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Day # 152: Circadian Rhythm Sleep-Wake Disorders

Today we will discuss Circadian Rhythm Sleep-Wake Disorders (CRSWDs). We will cover an introduction, definitions, diagnostic criteria, risk factors, and treatment.




Refresher on the Circadian Rhythm 1


•Circadian rhythm = roughly 24-hour cycle that is synchronized with the day-night cycle of the Earth.


•Sometimes called the body’s internal biological clock. It is a timing mechanism in the brain that uses light/dark exposure to synchronize the sleep-wake cycle with the external environment. It also regulates melatonin production and influences body temperature and hormonal regulation.


•Regulated by a central pacemaker located in the hypothalamus, specifically in the suprachiasmatic nucleus (SCN).


•See day #151 for more details.



Introduction and Definitions 2, 3


•Circadian rhythm sleep wake disorders (CRSWDs) are a group of disorders characterized by recurrent disruptions in the natural sleep-wake cycle that aligns with the 24-hour circadian rhythm.


•Put another way, they involve a misalignment between the person’s internal biological clock and a sleep-wake scheduled required by the individual’s external environmental cues or schedule.


Subtypes of CRSWDs include:

  • Delayed sleep phase

  • Advanced sleep phase

  • Irregular sleep-wake

  • Non-24-hour sleep-wake

  • Shift work

  • Jet lag (not in DSM-5-TR)


•Misalignment between someone’s internal rhythm and the environment can create a number of symptoms including: insomnia, excessive daytime sleepiness, sleep inertia, headaches, difficulty concentrating, frequent performance errors, increased reaction times, irritability, and waking up at inappropriate times.


When allowed to set their own schedule, individuals with delayed or advanced sleep phase type exhibit normal sleep quality and duration for their age.


•A thorough assessment is critical in order to establish a patient’s daily routines, sleep patterns, and rule out other conditions with overlapping symptoms (e.g., poor sleep hygiene, substance abuse (e.g., methamphetamine, ecstasy), depression, anxiety, bipolar disorder, obstructive sleep apnea, restless leg syndrome, etc.). These conditions may lead to alternating patterns of insomnia or prolonged wakefulness, rebound hypersomnia (“crashing”), or chaotic/disorganized sleep-wake patterns that resemble CRSWDs.



Types of CRSWDs 2, 3, 4


Delayed Sleep Phase Disorder (DSPD)


Definition: Chronic or recurrent delay in sleep onset and awakening times with preserved quality and duration of sleep. Occurs when the biological clock runs slower than 24 hours or is shifted later than the desired schedule. Individuals are more alert in the evening and early nighttime, stay up later, and are more tired in the morning. These individuals are commonly referred to as night owls.


Risk factors: Adolescence and young adulthood (due to temporal changes in melatonin secretion during puberty), family history of DSPD, caffeine and nicotine use, light exposure (including screen time) in the evening, irregular sleep schedules, and high stress levels. Also associated with depression, anxiety, bipolar disorder, personality disorder, somatic symptom disorder, and illness anxiety disorder.


Treatment: Options include: 1) Chronotherapy (delaying bedtime by 2-3 hours per night until desired sleep-wake cycle is achieved). 2) Light therapy during the early morning. 3) Administration of melatonin in the evening.



Advanced Sleep Phase Disorder (ASPD)


Definition: Chronic or recurrent pattern of sleep onset and awakening times earlier than desired with preserved quality and duration of sleep. Occurs when the circadian rhythm cycle is shifted earlier. Individuals are drowsy in the evening, want to retire to bed earlier, awaken earlier, and are more alert in the early morning. These individuals are sometimes called early birds or larks.


Risk factors: Older age, particularly >65 years old, family history of ASPD, changes in social/lifestyle factors such as limited social engagements or evening activities, and insufficient exposure to natural light during the day, particularly in the evening. Also associated with depression (early morning awakening) and bipolar disorder.


Treatment: Options include: 1) Chronotherapy (delaying bedtime by 15-30 minutes per night until desired sleep-wake cycle is achieved). 2) Light therapy prior in the evenings or prior to bedtime. 2) Early morning melatonin (this option is not preferred as it may cause daytime sedation).



Irregular Sleep-Wake Type


Definition: A disorganized sleep-wake pattern, such that the timing of sleep and wake periods is variable throughout the 24- hour period. Individuals have a normal total amount of sleep during a 24-hour period, however the the timing of sleep and wakefulness is unpredictable and fragmented into three or more sleep episodes.


Risk factors: Neurodegenerative disorders (e.g. Alzheimer), older age, traumatic brain injury (TBI), children with neurodevelopmental disorders, history of reclusion or isolation (decreased exposure to external stimuli such as inadequate exposure to sunlight, lack of structured daily routine, limited exposure to social cues).


Treatment: 1) Address any underlying conditions. 2) Establish a consistent daily routine with regular mealtimes, activities, exercise during daylight hours, social engagement, and exposure to natural light. 3) Light therapy in the morning. 4) Cognitive behavioral therapy for sleep disorders (CBT-I).



Non-24-Hour Sleep-Wake Type


Definition: Also known as “free running”. Non-24 is a pattern of sleep-wake cycles that are not synchronized to the 24-hour environment, and is not reset each morning, with a consistent daily drift (usually to later and later times) of sleep onset and wake times. This sub-type is most common among blind or visually impaired individuals who have decreased light perception. If their internal clock is longer than 24 hours and does not reset each day, they will experience progressively worsening sleep-onset insomnia (delayed phase) and daytime sleepiness until sleep problems peak when their internal clock and environment clocks are 12 hours out of phase. Sleep problems will then begin to lessen and look like progressively resolving advanced phase) sleep issues until the clocks correlate, and the sleep-wake cycle is normal for a few days, after which the cycle begins again.


Risk factors: Blindness, visually impaired, traumatic brain injury (TBI), and neurodegenerative disorders.


Treatment: Options include: 1) Tasimelteon, which is a melatonin receptor agonist (MT1 and MT2). It is the only FDA approved treatment for non-24. Administered in the evening. 2) May consider ramelteon (another melatonin receptor agonist) or melatonin instead of tasimelteon due to similar pharmacology but much more affordable. 3) Light therapy is being investigated.



Shift-Work Type


Definition: Sleep deprivation and misalignment of the circadian rhythm secondary to unconventional work hours.


Risk factors: Rotating shifts, night shifts, shifts lasting longer than 16 hours, being a medical resident, lack of social/family support to synchronize sleep and social/family activities/responsibilities with work hours (e.g., parents with small children), insufficient total sleep time, and morning-type disposition (“early birds”). The ability to adapt to shift work and irregular work hours may decline with age.


Treatment: Options include: 1) If possible, reduce risk factors by changing work schedules or requesting reduced tempo of changes to rotating shift schedule. 2) Light therapy to facilitate faster adaptation to the night shift. Ideally, light therapy should be performed prior to starting the shift and bright lights continued from early in the night shift through 2 hours before shift ends. 3) Modafinil, a wake-promoting agent, is the only FDA approved medication for shift work sleep disorder and may be used to treat sleepiness during night shift work.



Jet Lag Disorder


•Included in DSM-4-TR. It was removed from DSM-5-TR, but is loosely mentioned under the shift-work subtype. It is still recognized as a circadian rhythm sleep disorder by the ICSD.


• When an individual travels rapidly across many time zones, either a circadian phase advance or a phase delay is induced, depending on whether the direction of travel is eastward or westward.


•The number of time zones crossed is a critical factor. Typically, traveling across 1-2 time zones will not produce a sustained problem, but further distances create more difficulties in adaptation.


•Healthy individuals can generally adapt 1-2 time zones changes per day. For example, crossing 6 time zones may take 3-6 days to naturally adjust your circadian rhythm.


•Jet lag is usually self-limiting. Individuals may choose to accelerate their adaptation by using melatonin in the evening and/or light therapy in the mornings. Some individuals may even gradually adjust their sleep schedule to align with the destinations time zones in the days before travel by shifting their bedtime and wake-time by 1-2 hours each day.



Treatment Approaches 5, 6

(In More Detail)


Chronotherapy

  • A technique used to reset the biological clock. It involves progressively delaying bed time each night (phase delaying) until the desired sleep-wake cycle is achieved.

  • For delayed phase – delay bedtime by 2-3 hours per night until desired schedule is achieved.

  • For advanced phase – delay bedtime by 15-30 minutes per night until desired schedule is achieved. Slow down the rate of changes if the patient is struggling to adapt.

  • Progressively phase delaying is believed to be easier than progressively phase advancing (moving the bed time earlier each night). This is because it capitalizes on a natural tendency. When individuals are deprived of environmental time cues (e.g., light) and told to sleep when they feel sleepy, the typical “day” lasts 25-26 hours.

  • Combining chronotherapy and time bright light exposure is critical.


Light therapy

  • Bright lights (>10,000 lux) can adjust the internal biological clock.

  • Delayed sleep phase (and irregular type) –treat with early morning light exposure.

  • Advanced phase – treat with evening light exposure.

  • Shift-work type – treat with light exposure prior to starting their shift and bright lights continued from early in the night shift through 2 hours before shift ends.

  • Light therapy is being investigated in non-24.



Cognitive Behavioral Therapy for Insomnia (CBT-I)

  • CBT-I is designed to address and improve the thoughts, behaviors, and beliefs associated with chronic insomnia.

  • We will discuss this therapeutic technique in detail in the insomnia lesson.

  • For now, know that CBT-I can be used in CRSWDs to help address maladaptive thoughts and sleep behaviors that tend to develop in any sleep disorder.


Melatonin Agonists

  • Melatonin is produced in the pineal gland and is regulated by a central pacemaker which is a group of cells in the hypothalamus called the suprachiasmatic nucleus (SCN).

  • Melatonin is an important hormone that plays a key role in the sleep-wake cycle. In a sense, it is the signal of darkness in the brain and prepares the body for sleep.

  • Melatonin is typically produced in larger quantities in the evening and during the night which promotes sleepiness. Exposure to light, especially in the morning, activates the SCN which in turn suppresses melatonin production in the pineal gland, contributing to wakefulness.

  • It is recommended to take melatonin supplements 1-2 hours before the desired bedtime as this timing aligns with the natural increase in melatonin levels in the evening as the body prepares for sleep.

  • Melatonin receptor agonists can be used clinically to help promote normalization of the biological clock in patients with CRSWDs.

  • Melatonin: Over the counter (OTC) option. The quality, purity, and dosing can vary significantly among brands. Some brands may contain impurities or widely inaccurate dosages, so it’s important to choose reputable brand to adhere to quality standards. Dosing recommendations differ and there is no clear guidance, but more recent data suggest that less is more with melatonin. It is generally recommended to start with a low dose (anywhere from 0.3 – 1mg), which better mimics biological dosing. Doses higher than 5 or 6 mg are generally not recommended.

  • Ramelteon: Melatonin receptor agonist. FDA approved for sleep onset insomnia but used off label for the entire spectrum of CRSWDs.

  • Tasimelteon: Melatonin receptor agonist. FDA approved for treatment of non-24. Typically reserved for this condition alone due to high expense.



Conclusion


Next lesson we will discuss insomnia.


Resources for today's post include:

The articles referenced above

See our full list of book recommendations for the most up-to-date editions


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