12. Sleep-Wake Disorders

The Classification of sleep-wake disorders is intended for use by general mental health and medical clinicians (those caring for adult, geriatric, and pediatric patients). Sleep-wake disorders encompass 10 disorders or disorder groups: insomrua disorder, hypersomjiolence disorder, narcolepsy, breathing-related sleep disorders, circadian rhythm sleep-wake disorders, non-rapid eye movement (NREM) sleep arousal disorders, nightmare disorder, rapid eye movement (REM) sleep behavior disorder, restless legs syndrome, and substance/medication-induced sleep disorder. Individuals with these disorders typically present with sleep-wake complaints of dissatisfaction regarding the quality, timing, and amount of sleep. Resulting daytime distress and impairment are core features shared by all of these sleep-wake disorders.

The organization of this chapter is designed to facilitate differential diagnosis of sleepwake complaints and to clarify when referral to a sleep specialist is appropriate for further assessment and treatment planning. The DSM-5 sleep disorders nosology uses a simple, clinically useful approach, while also reflecting scientific advances in epidemiology, genetics, pathophysiology, assessment, and interventions research since DSM-IV. In some cases (e.g., insomnia disorder), a "lumping" approach has been adopted, whereas in others (e.g., narcolepsy), a "splitting" approach has been taken, reflecting the availability of validators derived from epidemiological, neurobiological, and interventions research. Sleep disorders are often accompanied by depression, anxiety, and cognitive changes that must be addressed in treatment planning and management. Furthermore, persistent sleep disturbances (both insomnia and excessive sleepiness) are established risk factors for the subsequent development of mental illnesses and substance use disorders. They may also represent a prodromal expression of an episode of mental illness, allowing the possibility of early intervention to preempt or to attenuate a full-blown episode.

The differential diagnosis of sleep-wake complaints necessitates a multidimensional approach, with consideration of possibly coexisting medical and neurological conditions. Coexisting clinical conditions are the rule, not the exception. Sleep disturbances furnish a clinically useful indicator of medical and neurological conditions that often coexist with depression and other common mental disorders. Prominent among these comorbidities are breathing-related sleep disorders, disorders of the heart and lungs (e.g., congestive heart failure, chronic obstructive pulmonary disease), neurodegenerative disorders (e.g., Alzheimer's disease), and disorders of the musculoskeletal system (e.g., osteoarthritis). These disorders not only may disturb sleep but also may themselves be worsened during sleep (e.g., prolonged apneas or electrocardiographic arrhythmias during REM sleep; confusional arousals in patients with dementing illness; seizures in persons with complex partial seizures). REM sleep behavior disorder is often an early indicator of neurodegenerative disorders (alpha synucleinopathies) like Parkinson's disease. For all of these reasons— related to differential diagnosis, clinical comorbidity, and facilitation of treatment planning—sleep disorders are included in DSM-5.

The approach taken to the classification of sleep-wake disorders in DSM-5 can be understood within the context of "lumping versus splitting." DSM-IV represented an effort to simplify sleep-wake disorders classification and thus aggregated diagnoses under broader, less differentiated labels. At the other pole, the International Classification of Sleep Disorders, 2nd Edition (ICSD-2) elaborated numerous diagnostic subtypes. DSM-IV was prepared for use by mental health and general medical clinicians who are not experts in sleep medicine. ICSD-2 reflected the science and opinions of the sleep specialist community and was prepared for use by specialists.
The weight of available evidence supports the superior performance characteristics (interrater reliability, as well as convergent, discriminant, and face validity) of simpler, lessdifferentiated approaches to diagnosis of sleep-wake disorders. The text accompanying each set of diagnostic criteria provides linkages to the corresponding disorders included in ICSD-2. The DSM-5 sleep-wake disorders classification also specifies corresponding nonpsychiatric listings (e.g., neurology codes) from the International Classification of Diseases (ICD).

The field of sleep disorders medicine has progressed in this direction since the publication of DSM-IV. The use of biological validators is now embodied in the DSM-5 classification of sleep-wake disorders, particularly for disorders of excessive sleepiness, such as narcolepsy; for breathing-related sleep disorders, for which formal sleep studies (i.e., polysomnography) are indicated; and for restless legs syndrome, which can often coexist with periodic limb movements during sleep, detectable via polysomnography.

12.1 Insomnia Disorder

Diagnostic Features

The essential feature of insomnia disorder is dissatisfaction with sleep quantity or quality with complaints of difficulty initiating or maintaining sleep. The sleep complaints are accompanied by clinically significant distress or impairment in social, occupational, or other important areas of functioning. The sleep disturbance may occur during the course of another mental disorder or medical condition, or it may occur independently.
Different manifestations of insomnia can occur at different times of the sleep period. Sleeponset insomnia (or initial insomnia) involves difficulty initiating sleep at bedtime. Sleep maintenance insomnia (or middle insomnia) involves frequent or prolonged awakenings throughout the night. Late insomnia involves early-morning awakening with an inability to return to sleep. Difficulty maintaining sleep is the most common single symptom of insomnia, followed by difficulty falling asleep, while a combination of these symptoms is the most common presentation overall. The specific type of sleep complaint often varies over time. Individuals who complain of difficulty falling asleep at one time may later complain of difficulty maintaining sleep, and vice versa. Symptoms of difficulty falling asleep and difficulty maintaining sleep can be quantified by the individual's retrospective self-report, sleep diaries, or other methods, such as actigraphy or polysomnography, but the diagnosis of insomnia disorder is based on the individual's subjective perception of sleep or a caretaker's report.

Nonrestorative sleep, a complaint of poor sleep quality that does not leave the individual rested upon awakening despite adequate duration, is a common sleep complaint usually occurring in association with difficulty initiating or maintaining sleep, or less frequently in isolation. This complaint can also be reported in association with other sleep disorders (e.g., breathing-related sleep disorder). When a complaint of nonrestorative sleep occurs in isolation (i.e., in the absence of difficulty initiating and/or maintaining sleep) but all diagnostic criteria with regard to frequency, duration, and daytime distress and impairments are otherwise met, a diagnosis of other specified insomnia disorder or unspecified insomnia disorder is made.
Aside from the frequency and duration criteria required to make the diagnosis, additional criteria are useful to quantify insomnia severity. These quantitative criteria, while arbitrary, are provided for illustrative purpose only. For instance, difficulty initiating sleep is defined by a subjective sleep latency greater than 20-30 minutes, and difficulty maintaining sleep is defined by a subjective time awake after sleep onset greater than 20-30 minutes. Although there is no standard definition of early-morning awakening, this symptom involves awakening at least 30 minutes before the scheduled time and before total sleep time reaches hours. It is essential to take into account not only the final awakening time but also the bedtime on the previous evening. Awakening at 4:00 A.M. does not have the same clinical significance in those who go to bed at 9:00 P.M. as in those who go to bed at 11:00 P.M. Such a symptom may also reflect an age-dependent decrease in the ability to sustain sleep or an age-dependent shift in the timing of the main sleep period.

Insomnia disorder involves daytime impairments as well as nighttime sleep difficulties. These include fatigue or, less commonly, daytime sleepiness; the latter is more common among older individuals and when insomnia is comorbid with another medical condition (e.g., chronic pain) or sleep disorder (e.g., sleep apnea). Impairment in cognitive performance may include difficulties with attention, concentration and memory, and even with performing simple manual skills. Associated mood disturbances are typically described as irritability or mood lability and less commonly as depressive or anxiety symptoms. Not all individuals with nighttime sleep disturbances are distressed or have functional impairment. For example, sleep continuity is often interrupted in healthy older adults who nevertheless identify themselves as good sleepers. A diagnosis of insomnia disorder should be reserved for those individuals with significant daytime distress or impairment related to their nighttime sleep difficulties.

Associated Features Supporting Diagnosis

Insomnia is often associated with physiological and cognitive arousal and conditioning factors that interfere with sleep. A preoccupation with sleep and distress due to the inability to sleep may lead to a vicious cycle: the more the individual strives to sleep, the more frustration builds and further impairs sleep. Thus, excessive attention and efforts to sleep, which override normal sleep-onset mechanisms, may contribute to the development of insomnia. Individuals with persistent insomnia may also acquire maladaptive sleep habits (e.g., spending excessive time in bed; following an erratic sleep schedule; napping) and cognitions (e.g., fear of sleeplessness; apprehensions of daytime impairments; clock monitoring) during the course of the disorder. Engaging in such activities in an environment in which the individual has frequently spent sleepless nights may further compound the conditioned arousal and perpetuate sleep difficulties. Conversely, the individual may fall asleep more easily when not trying to do so. Some individuals also report better sleep when away from their own bedrooms and their usual routines.

Insomnia may be accompanied by a variety of daytime complaints and symptoms, including fatigue, decreased energy, and mood disturbances. Symptoms of anxiety or depression that do not meet criteria for a specific mental disorder may be present, as well as an excessive focus on the perceived effects of sleep loss on daytime functioning. Individuals with insomnia may have elevated scores on self-report psychological or personality inventories with profiles indicating mild depression and anxiety, a worrisome cognitive style, an emotion-focused and internalizing style of conflict resolution, and a somatic focus. Patterns of neurocognitive impairment among individuals with insomnia disorder are inconsistent, although there may be impairments in performing tasks of higher complexity and those requiring frequent changes in performance strategy. Individuals with insomnia often require more effort to maintain cognitive performance.

Prevalence

Population-based estimates indicate that about one-third of adults report insomnia symptoms, 10%-15% experience associated daytime impairments, and 6%-10% have symptoms that meet criteria for insonmia disorder. Insomnia disorder is the most prevalent of all sleep disorders. u;i primary care settings, approximately 10%-20% of individuals complain of significant insomnia symptoms. Insomnia is a more prevalent complaint among females than among males, with a gender ratio of about 1.44:1. Although insomnia can be a symptom or an independent disorder, it is most frequently observed as a comorbid condition with another medical condition or mental disorder. For instance, 40%-50% of individuals with insomnia also present with a comorbid mental disorder.

Gender-Related Diagnostic issues

Insomnia is a more prevalent complaint among females than among males, with first onset often associated with the birth of a new child or with menopause. Despite higher prevalence among older females, polysomnographic studies suggest better preservation of sleep continuity and slow-wave sleep in older females than in older males.

Functional Consequences of Insomnia Disorder

Interpersonal, social, and occupational problems may develop as a result of insomnia or excessive concern with sleep, increased daytime irritability, and poor concentration. Decreased attention and concentration are common and may be related to higher rates of accidents observed in insomnia. Persistent insomnia is also associated with long-term consequences, including increased risks of major depressive disorder, hypertension, and myocardial infarction; increased absenteeism and reduced productivity at work; reduced quality of life; and increased economic burden.

12.2 Hypersomnolence Disorder

Diagnostic Features

Hypersomnolence is a broad diagnostic term and includes symptoms of excessive quantity of sleep (e.g., extended nocturnal sleep or involuntary daytime sleep), deteriorated quality of wakefulness (i.e., sleep propensity during wakefulness as shown by difficulty awakening or inability to remain awake when required), and sleep inertia (i.e., a period of impaired performance and reduced vigilance following awakening from the regular sleep episode or from a nap) (Criterion A). Individuals with this disorder fall asleep quickly and have a good sleep efficiency (>90%). They may have difficulty waking up in the morning, sometimes appearing confused, combative, or ataxic. This prolonged impairment of alertness at the sleep-wake transition is often referred to as sleep inertia (i.e., sleep drunkenness). It can also occur upon awakening from a daytime nap. During that period, the individual appears awake, but there is a decline in motor dexterity, behavior may be very inappropriate, and memory deficits, disorientation in time and space, and feelings of grogginess may occur. This period may last some minutes to hours.

The persistent need for sleep can lead to automatic behavior (usually of a very routine, low-complexity type) that the individual carries out with little or no subsequent recall. For example, individuals may find themselves having driven several miles from where they thought they were, unaware of the "automatic" driving they did in the preceding minutes. For some individuals with hypersomnolence disorder, the major sleep episode (for most individuals, nocturnal sleep) has a duration of 9 hours or more. However, the sleep is often nonrestorative and is followed by difficulty awakening in the morning. For other individuals with hypersomnolence disorder, the major sleep episode is of normal nocturnal sleep duration (6-9 hours). In these cases, the excessive sleepiness is characterized by several unintentional daytime naps. These daytime naps tend to be relatively long (often lasting 1 hour or more), are experienced as nonrestorative (i.e., unrefreshing), and do not lead to improved alertness. Individuals with hypersomnolence have daytime naps nearly everyday regardless of the nocturnal sleep duration. Subjective sleep quality may or may not be reported as good. Individuals typically feel sleepiness developing over a period of time, rather than experiencing a sudden sleep "attack." Unintentional sleep episodes typically occur in lowstimulation and low-activity situations (e.g., while attending lectures, reading, watching television, or driving long distances), but in more severe cases they can manifest in highattention situations such as at work, in meetings, or at social gatherings.

Associated Features Supporting Diagnosis

Nonrestorative sleep, automatic behavior, difficulties awakening in the morning, and sleep inertia, although common in hypersomnolence disorder, may also be seen in a variety of conditions, including narcolepsy. Approximately 80% of individuals with hypersomnolence report that their sleep is nonrestorative, and as many have difficulties awakening in the morning. Sleep inertia, though less common (i.e., observed in 36%-50% of individuals with hypersomnolence disorder), is highly specific to h)φersomnolence. Short naps (i.e., duration of less than 30 minutes) are often unrefreshing. Individuals with hypersomnolence often appear sleepy and may even fall asleep in the clinician's waiting area.A subset of individuals with hypersomnolence disorder have a family history of hypersomnolence and also have symptoms of autonomic nervous system dysfunction, including recurrent vascular-type headaches, reactivity of the peripheral vascular system (Raynaud's phenomenon), and fainting.

Prevalence

Approximately 5%-10% of individuals who consult in sleep disorders clinics with complaints of daytime sleepiness are diagnosed as having hypersomnolence disorder. It is estimated that about 1% of the European and U.S. general population has episodes of sleep inertia. Hypersomnolence occurs with relatively equal frequency in males and females.

Functional Consequences of Hypersomnoience Disorder

The low level of alertness that occurs while an individual fights the need for sleep can lead to reduced efficiency, diminished concentration, and poor memory during daytime activities. Hypersomnoience can lead to significant distress and dysfunction in work and social relationships. Prolonged nocturnal sleep and difficulty awakening can result in difficulty in meeting morning obligations, such as arriving at work on time. Unintentional daytime sleep episodes can be embarrassing and even dangerous, if, for instance, the individual is driving or operating machinery when the episode occurs.

12.3 Narcolepsy

Diagnostic Features

The essential features of sleepiness in narcolepsy are recurrent daytime naps or lapses into sleep. Sleepiness typically occurs daily but must occur at a minimum three times a week for at least 3 months (Criterion A). Narcolepsy generally produces cataplexy, which most commonly presents as brief episodes (seconds to minutes) of sudden, bilateral loss of muscle tone precipitated by emotions, typically laughing and joking. Muscles affected may include those of the neck, jaw, arms, legs, or whole body, resulting in head bobbing, jaw dropping, or complete falls. Individuals are awake and aware during cataplexy. To meet Criterion Bl(a), cataplexy must be triggered by laughter or joking and must occur at least a few times per month when the condition is untreated or in the past. Cataplexy should not be confused with ''weakness" occurring in the context of athletic activities (physiological) or exclusively after unusual emotional triggers such as stress or anxiety (suggesting possible psychopathology). Episodes lasting hours or days, or those not triggered by emotions, are unlikely to be cataplexy, nor is rolling on the floor while laughing hysterically.

In children close to onset, genuine cataplexy can be atypical, affecting primarily the face, causing grimaces or jaw opening with tongue thrusting ("cataplectic faces"). Alternatively, cataplexy may present as low-grade continuous hypotonia, yielding a wobbling walk. In these cases. Criterion Bl(b) can be met in children or in individuals within 6 months of a rapid onset.
Narcolepsy-cataplexy nearly always results from the loss of hypothalamic hypocretin (orexin)-producing cells, causing hypocretin deficiency (less than or equal to one-third of control values, or 110 pg/mL in most laboratories). Cell loss is likely autoimmune, and approximately 99% of affected individuals carry HLA-DQBl*06:02 (vs. 12%-38% of control subjects). Thus, checking for the presence of DQB1*06:02 prior to a lumbar puncture for evaluation of CSF hypocretin-1 immunoreactivity may be useful. Rarely, low CSF levels of hypocretin- 1 occur without cataplexy, notably in youths who may develop cataplexy later. CSF hypocretin-1 measurement represents the gold standard, excepting associated severe conditions (neurological, inflammatory, infectious, trauma) that can interfere with the assay. A nocturnal polysonrmographic sleep study followed by an MSLT can also be used to confirm the diagnosis (Criterion B3). These tests must be performed after the individual has stopped all psychotropic medications, following 2 weeks of adequate sleep time (as documented with sleep diaries, actigraphy). Short rapid eye movement (REM) latency (sleep-onset REM period, REM latency less than or equal to 15 minutes) during polysomnography is sufficient to confirm the diagnosis and meets Criterion B3. Alternatively, the MSLT result must be positive, showing a mean sleep latency of less than or equal to 8 minutes and two or more sleep-onset REM periods in four to five naps.

Associated Features Supporting Diagnosis

When sleepiness is severe, automatic behaviors may occur, with the individual continuing his or her activities in a semi-automatic, hazelike fashion without memory or consciousness. Approximately 20%-60% of individuals experience vivid hypnagogic hallucinations before or upon falling asleep or hypnopompic hallucinations just after awakening. These hallucinations are distinct from the less vivid, nonhallucinatory dreamlike mentation at sleep onset that occurs in normal sleepers. Nightmares and vivid dreaming are also frequent in narcolepsy, as is REM sleep behavior disorder. Approximately 20%-60% of individuals experience sleep paralysis upon falling asleep or awakening, leaving them awake but unable to move or speak. However, many normal sleepers also report sleep paralysis, especially with stress or sleep deprivation. Nocturnal eating may occur. Obesity is common. Nocturnal sleep disruption with frequent long or short awakenings is common and can be disabling.
Individuals may appear sleepy or fall asleep in the waiting area or during clinical examination. During cataplexy, individuals may slump in a chair and have slurred speech or drooping eyelids. If the clinician has time to check reflexes during cataplexy (most attacks are less than 10 seconds), reflexes are abolished—an important finding distinguishing genuine cataplexy from conversion disorder.

Prevalence

Narcolepsy-cataplexy affects 0.02%-0.04% of the general population in most countries. Narcolepsy affects both genders, with possibly a slight male preponderance.

Culture-Related Diagnostic issues

Narcolepsy has been described in all ethnic groups and in many cultures. Among African Americans, more cases present without cataplexy or with atypical cataplexy, complicating diagnosis, especially in the presence of obesity and obstructive sleep apnea.

Functional Consequences of Narcolepsy

Driving and working are impaired, and individuals with narcolepsy should avoid jobs that place themselves (e.g., working with machinery) or others (e.g., bus driver, pilot) in danger. Once the narcolepsy is controlled with therapy, patients can usually drive, although rarely long distances alone. Untreated individuals are also at risk for social isolation and accidental injury to themselves or others. Social relations may suffer as these individuals strive to avert cataplexy by exerting control over emotions.

12.4 Breathing-Related Sleep Disorders

The breathing-related sleep disorders category encompasses three relatively distinct disorders: obstructive sleep apnea hypopnea, central sleep apnea, and sleep-related hypoventilation.

12.4.1 Obstructive Sleep Apnea Hypopnea

Diagnostic Features

Obstructive sleep apnea hypopnea is the most common breathing-related sleep disorder. It is characterized by repeated episodes of upper (pharyngeal) airw^ay obstruction (apneas and hypopneas) during sleep. Apnea refers to the total absence of airflow, and hypopnea refers to a reduction in airflow. Each apnea or hypopnea represents a reduction in breathing of at least 10 seconds in duration in adults or two missed breaths in children and is typically associated with drops in oxygen saturation of 3% or greater and/or an electroencephalographic arousal. Both sleep-related (nocturnal) and wake-time symptoms are common. The cardinal symptoms of obstructive sleep apnea hypopnea are snoring and daytime sleepiness.
Obstructive sleep apnea hypopnea in adults is diagnosed on the basis of polysomnographic findings and symptoms. The diagnosis is based on symptoms of 1) nocturnal breathing disturbances (i.e., snoring, snorting/gasping, breathing pauses during sleep), or 2) daytime sleepiness, fatigue, or unrefreshing sleep despite sufficient opportunities to sleep that are not better explained by another mental disorder and not attributable to another medical condition, along with 3) evidence by polysomnography of five or more obstructive apneas or hypopneas per hour of sleep (Criterion Al). Diagnosis can be made in the absence of these symptoms if there is evidence by polysomnography of 15 or more obstructive apneas and/or hypopneas per hour of sleep (Criterion A2). Specific attention to disturbed sleep occurring in association with snoring or breathing pauses and physical findings that increase risk of obstructive sleep apnea hypopnea (e.g., central obesity, crowded pharyngeal airway, elevated blood pressure) is needed to reduce the chance of misdiagnosing this treatable condition.

Associated Features Supporting Diagnosis

Because of the frequency of nocturnal awakenings that occur with obstructive sleep apnea hypopnea, individuals may report symptoms of insomnia. Other common, though nonspecific, symptoms of obstructive sleep apnea hypopnea are heartburn, nocturia, morning headaches, dry mouth, erectile dysfunction, and reduced libido. Rarely, individuals may complain of difficulty breathing while lying supine or sleeping. Hypertension may occur in more than 60% of individuals with obstructive sleep apnea hypopnea.

Prevalence

Obstructive sleep apnea hypopnea is a very common disorder, affecting at least l%-2% of children, 2%-15% of middle-age adults, and more than 20% of older individuals. In the general community, prevalence rates of undiagnosed obstructive sleep apnea hypopnea may be very high in elderly individuals. Since the disorder is strongly associated with obesity, increases in obesity rates are likely to be accompanied by an increased prevalence of this disorder. Prevalence may be particularly high among males, older adults, and certain racial/ethnic groups. In adults, the male-to-female ratio of obstructive sleep apnea hypopnea ranges from 2:1 to 4:1. Gender differences decline in older age, possibly because of an increased prevalence in females after menopause. There is no gender difference among prepubertal children.

Culture-Related Diagnostic Issues

There is a potential for sleepiness and fatigue to be reported differently across cultures. In some groups, snoring may be considered a sign of health and thus may not trigger concerns. Individuals of Asian ancestry may be at increased risk for obstructive sleep apnea hypopnea despite relatively low BMI, possibly reflecting the influence of craniofacial risk factors that narrow the nasopharynx.

Gender-Related Issues

Females may more commonly report fatigue rather than sleepiness and may underreport snoring.

Functional Consequences of Obstructive Sleep Apnea Hypopnea

More than 50% of individuals with moderate to severe obstructive sleep apnea hypopnea report symptoms of daytime sleepiness. A twofold increased risk of occupational accidents has been reported in association with symptoms of snoring and sleepiness. Motor vehicle crashes also have been reported to be as much as sevenfold higher among individuals with elevated apnea hypopnea index values. Clinicians should be cognizant of state government requirements for reporting this disorder, especially in relationship to commercial drivers. Reduced scores on measures of health-related quality of life are common in individuals with obstructive sleep apnea hypopnea, with the largest decrements observed in the physical and vitality subscales.

12.4.2 Central Sleep Apnea

Diagnostic Features

Central sleep apnea disorders are characterized by repeated episodes of apneas and hypopneas during sleep caused by variability in respiratory effort. These are disorders of ventilatory control in which respiratory events occur in a periodic or intermittent pattern. Idiopathic central sleep apnea is characterized by sleepiness, insomnia, and awakenings due to dyspnea in association with five or more central apneas per hour of sleep. Central sleep apnea occurring in individuals with heart failure, stroke, or renal failure typically have a breathing pattern called Cheyne-Stokes breathing, which is characterized by a pattern of periodic crescendo-decrescendo variation in tidal volume that results in central apneas and hypopneas occurring at a frequency of at least five events per hour that are accompanied by frequent arousals. Central and obstructive sleep apneas may coexist; the ratio of central to obstructive apneas/hypopneas may be used to identify which condition is predominant. Alterations in neuromuscular control of breathing can occur in association with medications or substances used in individuals with mental health conditions, which can cause or exacerbate impairments of respiratory rhythm and ventilation. Individuals taking these medications have a sleep-related breathing disorder that could contribute to sleep disturbances and symptoms such as sleepiness, confusion, and depression. Specifically, chronic use of long-acting opioid medications is often associated with impairment of respiratory control leading to central sleep apnea.

Associated Features Supporting Diagnosis

Individuals with central sleep apnea hypopneas can manifest with sleepiness or insomnia. There can be complaints of sleep fragmentation, including awakening with dyspnea. Some individuals are asymptomatic. Obstructive sleep apnea hypopnea can coexist with Cheyne-Stokes breathing, and thus snoring and abruptly terminating apneas may be observed during sleep.

Prevalence

The prevalence of idiopathic central sleep apnea is unknown but thought to be rare. The prevalence of Cheyne-Stokes breathing is high in individuals with depressed cardiac ventricular ejection fraction. In individuals with an ejection fraction of less than 45%, the prevalence has been reported to be 20% or higher. The male-to-female ratio for prevalence is even more highly skewed toward males than for obstructive sleep apnea hypopnea. Prevalence increases with age, and most patients are older than 60 years. Cheyne-Stokes breathing occurs in approximately 20% of individuals with acute stroke. Central sleep apnea comorbid with opioid use occurs in approximately 30% of individuals taking chronic opioids for nonmalignant pain and similarly in individuals receiving methadone maintenance therapy.

Functional Consequences of Central Sleep Apnea

Idiopathic central sleep apnea has been reported to cause symptoms of disrupted sleep, including insomnia and sleepiness. Cheyne-Stokes breathing with comorbid heart failure has been associated with excessive sleepiness, fatigue, and insomnia, although many individuals may be asymptomatic. Coexistence of heart failure and Cheyne-Stokes breathing may be associated with increased cardiac arrhythmias and increased mortality or cardiac transplantation. Individuals with central sleep apnea comorbid with opioid use may present with symptoms of sleepiness or insomnia.

12.4.3 Sleep-Related Hypoventilation

Diagnostic Features

Sleep-related hypoventilation can occur independently or, more frequently, comorbid with medical or neurological disorders, medication use, or substance use disorder. Although symptoms are not mandatory to make this diagnosis, individuals often report excessive daytime sleepiness, frequent arousals and awakenings during sleep, morning headaches, and insomnia complaints.

Associated Features Supporting Diagnosis

Individuals with sleep-related hypoventilation can present with sleep-related complaints of insomnia or sleepiness. Episodes of orthopnea can occur in individuals with diaphragm weakness. Headaches upon awakening may be present. During sleep, episodes of shallow breathing may be observed, and obstructive sleep apnea hypopnea or central sleep apnea may coexist. Consequences of ventilatory insufficiency, including pulmonary hypertension, cor pulmonale (right heart failure), polycythemia, and neurocognitive dysfunction. can be present. With progression of ventilatory insufficiency, blood gas abnormalities extend into wakefulness. Features of the medical condition causing sleep-related hypoventilation can also be present. Episodes of hypoventilation may be associated with frequent arousals or bradytachycardia. Individuals may complain of excessive sleepiness and insomnia or morning headaches or may present with findings of neurocognitive dysfunction or depression. Hypoventilation may not be present during wakefulness.

Gender-Related Diagnostic Issues

Gender distributions for sleep-related hypoventilation occurring in association with comorbid conditions reflect the gender distributions of the comorbid conditions. For example, COPD is more frequently present in males and with increasing age.

Functional Consequences of Sleep-Related Hypoventilation

The consequences of sleep-related hypoventilation are related to the effects of chronic exposure to hypercapnia and hypoxemia. These blood gas derangements cause vasoconstriction of the pulmonary vasculature leading to pulmonary hypertension, which, if severe, can result in right-sided heart failure (cor pulmonale). Hypoxemia can lead to dysfunction of organs such as the brain, blood, and heart, leading to outcomes such as cognitive dysfunction, polycythemia, and cardiac arrhythmias. Hypercapnia can depress ventilatory drive, leading to progressive respiratory failure.

12.4.4 Circadian Rhythm Sleep-Wake Disorders

Delayed Sleep Phase Type

Diagnostic Features

The delayed sleep phase type is based primarily on a history of a delay in the timing of the major sleep period (usually more than 2 hours) in relation to the desired sleep and wakeup time, resulting in symptoms of insomnia and excessive sleepiness. When allowed to set their own schedule, individuals with delayed sleep phase type exhibit normal sleep quality and duration for age. Symptoms of sleep-onset insomnia, difficulty waking in the morning, and excessive early day sleepiness are prominent.

Associated Features Supporting Diagnosis

Common associated features of delayed sleep phase type include a history of mental disorders or a concurrent mental disorder. Extreme and prolonged difficulty awakening with morning confusion is also common. Psychophysiological insomnia may develop as a result of maladaptive behaviors that impair sleep and increase arousal because of repeated attempts to fall asleep at an earlier time.

Prevalence

Prevalence of delayed sleep phase type in the general population is approximately 0.17% but appears to be greater than 7% in adolescents. Although the prevalence of familial delayed sleep phase type has not been established, a family history of delayed sleep phase is present in individuals with delayed sleep phase type.

Functional Consequences of Delayed Sleep Phase Type

Excessive early day sleepiness is prominent. Extreme and prolonged difficulty awakening with morning confusion (i.e., sleep inertia) is also common. The severity of insomnia and excessive sleepiness symptoms varies substantially among individuals and largely depends on the occupational and social demands on the individual.

Advanced Sleep Phase Type

Diagnostic Features

Advanced sleep phase type is characterized by sleep-wake times that are several hours earlier than desired or conventional times. Diagnosis is based primarily on a history of an advance in the timing of the major sleep period (usually more than 2 hours) in relation to the desired sleep and wake-up time, with symptoms of early morning insomnia and excessive daytime sleepiness. When allowed to set their schedule, individuals with advanced sleep phase type will exhibit normal sleep quality and duration for age.

Associated Features Supporting Diagnosis

Individuals with advanced sleep phase type are "morning types," having earlier sleepwake times, with the timing of circadian biomarkers such as melatonin and core body temperature rhythms occurring 2-A hours earlier than normal. When required to keep a conventional schedule requiring a delay of bedtime, these individuals will continue to have an early rise time, leading to persistent sleep deprivation and daytime sleepiness. Use of hypnotics or alcohol to combat sleep-maintenance insomnia and stimulants to reduce daytime sleepiness may lead to substance abuse in these individuals.

Prevalence

The estimated prevalence of advanced sleep phase type is approximately 1% in middleage adults. Sleep-wake times and circadian phase advance in older individuals, probably accounting for increased prevalence in this population.

Culture-Related Diagnostic issues

African Americans may have a shorter circadian period and larger magnitude phase advances to light than do Caucasians, possibly increasing the risk for development of advanced sleep phase type in this population.

Functionai Consequences of Advanced Sieep Pliase Type

Excessive sleepiness associated with advanced sleep phase can have a negative effect on cognitive performance, social interaction, and safety. Use of wake-promoting agents to combat sleepiness or sedatives for early morning awakening may increase potential for substance abuse.

Irregular Sleep-Wake Type

Diagnostic Features

The diagnosis of irregular sleep-wake type is based primarily on a history of symptoms of insomnia at night (during the usual sleep period) and excessive sleepiness (napping) during the day. Irregular sleep-wake type is characterized by a lack of discernable sleep-wake circadian rhythm. There is no major sleep period, and sleep is fragmented into at least three periods d\iring the 24-hour day.

Associated Features Supporting Diagnosis

Individuals with irregular sleep-wake type typically present with insomnia or excessive sleepiness, depending on the time of day. Sleep and wake periods across 24 hours are fragmented, although the longest sleep period tends to occur between 2:00 A.M. and 6:00 A.M. and is usually less than 4 hours. A history of isolation or reclusion may occur in association with the disorder and contribute to the symptoms via a lack of external stimuli to help entrain a normal pattern. Individuals or their caregivers report frequent naps throughout the day. Irregular sleep-wake type is most commonly associated with neurodegenerative disorders, such as major neurocognitive disorder, and many neurodevelopmental disorders in children.

Prevalence

Prevalence of irregular sleep-wake type in the general population is unknown.

Functional Consequences of irregular Sleep-Wake Type

Lack of a clearly discernible major sleep and wake period in irregular sleep-wake type results in insomnia or excessive sleepiness, depending on the time of day. Disruption of the caregiver's sleep also often occurs and is an important consideration.

Non-24-Hour Sleep-Wake Type

Diagnostic Features

The diagnosis of non-24-hour sleep-wake type is based primarily on a history of symptoms of insomnia or excessive sleepiness related to abnormal synchronization between the 24-hour light-dark cycle and the endogenous circadian rhythm. Individuals typically present with periods of insomnia, excessive sleepiness, or both, which alternate with short asymptomatic periods. Starting with the asymptomatic period, when the individual's sleep phase is aligned to the external environment, sleep latency will gradually increase and the individual will complain of sleep-onset insomnia. As the sleep phase continues to drift so that sleep time is now in the daytime, the individual will have trouble staying awake during the day and will complain of sleepiness. Because the circadian period is not aligned to the external 24-hour environment, symptoms will depend on when an individual tries to sleep in relation to the circadian rhythm of sleep propensity.

Associated Features Supporting Diagnosis

Non-24-hour sleep-wake type is most common among blind or visually impaired individuals who have decreased light perception. In sighted individuals, there is often a history of delayed sleep phase and of decreased exposure to light and structured social and physical activity. Sighted individuals with non-24-hour sleep-wake type also demonstrate increased sleep duration.

Prevalence

Prevalence of non-24-hour sleep-wake type in the general population is unclear, but the disorder appears rare in sighted individuals. The prevalence in blind individuals is estimated to be 50%.

Functionai Consequences of Non-24-Hour Sieep-Walce Type

Complaints of insomnia (sleep onset and sleep maintenance), excessive sleepiness, or both are prominent. The unpredictability of sleep and wake times (typically a daily delay drift) results in an inability to attend school or maintain a steady job and may increase potential for social isolation.

12.4.5 Shift Work Type

Diagnostic Features

Diagnosis is primarily based on a history of the individual working outside of the normal 8:00 A.M. to 6:00 P.M. daytime window (particularly at night) on a regularly scheduled (i.e., non-overtime) basis. Symptoms of excessive sleepiness at work, and impaired sleep at home, on a persistent basis are prominent. Presence of both sets of symptoms are usually required for a diagnosis of shift work type. Typically, when the individual reverts to a daywork routine, symptoms resolve. Although the etiology is slightly different, individuals who travel across many time zones on a very frequent basis may experience effects similar to those experienced by individuals with shift work type who work rotating shifts.

Prevalence

The prevalence of shift work type is unclear, but the disorder is estimated to affect 5%-10% of the night worker population (16%-20% of the workforce). Prevalence rises with advancement into middle-age and beyond (Drake et al. 2004).

Functional Consequences of Shift Worl( Type

Individuals with shift work type not only may perform poorly at work but also appear to be at risk for accidents both at work and on the drive home. They may also be at risk for poor mental health (e.g., alcohol use disorder, substance use disorder, depression) and physical health (e.g., gastrointestinal disorders, cardiovascular disease, diabetes, cancer). Individuals with a history of bipolar disorder are particularly vulnerable to shift work type-related episodes of mania resulting from missed nights of sleep. Shift work type often results in interpersonal problems.

12.5 Prevalence

Parasomnias are disorders characterized by abnormal behavioral, experiential, or physiological events occurring in association with sleep, specific sleep stages, or sleep-wake transitions. The most common parasomnias—non-rapid eye movement (NREM) sleep arousal disorders and rapid eye movement (REM) sleep behavior disorder—represent admixtures of wakefulness and NREM sleep and wakefulness and REM sleep, respectively. These conditions serve as a reminder that sleep and wakefulness are not mutually exclusive and that sleep is not necessarily a global, whole-brain phenomenon.

12.5.1 Non-Rapid Eye Movement Sleep Arousal Disorder

Diagnostic Features

The essential feature of non-rapid eye movement (NREM) sleep arousal disorders is the repeated occurrence of incomplete arousals, usually beginning during the first third of the major sleep episode (Criterion A), that typically are brief, lasting 1-10 minutes, but may be protracted, lasting up to 1 hour. The maximum duration of an event is unknown. The eyes are typically open during these events. Many individuals exhibit both subtypes of arousals on different occasions, which underscores the unitary underlying pathophysiology. The subtypes reflect varying degrees of simultaneous occurrence of wakefulness and NREM sleep, resulting in complex behaviors arising from sleep with varying degrees of conscious awareness, motor activity, and autonomic activation. The essential feature of sleepwalking is repeated episodes of complex motor behavior initiated during sleep, including rising from bed and walking about (Criterion Al). Sleepwalking episodes begin during any stage of NREM sleep, most commonly during slowwave sleep and therefore most often occurring during the first third of the night. During episodes, the individual has reduced alertness and responsiveness, a blank stare, and relative unresponsiveness to communication with others or efforts by others to awaken the individual. If awakened during the episode (or on awakening the following morning), the individual has limited recall for the episode. After the episode, there may initially be a brief period of confusion or difficulty orienting, followed by full recovery of cognitive function and appropriate behavior. The essential feature of sleep terrors is the repeated occurrence of precipitous awakenings from sleep, usually beginning with a panicky scream or cry (Criterion A2). Sleep terrors usually begin during the first third of the major sleep episode and last 1-10 minutes, but they may last considerably longer, particularly in children. The episodes are accompanied by impressive autonomic arousal and behavioral manifestations of intense fear. During an episode, the individual is difficult to awaken or comfort. If the individual awakens after the sleep terror, little or none of the dream, or only fragmentary, single images, are recalled. During a typical episode of sleep terrors, the individual abruptly sits up in bed screaming or crying, with a frightened expression and autonomic signs of intense anxiety (e.g., tachycardia, rapid breathing, sweating, dilation of the pupils). The individual may be inconsolable and is usually unresponsive to the efforts of others to awaken or comfort him or her. Sleep terrors are also called "night terrors" or "pavor nocturnus."

Associated Features Supporting Diagnosis

Sleepwalking episodes can include a wide variety of behaviors. Episodes may begin with confusion: the individual may simply sit up in bed, look about, or pick at the blanket or sheet. This behavior then becomes progressively complex. The individual may actually leave the bed and walk into closets, out of the room, and even out of buildings. Individuals may use the bathroom, eat, talk, or engage in more complex behaviors. Running and frantic attempts to escape some apparent threat can also occur. Most behaviors during sleepwalking episodes are routine and of low complexity. However, cases of unlocking doors and even operating machinery (driving an automobile) have been reported. Sleepwalking can also include inappropriate behavior (e.g., commonly, urinating in a closet or wastebasket). Most episodes last for several minutes to a half hour but may be more protracted. Inasmuch as sleep is a state of relative analgesia, painful injuries sustained during sleepwalking may not be appreciated until awakening after the fact.

There are two "specialized" forms of sleepwalking: sleep-related eating behavior and sleep-related sexual behavior (sexsomnia or sleep sex). Individuals with sleep-related eating experience unwanted recurrent episodes of eating with varying degrees of amnesia, ranging from no awareness to full awareness without the ability to not eat. During these episodes, inappropriate foods may be ingested. Individuals witii sleep-related eating disorder may find evidence of their eating only the next morning. In sexsomnia, varying degrees of sexual activity (e.g., masturbation, fondling, groping, sexual intercourse) occur as complex behaviors arising from sleep without conscious awareness. This condition is more common in males and may result in serious interpersonal relationship problems or medicolegal consequences.
During a typical episode of sleep terrors, there is often a sense of overwhelming dread, with a compulsion to escape. Although fragmentary vivid dream images may occur, a storylike dream sequence (as in nightmares) is not reported. Most commonly, the individual does not awaken fully, but returns to sleep and has amnesia for the episode on awakening the next morning. Usually only one episode will occur on any one night. Occasionally several episodes may occur at intervals throughout the night. These events rarely arise during daytime naps.

Prevalence

Isolated or infrequent NREM sleep arousal disorders are very common in the general population. From 10% to 30% of children have had at least one episode of sleepwalking, and 2%-3% sleepwalk often. The prevalence of sleepwalking disorder, marked by repeated episodes and impairment or distress, is much lower, probably in the range of l%-5%. The prevalence of sleepwalking episodes (not sleepwalking disorder) is 1.0%-7.0% among adults, with weekly to monthly episodes occurring in 0.5%-0.7%. The lifetime prevalence of sleepwalking in adults is 29.2%, with a past-year prevalence of sleepwalking of 3.6%. The prevalence of sleep terrors in the general population is unknown. The prevalence of sleep terror episodes (as opposed to sleep terror disorder, in which there is recurrence and distress or impairment) is approximately 36.9% at 18 months of age, 19.7% at 30 months of age, and 2.2% in adults.

Gender-Related Diagnostic Issues

Violent or sexual activity during sleepwalking episodes is more likely to occur in adults. Eating during sleepwalking episodes is more commonly seen in females. Sleepwalking occurs more often in females during childhood but more often in males during adulthood. Older children and adults provide a more detailed recollection of fearful images associated with sleep terrors than do younger children, who are more likely to have complete amnesia or report only a vague sense of fear. Among children, sleep terrors are more common in males than in females. Among adults, the sex ratio is even.

Functional Consequences of Non-REIVI Sleep Arousal Disorders

For the diagnosis of a NREM sleep arousal disorder to be made, the individual or household members must experience clinically significant distress or impairment, although parasomnia symptoms may occur occasionally in nonclinical populations and would be subthreshold for the diagnosis. Embarrassment concerning the episodes can impair social relationships. Social isolation or occupational difficulties can result. The determination of a "disorder" depends on a number of factors, which may vary on an individual basis and will depend on the frequency of events, potential for violence or injurious behaviors, embarrassment, or disruption/distress of other household members. Severity determination is best made based on the nature or consequence of the behaviors rather than simply on frequency. Uncommonly, NREM sleep arousal disorders may result in serious injury to the individual or to someone trying to console the individual. Injuries to others are confined to those in close proximity; individuals are not "sought out." Typically, sleepwalking in both children and adults is not associated with significant mental disorders. For individuals with sleep-related eating behaviors, unknowingly preparing or eating food during the sleep period may create problems such as poor diabetes control, weight gain, injury (cuts and bums), or consequences of eating dangerous or toxic inedibles. NREM sleep arousal disorders may rarely result in violent or injurious behaviors with forensic implications.

12.5.2 Nightmare Disorder

Diagnostic Features

Nightmares are typically lengthy, elaborate, story like sequences of dream imagery that seem real and that incite anxiety, fear, or other dysphoric emotions. Nightmare content typically focuses on attempts to avoid or cope with imminent danger but may involve themes that evoke other negative emotions. Nightmares occurring after traumatic experiences may replicate the threatening situation ("'replicative nightmares"), but most do not. On awakening, nightmares are well remembered and can be described in detail. They arise almost exclusively during rapid eye movement (REM) sleep and can thus occur throughout sleep but are; more likely in the second half of the major sleep episode when dreaming is longer and more intense. Factors that increase early-night REM intensity, such as sleep fragmentation or deprivation, jet lag, and REM-sensitive medications, might facilitate nightmares earlier in the night, including at sleep onset. Nightmares usually terminate with awakening and rapid return of full alertness. However, the dysphoric emotions may persist into wakefulness and contribute to difficulty returning to sleep and lasting daytime distress. Some nightmares, known as "bad dreams," may not induce awakening and are recalled only later. If nightmares occur during sleeponset REM periods (hypnagogic), the dysphoric emotion is frequently accompanied by a sense of being both awake and unable to move voluntarily {isolated sleep paralysis).

Associated Features Supporting Diagnosis

Mild autonomic arousal, including sweating, tachycardia, and tachypnea, may characterize nightmares. Body movements and vocalizations are not characteristic because of REM sleep-related loss of skeletal muscle tone, but such behaviors may occur under situations of emotional stress or sleep fragmentation and in posttraumatic stress disorder (PTSD). When talking or emoting occurs, it is typically a brief event terminating the nightmare. Individuals with frequent nightmares are at substantially greater risk for suicidal ideation and suicide attempts, even when gender and mental illness are taken into account.

Prevalence

Prevalence of nightmares increases through childhood into adolescence. From 1.3% to 3.9% of parents report that their preschool children have nightmares "often" or "always". Prevalence increases from ages 10 to 13 for both males and females but continues to increase to ages 20-29 for females (while decreasing for males), when it can be twice as high for females as for males. Prevalence decreases steadily with age for both sexes, but the gender difference remains. Among adults, prevalence of nightmares at least monthly is 6%, whereas prevalence for frequent nightmares is l%-2%. Estimates often combine idiopathic and posttraumatic nightmares indiscriminately.

Culture-Related Diagnostic issues

The significance attributed to nightmares may vary by culture, and sensitivity to such beliefs may facilitate disclosure.

Gender-Related Diagnostic Issues

Adult females report having nightmares more frequently than do adult males. Nightmare content differs by sex, with adult females tending to report themes of sexual harassment or of loved ones disappearing/dying, and adult males tending to report themes of physical aggression or war/terror.

Functional Consequences of Niglitmare Disorder

Nightmares cause more significant subjective distress than demonstrable social or occupational impairment. However, if awakenings are frequent or result in sleep avoidance, individuals may experience excessive daytime sleepiness, poor concentration, depression, anxiety, or irritability. Frequent childhood nightmares (e.g., several per week), may cause significant distress to parents and child.

12.5.3 Rapid Eye Movement Sleep Behavior Disorder

Diagnostic Features

The essential feature of rapid eye movement (REM) sleep behavior disorder is repeated episodes of arousal, often associated with vocalizations and/or complex motor behaviors arising from REM sleep (Criterion A). These behaviors often reflect motor responses to the content of action-filled or violent dreams of being attacked or trying to escape from a threatening situation, which may be termed dream enacting behaviors. The vocalizations are often loud, emotion-filled, and profane. These behaviors may be very bothersome to the individual and the bed partner and may result in significant injury (e.g., falling, jumping, or flying out of bed; running, punching, thrusting, hitting, or kicking). Upon awakening, the individual is immediately awake, alert, and oriented (Criterion C) and is often able to recall dream mentation, which closely correlates with the observed behavior. The eyes typically remain closed during these events. The diagnosis of REM sleep behavior disorder requires clinically significant distress or impairment (Criterion E); this determination will depend on a number of factors, including the frequency of events, the potential for violence or injurious behaviors, embarrassment, and distress in other household members.

Associated Features Supporting Diagnosis

Severity determination is best made based on the nature or consequence of the behavior rather than simply on frequency. Although the behaviors are typically prominent and violent, lesser behaviors may also occur.

Prevalence

The prevalence of REM sleep behavior disorder is approximately 0.38%-0.5% in the general population. Prevalence in patients with psychiatric disorders may be greater, possibly related to medications prescribed for the psychiatric disorder.

Functional Consequences of Rapid Eye IViovement Sieep Behavior Disorder

REM sleep behavior disorder may occur in isolated occasions in otherwise unaffected individuals. Embarrassment concerning the episodes can impair social relationships. Individuals may avoid situations in which others might become aware of the disturbance, visiting friends overnight, or sleeping with bed partners. Social isolation or occupational difficulties can result. Uncommonly, REM sleep behavior disorder may result in serious injury to the victim or to the bed partner.

12.5.4 Restless Legs Syndrome

Diagnostic Features

Restless legs syndrome (RLS) is a sensorimotor, neurological sleep disorder characterized by a desire to move the legs or arms, usually associated with uncomfortable sensations typically described as creeping, crawling, tingling, burning, or itching (Criterion A). The diagnosis of RLS is based primarily on patient self-report and history. Symptoms are worse when the individual is at rest, and frequent movements of the legs occur in an effort to relieve the uncomfortable sensations. Symptoms are worse in the evening or night, and in some individuals they occur only in the evening or night. Evening worsening occurs independently of any differences in activity. It is important to differentiate RLS from other conditions such as positional discomfort and leg cramps (Criterion D). The symptoms of RLS can delay sleep onset and awaken the individual from sleep and are associated with significant sleep fragmentation. The relief obtained from moving the legs may no longer be apparent in severe cases. RLS is associated with daytime sleepiness and is frequently accompanied by significant clinical distress or functional impairment.

Associated Features Supporting Diagnosis

Periodic leg movements in sleep (PLMS) can serve as corroborating evidence for RLS, with up to 90% of individuals diagnosed with RLS demonstrating PLMS when recordings are taken over multiple nights. Periodic leg movements during wakefulness are supportive of an RLS diagnosis. Reports of difficulty initiating and maintaining sleep and of excessive daytime sleepiness may also support the diagnosis of RLS. Additional supportive features include a family history of RLS among first-degree relatives and a reduction in symptoms, at least initially, with dopaminergic treatment.

Prevalence

Prevalence rates of RLS vary widely when broad criteria are utilized but range from 2% to 7.2% when more defined criteria are employed. When frequency of symptoms is at least three times per week with moderate or severe distress, the prevalence rate is 1.6%; when frequency of symptoms is a minimum of one time per week, the prevalence rate is 4.5%. Females are 1.5-2 times more likely than males to have RLS. RLS also increases with age. The prevalence of RLS may be lower in Asian populations.

Gender-Related Diagnostic issues

Although RLS is more prevalent in females than in males, there are no diagnostic differences according to gender. However, the prevalence of RLS during pregnancy is two to three times greater than in the general population. RLS associated with pregnancy peaks during the third trimester and improves or resolves in most cases soon after delivery. The gender difference in prevalence of RLS is explained at least in part by parity, with nulliparous females being at the same risk of RLS as age-matched males.

Functionai Consequences of Restless Legs Syndrome

Forms of RLS severe enough to significantly impair functioning or associated with mental disorders, including depression and anxiety, occur in approximately 2%-3% of the population. Although the impact of milder symptoms is less well characterized, individuals with RLS complain of disruption in at least one activity of daily living, with up to 50% reporting a negative impact on mood, and 47.6% reporting a lack of energy. The most common consequences of RLS are sleep disturbance, including reduced sleep time, sleep fragmentation, and overall disturbance; depression, generalized anxiety disorder, panic disorder, and posttraumatic stress disorder; and quality-of-life impairments. RLS can result in daytime sleepiness or fatigue and is frequently accompanied by significant distress or impairment in affective, social, occupational, educational, academic, behavioral, or cognitive functioning.

12.5.5 Substance/Medication-Induced Sleep Disorder

Diagnostic Features

The essential feature of substance/medication-induced sleep disorder is a prominent sleep disturbance that is sufficiently severe to warrant independent clinical attention (Criterion A) and that is judged to be primarily associated with the pharmacological effects of a substance (i.e., a drug of abuse, a medication, toxin exposure) (Criterion B). Depending on the substance involved, one of four types of sleep disturbances is reported. Insomnia type and daytime sleepiness type are most common, while parasomnia type is seen less often. The mixed type is noted when more than one type of sleep disturbance-related symptom is present and none predominates. The disturbance must not be better explained by another sleep disorder (Criterion C). A substance/medication-induced sleep disorder is distinguished from insomnia disorder or a disorder associated with excessive daytime sleepiness by considering onset and course. For drugs of abuse, there must be evidence of intoxication or withdrawal from the history, physical examination, or laboratory findings. Substance/medication-induced sleep disorder arises only in association with intoxication or discontinuation/withdrawal states, whereas other sleep disorders may precede the onset of substance use or occur during times of sustained abstinence. As discontinuation/withdrawal states for some substances can be protracted, onset of the sleep disturbance can occur 4 weeks after cessation of substance use, and the disturbance may have features atypical of other sleep disorders (e.g., atypical age at onset or course). The diagnosis is not made if the sleep disturbance occurs only during a delirium (Criterion D). The symptoms must cause clinically significant distress or impairment in social, occupational, or other important areas of functioning (Criterion E). This diagnosis should be made instead of a diagnosis of substance intoxication or substance withdrawal only when the symptoms in Criterion A predominate in the clinical picture and when the symptoms warrant independent clinical attention.

Associated Features Supporting Diagnosis

During periods of substance/medication use, intoxication, or withdrawal, individuals frequently complain of dysphoric mood, including depression and anxiety, irritability, cognitive impairment, inability to concentrate, and fatigue.
Prominent and severe sleep disturbances can occur in association with intoxication with the following classes of substances: alcohol; caffeine; cannabis; opioids; sedatives, hypnotics, or anxiolytics; stimulants (including cocaine); and other (or unknown) substances. Prominent and severe sleep disturbances can occur in association with withdrawal from the following classes of substances: alcohol; caffeine; cannabis; opioids; sedatives, hypnotics, or anxiolytics; stimulant (including cocaine); tobacco; and other (or unknown) substances. Some medications that invoke sleep disturbances include adrenergic agonists and antagonists, dopamine agonists and antagonists, cholinergic agonists and antagonists, serotonergic agonists and antagonists, antihistamines, and corticosteroids.

Alcohol. Alcohol-induced sleep disorder typically occurs as insomnia type. During acute intoxication, alcohol produces an immediate sedative effect depending on dose, accompanied by increased stages 3 and 4 non-rapid eye movement (NREM) sleep and reduced rapid eye movement (REM) sleep. Following these initial effects, there may be increased wakefulness, restless sleep, and vivid and anxiety-laden dreams for the remaining sleep period. In parallel, stages 3 and 4 sleep are reduced, and wakefulness and REM sleep are increased. Alcohol can aggravate breathing-related sleep disorder. With habitual use, alcohol continues to show a short-lived sedative effect in the first half of the night, followed by sleep continuity disruption in the second half. During alcohol withdrawal, there is extremely disrupted sleep continuity, and an increased amount and intensity of REM sleep, associated frequently with vivid dreaming, which in extreme form, constitutes part of alcohol withdrawal delirium. After acute withdrawal, chronic alcohol users may continue to complain of light, fragmented sleep for weeks to years associated with a persistent deficit in slow-wave sleep.

Caffeine. Caffeine-induced sleep disorder produces insomnia in a dose-dependent manner, with some individuals presenting with daytime sleepiness related to withdrawal. Cannabis. Acute administration of cannabis may shorten sleep latency, though arousing effects with increments in sleep latency also occur. Cannabis enhances slow-wave sleep and suppresses REM sleep after acute administration. In chronic users, tolerance to the sleep-inducing and slow-wave sleep-enhancing effects develops. Upon withdrawal, sleep difficulties and unpleasant dreams have been reported lasting for several weeks. Polysomnography studies demonstrate reduced slow-wave sleep and increased REM sleep during this phase.
Opioids. Opioids may produce an increase in sleepiness and in subjective depth of sleep, and reduced REM sleep, during acute short-term use. With continued administration, tolerance to the sedative effects of opioids develops and there are complaints of insomnia. Consistent with their respiratory depressant effects, opioids exacerbate sleep apnea. Sedative, hypnotic, or anxiolytic substances. Sedatives, hypnotics, and anxiolytics (e.g., barbiturates, benzodiazepines receptor agonists, meprobamate, glutethimide, methyprylon) have similar effects as opioids on sleep. During acute intoxication, sedative-hypnotic drugs produce the expected increase in sleepiness and decrease in wakefulness. Chronic use (particularly of barbiturates and the older nonbarbiturate, nonbenzodiazepine drugs) may cause tolerance with subsequent return of insomnia. Daytime sleepiness may occur. Sedative-hypnotic drugs can increase the frequency and severity of obstructive sleep apnea events. Parasomnias are associated with use of benzodiazepine receptor agonists, especially when these medications are taken at higher doses and when they are combined with other sedative drugs. Abrupt discontinuation of chronic sedative, hypnotic, or anxiolytic use can lead to withdrawal but more commonly rebound insomnia, a condition of an exacerbation of insomnia upon drug discontinuation for 1-2 days reported to occur even with short-term use. Sedative, hypnotic, or anxiolytic drugs with short durations of action are most likely to produce complaints of rebound insomnia, whereas those with longer durations of action are more often associated with daytime sleepiness. Any sedative, hypnotic, or anxiolytic drug can potentially cause daytime sedation, withdrawal, or rebound insomnia.

Amphetamines and related substances and other stimulants. Sleep disorders induced by amphetamine and related substances and other stimulants are characterized by insomnia during intoxication and excessive sleepiness during withdrawal. During acute intoxication, stimulants reduce the total amount of sleep, increase sleep latency and sleep continuity disturbances, and decrease REM sleep. Slow-wave sleep tends to be reduced. During withdrawal from chronic stimulant use, there is both prolonged nocturnal sleep duration and excessive daytime sleepiness. Multiple sleep latency tests may show increased daytime sleepiness during the withdrawal phase. Drugs like 34-methylenedioxyrnethamphetamine (MDMA; "ecstasy") and related substances lead to restless and disturbed sleep within 48 hours of intake; frequent use of these compounds is associated with persisting symptoms of anxiety, depression, and sleep disturbances, even during longer-term abstinence.

Tobacco. Chronic tobacco consumption is associated primarily with symptoms of insomnia, decreased slow-wave sleep with a reduction of sleep efficiency, and increased daytime sleepiness. Withdrawal from tobacco can lead to impaired sleep. Individuals who smoke heavily may experience regular nocturnal awakenings caused by tobacco craving. Other or unknown substances/medications. Other substances/medications may produce sleep disturbances, particularly medications that affect the central or autonomic nervous systems (e.g., adrenergic agonists and antagonists, dopamine agonists and antagonists, cholinergic agonists and antagonists, serotonergic agonists and antagonists, antihistamines, corticosteroids).

Culture-Related Diagnostic issues

The consumption of substances, including prescribed medications, may depend in part on cultural background and specific local drug regulations.

Gender-Related Diagnostic issues

Gender-specific prevalences (i.e., females affected more than males at a ratio of about 2:1) exist for patterns of consumption of some substances (e.g., alcohol). The same amount and duration of consumption of a given substance may lead to highly different sleep-related outcomes in males and females based on, for example, gender-specific differences in hepatic functioning.

Functional Consequences of Substance/iVledication-induced Sleep Disorder

While there are many functional consequences associated with sleep disorders, the only unique consequence for substance/medication-induced sleep disorder is increased risk for relapse. The degree of sleep disturbance during alcohol withdrawal (e.g., REM sleep rebound predicts risk of relapse of drinking). Monitoring of sleep quality and daytime sleepiness during and after withdrawal may provide clinically meaningful information on whether an individual is at increased risk for relapse.