circadian-rhythm-disorders/non-24-hour-sleep-wake-rhythm. Accessed Accessed February 20, 2023.
- 4. Hetlioz (tasimelteon) [Package insert]. Washington, D.C.: Vanda Pharmaceuticals Inc. 2023.