Thirty-five percent of adults experience sleep-related symptoms over the course of a year, making them among the most common symptoms seen in medical practice. Ten to fifteen percent of adults suffer chronic insomnia and account for the largest proportion of patients seeing health care providers for sleep-related problems. Insomnia increases risk for other chronic diseases, including hypertension, diabetes, depression, and dementia. Daytime sleepiness impairs work performance and increases the risk of industrial and motor vehicle accidents. Sleep loss due to sleep-related breathing problems leads to profound sleepiness and life-threatening cardiovascular and pulmonary diseases. Sleep deprivation is known to increase risk for depression and dementia. Sleep medications themselves carry morbidity such as falls, daytime anxiety, and worsened sleep apnea. In this chapter, we review normal sleep, disorders of both sleep and wakefulness, and a logical clinical approach to these disorders.

Sleep has a structure, or architecture, that consists of nonrapid eye movement (non-REM) and REM sleep cycles. The wake electroencephalogram (EEG) contains low-voltage, high-frequency waveforms that become dominated by alpha waveforms (8–12 cps) as a person becomes drowsy. There are four stages of non-REM sleep. Stage 1 is defined by the disappearance of the alpha pattern, the appearance of slower theta waveforms (2–7 cps) along with slow, rolling eye movements. Stage 2 is defined by the appearance of low-frequency, high-amplitude discharges (K complexes) and brief high frequency (12–14 cps), variable-amplitude discharges (sleep spindles) on a background of theta waveforms similar to stage 1. The majority of sleep time is spent in stage 2 non-REM. The emergence of slow waves (high-amplitude, low-frequency [0.5–2 cps] delta waveforms) heralds stage 3 sleep, when they make up at least 20% of sleep time, and stage 4 sleep when they comprise more than 50% of sleep time. These two stages are known as the “deep stages” of sleep, because they are associated with high-arousal thresholds. REM sleep is a distinct state of sleep characterized by wake pattern EEG, skeletal muscle paralysis, and rapid, conjugate eye movements. The central nervous system (CNS) is predominantly active during REM sleep, and this is when a majority of dreams occur.

With the initiation of sleep, the healthy adult will descend through the non-REM stages within 45–60 minutes before beginning the first REM cycle, which tends to be brief. As the night progresses, less time is spent in slow-wave sleep, and REM cycle duration increases, eventually comprising 20–25% of total sleep time. The non-REM/REM cycle typically lasts 90–110 minutes, with about four complete cycles per night.

The timing and duration of sleep are controlled by many factors. Although most adults have some control over when they go to bed and when they get up, they have less control over how much sleep they need, and the quality of the sleep they get. Although stimulants such as caffeine and habituation to a state of chronic fatigue can help people cope with inadequate sleep, they must ultimately pay the price of diminished energy and mental efficiency. Individual sleep requirements vary; although most people need 6–9 hours of sleep per night, the human range is thought to be from 3 to 12 hours. Children generally need more sleep than adults, but after adolescence, daily sleep requirement remains fairly stable until late life. In old age, sleep need may increase or decrease, but the most dramatic changes are in sleep quality and duration. There is a gradual reduction in the amount of time spent in deep sleep as we age, plus a tendency to have more awakenings at night and more naps during the day.

The body clock (hypothalamic suprachiasmatic nucleus or SCN), functions as the circadian pacemaker. It superimposes a rhythm of sleepiness and alertness to days and nights and determines whether a person is a night owl, morning lark, or somewhere in between. The light–dark cycle and nightly rhythm of melatonin secretion by the pineal gland act synergistically to keep the body clock synchronized with the day–night cycle, allowing alertness during the day and sleepiness at night for people who are entrained to a conventional diurnal schedule. The interaction of the SCN, melatonin cycle, and exposure to dawn and dusk time cues determines how well a person adapts to changes in sleep schedule in order to accommodate travel across time zones, seasonal changes in photoperiod, or work and social schedules that keep people active during the night. Blindness imposes special challenges in adaptation of sleep to the light–dark cycle. Consequently, sleep complaints are common among visually impaired people.

Yawning is a phenomenon that has intrigued humans for decades. Yawning is thought to be an arousal mechanism that provides signals to the diencephalon to remain awake. It may also serve a social function. “Contagious” yawning is seen in most mammalian species and most commonly occurs between individuals that are closely related to each other or engaged in collaborative activity.

Childhood

Newborns typically spend about 70% of each day asleep, with more time in REM than older children and adults. A circadian pattern of wake and sleep does not usually develop until 1–2 months of age, and rhythmic melatonin secretion is identified at 12 weeks. Sleeping through the night is one of the first maturational milestones, and this development is of great interest to parents. Children’s sleep is initially polyphasic, with day as well as night sleep. There are decreasing amounts of daytime napping until the child is 4 or 5 years. From the age of 5 to 10 years, children are usually consummate nocturnal sleepers with few arousals. Total sleep time gradually decreases throughout childhood, but for hormonal and psychosocial reasons the amount and quality of sleep drops sharply with puberty.

Daytime restlessness, including the full spectrum of attention deficit hyperactivity disorder (AD/HD), should prompt consideration of obstructive sleep apnea (OSA) syndrome, often due to enlarged tonsils and adenoids in children (see Chapter 27). There is ongoing debate over household arrangements for children’s sleep. Some anthropologists point out that isolating a newborn in a separate bedroom is unique to western cultures and that co-sleeping with infants is more natural and may be beneficial. Recent studies have linked bed sharing with Sudden Infant Death Syndrome (SIDS), however, and the current recommendation of the American Academy of Pediatrics is to place infants in a separate sleeping area in the same room with the parent.

Adolescence and Young Adulthood

Adolescents are generally able to maintain the high sleep efficiency of childhood, with few nighttime arousals and little daytime sleepiness. In practice, adolescents frequently become more night-oriented, staying up late to do homework, work part-time jobs, chat with friends via text or phone, using Internet social media sites or socializing away from home. Many adolescents and young adults develop strong tendencies to being “night owls” (see Delayed Sleep Phase Disorder in the “Chronobiological” section of this chapter). Getting up for school may become an extreme challenge for some, and overall sleep deprivation with daytime sleepiness (especially in the morning) is endemic in high schools. Also, high prevalence rates of mood and anxiety disorders and the normal emotional highs and lows of this period of life make transient insomnia more common, with difficulty falling asleep, staying asleep or both. Early experiences with various substances affecting sleep, such as caffeine, nicotine, alcohol, marijuana, hallucinogens, and stimulants also can be strong factors. Serious mental illness such as schizophrenia or bipolar spectrum mood disorders start to express themselves with significant prevalence in adolescence and young adulthood, sometimes expressed with sleep or wake disorders. Physical illnesses producing inflammation, pain, endocrine, and metabolic imbalances can all impact sleep and need to be considered in clinical assessment. Excessive daytime sleepiness at this age is usually due to sleep deprivation, but substance abuse and narcolepsy need to be considered. People may suffer for many years with narcolepsy before the diagnosis is made. It should be considered in anyone with spells of sleepiness off and on during the day, especially if a very brief nap is very helpful for an hour or two.

Middle Adulthood and Old Age

Sleep tends to be lighter as people age, with more frequent awakenings and the near disappearance of deep or slow-wave sleep. Sleep timing may “phase advance” with earlier bedtimes and early morning awakenings. Whereas younger insomniacs typically struggle with sleep onset, older people with insomnia may just as likely complain of sleep maintenance problems due to this tendency toward phase-advanced sleep–wake cycle. More frequent daytime napping, either through boredom or need, is very common in older adults. This, along with decreased daytime physical activity, further erodes nighttime sleep efficiency. Frequent nocturia and esophageal reflux can make a bad situation worse with regard to sleep. Clinical sleep disorders also increase with age. Obstructive sleep apnea, periodic leg movements, restless legs syndrome (RLS), depression, anxiety, alcohol, and pain all affect the restorative qualities of sleep. Little wonder, then, that insomnia becomes more prevalent in midlife, especially in women and people with multiple chronic diseases.

Sleep disorders are generally grouped into three categories: disorders of initiating and maintaining sleep (insomnia); disorders of excessive daytime sleepiness (hypersomnia); and abnormal sleep behaviors (parasomnia) (Table 31-1).

Every review of systems should include screening patients for daytime sleepiness and nighttime sleep problems. Four basic questions give clinicians a head start in diagnosing sleep disorders and determining whether they warrant treatment:

• 
  

  How are you sleeping?

  
  
• 
  

  How much sleep do you get in a typical night?

  
  
• 
  

  How much sleep do you typically need to feel your best?

  
  
• 
  

  Do you feel alert during the day?

Follow-up questions should sharpen the differential diagnosis of specific disorders of either sleep or wakefulness. In both pediatrics and geriatrics, it is often the parent, spouse, or caregiver who notices a problem. With children, ascertain whether the parent or caregiver is knowledgeable about normal sleep patterns for children. If the behavior is outside of the norm, then further questioning is necessary for diagnosis.

The sleep–wake cycle is a complex electrophysiologic process consisting of alternating periods of wakefulness, REM sleep, and non-REM sleep. Each of these periods has a characteristic EEG, peripheral muscle, and autonomic nervous system pattern that can be documented by polysomnographic (PSG) recording in hospital and clinic-based sleep laboratories or in the home, using technologies that allow for unattended in-home recordings. PSG allows clinicians to make specific diagnoses based on electrophysiologic monitoring of EEG, electrooculogram, electromyogram, nasal airflow, ear oximetry, and electrocardiogram.

Insomnia: Insufficient and Nonrestorative Sleep

Transient and Chronic Insomnia

Insomnia is one of the most common complaints in primary care practice. It is diagnosed when there is either insufficient or nonrestorative sleep. It is essentially a subjective diagnosis although more objective means of assessment will be discussed later in the chapter. Certainly one of the first tasks is to confirm deficient sleep quantity or quality relative to normal sleep requirement for that person. Sleep requirement is best defined by how much sleep a person needs to be alert through the day, with perhaps a brief dip in alertness midday. Sleep requirement is genetically determined and also influenced by age, activity, and health. Eight hours is the adult mean sleep requirement with a range of 6–9 hours for most people. There can also be seasonal variation at high latitudes. Nonrestorative sleep diagnoses (e.g., sleep apnea, periodic leg movements, pain, depression, nightmares, etc.) should be pursued when there is adequate sleep time but poor daytime function.

It is best to think of insomnia as a symptom rather than a diagnosis. Many factors combine to produce insomnia, which often occurs when a delicate balance is tipped; for example, a constitutionally light sleeper may be fine until he or she enters a period of stress or uses a medication that has alerting effects. It may be necessary to deal with several causative factors concurrently to restore a natural sleep cycle.

Insomnia is often described as initial insomnia (trouble falling asleep), and middle or terminal insomnia (trouble staying asleep or early awakening). Insomnia may be transient (self-limited) or chronic (persistent or relapsing). Transient insomnia can evolve into chronic insomnia through a number of factors.

Transient insomnia caused by stress, environment (cold, noise, new baby), acute illness, or pain is easy to identify and usually needs no special intervention other than addressing the underlying problem. A brief course of sedative–hypnotic medication is occasionally warranted and may reduce the risk of developing long-term insomnia. Travel across time zones can cause a mismatch between the body clock and the day–night cycle, resulting in transient insomnia known as “jet lag.” Combined with fatigue from travel, jet lag can ruin the first few days of a trip. Shift workers may experience the same phenomenon and can suffer severe health and social consequences because of it.

Persistent or chronic insomnia accounts for 40–88% of patients who present with a primary complaint of insomnia. Chronic insomnia is a diagnosis of exclusion, and must be differentiated from the many other causes of long-term sleep disruption. Chronic insomnia may be due to persistence of the stress that initially caused transient insomnia. Occasionally, the insomnia continues even when the precipitating factors have resolved, presumably through a process of operant conditioning to an arousal state incompatible with sustained, restful sleep. “Conditioned” or learned insomnia may persist secondary to poor sleep hygiene, such as erratic sleep schedules, alcohol, caffeine, nicotine, work on finances, nighttime television or Internet and other habits that can prevent achieving the peaceful state of mind that is important to overcome sleep resistance. Growing frustration with failed attempts to sleep increases the psychophysiologic arousal that is the underlying cause of sleeplessness. In fact, this type of insomnia, developing over time in association with stress, worry, and frustration over sleep, is often called “psychophysiologic” insomnia. People with this type of insomnia show high levels of physiologic stress markers (hormonal, autonomic, and cognitive). Despite severe sleep deprivation and pent up sleep drive, the arousal mechanisms of the stress response create too much sleep resistance to be overcome. Occasionally, this psychophysiologic arousal may be seen early in life in a form of “primary insomnia” due to intrinsic biological variation in either sleep drive (reduced) or stress response (increased). In contrast to people with transient insomnia and sleep deprivation, patients with the psychophysiologic and primary forms of chronic insomnia report inability to nap.

As a model psychosomatic illness, chronic insomnia requires a holistic approach that can include use of medication as well as cognitive strategies to reduce anxiety and changes to improve sleep hygiene (Table 31-2). Short-term use of sedative–hypnotic medications is appropriate to break the cycle of anxiety, arousal, and insomnia (see “Medical Treatment,” below). In some patients, the symptoms suggest another disorder that can be targeted separately (depression, RLS, pain, etc.).

Chronobiological Disorders

Many cases of both transient and chronic insomnia are due to underlying chronobiological or circadian rhythm disturbances. If there is a mismatch between a person’s attempts to sleep and their endogenous circadian rhythm for sleep, insomnia may result. The circadian rhythm of the sleep–wake cycle is driven by the hypothalamic circadian pacemaker or “body clock.” Disturbances in the circadian timing of sleep may be transient, as in jet lag and shift work syndromes, or chronic, as in delayed sleep phase syndrome (DSPS), advanced sleep phase syndrome, and free-running sleep syndrome. The last is most common in blind persons, who lack the critical input of the light–dark cycle in regulating circadian rhythms. Diagnosis of chronobiological disorders is based on the understanding that except for its timing, sleep is normal in these conditions.

In DSPS, patients are “obligate” night owls, staying up late into the night through varying proportions of choice and biological drive. Patients with this condition struggle to awaken in the morning for school or work. They tend to have more energy as the day progresses and may “come alive” in the evening. Attempts to fall asleep before midnight can result in hours of tossing and turning. Sleep efficiency is usually normal when they are free to choose their own bedtimes. The condition is common in young people but can persist into middle adulthood and even old age, although it does tend to moderate with time. Adults with DSPS typically migrate to jobs in which they can work swing or night shifts, or keep totally flexible hours. They may have particular difficulty flying east across time zones, as they are relatively resistant to circadian “phase advance.” Most “night owls” have flexibility in their circadian pacemaker and can adapt to earlier sleep hours with effort. Those with true DSPS cannot adjust to conventional hours at all, or only with great effort and treatment.

Children and adolescents with DSPS may be thought of as “lazy” because of how difficult it is for them to get out of bed in the morning and their tendency to “sleep in” on weekends. When school is in session, Sunday night bedtime and Monday morning awakenings are particularly challenging. With a late sleep-onset, the child has trouble waking up Monday mornings and this starts the week off “on the wrong side of the bed.” This may lead to disruptive behavior, hyperactivity, distractibility, failure to attend, and learning problems in school. Parents and teachers must recognize that DSPS is not a behavioral problem but a circadian rhythm disorder that can improve with proper treatment. A phase shift approach by the whole family of consistent bed times 7 days a week is very helpful. Practicing good sleep hygiene, bright light therapy and melatonin have been shown to be effective (see “Treatment for Insomnia”).

Other forms of chronobiological sleep disorders are seen in practice. Shift workers often try to live on a conventional schedule to spend days off with friends or family. This can result in failure to adapt to either day or night and leads to poor sleep, poor energy, and chronically elevated risk for chronic illness and premature death. Scheduled exposure to bright light and melatonin can accelerate adaptation to shift work schedules.

Many blind individuals also have problems maintaining synchronicity between sleep and the day–night cycle. Lacking photic input to the circadian pacemaker via the retinohypothalamic tract, blind individuals can have an internal sleep propensity rhythm that is chronically out of phase with the day–night cycle, leading to frequent bouts of insomnia. Chronobiological insomnia from “free-running” circadian rhythms in blind patients is treatable with properly timed melatonin administration, but this and other chronobiological disorders should be treated in consultation with a sleep disorder specialist.

Neuropsychiatric Disorders

Sleep disturbances are among the most common symptoms of mental illnesses, particularly mood and anxiety disorders. Depression should always be considered in patients complaining of frequent nighttime awakenings and early morning arousal, particularly when those arousals are accompanied by anxiety and worry. On the other hand, many depressed patients complain of hypersomnia with fatigue and difficulty getting going in the morning. This symptom is especially characteristic of seasonal affective disorder (SAD) and so-called atypical depression. Both are common in young and middle-aged adults. Depressed patients find the sleep changes of their mood disorder very distressing, in contrast to manic patients. Bipolar patients in manic or less severe hypomanic states, typically experience less sleep drive and will enjoy their round-the-clock energy even as it impairs their judgment and physical health (see Chapter 25).

Sedating antidepressant medications (e.g., mirtazapine) may help with the insomnia secondary to depression, but can also lead to daytime sedation. Trazodone and the more sedating tricyclic antidepressants (TCAs)—e.g., doxepin, amitriptyline, and nortriptyline—may be considered. The TCAs combine moderate-to-severe sedation with effective antidepressant activity but must be used with caution due to overdose toxicity and anticholinergic effects. Serotonin reuptake inhibitors (either SSRIs or SNRIs) generally will not improve sleep immediately, and can even increase leg movements and arousals. A brief course of a sedative–hypnotic agent for help with sleep is a comforting strategy for some patients. The sleep medication can be tapered and discontinued as the depression and secondary insomnia improve.

Anxiety disorders can also present with initial and middle insomnia (see Chapter 26). Nightmares, particularly in posttraumatic stress disorder (PTSD), frequently complicate the picture. Antidepressant medications, prazosin, and clonidine have been reported to be helpful with the sleep-related symptoms. Bereavement is usually accompanied by anxiety and insomnia. Short-term use of sedative–hypnotic medications may help patients who struggle to get through long nights.

Attention deficit disorder (ADD) and AD/HD may be associated with disturbances in REM sleep as well as frequent myoclonic or periodic movements throughout the night. Insomnia is common; many patients with the condition report difficulty controlling racing thoughts and restlessness day or night. Snoring and obstructive apneas are frequently present in children who have mild symptoms of ADD–AD/HD. In these cases, the cognitive and behavioral syndrome of ADD–AD/HD can improve with treatment of the sleep-related breathing disorder by tonsillectomy or dental appliances.

Traumatic brain injuries and stroke impair alertness more often than sleep, but disruption of circadian rhythms with daytime sleep and nighttime awakenings are common. Neurodegenerative diseases such as Alzheimer disease (AD) and Parkinson disease (PD) disrupt sleep. Alzheimer disease can erode normal diurnal sleep–wake patterns, resulting in long nighttime awakenings and increased daytime sleep. This can be stressful for caregivers, who must be vigilant during these nocturnal wanderings. Sleep disruption is among the most stressful aspects of caring for a person with dementia at home. Severe insomnia can develop in some patients with AD, with little sleep day or night. Others may sleep all the time, creating a form of chronic delirium as the disease progresses into late stages. Structured daytime activity can help reduce daytime sleepiness, especially if boredom appears to be one of the contributing factors. Antihistamines and benzodiazepines should be avoided given the risk for confusion and paradoxical excitement. Cautious use of melatonin, trazodone, or quetiapine may be helpful, although the data are limited. However, given how stressful sleep disruption is for families and patients, trials of sleep-promoting medications at low doses can be justified.

Parkinson Disease patients can also have severe sleep problems. Akinesia causes physical discomfort over pressure points that normally would be relieved by tossing and turning in sleep. Medications used to treat PD can also impair sleep. Furthermore, the neurodegenerative and neurotransmitter changes caused by the disease adversely affect sleep quality. Dementia with Lewy Bodies, a disease related to PD, is associated both with impaired nighttime sleep, poor daytime alertness, and increased motor activity during REM sleep (see “REM Behavior Disorder,” below).

Alcohol and Drugs