Non-24-hour sleep–wake disorder

Overview

Non-24-hour sleep–wake disorder (Non-24), also known as Non-24, is a chronic circadian rhythm sleep disorder in which a person's internal body clock fails to synchronize with the 24-hour day-night cycle. As a result, sleep and wake times gradually shift later each day, leading to a pattern that constantly rotates around the clock. This disorder is most commonly seen in individuals who are completely blind, though it can also occur in sighted individuals.

Non-24 disrupts the timing of sleep, alertness, and biological rhythms, severely affecting daily functioning and quality of life. Individuals with this condition often experience insomnia, excessive daytime sleepiness, and difficulty maintaining regular social, occupational, or educational routines.

Causes

Non-24 is caused by a mismatch between the body’s internal circadian rhythm and the external 24-hour day. The circadian rhythm in humans is slightly longer than 24 hours, averaging about 24.2 hours. In most people, environmental cues like sunlight and social activity help reset the body clock daily. However, in individuals with Non-24, this resetting mechanism fails.

Primary Causes

• Total blindness: The most common cause, as the absence of light perception prevents the eyes from transmitting light cues to the brain’s master clock (the suprachiasmatic nucleus or SCN)

• Circadian system dysfunction: In sighted individuals, disruptions in melatonin production or abnormalities in the SCN may cause the body clock to drift

• Genetic or neurological factors: In rare cases, mutations affecting circadian rhythm regulation or brain injuries may contribute

Symptoms

Symptoms of Non-24-hour sleep–wake disorder arise due to a continually shifting sleep schedule. Over time, individuals cycle through periods of normal sleep, followed by insomnia and daytime sleepiness as their internal rhythm becomes misaligned with societal norms.

Common Symptoms

• Chronic sleep disturbances: Difficulty falling asleep or staying asleep at the desired time

• Excessive daytime sleepiness: Especially when internal rhythm promotes sleep during waking hours

• Fatigue and low energy: Resulting from poor sleep quality and timing mismatch

• Impaired concentration and cognitive function

• Depressive symptoms: Common due to social isolation and disrupted routines

• Irregular sleep–wake patterns: Sleep and wake times that delay progressively over several weeks

Diagnosis

Diagnosing Non-24 requires a detailed assessment of sleep patterns and medical history. It is often underdiagnosed, especially in sighted individuals, due to its overlap with insomnia or delayed sleep–wake phase disorder.

Diagnostic Steps

• Sleep logs or diaries: Recording sleep and wake times over 2 to 4 weeks to identify circadian drift

• Actigraphy: A wrist-worn device that measures movement and helps track sleep-wake cycles over time

• Melatonin profiling: Measuring the timing of melatonin secretion to assess internal circadian rhythm

• Clinical interview: Evaluation of symptoms, blindness status, and exclusion of other sleep disorders

• Polysomnography: May be used to rule out other sleep disorders but is not diagnostic for Non-24

Treatment

Treatment of Non-24 focuses on aligning the internal body clock with the external 24-hour day. This may involve light therapy, melatonin or melatonin receptor agonists, and behavioral strategies. Treatment is often more effective in sighted individuals than in those who are totally blind.

Pharmacological Treatments

• Tasimelteon (Hetlioz): A melatonin receptor agonist approved by the FDA for Non-24 in totally blind individuals. It helps regulate the sleep–wake cycle and promote entrainment.

• Melatonin supplements: May be taken at a specific time in the evening to help advance sleep onset and stabilize rhythms

Non-Pharmacological Therapies

• Light therapy: Bright light exposure in the morning for sighted individuals to reset circadian rhythms

• Strict sleep schedule: Maintaining consistent sleep and wake times as much as possible

• Behavioral therapy: Cognitive behavioral therapy for insomnia (CBT-I) can help improve sleep quality and coping mechanisms

Lifestyle Modifications

• Avoid caffeine and stimulants late in the day

• Use blue light filters in the evening to reduce circadian disruption

• Engage in regular physical activity and maintain social interaction during daylight hours

Prognosis

The prognosis of Non-24-hour sleep–wake disorder varies depending on the individual’s degree of visual impairment and response to treatment. In totally blind individuals, the disorder is typically lifelong, but symptoms can often be managed effectively with medications like tasimelteon.

Sighted individuals may have a better chance of achieving entrainment using light therapy and behavioral strategies, although persistent circadian misalignment can be challenging to overcome. Left untreated, Non-24 can severely impair occupational, educational, and social functioning and may contribute to secondary mental health issues.

With consistent treatment and lifestyle support, many individuals with Non-24 can improve sleep quality, align more closely with a 24-hour day, and regain functional daily routines.