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Approach to the Patient With a Sleep or Wakefulness Disorder

By

Richard J. Schwab

, MD, University of Pennsylvania, Division of Sleep Medicine

Last full review/revision Jun 2020| Content last modified Jun 2020
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Almost half of all people in the US report sleep-related problems. Disordered sleep can cause emotional disturbance, memory difficulty, poor motor skills, decreased work efficiency, and increased risk of traffic accidents. It can even contribute to cardiovascular disorders and mortality.

The most commonly reported sleep-related symptoms are insomnia and excessive daytime sleepiness (EDS).

EDS is not a disorder but a symptom of various sleep-related disorders. Insomnia can be a disorder, even if it exists in the context of other disorders, or can be a symptom of other disorders.

Pathophysiology of Sleep or Wakefulness Disorders

There are 2 states of sleep, each marked by characteristic physiologic changes:

Progression through the 3 stages, typically followed by a brief interval of REM sleep, occurs cyclically 5 to 6 times a night (see figure Typical sleep pattern in young adults Typical sleep pattern in young adults Almost half of all people in the US report sleep-related problems. Disordered sleep can cause emotional disturbance, memory difficulty, poor motor skills, decreased work efficiency, and increased... read more ). Brief periods of wakefulness (stage W) occur periodically.

Nonrapid eye movement (NREM) EEG

These EEG tracings show characteristic theta waves, sleep spindles, and K complexes during stages 1 (N1), 2 (N2), and 3 (N3) NREM sleep.

Nonrapid eye movement (NREM) EEG

Rapid eye movement (REM) EEG

This figure includes an EEG tracing (showing characteristic sawtooth waves) and an eye tracing (showing rapid eye movements), which occur during REM sleep.

Rapid eye movement (REM) EEG

Individual sleep requirements vary widely, ranging from 6 to 10 hours/24 hours. Infants sleep a large part of the day; with aging, total sleep time and deep sleep tend to decrease, and sleep becomes more interrupted. In older people, stage N3 may disappear. These changes may account for increasing EDS and fatigue with aging, but their clinical significance is unclear.

Typical sleep pattern in young adults

Rapid eye movement (REM) sleep occurs cyclically throughout the night every 90–120 min. Brief periods of wakefulness (stage W) occur periodically. Sleep time is spent as follows:

  • Stage N1: 2–5%

  • Stage N2: 45–55%

  • Stage N3: 13–23%

  • REM: 20–25%

Typical sleep pattern in young adults

Etiology of Sleep or Wakefulness Disorders

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  • An insomnia disorder (eg, adjustment sleep disorder, psychophysiologic insomnia)

  • Inadequate sleep hygiene

  • Psychiatric disorders, particularly mood, anxiety, and substance use disorders

  • Miscellaneous medical disorders such as cardiopulmonary disorders, musculoskeletal conditions, and chronic pain

Inadequate sleep hygiene refers to behaviors that are not conducive to sleep. They include

  • Consumption of caffeine or sympathomimetic or other stimulant drugs (typically near bedtime, but even in the afternoon for people who are particularly sensitive)

  • Exercise or excitement (eg, a thrilling television show) late in the evening

  • An irregular sleep-wake schedule

Patients who compensate for lost sleep by sleeping late or by napping further fragment their nocturnal sleep.

Adjustment insomnia results from acute emotional stressors (eg, job loss, hospitalization) that disrupt sleep.

Psychophysiologic insomnia is insomnia (regardless of cause) that persists well beyond resolution of precipitating factors, usually because patients feel anticipatory anxiety about the prospect of another sleepless night followed by another day of fatigue. Typically, patients spend hours in bed focusing on and brooding about their sleeplessness, and they have greater difficulty falling asleep in their own bedroom than falling asleep away from home.

Most major mental disorders are associated with EDS and insomnia. About 80% of patients with major depression Depressive Disorders Depressive disorders are characterized by sadness severe enough or persistent enough to interfere with function and often by decreased interest or pleasure in activities. Exact cause is unknown... read more report EDS and insomnia; conversely, 40% of chronic insomniacs have a major mental disorder, most commonly a mood disorder.

Insufficient sleep syndrome involves not sleeping enough at night despite adequate opportunity to do so, typically because of various social or employment commitments.

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Circadian rhythm sleep disorders Circadian Rhythm Sleep Disorders Circadian rhythm sleep disorders are caused by desynchronization between internal sleep-wake rhythms and the light-darkness cycle. Patients typically have insomnia, excessive daytime sleepiness... read more result in misalignment between endogenous sleep-wake rhythms and environmental light-darkness cycle. The cause may be external (eg, jet lag disorder, shift work disorder) or internal (eg, delayed or advanced sleep phase disorder).

Central sleep apnea Central Sleep Apnea Central sleep apnea (CSA) is a heterogeneous group of conditions characterized by changes in ventilatory drive without airway obstruction. Most of these conditions cause asymptomatic changes... read more consists of repeated episodes of breathing cessation or shallow breathing during sleep, lasting at least 10 seconds and caused by diminished respiratory effort. The disorder typically manifests as insomnia or as disturbed and unrefreshing sleep.

Obstructive sleep apnea Obstructive Sleep Apnea Obstructive sleep apnea (OSA) consists of episodes of partial or complete closure of the upper airway that occur during sleep and lead to breathing cessation (defined as a period of apnea or... read more consists of episodes of partial or complete closure of the upper airway during sleep, leading to cessation of breathing for ≥ 10 seconds. Most patients snore, and sometimes patients awaken, gasping. These episodes disrupt sleep and result in a feeling of unrefreshing sleep and EDS.

  • Cataplexy is momentary muscular weakness or paralysis without loss of consciousness that is evoked by sudden emotional reactions (eg, laughter, anger, fear, joy, surprise). Weakness may be confined to the limbs (eg, patients may drop the rod when a fish strikes their line) or may cause a limp fall during hearty laughter (as in “weak with laughter”) or sudden anger. Cataplexy can also manifest as blurred vision or slurred speech.

  • Sleep paralysis is the momentary inability to move when just falling asleep or immediately after awakening.

  • Hypnagogic and hypnopompic phenomena are vivid auditory or visual illusions or hallucinations that occur when just falling asleep (hypnagogic) or, less often, immediately after awakening (hypnopompic).

Periodic limb movement disorder Periodic Limb Movement Disorder (PLMD) and Restless Legs Syndrome (RLS) Periodic limb movement disorder (PLMD) and restless legs syndrome (RLS) are characterized by abnormal motions of and, for RLS, usually sensations in the lower or upper extremities, which may... read more is characterized by repetitive (usually every 20 to 40 seconds) twitching or kicking of the lower extremities during sleep. Patients usually complain of interrupted nocturnal sleep or EDS. They are typically unaware of the movements and brief arousals that follow, and they have no abnormal sensations in the extremities.

Restless legs syndrome Periodic Limb Movement Disorder (PLMD) and Restless Legs Syndrome (RLS) Periodic limb movement disorder (PLMD) and restless legs syndrome (RLS) are characterized by abnormal motions of and, for RLS, usually sensations in the lower or upper extremities, which may... read more is characterized by an irresistible urge to move the legs and, less frequently, the arms, usually accompanied by paresthesias (eg, creeping or crawling sensations) in the limbs when reclining. To relieve symptoms, patients move the affected extremity by stretching, kicking, or walking. As a result, they have difficulty falling asleep, repeated nocturnal awakenings, or both.

Evaluation of Sleep or Wakefulness Disorders

History

History of present illness should include duration and age at onset of symptoms and any events (eg, a life or work change, new drug, new medical disorder) that coincided with onset. Symptoms during sleeping and waking hours should be noted.

The quality and quantity of sleep are identified by determining

  • Bedtime

  • Latency of sleep (time from bedtime to falling asleep)

  • Number and time of awakenings

  • Final morning awakening and arising times

  • Frequency and duration of naps

  • Quality of sleep (whether it is refreshing)

Having patients keep a sleep log for several weeks is more accurate than questioning them. Bedtime events (eg, food or alcohol consumption, physical or mental activity) should be evaluated. Intake of and withdrawal from drugs, alcohol, caffeine, and nicotine as well as level and timing of physical activity should also be included.

If excessive daytime sleepiness is the problem, severity should be quantified based on the propensity for falling asleep in different situations (eg, resting comfortably versus when driving a car). The Epworth Sleepiness Scale Epworth Sleepiness Scale Almost half of all people in the US report sleep-related problems. Disordered sleep can cause emotional disturbance, memory difficulty, poor motor skills, decreased work efficiency, and increased... read more may be used; a cumulative score 10 represents excessive daytime sleepiness.

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Review of systems should check for symptoms of specific sleep disorders, including

Bed partners or other family members can best identify some of these symptoms.

Past medical history should check for known disorders that can interfere with sleep, including chronic obstructive pulmonary disease Chronic Obstructive Pulmonary Disease (COPD) Chronic obstructive pulmonary disease (COPD) is airflow limitation caused by an inflammatory response to inhaled toxins, often cigarette smoke. Alpha-1 antitrypsin deficiency and various occupational... read more Chronic Obstructive Pulmonary Disease (COPD) (COPD), asthma Asthma Asthma is a disease of diffuse airway inflammation caused by a variety of triggering stimuli resulting in partially or completely reversible bronchoconstriction. Symptoms and signs include dyspnea... read more , heart failure Heart Failure (HF) Heart failure (HF) is a syndrome of ventricular dysfunction. Left ventricular failure causes shortness of breath and fatigue, and right ventricular failure causes peripheral and abdominal fluid... read more Heart Failure (HF) , hyperthyroidism Hyperthyroidism Hyperthyroidism is characterized by hypermetabolism and elevated serum levels of free thyroid hormones. Symptoms are many and include tachycardia, fatigue, weight loss, nervousness, and tremor... read more Hyperthyroidism , gastroesophageal reflux Gastroesophageal Reflux Disease (GERD) Incompetence of the lower esophageal sphincter allows reflux of gastric contents into the esophagus, causing burning pain. Prolonged reflux may lead to esophagitis, stricture, and rarely metaplasia... read more Gastroesophageal Reflux Disease (GERD) , neurologic disorders (particularly movement and degenerative disorders), and painful disorders (eg, rheumatoid arthritis). Risk factors for obstructive sleep apnea include obesity, heart disorders, hypertension, stroke, smoking, snoring, and nasal trauma. Drug history should include questions about use of any drugs associated with sleep disturbance (see table Some Drugs That Interfere With Sleep Some Drugs That Interfere With Sleep Almost half of all people in the US report sleep-related problems. Disordered sleep can cause emotional disturbance, memory difficulty, poor motor skills, decreased work efficiency, and increased... read more ).

Physical examination

The physical examination is useful mainly for identifying signs associated with obstructive sleep apnea:

Modified Mallampati scoring

Modified Mallampati scoring is as follows:

  • Class 1: Tonsils, uvula, and soft palate are fully visible.

  • Class 2: Hard and soft palate, upper portion of tonsils, and uvula are visible.

  • Class 3: Soft and hard palate and base of the uvula are visible.

  • Class 4: Only the hard palate is visible.

Modified Mallampati scoring

The chest should be examined for expiratory wheezes and kyphoscoliosis. Signs of right ventricular failure, including lower-extremity edema, should be noted. A thorough neurologic examination should be done.

Red flags

The following findings are of particular concern:

  • Falling asleep while driving or other potentially dangerous situations

  • Repeated sleep attacks (falling asleep without warning)

  • Breathing interruptions or awakening with gasping reported by bed partner

  • Unstable cardiac or pulmonary status

  • Recent stroke

  • Status cataplecticus (continuous cataplexy attacks)

  • History of violent behaviors or injury to self or others during asleep

  • Frequent sleepwalking or other out-of-bed behavior

Interpretation of findings

Inadequate sleep hygiene and situational stressors are usually apparent in the history. EDS that disappears when sleep time is increased (eg, on weekends or vacations) suggests inadequate sleep syndrome. EDS that is accompanied by cataplexy, hypnagogic/hypnopompic hallucinations, or sleep paralysis suggests narcolepsy.

Difficulty falling asleep (sleep-onset insomnia) should be distinguished from difficulty maintaining sleep and early awakening (sleep maintenance insomnia).

Clinicians should suspect obstructive sleep apnea in patients with significant snoring, frequent awakenings, and other risk factors. The STOP-BANG score can help predict risk of obstructive sleep apnea (see table STOP-BANG Risk Score for Obstructive Sleep Apnea STOP-BANG Risk Score for Obstructive Sleep Apnea Almost half of all people in the US report sleep-related problems. Disordered sleep can cause emotional disturbance, memory difficulty, poor motor skills, decreased work efficiency, and increased... read more ).

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Testing

Tests are usually done when specific symptoms or signs suggest obstructive sleep apnea, nocturnal seizures, narcolepsy, periodic limb movement disorder, or other disorders whose diagnosis relies on identification of characteristic polysomnographic findings. Tests are also done when the clinical diagnosis is in doubt or when response to initial presumptive treatment is inadequate. If symptoms or signs strongly suggest certain causes (eg, restless legs syndrome, poor sleep habits, transient stress, shift work disorder), testing is not required.

Polysomnography is particularly useful when obstructive sleep apnea, narcolepsy, nocturnal seizures, periodic limb movement disorder, or parasomnias are suspected. It also helps clinicians evaluate violent and potentially injurious sleep-related behaviors. It monitors brain activity (via EEG), eye movements, heart rate, respirations, oxygen saturation, and muscle tone and activity during sleep. Video recording may be used to identify abnormal movements during sleep. Polysomnography is typically done in a sleep laboratory; home sleep studies are now commonly used to diagnose obstructive sleep apnea, but not any other sleep disorders (1) Evaluation reference Almost half of all people in the US report sleep-related problems. Disordered sleep can cause emotional disturbance, memory difficulty, poor motor skills, decreased work efficiency, and increased... read more .

The multiple sleep latency test assesses speed of sleep onset in 5 daytime nap opportunities 2 hours apart during the patient’s typical daytime. Patients lie in a darkened room and are asked to sleep. Onset and stage of sleep (including REM) are monitored by polysomnography to determine the degree of sleepiness. This test’s main use is in the diagnosis of narcolepsy.

For the maintenance of wakefulness test, patients are asked to stay awake in a quiet room during 4 wakefulness opportunities 2 hours apart while they sit in a bed or a recliner. This test is probably a more accurate measure of ability to remain awake in everyday situations.

Patients with EDS may require laboratory tests of renal, liver, and thyroid function.

Evaluation reference

  • 1. Rosen IM, Kirsch DB, Chervin RD, et al: Clinical Use of a Home Sleep Apnea Test: An American Academy of Sleep Medicine Position Statement. J Clin Sleep Med 13 (10):1205–1207, 2017. doi: 10.5664/jcsm.6774.

Treatment of Sleep or Wakefulness Disorders

Specific conditions are treated. The primary treatment for insomnia is cognitive-behavioral therapy, which ideally should be done before hypnotics are prescribed. Good sleep hygiene Sleep Hygiene Almost half of all people in the US report sleep-related problems. Disordered sleep can cause emotional disturbance, memory difficulty, poor motor skills, decreased work efficiency, and increased... read more is a component of cognitive-behavioral therapy that is important whatever the cause and is often the only treatment patients with mild problems need.

Cognitive-behavioral therapy

Cognitive-behavioral therapy for insomnia focuses on managing the common thoughts, worries, and behaviors that interfere with sleep. It is typically done in 4 to 8 individual or group sessions but can be done remotely online or by telephone; however, evidence for the effectiveness of remote therapy is weaker.

Cognitive-behavioral therapy for insomnia consists of the following:

Restricting the amount of time spent in bed aims to limit the time patients spend lying in bed trying unsuccessfully to sleep. Initially, time in bed is limited to the average nightly total sleep time, but not to < 5.5 hours. Patients are asked to get out of bed in the morning at a fixed time and then calculate a bed time based on total sleep time. After a week, this approach typically improves quality of sleep. Then, the time spent in bed can be increased by gradually making bed time earlier, as long as awakenings in the middle of the night remain minimal.

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Hypnotics

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For commonly used hypnotics, see table Oral Hypnotics in Common Use Oral Hypnotics in Common Use Almost half of all people in the US report sleep-related problems. Disordered sleep can cause emotional disturbance, memory difficulty, poor motor skills, decreased work efficiency, and increased... read more . All hypnotics (except ramelteon, low-dose doxepin, and suvorexant) act at the benzodiazepine recognition site on the gamma-aminobutyric (GABA) receptor and augment the inhibitory effects of GABA.

Hypnotics differ primarily in elimination half-life and onset of action. Drugs with a short half-life are used for sleep-onset insomnia. Drugs with a longer half-life are useful for both sleep-onset and sleep maintenance insomnia, or, in the case of low-dose doxepin, only for sleep maintenance insomnia. Some hypnotics (eg, older benzodiazepines) have greater potential for daytime carryover effects, especially after prolonged use and/or in older people. New drugs with a very short duration of action (eg, low-dose sublingual zolpidem) can be taken in the middle of the night, during a nocturnal awakening, as long as patients stay in bed for at least 4 hours after use.

Patients who experience daytime sedation, incoordination, or other daytime effects should avoid activities requiring alertness (eg, driving), and the dose should be reduced, the drug stopped, or, if needed, another drug used. Other adverse effects include amnesia, hallucinations, incoordination, and falls. Falling is a significant risk with all hypnotics.

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Suvorexant is a newer treatment for sleep-onset insomnia that acts by blocking brain orexin receptors, thereby blocking orexin-induced wakefulness signals and enabling sleep initiation. Recommended dose is 10 mg, taken no more than once a night and taken within 30 minutes of going to bed, with at least 7 hours before the planned time of awakening. The dose can be increased but should not to exceed 20 mg once a day. The most common adverse effect is somnolence.

Hypnotics should be used cautiously in patients with pulmonary insufficiency. In older patients, any hypnotic, even in small doses, can cause restlessness, excitement, falls, or exacerbation of delirium and dementia. Rarely, hypnotics can cause complex sleep-related behaviors, such as sleepwalking and even sleep driving; use of higher-than-recommended doses and concurrent consumption of alcoholic beverages may increase risk of such behaviors. Rarely, severe allergic reactions occur.

Prolonged use of hypnotics Anxiolytics and Sedatives Anxiolytics and sedatives include benzodiazepines, barbiturates, and related drugs. High doses can cause stupor and respiratory depression, which is managed with intubation and mechanical ventilation... read more is typically discouraged because tolerance can develop and because abrupt discontinuation can cause rebound insomnia or even anxiety, tremor, and seizures. These effects are more common with benzodiazepines (particularly triazolam) and less common with nonbenzodiazepines. Difficulties can be minimized by using the lowest effective dose for brief periods and by tapering the dose before stopping the drug (see also Withdrawal and detoxification Withdrawal and detoxification Anxiolytics and sedatives include benzodiazepines, barbiturates, and related drugs. High doses can cause stupor and respiratory depression, which is managed with intubation and mechanical ventilation... read more ).

Other sedatives

Many drugs not specifically indicated for insomnia are used to induce and maintain sleep.

Alcohol is used by many patients to help with sleep, but alcohol is a poor choice because after prolonged use and at higher doses, it produces unrefreshing, disturbed sleep with frequent nocturnal awakenings, often increasing daytime sleepiness. Alcohol can further impair respiration during sleep in patients with obstructive sleep apnea and other pulmonary disorders such as chronic obstructive pulmonary disease (COPD).

Over-the-counter (OTC) antihistamines (eg, doxylamine, diphenhydramine) can induce sleep. However, efficacy is unpredictable, and these drugs have long a half-life and have adverse effects such as daytime sedation, confusion, urinary retention, and other systemic anticholinergic effects, which are particularly worrisome in older people.

Antidepressants taken in low doses at bedtime (eg, doxepin 25 to 50 mg, paroxetine 5 to 20 mg, trazodone 50 mg, trimipramine 75 to 200 mg) may improve sleep. However, antidepressants should be used in these low doses mainly when standard hypnotics are not tolerated (rare) or in higher (antidepressant) doses when depression is present. Ultra low dose doxepin (3 or 6 mg) is indicated for sleep maintenance insomnia.

Melatonin is a hormone that is secreted by the pineal gland (and that occurs naturally in some foods). Darkness stimulates secretion, and light inhibits it. By binding with melatonin receptors in the suprachiasmatic nucleus, melatonin mediates circadian rhythms, especially during physiologic sleep onset. Oral melatonin (typically 0.5 to 5 mg at bedtime) may be effective for sleep problems due to delayed sleep phase syndrome. When used to treat this disorder, it must be taken at the appropriate time (a few hours before the evening increase in endogenous melatonin secretion—in early evening for most people, typically 3 to 5 hours before the intended bedtime) and at a low dose of 0.5 to 1 mg; taken at the wrong time, it can aggravate sleep problems. For other forms of insomnia, melatonin's efficacy is largely unproved. Nevertheless, worrisome adverse effects have not been reported after widespread use. Available preparations of melatonin are unregulated, so content and purity cannot be ensured, and the effects of long-term use are unknown.

Key Points

  • Poor sleep hygiene and situational disruptors (eg, shift work, emotional stressors) cause many cases of insomnia.

  • Consider medical disorders (eg, sleep apnea syndromes, pain disorders) and psychiatric disorders (eg, mood disorders) as possible causes.

  • Usually, consider sleep studies (eg, polysomnography) when sleep apnea syndromes, periodic limb movements, or other sleep disorders are suspected, when the clinical diagnosis is in doubt, or when response to initial presumptive treatment is inadequate.

  • Good sleep hygiene, sometimes as part of cognitive-behavioral therapy, is first-line treatment.

  • Use hypnotics and sedatives with caution, especially in older people.

Drugs Mentioned In This Article

Drug Name Select Trade
No US trade name
LEVOPHED
Trimipramine
LUNESTA
INDERAL
PAXIL
Suvorexant
No US brand name
UNISOM
OLEPTRO
ROZEREM
HALCION
DILANTIN
RESTORIL
AMBIEN
DORAL
COMMIT, NICORETTE, NICOTROL
SONATA
ZONALON
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