Sleeplessness and Circadian Rhythm Disorders

• A person's circadian rhythm is an internal biological clock that regulates a variety of biological processes according to an approximate 24-hour period. Most of a person's body systems demonstrate circadian variations. The body systems with the most prominent circadian variations are the sleep-wake cycle, the temperature regulation system, and the endocrine system.
• Symptoms of a biological sleep disorder include:
  • Poor concentration
  • Depression
  • Difficulty concentrating
  • Daytime sleepiness
  • Problems falling asleep and staying asleep
  • Problems with school or work performance
  • Decreased cognitive skills
  • Headaches
  • Problems with coordination
  • Digestive problems
• The malfunctioning of a person's circadian system, or biological clock, causes circadian rhythm disorders.
• The sleep-wake cycle is a type of circadian rhythm disorder and can be categorized into two main groups, transient disorders (short-term) and chronic disorders.
• Examples of transient disorders that cause biological clock disorders include jet lag, altered sleep schedule due to work hours or social responsibilities, and illness.
• Irregular sleep-wake cycle, delayed sleep-phase syndrome (DSPS), and advanced sleep-phase syndrome (ASPS) are examples of chronic biological clock disorders.
• The advanced sleep-phase syndrome is characterized by a persistent early evening sleep onset time (between 6:00 pm and 9:00 pm) and an early morning wake-up time (between 3:00 am and 5:00 am).
• An irregular sleep-wake schedule features multiple sleep episodes without evidence of recognizable ultradian (a series of shorter biological rhythms occurring within a 24-hour period) or circadian features of sleep and wakefulness. This is most common in individuals in nursing homes and other environments lacking in time cues.
• DSPS is characterized by a persistent (that is, lasting longer than 6 months) inability to fall asleep and awaken at socially acceptable times. People with DSPS fall asleep late (for example, in the early morning hours) and wake up late (for example, in the late morning hours or in the early afternoon hours). This disorder is more common in teens and young adults than in older people.
• Once asleep, however, persons with DSPS are able to maintain their sleep and have normal total sleep times. In contrast, persons without DSPS who are unable to sleep because of difficulties initiating and maintaining sleep have a lower than normal total sleep time than persons with DSPS.
• ASPS occurs less frequently than DSPS and is most commonly seen in the elderly and in individuals who are depressed.
• Total sleep time is normal in individuals with ASPS, DSPS, and an irregular sleep-wake schedule.
• Daily sleep logs demonstrate irregularity not only of sleep but also of daytime activities, including eating and other things that may disrupt the person’s biological clock.

10 Symptoms commonly found in persons with a circadian rhythm disorder related to the sleep-wake cycle can include the following:

1. Difficulty initiating sleep
2. Difficulty maintaining sleep
3. Nonrestorative or poor quality sleep
4. Daytime sleepiness
5. Poor concentration
6. Impaired performance at school or work, including a decrease in cognitive skills
7. Poor psychomotor coordination
8. Headaches
9. Depression
10. Gastrointestinal distress

Most of the time, a person's biological clock, or circadian rhythm, is in synchronization with the 24-hour day-night environment. In some individuals, however, the biological circadian rhythm of sleep and wakefulness is out of phase with the conventional or desired sleep-wake schedule.

• Sensitivity to zeitgebers ("time givers," or time cues such as light and other environmental cues): This sensitivity may be altered or disrupted, which can be demonstrated under certain conditions. Altered or disrupted sensitivity to zeitgebers is probably the most common cause of the circadian rhythm disorder of the sleep-wake cycle. Patients with blindness may experience difficulty with circadian rhythm because they lack light cues through the visual system.
• Disrupted pacemaker function: A dysfunction may be present in the internal coupling mechanisms of biological pacemakers, for example, the coupling of the sleep-wake cycle with the temperature cycle.
• Environment: Light, higher noise levels, and elevated room temperature are not conducive to good sleep and are important variables to consider in both shift workers and night workers.
• Travel: The severity of jet lag is related to the direction of travel and is more frequently seen in individuals traveling in an eastward direction. The number of time zones crossed also affects the severity of jet lag, with most individuals experiencing jet lag if they cross 3 or more time zones. The rate of adjustment is 1.5 hours per day after a westward flight and 1 hour per day after an eastward flight.
• Neurological disease: Alzheimer's disease is one of the more common examples of neurological disease associated with a circadian rhythm disturbance; however, irregular sleep-wake cycles can also be seen in other neurodegenerative diseases. Sundowning, which is a common phenomenon in persons with Alzheimer's disease, is characterized by sleep disruptions with awakenings and confusion.
• Shift work: Rapid shift changes and shift changes in the counterclockwise direction are most likely to cause symptoms of a circadian rhythm disorder.
• Lifestyle and social pressure: staying up late can exacerbate a circadian rhythm disorder.

• A sleep log identifies the sleep-wake cycles in a person's normal environment, and it allows subjective assessment of alertness over a 2-week period. In keeping a sleep log, a person is asked to maintain a sleep diary describing the previous night's sleep. Data from the sleep diary may help to minimize distortions in sleep information recalled some time later while in the health care provider's office. Sleep logs can also be used for self-monitoring and as an addition to behavioral treatment.
• Imaging studies, such as CT scans and MRIs, may be done to evaluate for neurodegenerative diseases.
• A multiple sleep latency test allows for objective measurement of sleepiness. This test is indicated when the clinical history is suggestive of narcolepsy.
• The Epworth Sleepiness Scale is based on a questionnaire that rates a person's responses to 8 situations on a scale of 0-3 based on whether the situation was likely to be associated with dozing behavior. Although controversy exists as to what score constitutes abnormal sleepiness, a total score above 10 generally warrants investigation.
• Actigraphy is done with the help of an Actigraph. An Actigraph is a small, motion-sensing device worn on the non-dominant wrist, generally for 1 week. Actigraphy is based on the premise that a person's wrist motion decreases during sleep. This allows an overall measure of sleep-wake cycles over time.

As always, maintaining good sleep hygiene is important. Good sleep hygiene consists of measures to reinforce the body's natural tendency to sleep, including the following:

• Adhering to consistent sleep and wake times
• Avoiding napping
• Using the bed only for sleeping and intimacy
• Avoiding stress, fatigue, and sleep deprivation
• Avoid vigorous exercise at least 4 hours prior to bedtime (Regular exercise is recommended.)
• Avoiding cigarettes, alcohol, and caffeine at least 4-6 hours prior to bedtime
• Avoiding large meals and excessive fluids before bedtime
• Controlling the environment, including light, noise, and room temperature (A controlled sleeping environment is especially important for shift workers and night workers.)

Common circadian rhythm disorder treatments can include these behavioral and environmental therapies.

• Chronotherapy: This behavioral treatment consists of gradually shifting the sleep time in accordance with the person's desired schedule. Thus, in DSPS, a progressive delay of 3 hours per day is prescribed, followed by a strict maintenance of a regular bedtime hour once the desired schedule is achieved. In ASPS, chronotherapy focuses on advancing a regular bedtime hour by 2-3 hours per night for 1 week until the desired schedule is achieved. Persons with DSPS who respond initially to chronotherapy may gradually shift back to their old sleep pattern. Often, chronotherapy must be repeated every few months to maintain long-lasting results.
• Bright light therapy: People with a circadian rhythm disorder respond well to light therapy, especially bright light therapy (greater than 600 lux). To modify the phase of the circadian rhythm, bright room light over time may also be sufficient; however, a higher intensity of light (greater than 6000 lux over 30-60 minutes) is often necessary to accomplish significant changes in sleep cycles. The timing of light therapy is also important because it affects the degree and the direction of the rhythm shift. For example, for persons with ASPS, light therapy applied in the early evening and nighttime hours delays the cycle, whereas, for persons with DSPS, light therapy applied in the early morning hours stimulates morning alertness and an earlier bedtime.
• Enhancing environmental cues: This part of the treatment of a circadian rhythm disorder is important. Persons are encouraged to keep a dark and quiet room during sleep and a well-lit room upon awakening. Avoiding bright light exposure in the evening and enforcing regular hours for eating and other activities also help.
• Lifestyle changes: People with circadian rhythm disorders may respond to shifts in their active phases by exhibiting signs of sleep deprivation. For example, teenagers may have difficulty keeping late hours and getting up for an early morning class. Shift workers may have difficulty adjusting to new sleep cycles if their shifts are changed too rapidly before their bodies have had a chance to adjust.

Therapy for a circadian rhythm disorder is largely behavioral. Light therapy has been shown to be an effective modifier of circadian rhythms. The short-term use of hypnotics (medications that promote sleep) is a useful option in treating a circadian rhythm disorder and has improved the therapeutic response, especially in persons with Alzheimer's disease.

Melatonin

Melatonin has been reported to be useful in the treatment of jet lag and sleep-onset insomnia in elderly persons with a melatonin deficiency. Melatonin is used for enhancing the natural sleep process and for resetting the body's internal time clock when traveling through different time zones. Melatonin is believed to be effective when crossing 5 or more time zones but is less effective when traveling in a westward direction. Melatonin has also been used in the treatment of circadian rhythm sleep disorder in persons who are blind with no light perception.

Melatonin is available as an over-the-counter (OTC) preparation. Melatonin is still considered a diet supplement, and dosing guidelines have not been established. Because of the effect of melatonin on immune function, persons with immune disorders and those taking systemic corticosteroids or immunosuppressive drugs should be cautioned against taking melatonin. Melatonin may interact with other medications. It is important to consult your doctor before using melatonin.

Melatonin stimulants

Ramelteon (Rozerem) is a prescription drug that stimulates melatonin receptors. Melatonin is a hormone produced by the pineal gland during the dark hours of the day-night cycle (circadian rhythm). Melatonin levels in the body are low during daylight hours. The pineal gland (located in the brain) responds to darkness by increasing melatonin levels in the body. This process is thought to be integral to maintaining circadian rhythm. Ramelteon promotes the onset of sleep and helps normalize circadian rhythm disorders. Ramelteon is approved by the Food and Drug Administration (FDA) for insomnia characterized by difficulty falling asleep.

Hypnotics

Short-term use of hypnotics may be beneficial in selected patients. Patients interested in the use of hypnotics for a circadian rhythm disorder should discuss them with their doctor.

Benzodiazepines

Short-acting benzodiazepines are often chosen in the early treatment of a circadian rhythm disorder and are used in conjunction with behavioral therapy. Triazolam (Halcion) is a benzodiazepine frequently chosen for short-term use in addition to behavioral therapy. This short-acting agent is effective in helping persons fall asleep.

Triazolam is not always effective in persons with sleep maintenance issues. For persons with sleep maintenance insomnia, a benzodiazepine with an intermediate half-life (for example, estazolam [ProSom]) or a long half-life (for example, lorazepam [Ativan] or temazepam [Restoril]) may be considered.

Nonbenzodiazepine hypnotics

Nonbenzodiazepine hypnotics are gaining popularity because they do not have a significant effect on sleep architecture and are not associated with the rebound phenomenon seen with benzodiazepines. Zolpidem (Ambien) is a good short-term option for persons with DSPS who require pharmacologic support.

Treatment of sleep disorders associated with shift work

Modafinil (Provigil) is a stimulant indicated to treat workers with sleep disorders caused by their shift work. Modafinil has wake-promoting actions and is taken 1 hour before the start of the work shift.

For more information, see Understanding Insomnia Medications.

• Control of the sleep environment with regulation of light-dark exposure has been helpful to shift workers in maintaining sleep.
• For shift workers, shifting the schedule in a clockwise direction is better tolerated.
• For persons who are traveling across multiple time zones, adjusting to the time zone of the new location prior to departure can modify the effects of jet lag.
• Maintaining good sleep hygiene can prevent sleep disorders.

Medical care may be necessary if any of the following occur:

• When poor sleep for more than 1 month is accompanied by one or more of the following:
  • Poor concentration
  • Forgetfulness
  • Decreased motivation
  • Excessive daytime sleepiness
• Difficulty falling asleep
• Nonrefreshing sleep
• Habitual snoring

A doctor may be able to answer questions about sleep-related issues. The following questions may help in identifying ways to improve sleep:

• How can I make my environment more conducive to sleep?
• Do any of my medications or herbal preparations cause insomnia?
• How does caffeine influence my ability to fall asleep?
• How can I minimize the effect of changing shift work on my ability to sleep?
• How can I minimize the effect of jet lag when I travel?
• What techniques can I use on my own to improve my ability to fall asleep and stay asleep?
• How can I minimize my reaction to daytime stresses so I can fall asleep?
• How does my family history influence my likelihood of having a sleep disorder?
• What can I do to help my teenager not only fall asleep but also wake up in time for school?

The following provide an outlook into some sleep disorders:

• Jet lag: This is a transient condition that has a good prognosis.
• Shift work: Abrupt changes in schedule and counterclockwise shifts are associated with daytime sleepiness and impaired performance. Older persons may not adjust well to shift changes.
• DSPS: This is typically seen in adolescents and young adults. This sleep pattern often resolves in adulthood.
• ASPS: This is prominent in the elderly and often responds well to a combination of behavioral and pharmacologic intervention.