Circadian Rhythm Sleep–Wake Disorder

Circadian rhythm sleep–wake disorders are a group of conditions marked by recurrent patterns of sleep disruption. These disorders can be due to an alteration of the circadian system (intrinsic) or a misalignment between an individual’s inner circadian rhythm and the environment (extrinsic). The disruption impairs the individual’s daily activities. There are 6 different subtypes, including delayed and advanced sleep–wake phase disorder, irregular and non-24-hour sleep–wake rhythm disorder, shift-work disorder, and jet lag. Diagnosis is generally clinical, but using tools such a sleep diary and actigraphy help in determining the disorder. Management for circadian rhythm sleep–wake disorders involves light therapy, behavioral modification, and pharmacotherapy, such as with melatonin.

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Overview

Definition

Circadian rhythm sleep–wake disorders describe an imbalance between the internal circadian system and awakening times. These disorders affect sleep timing rather than sleep generation. The etiology of circadian sleep–wake rhythm disorders can be divided into:

  • Intrinsic: 
    • Abnormality in the circadian system itself, which can be due to age, genetic factors, or medical conditions.
    • Seen in delayed/advance sleep–wake phase disorder
  • Extrinsic: 
    • Abnormality in the environment, which requires the patient to be awake at unusual times 
    • Seen in jet lag, shift work

Intrinsic circadian system

  • Endogenous biologically active 24-hour cyclic system that controls sleep 
  • Regulated by the suprachiasmatic nucleus of the hypothalamus 
  • Functions:
    • Influences depth, quality, and waking time of sleep episodes
    • Maintains wakefulness during the day
    • Modulates other systems such as: 
      • Core body temperature
      • Cortisol
      • Appetite

Clinical Presentation

Types of circadian rhythm sleep disorders

Delayed sleep–wake phase disorder:

  • Description:
    • Sleep onset: delayed
    • Awakening times: delayed
    • Preserved sleep quality and duration
  • Risk factors:
    • Puberty (associated with changes in melatonin secretion)
    • Caffeine and nicotine use
    • Irregular sleep schedule
    • Depression
    • ADHD in children
  •   Presentation:
    • Difficulty with jobs that start in the morning
    • Sleep is normal when patient is able to arrange his/her schedule. 
    • Example: Patient cannot fall asleep until 3 AM and wakes up at 11 AM feeling well.
    • Night owl

Advanced sleep–wake phase disorder:

  • Description:
    • Sleep onset: earlier than desired
    • Awakening: earlier than desired
    • Sleep quality and duration: preserved
  • Risk factors:
    • Old age 
    • Autosomal dominant familial variant (missense mutations shorten the circadian period)
  • Presentation: 
    • Patient cannot stay awake during the evening. 
    • Example: Patient goes to bed at 8:00 PM to arise early in the morning.
    • Early bird

Irregular sleep–wake rhythm disorder:

  • Description: 
    • Periods of wakefulness and sleep are not consolidated, leading to fragmented sleep episodes in 24 hours.
    • Dysfunction of the suprachiasmatic nucleus likely has a major impact.
  • Risk factors: neurodegenerative disorders (e.g., dementia)
  • Presentation: Patient reports ≥ 3 bouts of sleep, with each lasting 1–4 hours.

Non-24-hour sleep–wake rhythm disorder:

  • Description:
    • Circadian sleep–wake cycle > 24 hours or < 24 hours without reset in the morning
    • Free-running disorder
  • Risk factors:
    • Blindness (loss of light–dark cycle)
    • Traumatic brain injury
    • Developmental delay, such as autism (impaired perception of environmental time cues)
  • Presentation:
    • Insomnia at night
    • Difficulty in morning arousal
    • Increased daytime sleepiness
    • At times, patient’s sleep–wake timing is aligned with the environment.

Shift-work disorder:

  • Description: impaired sleep cycle secondary to work shifts that are opposite to the light–dark cycle
  • Risk factors: 
    • Inverted schedule of night-shift workers
    • Shift > 16 hours
  • Presentation:
    • Sleepiness while awake
    • Decreased cognition and psychomotor function
    • Errors and accidents (e.g., while driving)

Jet-lag disorder:

  • Description:
    • Difficulty in initiating and/or maintaining sleep after travel across ≥ 2 time zones
    • Also affected by travel conditions (e.g., mobility, alcohol intake) and direction of travel (e.g., more difficult to adapt when going east)
    • Transient
  • Presentation:
    • Excessive daytime sleepiness until there is alignment with light–dark cycle
    • Somatic symptoms: decreased appetite, constipation

Clinical features of disorders

Symptoms:

  • Daytime sleepiness
  • Insomnia (difficulty sleeping)
  • Sleep inertia (cognitive and sensory-motor impairment after awakening)
  • Headaches
  • Irritability
  • Diminished concentration and increased performance errors
  • Awakening at inappropriate times
  • Fatigue

Symptoms can be:

  • Episodic: occur for ≥ 1 month but < 3 months
  • Persistent: symptoms present for ≥ 3 months
  • Recurrent: ≥ 2 within a year

Diagnosis

Approach

  • Diagnosis is made clinically on the basis of the criteria outlined above.
  • Polysomnography:
    • Usually not indicated
    • Perform if other sleep pathology (e.g., obstructive sleep apnea) is suspected

Tests

  • Sleep diary: 
    • Useful self-report tool to aid diagnosis
    • Patient is asked to record:
      • Bedtime and wake-up time
      • Estimated time to fall asleep
      • Frequency of awakenings
      • Total sleep time
  • Actigraphy: 
    • Patient wears movement sensor on nondominant wrist to determine total sleep time and sleep efficiency.
    • Useful when sleep diary is not feasible (e.g., in patients with neurodegenerative disorders) 
  • Melatonin sampling:
    • Can provide objective evaluation of impairment of circadian rhythm 
    • Melatonin:
      • Released by the pineal gland about 90–120 minutes before usual bedtime
      • Suppressed by bright light
    • Dim light melatonin onset (DLMO) protocol:
      • Commonly uses saliva sample (other option is blood)
      • Sample is obtained every 30–60 minutes for 6 hours before and 1 hour after usual sleep time.
      • The timing of melatonin increasing above the threshold is a marker for the circadian phase.

Management

Treatment approach

The goal of management is to achieve realignment of sleep–wake timing.

Nonpharmacologic options:

  • Behavioral intervention: 
    • Sleep hygiene:
      • Avoid stimulants such as caffeine and alcohol before bedtime.
      • Use bed for sleep or sex only. 
      • Avoid stimulating activities for 2 hours before bedtime.
      • Avoid daytime naps.
      • Regular exercise
    • Chronotherapy: 
      • Technique used to reset biologic clock
      • Sleep–wake cycle adjusted gradually (e.g., delaying bedtime and waking time) until desired schedule is achieved.
  • Light or phototherapy (at a specific and regular length of time): 
    • Bright-light therapy (e.g., using light boxes with 10,000 lux) 
    • Phototherapy with blue-enriched light during the morning hours (to stimulate wakefulness)

Pharmacologic:

  • Melatonin:
    • Functions as the signal of night; levels rise in the evening
    • Options: exogenous melatonin or melatonin agonists 
  • Modafinil: indicated for treating drowsiness during nighttime shift work

Treatment of specific disorders

Table: Treatment of specific circadian rhythm sleep–wake disorders
Disorder Treatment
Delayed sleep–wake phase disorder
  • Sleep hygiene
  • Minimize light exposure during evening.
  • Light therapy during early morning (to enhance wakefulness)
  • Melatonin in the evening
  • Advancing bedtime each night
Advanced sleep-phase disorder Light therapy in the afternoon or prior to bedtime (opposite to delayed sleep-phase disorder)
Irregular sleep–wake rhythm disorder
  • Light therapy in the morning
  • Behavioral interventions (consolidated sleep at night and increased daytime social/physical activities)
Non-24-hour sleep–wake rhythm disorder
  • Light therapy
  • Melatonin
  • Melatonin agonist (tasimelteon, ramelteon)
Shift-work disorder
  • Light therapy to facilitate rapid adaptation to night shift
  • Modafinil may be helpful in severe cases.
Jet lag Self-limiting disorder; no therapy needed

Differential Diagnosis

  • Parasomnias: sleep disorders marked by unusual actions, activities, or physiologic events that occur during sleep or sleep–wake transitions. Symptoms may include abnormal movements, emotions, dreams, and autonomic activity. Unlike parasomnias, circadian sleep–wake disorder does not require polysomnography for diagnosis and patient is fully aware of problems with sleep. 
  • Narcolepsy: sleep disorder characterized by excessive daytime sleepiness and falling asleep at inappropriate times. Narcolepsy is associated with hallucinations (hypnagogic and hypnopompic, which occur upon falling asleep and waking from sleep, respectively), cataplexy (emotionally triggered loss of muscle tone). Unlike narcolepsy, circadian rhythm sleep disorders are marked by impairment in sleep initiation. 
  • Obstructive sleep apnea: episodic apnea, or cessation of breathing during sleep, in which the period of apnea lasts > 10 seconds. Obstructive sleep apnea is usually due to a partial or complete collapse of the upper airway and is associated with snoring, restlessness, daytime headache, and somnolence.

References

  1. Abbott, S. (2021). Non-24-hour sleep-wake rhythm disorder. UpToDate. Retrieved May 30, 2021, from https://www.uptodate.com/contents/non-24-hour-sleep-wake-rhythm-disorder
  2. Cheng, P., Drake, C. (2021). Sleep-wake disturbances in shift workers. UpToDate. Retrieved May 30, 2021, from https://www.uptodate.com/contents/sleep-wake-disturbances-in-shift-workers
  3. Ganti, L., Kaufman, M., Blitzstein, S. (2016). Sleep-wake disorders. First Aid for the Psychiatry Clerkship, 4th ed. McGraw-Hill, pp. 165–166.
  4. Neikrug, A., Ankoli-Israel, S. (2021). Sleep-wake disturbances and sleep disorders in patients with dementia. UpToDate. Retrieved May 30, 2021, from https://www.uptodate.com/contents/sleep-wake-disturbances-and-sleep-disorders-in-patients-with-dementia
  5. Sadock, B. J., Sadock, V. A., Ruiz, P. (2014). Sleep-wake disorders. Chapter 16 of Kaplan and Sadock’s Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry, 11th ed. Philadelphia: Lippincott Williams and Wilkins, pp. 533–563.
  6. Wyatt, J. (2021) Overview of circadian sleep-wake rhythm disorders. UpToDate. Retrieved May 30, 2021, from https://www.uptodate.com/contents/overview-of-circadian-sleep-wake-rhythm-disorders
  7. Zhu, L., Zee, P. C. (2012). Circadian rhythm sleep disorders. Neurologic Clinics 30:1167–1191. https://doi.org/10.1016/j.ncl.2012.08.011

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