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Sleeplessness And Circadian Disorder

Sleeplessness And Circadian Disorder

Article Author:
Hajira Basit
Article Author:
Thomas Damhoff
Article Editor:
Martin Huecker
6/26/2020 6:24:10 PM
For CME on this topic:
Sleeplessness And Circadian Disorder CME
PubMed Link:
Sleeplessness And Circadian Disorder


Proper sleep is essential to maintain health and optimize overall functioning during wakefulness. Sleeplessness has been linked with several health problems from including diabetes, obesity, and heart disease. Sleeplessness also leads to decreased work performance, traffic accidents, mood and relationship problems, and countless other issues.  The American Academy of Sleep Medicine. International Classification of Sleep Disorders lists 7 broad categories of sleep disorders: insomnia, sleep-related breathing disorders, central disorders of hypersomnolence, circadian rhythm sleep-wake disorders, parasomnia, sleep-related movement disorders, and other sleep disorders. This article will focus on circadian rhythm sleep-wake disorders.[1][2][3]


The circadian system regulates sleep consolidation and many other physiologic parameters necessary for health and optimal functioning.  The circadian system is an endogenous cycle entrained by external cues, most importantly light. The circadian rhythm can be measured by evaluating melatonin levels, cortisol levels, and core body temperature. Structurally, the circadian rhythm exists within the suprachiasmatic nuclei of the hypothalamus. The suprachiasmatic nuclei receive direct information on illumination from ganglion cells in the retina. Ganglion cells contain a photopigment called melanopsin and transmit signals to the suprachiasmatic nuclei through the retinohypothalamic tract. The suprachiasmatic nuclei then process this information and stimulate the pineal gland to release melatonin.  Melatonin increases in the evening in response to dim light and peaks around 3 hours before waking. Melatonin receptors are found primarily in the retina, the pars tuberalis of the pituitary gland, and the suprachiasmatic nuclei. This feedback onto the suprachiasmatic nuclei serves as a feedback mechanism, which supports the circadian rhythm. 

As sleep pressure accumulates during periods of wakefulness, the circadian rhythm system also works to maintain wakefulness. The circadian rhythm system has an intrinsic cycle, which on average is just over 24 hours. To compensate for the 24 hour day, the system must undergo phase shifts. These shifts are driven by time cues called zeitgebers, of which the light-dark cycle is the most effective. The circadian rhythm system works in harmony with the sleep homeostatic system to ensure proper sleep. Such a complex system that also relies on external stimuli is subject to dysfunction at many levels. The circadian rhythm system disorders can result from intrinsic dysfunction or the result of environmental factors. Six recognized disorders will be discussed below.


The prevalence of the various circadian rhythm sleep disorders is unknown.


Delayed Sleep-Wake Phase Disorder[4][5]

Characterized by delayed sleep and wake times relative to what is desired or expected. Not simply "night owls," those with delayed sleep-wake phase disorder may not prefer such a sleep schedule, but find it difficult to adjust to desired sleep and wake times. Inadequate sleep and resultant daytime functional impairment are hallmarks of the condition. Relative to the optimal amount of sleep, those affected lose at least 2 hours of sleep per night, on average. Those affected may have great difficulty waking up and require a significant amount of support to do so. Sleep inertia may lead to confusion and frustration upon waking.  When able, (weekends, days off) affected patients generally get a sufficient quantity and quality of sleep, but the delayed phase will remain, and patients may sleep well into the day. The incidence of delayed sleep-wake phase disorder peaks in adolescents and is often accompanied by depression. Some evidence suggests adolescents have longer intrinsic circadian cycles, referred to as tau, that often exceed 24 hours, thus exacerbating the condition. While most adolescents prefer a later sleep cycle, delayed sleep-wake phase disorder represents a distinct condition detrimental to functioning well beyond the typical adolescent experience. Diagnosis is based primarily on the history of persistent delayed sleep-wake cycles that interfere with desired daytime functioning. Sleep logs may aid in diagnosis. Other causes of delayed sleep cycle such as caffeine use and excessive evening light exposure from electronic devices should be screened. Treatment consists of behavioral modification, including good sleep hygiene, and gradually moving sleep and wake times earlier. With strict adherence to deliberate sleep schedules, most patients can achieve reasonable success in normalization of sleep schedule. Caffeine, alcohol, nicotine, and daytime naps should be avoided. Melatonin supplementation and circadian rhythm-light training may also be used if needed. 

Advanced Sleep-Wake Phase Disorder[6][7][8]

This disorder is characterized by excessive evening sleepiness and early morning awakening. Patients may get adequate quality and quantity of sleep if no external pressures dictate that patients stay awake in the evening, but often patients are distressed and sleep deprived because societal obligations require patients to stay awake longer than desired in the evening. Patients with advanced sleep-wake phase disorder will wake at the same early time whether they have forced themselves to stay up later, leading to sleep deprivation and daytime sleepiness. It is hypothesized that advanced sleep-wake phase disorder results from an intrinsic circadian cycle that is less than 24 hours. Advanced sleep-wake phase disorder is more prevalent in older adults and males. Diagnosis is made with history and sleep logs. Treatment is primarily achieved with evening bright light therapy. Pharmacotherapy is not indicated for this condition.

Irregular Sleep-Wake Rhythm Disorder

This disorder represents a failure of the circadian rhythm system to consolidate sleep, leading to multiple short periods of sleep and wakefulness. Diagnosis is made when no clear circadian rhythm pattern can be identified and at least 3 periods or wakefulness lasting at least one hour occur during an average 24-hour period. This disorder is generally found in patients with dementia and is attributed to dysfunction of the suprachiasmatic nuclei. Lack of exposure to external time cues (zeitgebers) may also contribute to this disorder. This may also explain why this condition is more prevalent in the elderly and dementia patients as they are less likely to have consistent commitments and schedules. Behavioral modification and melatonin supplementation may help patients establish more consistent circadian rhythms.

Jet Lag Disorder

Jet lag occurs when air travel allows a person to move time zones in a short amount of time, thus causing the intrinsic circadian rhythm to be in desynchrony with external light cues. This occurs when traveling through at least two time zones. Symptoms include the inability to sleep when desired, daytime sleepiness, and decreased alertness and cognitive performance. Symptoms are usually most prevalent on the day after arrival at destination. The intrinsic circadian rhythm will adjust to destination cues at a rate of 1 to 1.5 time zones per day.  Eastward travel is more difficult to adjust to than westward travel.  Treatment consists of timed light exposure and melatonin. For longer trips across several time zones, timed light exposure and melatonin can be initiated before travel to get the adjustment process started.

Shift Work Disorder

Approximately one-third of night shift or swing shift workers meet criteria for shift work disorder. While some shift workers can adjust easily, others cannot synchronize their circadian rhythm with their sleep debt and schedule demands. This leads to decreased sleep quality and quantity. While day shift workers have maximum sleep debt and pressure at the end of the day, when their circadian rhythm is also promoting sleep, night shift workers often find these 2 drivers of sleep and alertness in conflict with each other. The result is less sleep and lower quality sleep. Insomnia occurs despite sleep debt when circadian rhythm is promoting alertness and preventing sleep.

Conversely, even after sleep, night shift workers often experience sleepiness when circadian rhythms promote sleep during night-time hours. Workers who consistently work the night shift do better than those with rotating schedules. Of those with rotating schedules, workers tend to do well when shifts are grouped and the swings progress later in the day instead of earlier. Treatment consists of first attempting to improve daytime sleep quality and quantity. Sleep hygiene is important, and sleep schedules should be consistent even when not working. A dark, cool, quiet environment is preferred. If the desired amount of sleep cannot be obtained in 1 sitting due to outside constraints, an attempt should be made to obtain at least 3 to 4 hours of "anchor" sleep at the same time every day. Melatonin and other sleep aids may be of some benefit but may also contribute to residual sleepiness when wakefulness is desired during the subsequent night. Bright light during times of desired wakefulness and light avoidance during to and before desired times of sleep may help entrain circadian rhythm to the desired schedule. Short naps just before or during the shift may improve alertness. Caffeine may improve alertness but should not be used within 8 hours of desired sleep.

Non-24 Sleep-Wake Rhythm Disorder

Non-24 sleep-wake rhythm disorder results from a circadian rhythm system that is not entrained or runs without apparent regulation. This may result from blindness where light-dark cues cannot be received, but can also occur in those with normal vision. Diagnosis is based on a history of intermittent insomnia and daytime sleepiness alternating with asymptomatic periods when the circadian rhythm happens to fall in line with desired schedules. Treatment is aimed at entrainment of the circadian rhythm system when able. Tasimelteon is a melatonin-receptor agonist approved for treatment of non 24 sleep-wake rhythm disorder caused by blindness.

Treatment / Management

Treatment varies by condition. Please see specific disease discussions above.[9][10][11][12]

Enhancing Healthcare Team Outcomes

Sleeping difficulty is a common complaint encountered in clinical practice. With many causes, the condition is best managed by a multidisicplinary team that includes a pharmacist, nurse practitioner, neruologist, psychiatrist, primary care provider, psychotherapist and an internist.

Proper sleep is essential to maintain health and optimize overall functioning during wakefulness. Sleeplessness has been linked with several health problems from including diabetes, obesity, and heart disease. Sleeplessness also leads to decreased work performance, traffic accidents, mood and relationship problems, and countless other issues.  

Simply prescribing sedatives and hypnotics is not the answer and healthcare workers address the cause and manage it. Unfortunately, chronic sleep disorders cannot be cured in most cases and often lead to a poor quality of life.[13][14]


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