Sleep Homeostasis

A common observation is that once children try to maintain alertness beyond the usual 12 to 16 hours of the habitual waking day, each passing hour makes it more and more difficult to fend off sleep. Indeed, just as appetite grows in the hours subsequent to eating, the brain keeps track of each hour of sustained wakefulness, commonly referred to as the homeostatic drive for sleep or sleep homeostasis. The concept of “homeostasis” is often credited to the work of American physiologist Walter Bradford Cannon in the early 1900s, who wrote that the body actively modulates physiology to maintain internal constancy in the face of environmental and other challenges that may offset that balance.

Perhaps the easiest way to understand sleep homeostasis is to begin at morning wake time, in a child who has obtained a full night of sleep and is free of sleep disorders. Being fully rested, there is essentially no sleep homeostatic drive at wake time, although it begins a slow and persistent buildup with each subsequent hour of wakefulness. Near evening bedtime, great accumulation of sleep homeostatic pressure is the primary process allowing for rapid sleep initiation, as well as the prominence of deep or “slow-wave sleep” seen typically in the first third to half of the nocturnal sleep episode. A much-studied marker of the strength of sleep homeostatic drive during sleep is the amount of electroencephalogram (EEG) power in the slower frequencies (eg, “slow-wave activity” or “SWA,” the 0.75-Hz to 4.50-Hz band). After sleep deprivation, recovery sleep shows a significant increase in SWA particularly in the first few non–rapid eye movement (NREM) cycles. In normal sleep, with each passing NREM cycle, sleep homeostatic drive dissipates, as reflected in less and less SWA in subsequent NREM cycles. During naps, sleep homeostatic drive is rapidly dissipated, which is thought to explain the great restorative benefit experienced after a nap. Of the possible markers for the accumulation of sleep homeostatic drive during sustained wakefulness, frontal EEG power in the 0.75-Hz to 4.50-Hz band has also shown great promise.

When moving from models and markers to actual physiologic substrates of sleep homeostasis, the science quickly becomes more complex. Without attempting to decipher this biologic enigma in this article, several key observations are noted. Much work has been published on the role of adenosine as a pharmacologic substrate of sleep homeostasis. In animal models, increase and decrease in adenosine is observed during sustained wake and sleep, respectively. Perhaps easier to appreciate is the human preference for drinking a caffeinated beverage as a legal, relatively inexpensive, nonprescription wake-promoting substance, owing to caffeine’s ability to attenuate the expression of sleep homeostatic drive because of its function as an adenosine receptor antagonist. However, there are likely many neurotransmitters and neuromodulators functioning within the sleep homeostatic system. Orexin, a substance nearly absent in narcolepsy, is likely an endogenous wake-promoting substance (reviewed in ref. ). Histamine has wake-promoting properties (reviewed in ref. ), known to anyone who has taken an antihistaminergic medication perhaps for allergies or motion sickness.

Given that sleep homeostatic drive increases with every hour of sustained wakefulness, questions can be raised. How can a young child skip a nap and manage to remain awake as long as 12 hours? How can a teenager remain awake for 18 to 20 hours? Why do well-rested teenagers typically note a relatively stable level of alertness for the entire waking day instead of a progressive, linear increase in daytime sleepiness? Consolidation of wakefulness during the daytime, and indeed sleep at night, is possible owing to the interaction of the aforementioned sleep homeostatic system with the intrinsic circadian timekeeping system.

Circadian Rhythms

In mammals, including humans, the primary, CNS circadian oscillator is found in the suprachiasmatic nucleus (SCN) of the hypothalamus. Extirpation of the SCN results in a lack of 24-hour rest-activity and sleep-wake rhythms, as well as greatly decreased durations of individual sleep and wake episodes. In mammals, the SCN gets its primary time cue (or “zeitgeber”) needed to properly synchronize internal biology to the 24-hour day from the external light-dark cycle, transduced by a special class of retinal ganglion cells and transmitted to the SCN via the retinohypothalamic tract. Without daily time cues or “zeitgebers” forcing small phase shifts to “entrain” to the 24-hour light-dark cycle, the circadian system “free runs” or expresses its intrinsic period length, which is approximately 24.2 hours. But with proper entrainment, the circadian system uses its many output pathways to coordinate the daily oscillation of many biologic functions (eg, sleep-wake, core body temperature, pineal melatonin production). As with the description of sleep homeostasis given previously, this is indeed a dramatic oversimplification of the richness and complexity of the circadian timekeeping system, which has myriad neurophysiological and pharmacologic input and output pathways, allowing communication with other hypothalamic nuclei as well as other structures within the brain and body.

Shared Homeostatic and Circadian Modulation of Sleep and Wake

There are a host of graphical and mathematical models of simple or complex interactions of the homeostatic and circadian systems and their modulation of sleep and wakefulness. One such model is the “2-process model” of Borbély, which has served as the basis of decades of subsequent work by many research groups. Recent research studies using the “forced desynchrony” protocol have greatly advanced our understanding of the modulatory effects of each process on sleep and wakefulness, as well as their complex interaction. We now know that the low level of sleep homeostatic drive existing after a sufficient duration of nocturnal sleep allows an individual with normal sleep to have good alertness for the first half of the normal waking day. The active promotion of wakefulness by the circadian system opposes the buildup of sleep homeostatic drive during the second half of the waking day, maintaining alertness at high levels. Following the “wake maintenance zone” (also called the “forbidden zone for sleep” ) located approximately 2 hours before habitual bedtime, the circadian system ceases its drive for wakefulness and the accumulated homeostatic sleep pressure allows for swift onset of the nocturnal sleep episode, as well as consolidation of approximately the first half to two-thirds of the sleep episode. However, as sleep pressure is satiated during sleep and is no longer sufficient to maintain uninterrupted sleep, the circadian system actively promotes sleep. The circadian system in fact strongly promotes sleep in the second half of the night, reaching peak sleep promotion at and for 2 hours after one’s habitual, morning wake time—the “circadian sleep maintenance zone.” Thus, proper functioning of the sleep homeostatic and circadian systems, as well as maintenance of a nocturnal sleep schedule, avoiding durations of sustained wakefulness beyond 14 to 16 hours, and keeping a consistent sleep-wake cycle set the conditions for optimal consolidation of sleep and wake. Alternatively, violation of one or more of these conditions can set the stage for the emergence (or maintenance) of a circadian rhythm sleep disorder.

Circadian Rhythm Sleep Disorder: Delayed Sleep Phase Type

From the perspective of pediatrics, the most common of the circadian rhythm sleep disorders seen in the clinic is the delayed sleep phase type. This disorder can also be called delayed sleep phase disorder (DSPD), and in the past was called delayed sleep phase syndrome (DSPS). Formally reported in 1981, this disorder is typified by complaints of difficulty falling asleep until much later than preferred, accompanied by difficulty or frank inability to arise in the morning at the desired hour. When permitted to go to bed and awaken on a later sleep schedule, however, sleep initiation is rapid, sleep consolidation is good, and final awakening is easier. Per the ICSD-2, at least 1 week of a sleep diary alone or accompanied by wrist actigraphy is required to confirm the diagnosis. Ideally, the sleep diary would capture an “early” sleep schedule such as one requiring an early bedtime and wake time for school or a day-shift job, and a “late” ad lib sleep schedule over a weekend. Thus, the early sleep schedule would demonstrate increased sleep latency and decreased total sleep time, and the late sleep schedule would demonstrate resolution of symptoms. However, the American Academy of Sleep Medicine’s (AASM) 2007 practice parameter found moderate-strength evidence justifying the use of sleep diaries or wrist actigraphy for diagnosing DSPD. Although chronotype questionnaires such as the “Owl and Lark” or “Morningness-Eveningness Questionnaire” make sense as a diagnostic questionnaire for DSPD, the practice parameter cited insufficient evidence for such instruments, as well as for actual measurement of biologic circadian parameters.

The pathophysiology of DSPD has been a source of much speculation, without great supporting evidence. It has been proposed that for unknown reasons, the intrinsic circadian system is “stuck” at a later phase (and hence a later clock hour) in a patient with DPSD, and thus the wake maintenance zone makes it difficult to fall asleep at the desired, socially appropriate bedtime. Similarly, the circadian sleep maintenance zone occurs at a later clock time, greatly increasing the difficulty arising at the morning wake time. There have been reports that the trough of core body temperature, a marker of circadian phase, occurs abnormally early in the sleep episode in patients with DSPD, although a more recent report found no difference in the timing of the presleep release of melatonin by the circadian system relative to the habitually timed sleep wake cycle. Other proposed mechanisms for the genesis of DSPD include an abnormally long intrinsic circadian period or “tau,” an impaired ability to make the small, daily phase advances required to entrain the circadian system to the 24-hour light-dark cycle, and even contributions of psychological or other factors (see Wyatt for review). The prevalence estimates for DSPD vary widely, from slightly above 0.1% to as high as 3.0%.

Treatment options for DSPD include sleep scheduling, exogenous melatonin, and properly timed exposure to light and darkness. According to the recent standard of practice paper from the AASM, the use of sleep scheduling, including chronotherapy, has only weak evidence supporting treatment efficacy, exogenous melatonin has moderate strength evidence, and phototherapy has moderate strength evidence.

The first treatment proposed for DSPD was chronotherapy. In the original model, the patient was instructed to maintain a reasonable time-in-bed per sleep episode (eg, 8 hours) but to delay each successive bedtime and wake time by 3 hours per day. Thus, the patient would sleep “around the clock,” ceasing the delaying sleep schedule on reaching their desired, earlier clock times for bedtime and morning wake time. The original case series reported good efficacy and continued resolution of symptoms months later. Further reports of chronotherapy have been published, although typically as part of a multicomponent treatment (eg, Yamadera and colleagues and Okawa and colleagues ). A curious facet of chronotherapy was that it was devised as a treatment before the demonstration that artificial bright light could phase shift the human circadian system. Given our current understanding of circadian physiology, it is unlikely that chronotherapy as a stand-alone treatment actually causes the circadian system to phase delay 3 hours each day, and hence, the actual mechanism whereby chronotherapy treats DSPD remains unknown.

Exogenous melatonin administration causes a phase advance or a phase delay of the circadian rhythm depending on the timing of administration relative to circadian phase, which can be graphically depicted as a “phase response curve for melatonin.” For DSPD, melatonin would be delivered in the phase advance region of the circadian phase response curve (PRC) to melatonin to pull the circadian rhythm earlier. In individuals with normal sleep, Burgess and colleagues showed that maximal phase advancing comes from exogenous melatonin administration at 9 to 11 hours before the middle of the habitual sleep episode for a 0.5-mg dose, and 11 to 13 hours before the middle of the sleep episode for a 3.0-mg dose. To the contrary, there was no difference in the direct, sleep-promoting effect of 0.3 mg versus 5.0 mg melatonin on sleep episodes that were scheduled before the normal nocturnal release of melatonin. There are numerous reports of 5.0 mg (or lower dose) melatonin successfully phase advancing the clock time of sleep onset and/or circadian markers in DPSD patients, with ingestion typically being anywhere from 5 hours before bedtime or simply before bedtime at a time of the patient’s choosing. However, it appears that relapse may be quite high after exogenous melatonin discontinuation, raising the possibility that this may be a chronic treatment. There is also concern over giving a hormone, with demonstrated importance to the reproductive endocrine system in seasonal breeding mammals, to children with maturing reproductive systems. The risk-benefit ratio takes on paramount importance in consideration of exogenous melatonin administration in children. Although not always formally diagnosed with DSPD, there are numerous reports of successful treatment of DSPD-like sleep problems in children with significant neurodevelopmental disorders (eg, autism and Angelman syndrome ).

Phototherapy has also been reported as a treatment for DSPD. Artificial bright light is delivered during the phase advance portion of the phase response curve (PRC) to light, repeated daily, with gradual scheduled or ad lib advancement of the sleep schedule. Studies have varied in the light source (light visor vs traditional light box ), light intensity (up to several thousand lux), duration of light exposure, and timing of light exposure relative to circadian phase and/or the timing of sleep. Given the lack of a PRC to light derived specifically in patients with DSPD, the precision of treatment recommendations is lacking. However, it does seem that preventing bright light exposure for several hours before bedtime is important to minimize the potential for phase-delaying light exposure. After awakening, daily, scheduled exposure to bright light of 2000 to 8000 lux appears to gradually phase advance the circadian system and allows earlier timing of the major sleep episode. Without requiring a laboratory assessment of circadian phase, a conservative approach would be to begin the first day’s phototherapy treatment at the habitual, late wake time, and to gradually advance the sleep schedule by 15 to 30 minutes per day. Phototherapy is recommended at the “guideline” level as a treatment for DSPD in the AASM’s 2007 practice parameter.

In summary, although chronotherapy is perhaps the easiest treatment for DSPD, it has the least empirical support to document efficacy. Exogenous melatonin and phototherapy have equivalent, moderate levels of supporting evidence. In this author’s opinion, phototherapy is favored as a first-line approach over melatonin treatment, given that phototherapy yields larger phase advances per day of treatment and lacks the potential adverse consequences on reproductive endocrine systems.

Circadian Rhythm Sleep Disorder: Free-running Type (or) Nonentrained Type

As noted earlier, in the absence of time cues required to align the circadian system with Earth’s 24-hour light-dark cycle, the SCN free runs with a period of approximately 24.2 hours. Many individuals who are retinally blind also cannot transmit light-dark information from the retina to the SCN, and hence, their circadian systems free run at their intrinsic period, which is typically close to but not exactly 24 hours (reviewed in Sack and Lewy ). Hence, they may have a presenting complaint of a progressive (typically later each day) daily shift of their sleep-wake cycle in synchrony with the drifting circadian phase. Alternatively, they may present with episodic insomnia every few weeks to few months, during periods where their circadian system has drifted sufficiently such that the patient is attempting to sleep at night but the circadian system has drifted to a phase where it is actively promoting alertness instead of sleep at night. For unknown reasons, there have been documented cases of free running in individuals who are not blind (eg, Hashimoto and colleagues ), suggesting that there may be more than one subtype of free-running disorder, each with different causes. Further, there are some blind patients who appear to retain integrity of the circadian visual pathway. There are also case reports (eg, Boivin and colleagues ) of patients alternating between DSPD and free-running type symptoms, suggesting possible overlap of these disorders. In addition to the presenting complaints noted previously, the ICSD-2 requires at least 1 week of a daily sleep diary with or without wrist actigraphy confirming the complaint (eg, a progressively delaying sleep schedule).

Treatment options include trying to strengthen the light-dark cycle, particularly in sighted individuals but also in blind individuals who may lack conscious light perception but still have an intact circadian visual pathway. Keeping a regular sleep-wake schedule is also recommended, as sleep itself or the rest-activity cycle may act as a zeitgeber helping to entrain the circadian system. Napping should be discouraged, as it will lessen homeostatic sleep drive and could delay nocturnal sleep onset. The strongest treatment evidence comes from studies demonstrating the efficacy of nightly exogenous melatonin administration as a phase-entraining agent, essentially stopping progressive circadian drifting or free running. Doses initially studied were in the multi-milligram range, but efficacy has more recently been demonstrated with melatonin doses of 0.3 to 0.5 mg.

Circadian Rhythm Sleep Disorder: Irregular Sleep-Wake Rhythm

The fundamental observation in irregular sleep-wake rhythm disorder is a lack of consolidation of major sleep and wake episodes. Hence, across the 24-hour day there are 3 or more sleep episodes, and this must be verified with at least 1 week of a daily sleep diary with or without wrist actigraphic monitoring. Although sleep is polyphasic, total sleep time per 24 hours is typically within normal limits. Obviously, this disorder should not be diagnosed in an infant or a very young child who has not yet reached the developmental stage when sleep could be expected to be consolidated into a major nocturnal sleep episode with no or only one daytime nap. The presenting complaint can be of insomnia, excessive daytime sleepiness, or both.

Pathophysiology of this disorder could be either an entirely absent or dysfunctional circadian system, which cannot exert its normal functions, to actively promote daytime alertness in service of consolidating a single major wake episode, and consolidating nocturnal sleep to allow for a normal-duration sleep episode. In fact, this deranged sleep-wake pattern is similar to what is observed in an animal model when the SCN has been removed. This absence of consolidated sleep and wake bouts can be observed in children with severe neurodevelopmental disorders. In the pediatrics literature, it is often difficult to discern if the patients had circadian problems suggestive of delayed sleep phase type, free-running type, irregular sleep-wake rhythm type, or a combination. Unfortunately, most of the research in the irregular sleep-wake rhythm type has been conducted on older adults, particularly in patients with neurodegenerative diseases such as Alzheimer’s.

Caveats aside, presleep melatonin administration has been shown to decrease daytime sleep duration and increase nighttime sleep duration in children with severe psychomotor retardation and in other clinical populations where irregular sleep-wake rhythm may have been a factor (eg, Jan and colleagues ). Prescribing a regular sleep-wake schedule with active parental involvement is also recommended at the “option” level by the AASM practice parameter, although the supporting evidence base is relatively weak.

Circadian Rhythm Sleep Disorder: Jet Lag Type

With an understanding of the shared modulation of sleep and wakefulness from the sleep homeostatic and circadian systems, the easiest circadian rhythm sleep disorders to understand are jet lag and shift work. These two disorders share much in common, in terms of symptomatology, the “voluntary” circumstances that initiate them, and the treatment alternatives.

Developments in aviation over the past century have occurred in many areas. Speed nears the sound barrier, owing first to turbojet and now turbofan engines found on modern commercial aircraft. The efficiency of turbofan engines and increased fuel capacity allow aircraft to travel distances up to halfway around the world, in fact more than 12,000 miles. To achieve high speed and fuel efficiency requires travel at high altitudes where the air density is extremely low, typically in the 30,000-ft to 45,000-ft range above sea level, requiring cabin pressurization. Unfortunately, cabin pressurization is typically well below the air pressure found at ground elevation, resulting in a condition similar to acute mountain sickness. Also, to avoid premature deterioration of the aircraft cabin’s aluminum skin, cabin humidity is kept very low, which leads to further physical discomfort (eg, dry skin, eyes, and nasal passages, as well as dehydration). Stress and/or time spent in preparation for travel before a flight can lead to curtailment of the sleep episode preceding travel, and hence the traveler has excessive daytime (or nighttime) sleepiness and fatigue. Many seek the aid of caffeine to maintain alertness before or during the flight, perhaps impairing subsequent sleep and causing further dehydration in flight. Alcohol is commonly used (by adults and hopefully not by children) as a sleep aid and/or anxiolytic, yet alcohol further compounds dehydration, and risks rebound alerting and even anxiety. These are many of the features commonly encountered in jet travel that have nothing to do with crossing time zones. In essence, much of the constellation of symptoms noted after crossing time zones have nothing to do with adaptation to the new time zone, but are rather attributable to the previously listed contributing factors. However, behavioral treatments can address many of these threats, such as keeping the child hydrated, avoiding dehydrating substances, and minimizing stress and optimizing sleep before travel.

The “true” pathophysiology of the circadian features of jet lag are attributable to the attempt to sleep and be awake in a new time zone, and hence, at different circadian phases than in one’s home time zone. Travel eastward, such as the 4 to 8 hours encountered from the United States to the European Union forces the traveler to attempt to initiate sleep much earlier than normal, during the wake-promoting region of the circadian system’s “daytime.” Sleep onset may be further delayed because the new “bedtime” on arrival occurs hours earlier than the previous sleep episode, and hence not as much sleep homeostatic pressure may have accumulated during the wake episode preceding the first sleep attempt on arrival. Similarly, the circadian system will lag many hours behind the new, earlier sleep schedule and hence for up to the first half of the daytime hours in the new time zone, the circadian system will still be promoting sleep, impairing alertness and concentration. Travel westbound, such as from the East Coast to the West Coast or Hawaii is typically accompanied by milder symptoms of circadian misalignment. It is typically easier to extend the duration of wake by several hours and build additional sleep homeostatic drive, which will further increase ease of sleep initiation and sleep consolidation. However, an early morning awakening may occur, because the circadian system will begin its “morning” stimulation of wakefulness too early for the new “later” time zone.

The official diagnosis of jet lag per the ICSD-2 requires a complaint of insomnia and/or excessive daytime sleepiness following crossing 2 or more time zones, accompanied by physical or other consequences within 2 days of arrival. Sequelae are many and vary across individuals, and can include gastrointestinal complaints, general malaise, and impaired cognitive functioning. No objective testing is required to make the diagnosis.

Treatments for jet lag can be divided up many ways: homeostatic versus circadian, behavioral versus pharmacologic, or preflight versus in flight versus postflight. The last model will be used here. Before the flight, many behavioral strategies will be important, not only for children but for adults as well. Optimization of sleep on the nights leading up to travel is critical to avoid sleep deprivation before flight. If the flight is to be of sufficient duration to permit sleep, then it will be best to have the child avoid caffeine intake before flight, minimizing dehydration and also the sleep-impairing effects of caffeine. Finally, many children experience anxiety surrounding travel, and hence, strategies to minimize this anticipatory (and subsequent real-time) anxiety will be helpful.

During the flight, as noted earlier, adequate fluid intake is important to avoid dehydration and associated tissue irritation. Optimization of opportunity for sleep is important, particularly on longer flights or if sleep loss occurred before flight. Just as sleep hygiene is recommended for optimal sleep at home, measures can be taken to improve sleep in flight, such as the use of an eye mask or sunglasses, ear plugs or noise-cancelling headphones, and adding or removing layers of clothing for temperature regulation. On arrival at the destination, recommendations for sleep depend on the direction and the number of time zones crossed. For shorter flights and minimal time zone difference, such as a westbound flight crossing 3 time zones, it may be enough to supplement with an in-flight nap, allowing children sufficient sleep to remain awake 3 hours “later” that evening to maintain their “at home” bedtime in the new time zone (eg, even though it might be midnight at home in New York, the child can remain awake until their normal “9 pm bedtime” in Los Angeles).

The most sophisticated treatments for jet lag involve increasing the rate of circadian phase shifting on arrival, or in more recent advances, even “preadapting” by partially or fully shifting circadian phase before travel. Most of the phase-shifting literature on jet lag involves the use of exogenous melatonin, which unfortunately is not typically recommended for use in young children or adolescents, given potential effects on the reproductive endocrine system. But because of the high quality of evidence showing efficacy of exogenous melatonin as a treatment for jet lag, it is recommended at the “standard of practice” level in the AASM’s 2007 practice parameter. However, the use of properly timed, artificial bright light is an effective treatment to preadapt before jet lag, although the studies have typically involved only adult participants. For an extremely comprehensive description of multicomponent (eg, sleep schedule shifting, exogenous melatonin, and both sunlight and artificial bright light) protocols to preadapt before jet travel, the reader is referred to the work of Charmane Eastman and colleagues.

Circadian Rhythm Sleep Disorder: Shift Work Type

Given child labor laws and the fact that most are attending daytime school, it is extremely rare to encounter shift work disorder in children or adolescents. However, many adolescents are involved in after-school jobs to supplement their or their family’s income, many of these jobs going well into the evening hours, such as the traditional “second shift.” Further, the pediatrician could be the first to note significant daytime sleepiness in a parent who works rotating or night-shift work. Thus, indirectly, by encouraging the parent to note the significance of their sleepiness and the ability to seek treatment for shift work disorder, caregiving of the child may improve in the balance. Thus, shift work disorder will be covered briefly in this article.

Typically, the patient reports difficulty obtaining sufficient total sleep time (insomnia) during a sleep episode falling outside of the typical nocturnal hours, inability to maintain optimal alertness during work hours that fall outside of a normal day shift, or both. The shift work schedule has to have been worked for at least 1 month, and accompanying physical or other seqeulae must be reported, as with jet lag. At least 1 week of a daily sleep diary with or without actigraphic monitoring must suggest sleep episodes are attempted at an adverse circadian phase, although circadian phase itself does not have to be objectively measured. Just as with jet lag, the symptoms of shift work disorder are multifactorial, and caused by similar factors. Behavioral and pharmacologic factors come into play, such as unintentional dehydration owing to ingestion of caffeine in an attempt to minimize excessive sleepiness during the work shift, or side effects experienced from alcohol or drugs used to self-medicate insomnia. As a general note, and across the circadian rhythm (and other) sleep disorders, the clinician is advised to ask in the clinical history about recreational or self-medication use of alcohol and/or illicit substances.

Pharmacologic strategies have shown great promise for increasing on-the-job alertness and performance during real or simulated shift work in adult research subjects, such as the planned use of caffeine before or during work, or ingestion of the wake-promoting substances modafinil and armodafinil before the work shift. Although many would be hesitant to prescribe a wake-promoting medication for a child, it is a reality that caffeine is commonly used in the pediatric population, perhaps for a variety of biologic, social, and psychological factors. Melatonin has also shown great promise as a sleep-promoting substance for daytime sleep episodes in shift work or when given to shift circadian phase into proper alignment with the new sleep-wake schedule required by the shift work. It is likely the case that a sleep-promoting effect of exogenous melatonin does not occur with ingestion before nighttime sleep episodes, and that the hypnotic effect is present only during daytime administration, at times when endogenous melatonin from the pineal is at very low levels or even absent. But as noted earlier, exogenous melatonin is not typically recommended for children, and the efficacy and safety of many of the wake-promoting substances have not been studied in children. Scheduled exposure to artificial bright light, phototherapy, has been demonstrated in numerous publications to effectively shift circadian phase into proper alignment in night-shift workers to increase nighttime alertness and increase daytime sleep duration. Phototherapy is in fact recommended at the “guideline” level as a treatment for shift work disorder in the AASM’s 2007 practice parameter. However, this approach is not practical for young children and adolescents who essentially are not part of the night-shift working population. Sleep scheduling is recommended at the “standard of practice” level for shift work disorder. Scheduled, prophylactic naps are of particular utility for teenagers or adults working into the evening hours, and can be critical for those working the night shift to supplement their typically shortened daytime sleep episode.

Circadian Rhythm Sleep Disorder: Advanced Sleep Phase Type

Advanced sleep phase disorder is nearly the opposite of DSPD; the primary complaints in ASPD are difficulty remaining awake until the desired evening bedtime and early morning awakening. Sleep is of reasonable duration and quality when initiated at this earlier hour. As with DSPD, the diagnosis of ASPD requires at least 1 week of a daily sleep diary with or without accompanying wrist actigraphic monitoring that verifies the earlier or advanced timing of sleep. The suspected pathophysiology of ASPD is that for reasons unknown, the patient’s circadian phase has shifted too early relative to the desired sleep-wake schedule, and thus the circadian promotion of wakefulness ceases too far in advance of the desired bedtime, resulting in the advanced timing of sleep onset. Further, the circadian sleep maintenance zone ends too early to sustain the nocturnal sleep episode until the desired wake time, leading to the early morning awakening. There may also be contributions of changes in how the circadian system engages in sleep regulation; it is noted that even healthy older adults are more likely to describe themselves as “morning larks” are less “phase tolerant” of sleeping in late (they awaken at an earlier circadian phase and hence an earlier clock hour). Treatment options for ASPD include hypnotics to extend sleep duration, afternoon or evening bright light exposure to cause a circadian phase delay, and chronotherapy. Given the observation that ASPD is not a disorder typically found in young children or adolescents and hence is not relevant to the theme of this book, readers are encouraged to consult any of a number of excellent reviews for further information.

Clinical Challenges

The reader is encouraged to think about the circadian rhythm sleep disorders as having been well-specified in terms of clinical presentation, but highly variable in terms of degree of certainty of pathophysiology (eg, DSPS and ASPD). Thus, objective and subjective measures should be used to make the diagnosis and/or measure response to treatment, as well as the efficacy and effectiveness of treatments. A particular problem in pediatrics and pediatric sleep medicine is that although commonly prescribed, there is a lack of data in children for efficacy and safety for most hypnotic and wake-promoting medications. Another challenge is appreciating that in certain clinical populations, such as in severe neurodevelopmental disorders, there may be diffuse sleep complaints from the patient and/or by proxy from the parents that do not fit neatly within a single ICSD-2 insomnia or circadian rhythm sleep disorder diagnosis, but nonetheless may be responsive to single or multicomponent treatment approaches.