What is Non-24 (Non-24-hour sleep-wake disorder)?

From the Guidelines

Non-24-Hour Sleep-Wake Disorder (Non-24) should be treated with strategically timed melatonin, as suggested by the American Academy of Sleep Medicine clinical practice guideline 1. This condition is a circadian rhythm disorder where a person's internal body clock runs longer than 24 hours, causing their sleep times to progressively delay. The main characteristics of Non-24 include:

• Periodic nighttime insomnia and daytime somnolence as the circadian rhythms of sleep propensity and alertness drift in and out of synchrony with the 24-hour day
• Primarily occurs in blind individuals, with at least 50% of the totally blind thought to suffer from the disorder
• Etiology in the blind is a loss of photic input to the pacemaker, while the pathophysiology among sighted individuals is unknown The treatment of Non-24 involves:
• Strategically timed melatonin, which can help regulate sleep patterns
• Maintaining strict sleep hygiene and consistent sleep-wake schedules is essential for management
• Tasimelteon (Hetlioz), an FDA-approved medication that acts as a melatonin receptor agonist, taken at the same time each night at a dose of 20mg, can also be used
• Melatonin supplements (0.5-5mg) taken 1-2 hours before desired bedtime can help regulate sleep patterns It is essential to note that the American Academy of Sleep Medicine clinical practice guideline suggests that clinicians use strategically timed melatonin for the treatment of N24SWD in blind adults 1. Additionally, the guideline recommends that entrainment status be used as an outcome measure, as it physiologically defines this disorder 1.

From the Research

Definition and Prevalence of Non-24

• Non-24-h sleep-wake disorder (non-24) is a circadian rhythm disorder that occurs in 55-70% of totally blind individuals, where the 24-h biological clock is no longer synchronized to the 24-h day 2.
• The disorder is characterized by a recurrent pattern of daytime hypersomnolence and night-time insomnia, resulting from the gradual shift of the overt rhythms controlled by the biological clock 2.
• Non-24 can also occur in sighted individuals, although it is less common, and can be challenging to diagnose and treat 3, 4.

Diagnosis and Treatment

• Diagnosis of non-24 can be aided by tools such as sleep diaries, wrist actigraphy, and salivary melatonin levels 3, 4.
• Treatment of non-24 typically involves the use of melatonin or melatonin receptor agonists, such as tasimelteon, to entrain the circadian clock and improve night-time sleep and daytime alertness 2, 5, 6.
• The timing of melatonin administration is crucial, and should be considered carefully to ensure effective entrainment of the circadian clock 2.
• Tasimelteon has been shown to be effective in treating non-24 in both blind and sighted individuals, and is currently the only approved medication for non-24 by the US Food and Drug Administration and the European Medicines Agency 5, 6.

Challenges and Future Directions

• Non-24 can be a chronic and debilitating disorder, and treatment can be challenging due to the need for ongoing entrainment of the circadian clock 3, 4.
• Further research is needed to fully understand the pathophysiology of non-24 and to develop effective treatments for this disorder 4, 5.
• The use of melatonin and melatonin receptor agonists, such as tasimelteon, shows promise as a treatment for non-24, but more research is needed to determine the optimal dosage and timing of administration 2, 5, 6.