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Approach to the Patient With a Sleep or Wakefulness Disorder
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. Parasomnias are abnormal sleep-related events (eg, night terrors, sleepwalking—see Parasomnias).
There are 2 states of sleep, each marked by characteristic physiologic changes:
Nonrapid eye movement (NREM): NREM sleep constitutes about 75 to 80% of total sleep time in adults. It consists of 3 stages (N1 to N3) in increasing depth of sleep. Slow, rolling eye movements, which characterize quiet wakefulness and early stage N1 sleep, disappear in deeper sleep stages. Muscle activity also decreases. Stage N3 is referred to as deep sleep because arousal threshold is high; people may perceive this stage as high-quality sleep.
Rapid eye movement (REM): REM sleep follows each cycle of NREM sleep. It is characterized by low-voltage fast activity on the EEG and postural muscle atonia. Respiration rate and depth fluctuate dramatically. Most dreams occur during REM sleep.
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.). Brief periods of wakefulness (stage W) occur periodically.
Individual sleep requirements vary widely, ranging from 6 to 10 h/24 h. 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 the elderly, stage N3 may disappear. These changes may account for increasing EDS and fatigue with aging, but their clinical significance is unclear.
Some disorders can cause either insomnia or EDS (sometimes both), and some cause one or the other (see Table: Some Causes of Insomnia and Excessive Daytime Sleepiness).
Some Causes of Insomnia and Excessive Daytime Sleepiness
Insomnia (see Insomnia and Excessive Daytime Sleepiness (EDS)) is most often caused by
EDS (see Insomnia and Excessive Daytime Sleepiness (EDS)) is most often caused by
Inadequate sleep hygiene refers to behaviors that are not conducive to sleep (see Sleep Hygiene). They include
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.
Physical disorders that cause pain or discomfort (eg, arthritis, cancer, herniated disks), particularly those that worsen with movement, can cause transient awakenings and poor sleep quality. Nocturnal seizures can also interfere with sleep.
Most major mental disorders are associated with EDS and insomnia. About 80% of patients with major depression 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.
Drug-related sleep disorders result from chronic use of or withdrawal from various drugs (see Table: Some Drugs That Interfere With Sleep).
Some Drugs That Interfere With Sleep
Circadian rhythm disorders (see Circadian Rhythm Sleep Disorders) 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 (see Central Sleep Apnea) consists of repeated episodes of breathing cessation or shallow breathing during sleep, lasting at least 10 sec and caused by diminished respiratory effort. The disorder typically manifests as insomnia or as disturbed and unrefreshing sleep.
Obstructive sleep apnea (see Obstructive Sleep Apnea) consists of episodes of partial or complete closure of the upper airway during sleep, leading to cessation of breathing for ≥ 10 sec. Most patients snore, and sometimes patients awaken, gasping. These episodes disrupt sleep and result in a feeling of unrefreshing sleep and EDS.
Narcolepsy (see Narcolepsy) is characterized by chronic EDS, often with cataplexy, sleep paralysis, and hypnagogic or hypnopompic hallucinations:
Cataplexy is momentary muscular weakness or paralysis without loss of consciousness that is evoked by sudden emotional reactions (eg, mirth, 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.
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 (see Periodic Limb Movement Disorder (PLMD) and Restless Legs Syndrome (RLS)) is characterized by repetitive (usually every 20 to 40 sec) 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 (see Periodic Limb Movement Disorder (PLMD) and Restless Legs Syndrome (RLS)) 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.
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
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 EDS is the problem, severity should be quantified based on the propensity for falling asleep in different situations (eg, resting comfortably vs when driving a car). The Epworth Sleepiness Scale (see Table: Epworth Sleepiness Scale) may be used; a cumulative score ≥ 10 represents abnormal daytime sleepiness.
Epworth Sleepiness Scale
Review of systems should check for symptoms of specific sleep disorders, including
Snoring, interrupted breathing patterns, and other nocturnal respiratory disturbances (sleep apnea syndromes)
Depression, anxiety, mania, and hypomania (mental sleep disorders)
Restlessness in the legs, an irresistible desire to move them, and jerking leg movements (restless legs syndrome)
Cataplexy, sleep paralysis, and hypnagogic phenomena (narcolepsy)
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 COPD, asthma, heart failure, hyperthyroidism, gastroesophageal reflux, neurologic disorders (particularly movement and degenerative disorders), and painful disorders (eg, RA). 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).
The physical examination is useful mainly for identifying signs associated with obstructive sleep apnea:
Obesity with fat distributed around the neck or midriff
Large neck circumference (≥ 43.2 cm in males, ≥ 40.6 cm in females)
Mandibular hypoplasia and retrognathia
Enlarged tonsils, tongue, uvula, or soft palate (Mallampati score 3 or 4—see Figure: Mallampati scoring.)
Decreased pharyngeal patency
Increased obstruction of uvula and soft palate by the tongue
Redundant pharyngeal mucosa
The chest should be examined for expiratory wheezes and kyphoscoliosis. Signs of right ventricular failure should be noted. A thorough neurologic examination should be done.
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
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
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).
Sleep-onset insomnia suggests delayed sleep phase syndrome, chronic psychophysiologic insomnia, restless legs syndrome, or childhood phobias.
Sleep maintenance insomnia suggests major depression, central or obstructive sleep apnea, periodic limb movement disorder, or aging.
Falling asleep early and awakening early suggest advanced sleep phase syndrome.
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
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, O2 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; equipment for home use has been devised but is intended to help diagnose only obstructive sleep apnea, not any other sleep disorders.
The multiple sleep latency test assesses speed of sleep onset in 5 daytime nap opportunities 2 h 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 h 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.
Specific conditions are treated. Good sleep hygiene (see Table: Sleep Hygiene) is important whatever the cause and is often the only treatment patients with mild problems need.
General guidelines for use of hypnotics (see Table: Guidelines for the Use of Hypnotics) aim at minimizing abuse, misuse, and addiction.
Guidelines for the Use of Hypnotics
For commonly used hypnotics, see Table: Oral Hypnotics in Common Use. All hypnotics (except ramelteon, low-dose doxepin, and suvorexant) act at the benzodiazepine recognition site on the γ-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 the elderly. New drugs with a very short duration of action (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 h 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.
Oral Hypnotics in Common Use
Recently approved hypnotics include suvorexant and tasimelteon.
Suvorexantis a new treatment for 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/night and taken within 30 min of going to bed, with at least 7 h before the planned time of awakening. The dose can be increased but should not to exceed 20 mg once/day. The most common adverse effect is somnolence.
Tasimelteon, a melatonin receptor agonist, can increase nighttime sleep duration and decrease daytime sleep duration in totally blind patients who have non–24-h sleep-wake syndrome. The dose is 20 mg once/day before bedtime, at the same time every night. The most common adverse effects are headaches and abnormal dreams or nightmares. Tasmelteon does not appear to have abuse potential.
Hypnotics should be used cautiously in patients with pulmonary insufficiency. In the elderly, any hypnotic, even in small doses, can cause restlessness, excitement, 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 is typically discouraged because tolerance can develop (see Anxiolytics and Sedatives) 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 Anxiolytics and Sedatives : Withdrawal and detoxification). Nevertheless, many patients with chronic insomnia require long-term treatment with hypnotics; such treatment should not be withheld because chronic sleeplessness by itself can disrupt emotional and physical well-being.
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 COPD.
OTC antihistamines (eg, doxylamine, diphenhydramine) can induce sleep. However, efficacy is unpredictable, and these drugs have adverse effects such as daytime sedation, confusion, urinary retention, and other systemic anticholinergic effects, which are particularly worrisome in the elderly.
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 h 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, and its safety is in question because it appears to stimulate coronary artery changes in animals. 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. Its use should be supervised by a physician.
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.
Use hypnotics and sedatives with caution in the elderly.
Good sleep hygiene may be the only treatment needed by patients with mild insomnia problems.
Drug NameSelect Trade
nicotineCOMMIT, NICORETTE, NICOTROL
diphenhydramineNo US trade name
FlurazepamNo US brand name
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