Approach to the Patient With a Sleep or Wakefulness Disorder

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 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 may be used; a cumulative score ≥ 10 represents excessive daytime sleepiness.

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 (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 (LV) failure causes shortness of breath and fatigue, and right ventricular (RV) failure causes peripheral and abdominal... read more , hyperthyroidism Hyperthyroidism Hyperthyroidism is characterized by hypermetabolism and elevated serum levels of free thyroid hormones. Symptoms include palpitations, fatigue, weight loss, heat intolerance, anxiety, and tremor... read more , 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 , neurologic disorders (particularly movement and degenerative disorders), urinary incontinence Urinary Incontinence in Adults Urinary incontinence is involuntary loss of urine; some experts consider it present only when a patient thinks it is a problem. The disorder is greatly underrecognized and underreported. Many... read more , other urinary 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 ).

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

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.

The following findings are of particular concern:

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 Circadian rhythm sleep disorder, altered sleep phase types 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 , chronic psychophysiologic insomnia, 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 , or childhood phobias.

Sleep maintenance insomnia suggests major depression Major depression (unipolar disorder) 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 , 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 , obstructive sleep apnea Obstructive Sleep Apnea (OSA) Obstructive sleep apnea (OSA) consists of multiple episodes of partial or complete closure of the upper airway that occur during sleep and lead to breathing cessation (defined as a period of... read more , 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 , or aging.

Falling asleep early and awakening early suggest advanced sleep phase syndrome Circadian rhythm sleep disorder, altered sleep phase types 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 .

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, 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 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 4 to 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.

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

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.

General guidelines for use of hypnotics (see table Guidelines for the Use of Hypnotics Guidelines for the Use of Hypnotics ) aim at minimizing abuse, misuse, and addiction.

For commonly used hypnotics, see table Oral Hypnotics in Common Use Oral Hypnotics in Common Use . 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.

When benzodiazepines are to be stopped, they should be tapered and not stopped abruptly.

Three dual orexin receptor antagonists (daridorexant, lemborexant, suvorexant) can be used to treat sleep-onset and maintenance insomnia. They block orexin receptors in the brain, thereby blocking orexin-induced wakefulness signals and enabling sleep initiation. Dual orexin receptor antagonists block orexin receptors-1 and -2. The orexin receptor-1 is involved in suppressing the onset of rapid eye movement (REM) sleep; the orexin receptor-2 is involved in suppressing non-REM sleep onset and, to some extent, in controlling REM sleep. However, the mechanism of action for dual orexin receptor antagonists is not fully understood. They are used to treat sleep-onset and/or sleep maintenance insomnia, but these drugs are not overly effective for insomnia, and clinicians should consider the half-lives of these drugs.

For suvorexant, the 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.

Lemborexant 5 mg is taken once a day within 30 minutes of going to bed; the dose can be increased to 10 mg (maximum dose) based on patient response and tolerability.

Daridorexant 25 to 50 mg is taken once a day within 30 minutes of going to bed. Daridorexant has the shortest half-life (8 hours) of the dual oxexin receptor antagonists.

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 Sedatives Sedatives include benzodiazepines, barbiturates, and related drugs. High doses can cause decreased level of consciousness and respiratory depression, which may require intubation and mechanical... 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 Sedatives include benzodiazepines, barbiturates, and related drugs. High doses can cause decreased level of consciousness and respiratory depression, which may require intubation and mechanical... read more ).

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 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. Over-the-counter antihistamines should not be used to treat insomnia.

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.

Melatonin can cause headache, dizziness, nausea, and drowsiness. However, after widespread use, no other worrisome adverse effects have been reported. Available preparations of melatonin are unregulated, so content and purity cannot be ensured, and the effects of long-term use are unknown.

Cannabinoids Marijuana (Cannabis) Marijuana is a euphoriant that can cause sedation or dysphoria in some users. Psychologic dependence can develop with chronic use, but very little physical dependence is clinically apparent... read more include the following:

Whether cannabis is effective for insomnia is unclear, but it is useful for chronic pain.

Tolerance can develop; stopping cannabis after long-term use results in insomnia.