Sleep/Insomnia

Introduction

Insomnia is defined as repeated difficulty with sleep initiation, maintenance, consolidation, or quality that occurs despite adequate time and opportunity for sleep and that results in some form of daytime impairment. Specific criteria vary, but common ones include taking longer than 30 minutes to fall asleep, staying asleep for less than 6 hours, waking more than 3 times a night, or experiencing sleep that is chronically nonrestorative or poor in quality.

Associated Anatomy

Sleep and wakefulness is a tightly regulated process. Reciprocal connections in the brain produce consolidated periods of wakefulness and sleep that are entrained by environmental light to occur at specific times of the 24-hour cycle.

Brain areas critical for wakefulness consist of several discrete neuronal groups centered around the pontine and medullary reticular formation and its extension into the hypothalamus. Although diverse in terms of neurochemistry, these cell groups share the features of a diffuse “ascending” projection to the forebrain and a “descending” projection to brainstem areas involved in regulating sleep-wake states. The neurotransmitters involved, along with the main cell groups that produce them, are as follows:

Histamine – histaminergic cells in the tuberomammillary nucleus (TMN) in the posterior hypothalamus

• Norepinephrine – norepinephrine-producing neurons in the locus coeruleus (LC)
• Serotonin – serotonergic neurons in the dorsal raphe nuclei (DRN)
• Dopamine – dopaminergic neurons in the ventral tegmental area (VTA)
• Acetylcholine – cholinergic neurons of the basal forebrain

Each region and neurotransmitter contributes to the promotion of wakefulness, but chronic lesions of any one system do not disrupt wakefulness. This suggests a redundant system, wherein the absence of one neurotransmitter may be compensated by the other systems.

The anterior hypothalamus includes the ventrolateral preoptic nucleus (VLPO), containing gamma-aminobutyric acid (GABA) and the peptide galanin, which are inhibitory and promote sleep. These project to the TMN and the brainstem arousal regions to inhibit wakefulness.

Both animal and human studies support a model of 2 processes that regulate sleep and wakefulness: homeostatic and circadian. The homeostatic process is the drive to sleep that is influenced by the duration of wakefulness. The circadian process transmits stimulatory signals to arousal networks to promote wakefulness in opposition to the homeostatic drive to sleep.

Causes

Sleep habits we learned as children may affect our sleep behaviors as adults. Poor sleep or lifestyle habits that may cause insomnia or make it worse include:

• Going to bed at a different time each night
• Daytime napping
• Poor sleeping environment, such as too much noise or light
• Spending too much time in bed while awake
• Working evenings or night shifts
• Not getting enough exercise
• Using the television, computer, or a mobile device in bed

The use of some medicines and drugs may also affect sleep, including:

• Alcohol or other drugs
• Heavy smoking
• Too much caffeine throughout the day or drinking caffeine late in the day
• Getting used to certain types of sleep medicines
• Some cold medicines and diet pills
• Other medicines, herbs, or supplements

Physical, social, and mental health issues can affect sleep patterns, including:

• Bipolar disorder.
• Feeling sad or depressed. (Often, insomnia is the symptom that causes people with depression to seek medical help.)
• Stress and anxiety, whether it is short-term or long-term. For some people, the stress caused by insomnia makes it even harder to fall asleep.

Health problems may also lead to problems sleeping and insomnia:

• Pregnancy
• Physical pain or discomfort.
• Waking up at night to use the bathroom, common in men with enlarged prostate
• Sleep apnea

With age, sleep patterns tend to change. Many people find that aging causes them to have a harder time falling asleep, and that they wake up more often.

Differential Diagnosis

Disorders to consider in the differential diagnosis of insomnia include the following:

• Central sleep apnea (primary or due to drug or substance)
• Cheyne-Stokes breathing pattern (associated with heart failure)
• High-altitude periodic breathing
• Jet-lag disorder
• Medication-related insomnia

Medications associated with insomnia are as follows:

• Central nervous system stimulants (dextroamphetamine, methylphenidate)
• Antihypertensives (alpha blockers, beta blockers)
• Respiratory medications (albuterol, theophylline)
• Decongestants (phenylephrine, pseudoephedrine)
• Hormones (corticosteroids, thyroid medications)
• Antiepileptic drugs (lamotrigine)
• Other noncontrolled substances (caffeine, alcohol, nicotine)

Drugs

Medications used in the treatment of insomnia include nonbenzodiazepine receptor agonists, benzodiazepine receptor agonists, the selective melatonin receptor agonist ramelteon, and sedating antidepressants. All can be considered first-line agents for insomnia; agent choice is largely dictated by past trials, cost, side-effect profile, drug interactions, and patient preference. Pharmacologic therapy is used in concert with behavioral and psychological interventions.

Sedative-Hypnotics:

Zaleplon (Sonata)

A sedative-hypnotic of the pyrazolopyrimidine class, zaleplon has a rapid onset of action and an ultra-short duration of action, making it a good choice for treatment of sleep-onset insomnia. A second dose can be used during the middle of the night without residual sedation in the morning (this is believed to be an advantage of this hypnotic over others).

Zolpidem (Ambien, Ambien CR, Edluar, Intermezzo, Zolpimist)

A sedative-hypnotic of the imidazopyridine class, zolpidem has a rapid onset and short duration of action. It is a good first choice for treatment of sleep-onset insomnia and produces no significant residual sedation in the morning.

The extended-release product (Ambien CR) consists of a coated 2-layer tablet and is useful for insomnia characterized by difficulties with sleep onset and/or sleep maintenance. The first layer releases drug content immediately to induce sleep; the second layer gradually releases additional drug to provide continuous sleep. The higher-dose sublingual product (Edluar) is available as 5- and 10-mg tablets; an oral spray (Zolpimist) is also available for sleep-onset and/or sleep-maintenance insomnia. The low-dose sublingual product (Intermezzo) is indicated for middle-of-the-night awakening.

Eszopiclone (Lunesta)

Eszopiclone is a nonbenzodiazepine hypnotic pyrrolopyrazine derivative of the cyclopyrrolone class. The precise mechanism of action is unknown, but this agent is believed to interact with GABA receptors at binding domains close to or allosterically coupled to benzodiazepine receptors. It is indicated for insomnia to decrease sleep latency and improve sleep maintenance. It has a short half-life (6 h).

The starting dose is 1 mg immediately before bedtime, with at least 7-8 h remaining before the planned time of awakening. The dose may be increased if clinically warranted to 2-3 mg HS in nonelderly adults, and 2 mg in elderly or debilitated patients.

Triazolam (Halcion)

Triazolam depresses all levels of the CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA. It is indicated for short-term insomnia. Triazolam was the first short-acting benzodiazepine for promoting sleep but fell out of favor after high-profile reports of amnesia with its use.

Estazolam

Estazolam is an intermediate-acting benzodiazepine with a slow onset of action and a long duration. Estazolam is a good agent for sleep-maintenance insomnia.

Temazepam (Restoril)

Temazepam is a short- to intermediate-acting benzodiazepine with longer latency to onset and half-life. Temazepam may be more helpful in sleep-maintenance insomnia than in sleep-onset insomnia.

Ramelteon (Rozerem)

Ramelteon is a melatonin receptor agonist that is indicated for insomnia characterized by difficulty with sleep onset. This agent has high selectivity for human melatonin MT1 and MT2 receptors. MT1 and MT2 are thought to promote sleep and to be involved in maintenance of the circadian rhythm and normal sleep-wake cycle. Stimulation of the MT1 receptor in the suprachiasmatic nucleus (SCN) inhibits neuronal firing (reduces alerting effect of the SCN), and stimulation of the MT2 receptor in the SCN affects the circadian rhythm, causing a phase advance (earlier sleep time).

Suvorexant (Belsomra)

Suvorexant is an orexin receptor antagonist. The orexin neuropeptide signaling system is a central promoter of wakefulness. Blocking the binding of wake-promoting neuropeptides orexin A and orexin B to receptors OX1R and OX2R by suvorexant is thought to suppress wake drive. It is indicated for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance.

Antidepressants, TCAs:

Amitriptyline

Amitriptyline is a tricyclic antidepressant (TCA) with sedative effects. It inhibits reuptake of serotonin and/or norepinephrine at the presynaptic neuronal membrane, which increases concentration in the central nervous system (CNS).

Doxepin (Silenor)

Low-dose doxepin is FDA approved for sleep-maintenance insomnia. It is available in 3- and 6-mg tablets.

Nortriptyline (Pamelor)

Nortriptyline has demonstrated effectiveness in the treatment of chronic pain.

By inhibiting the reuptake of serotonin and/or norepinephrine by the presynaptic neuronal membrane, this drug increases the synaptic concentration of these neurotransmitters in the CNS.

Antidepressants, Other:

Mirtazapine (Remeron, Remeron SolTab)

Mirtazapine exhibits both noradrenergic and serotonergic activity. In cases of depression associated with severe insomnia and anxiety, it has been shown to be superior to other selective serotonin reuptake inhibitors (SSRIs). In patients with depression, the sedative properties of mirtazapine may help with sleep-onset insomnia. This drug is not an FDA-approved treatment for insomnia, and no randomized, placebo-controlled trials have demonstrated its efficacy for insomnia.

Trazodone (Oleptro)

A nontricyclic antidepressant with short onset of action, trazodone consolidates sleep. It is an antagonist at the type 2 serotonin (5-HT2) receptor and inhibits reuptake of 5-HT; it also has negligible affinity for cholinergic and histaminergic receptors.

Nefazodone

Nefazodone inhibits serotonin reuptake and is a potent antagonist at the 5-HT2 receptor. It also has negligible affinity for cholinergic, histaminic, or alpha-adrenergic receptors. The FDA has added a Black Box warning regarding rare cases of liver failure with this drug.

Epidemiology

Approximately one third of adults report some difficulty falling asleep and/or staying asleep during the previous 12 months, with 17% reporting this problem as a significant one. From 9-12% experience daytime symptoms, 15% are dissatisfied with their sleep, and 6-10% meet the diagnostic criteria of insomnia syndrome.

Insomnia is more prevalent in women; middle-aged or older adults; shift workers; and patients with medical and psychiatric diseases. In young adults, difficulties of sleep initiation are more common; in middle-aged and older adults, problems of maintaining sleep are more common.

As many as 95% of Americans have reported an episode of insomnia at some point during their lives. The 2008 update to the American Academy of Sleep Medicine (AASM) guideline for the evaluation and management of chronic insomnia calls insomnia an important public health issue.

In an epidemiologic study from Quebec, 29.9% of 2001 respondents reported insomnia symptoms, and 9.5% met criteria for insomnia syndrome. A study of young adults in Switzerland indicated a 9% rate of chronic insomnia. A World Health Organization study of 15 sites found a prevalence of approximately 27% for patients reporting “difficulty sleeping.”

National surveys in England showed a modest but steady increase in the prevalence of insomnia from 1993-2007. The percentage of respondents reporting any insomnia symptoms increased from 35.0% to 38.6% over that period, while insomnia diagnosis rose from 3.1% to 5.8%.

Women are 1.4 times as likely as men to report insomnia symptoms. Epidemiologic data indicate that 40% of women between the ages of 40 and 55 years report recent sleep difficulty resembling insomnia.

A study by Strine and colleagues indicated that women who have menstrual-related problems are more likely to have insomnia than are women without such problems. In fact, after adjustments were made for age, race and ethnicity, education, marital status, and employment status, women who had menstrual-related problems were 2.4 times as likely to report insomnia as women without such problems.

Ethnic groups appear to differ in the prevalence and severity of disordered sleep symptoms. A meta-analysis by Ruiter et al found that African Americans have a higher prevalence and greater severity of sleep-disordered breathing but that whites report more insomnia symptoms.

Chronic insomnia increases in frequency with age and is more common in the elderly. This is presumed to be the result of greater psychosocial stressors, losses, and medical illnesses. Epidemiologic data indicate that the prevalence of chronic insomnia increases from 25% in the adult population to nearly 50% in the elderly population.

Prognosis

A prospective cohort study in ethnic Chinese in Taiwan demonstrated that sleep duration and insomnia severity were associated with all-cause death and cardiovascular disease events.  Other studies have yielded conflicting results regarding the cardiovascular consequences of insomnia. A 6-year prospective cohort study did not find an association between the development of hypertension and insomnia. Other studies, however, indicate an association between short sleep or sleep restriction and hypertension.

A study of persons with insomnia and short sleep duration demonstrated an increased risk of hypertension to a degree comparable to that seen with sleep-disordered breathing. A case-control study in normotensive subjects with chronic insomnia showed a higher nighttime systolic blood pressure and blunted day-to-night blood pressure dipping.

Knutson et al found that the quantity and quality of sleep correlate with future blood pressure. In an ancillary study to the Coronary Artery Risk Development in Young Adults (CARDIA) cohort study, measurement of sleep for 3 consecutive days in 578 subjects showed that shorter sleep duration and lower sleep maintenance predicted both significantly higher blood pressure levels and adverse changes in blood pressure over the next 5 years.

Patients with insomnia report decreased quality of life compared with normal controls in all dimensions of the 36-item Short Form Health Survey (SF-36). Patients with insomnia report excessive fatigue as measured by the Fatigue Severity Scale and the Profiles of Mood Status (POMS).

Pathophysiology

Insomnia usually results from an interaction of biological, physical, psychological, and environmental factors. Although transient insomnia can occur in any person, chronic insomnia appears to develop only in a subset of persons who may have an underlying predisposition to insomnia. The evidence supporting this theory is that compared with persons who have normal sleep, persons with insomnia have the following:

• Higher rates of depression and anxiety
• Higher scores on scales of arousal
• Longer daytime sleep latency
• Increased 24-hour metabolic rates
• Greater night-to-night variability in their sleep
• More electroencephalographic (EEG) beta activity (a pattern observed during memory processing/performing tasks) at sleep onset
• Increased global glucose consumption during the transition from waking to sleep onset, on positron emission tomography of the brain

Hyperarousal

In experimental models of insomnia, healthy subjects deprived of sleep do not demonstrate the same abnormalities in metabolism, daytime sleepiness, and personality as subjects with insomnia. However, in an experimental model in which healthy individuals were given caffeine, causing a state of hyperarousal, the healthy subjects had changes in metabolism, daytime sleepiness, and personality similar to the subjects with insomnia.

Clinical research has also shown that patients with chronic insomnia show evidence of increased brain arousal. For example, studies have indicated that patients with chronic primary insomnia demonstrate increased fast-frequency activity during non–rapid eye movement (NREM) sleep, which is an EEG sign of hyperarousal, and evidence of reduced deactivation in key sleep/wake regions during NREM sleep compared with controls.

Furthermore, patients with insomnia have higher day and night body temperatures, urinary cortisol and adrenaline secretion, and adrenocorticotropic hormone (ACTH) levels than patients with normal sleep. These results support a theory that insomnia is a manifestation of hyperarousal. In other words, the poor sleep itself may not be the cause of the daytime dysfunction, but merely the nocturnal manifestation of a general disorder of hyperarousability.

Spielman model

The Spielman model of chronic insomnia posits 3 components: predisposing factors, precipitating factors, and perpetuating factors. According to this model, predisposing factors may cause the occasional night of poor sleep, but in general, the person sleeps well until a precipitating event (eg, death of a loved one) occurs, which triggers acute insomnia. If bad sleep habits develop or other perpetuating factors set in, the insomnia becomes chronic and will persist even with removal of the precipitating factor.

Genetics

A number of individual genes that are involved in sleep and wakefulness have been isolated. However, current evidence suggests that a network of genes, rather than a single gene or a subset of genes, is responsible for sleep. The neurotransmitters and signaling pathways that serve wakefulness also serve other functions.

Studies indicate differential genetic susceptibility to exogenous influences such as caffeine, light, and stress. For example, one study found that differences in the adenosine 2A receptor gene (ADORA2) determine differential sensitivity to caffeine’s effect on sleep. The ADORA2A 1083T>C genotype determined how closely the caffeine-induced changes in brain electrical activity (ie, increased beta activity) during sleep resembled the alterations observed in patients with insomnia.

In addition, circadian clock genes have been identified that regulate the circadian rhythm. Such genes include CLOCK and Per2. A mutation or functional polymorphism in Per2 can lead to circadian rhythm disorders, such as advanced sleep phase syndrome (sleep and morning awakening occur earlier than normal) and delayed sleep phase syndrome (sleep and morning awakening are delayed).

A missense mutation has been found in the gene encoding the GABAA beta 3 subunit in a patient with chronic insomnia. Polymorphisms in the serotonin receptor transporter gene may modulate the ability of an individual to handle stress or may confer susceptibility to depression. In depression, serotonin is an important neurotransmitter for arousal mechanisms. Furthermore, antagonism of the serotonin 5-HT2 receptor promotes slow-wave sleep.

Fatal familial insomnia

A rare condition, fatal familial insomnia (FFI, previously known as thalamic dementia) is an autosomal dominant human prion disease caused by changes in the PRNP (prion protein) gene. FFI involves a severe disruption of the physiologic sleep pattern that progresses to hallucinations, a rise in catecholamine levels, autonomic disturbances (tachycardia, hypertension, hyperthermia, and diaphoresis), and significant cognitive and motor deficits. Mean age of onset is 50 years, and average survival is 18 months.

FFI and a subtype of familial Creutzfeldt-Jakob disease (CJD) share the same mutation at codon 178 (Asn178) in the PRNP gene. They differ in that a methionine-valine polymorphism is present at codon 129 in PRNP in this subtype of familial CJD.

Sporadic fatal insomnia (SFI) shares a similar clinic course with FFI but does not appear to be inherited. A mutation at codon 178 of the PRNP gene is not found in these patients, but patients have been found to be homozygous for methionine at codon 129 in PRNP.

Possible Complications

Treatment of insomnia can improve these patients’ perceived health, function, and quality of life. Consequences of untreated insomnia may include the following:

• Impaired ability to concentrate, poor memory, difficulty coping with minor irritations, and decreased ability to enjoy family and social relationships
• Reduced quality of life, often preceding or associated with depression and/or anxiety
• More than 2-fold increase in the risk of having a fatigue-related motor vehicle accident

Apparent increase in mortality for individuals who sleep fewer than 5 hours each night

Possible Treatment

The American Association of Sleep Medicine (AASM) guideline states that the 2 primary goals of treatment are to improve sleep quality and to improve related daytime impairments. Strategies for achieving these goals will vary depending on the underlying etiology. If the patient has a medical, neurologic, or sleep disorder, treat the disorder. In particular, adequate pain control can greatly relieve the insomnia associated with pain syndromes. In 2017, the AASM released an updated guideline for the pharmacologic treatment of chronic insomnia in adults.

The AASM guideline recommends psychological and behavioral interventions (including, but not limited to, cognitive-behavioral therapy [CBT]) as effective in the treatment of chronic comorbid insomnia as well as primary insomnia. The guideline also encourages these interventions as initial therapy when appropriate.

The treatment of primary (psychophysiologic) insomnia begins with education about the sleep problem and appropriate sleep hygiene measures (elements of good sleep hygiene are described in Patient Education). Before therapy is instituted, most patients are asked to maintain a sleep diary for 1-2 weeks. This provides a clearer picture of the degree of sleep disturbance and allows development of a tailored treatment.

Strong evidence supports the use of nonpharmacologic interventions (eg, CBT) for insomnia. Head-to-head comparison has shown that the long-term benefits of nonpharmacologic interventions are superior to those of medication. CBT is now considered the most appropriate treatment for patients with primary insomnia. Use of this therapy is based on the fact that primary insomnia is associated with physiologic, emotional, and cognitive arousal and conditioning to arousal in bed.

If the patient has a psychiatric disorder, the disorder should be treated. Management may involve medications, psychotherapy, and possible referral to a psychiatrist, psychologist, or therapist. If the insomnia is related to medication or drug abuse, the offending medication or drug must be slowly tapered and withdrawn.

Even when comorbid causes of insomnia (ie, medical, psychiatric) are treated, however, variable degrees of insomnia persist that require additional interventions. These patients can benefit from CBT and a short course of a sedative-hypnotic or melatonin receptor agonist. In the case of a psychiatric disorder (eg, depression or anxiety), CBT and a short-term sedative-hypnotic in conjunction with an antidepressant can be beneficial.

Primary Prevention

Good sleep habits, also called sleep hygiene, can help you get a good night’s sleep. For example:

• Think positive.Avoid going to bed with a negative mindset, such as “If I don’t sleep for 8 hours, I will feel terrible tomorrow.”
• Try to go to sleep at the same time each night and get up at the same time each morning. Try not to take naps during the day because naps may make you less sleepy at night.
• Avoid caffeine, nicotine, and alcohollate in the day. Caffeine and nicotine are stimulants and can keep you from falling asleep. Alcohol can cause waking in the night and interferes with sleep quality.
• Get regular exercise.Try not to exercise close to bedtime because it may stimulate you and make it hard to fall asleep. Experts suggest not exercising for 4 hours before the time you go to sleep.
• Don’t eat a heavy meallate in the day. A light snack before bedtime, however, may help you sleep.
• Make your sleeping place comfortable.Be sure that it is dark, quiet, and not too warm or too cold. If light is a problem, try a sleeping mask. If noise is a problem, try earplugs or a fan.
• Relax before going to bedby reading a book, listening to music, taking a bath, or enjoying another activity you find relaxing.
• Avoid using your bedfor anything other than sleep or sex.
• If you can’t fall asleep and don’t feel drowsy, get up and read or do somethingthat is not overly stimulating until you feel sleepy.
• If you have trouble lying awake worrying about things, try making a to-do list before you go to bed.This may help you to not focus on those worries overnight.
• Stop clockwatching.Turn the clock around and only use the alarm.

Secondary Prevention

The secondary prevention of insomnia is similar to its primary prevention.

Risk factors

Following risk factors are associated with insomnia:

• Advancing age
• Anxiety or worry-prone personality
• Chronic daily stress
• Cognitive styles
• Familial disposition
• Fear of not sleeping
• Female gender
• High altitude
• Increased arousal
• Irregular sleep scheduling

• Excessive caffeine use
• Irregular sleep schedules

• Light
• Major life events (e.g., illness, separation)
• Noise
• Poor sleep habits
• Poor sleep hygiene practices
• Tendency to repress emotions
• Uncomfortably high or low temperature

Signs or Symptoms

Insomnia symptoms may include:

• Difficulty falling asleep at night
• Waking up during the night
• Waking up too early
• Not feeling well-rested after a night’s sleep
• Daytime tiredness or sleepiness
• Irritability, depression or anxiety
• Difficulty paying attention, focusing on tasks or remembering
• Increased errors or accidents
• Ongoing worries about sleep

Stage

Insomnia may be classified according to the duration of insomnia or pattern of insomnia.

Duration of insomnia

Three types of insomnia exist: transient, acute, and chronic

• Transient insomnia lasts from one night to a few weeks. Most people occasionally suffer from transient insomnia due to such causes as jet lag or short-term anxiety. If this form of insomnia continues to occur from time to time, the insomnia is classified as intermittent.
• Acute insomnia is the inability to consistently sleep well for a period of between three weeks to six months.
• Chronic insomnia is regarded as the most serious; persists almost nightly for at least a month.

Patterns of Insomnia

The pattern of insomnia is often related to the etiology.

• Initial insomnia – difficulty falling asleep at the beginning of the night, often associated with anxiety disorders.
• Middle insomnia – waking during the middle of the night, difficulty maintaining sleep. Often associated with pain syndromes or medical illness.
• Terminal (or late) insomnia – early morning waking. Characteristic of Clinical depression.

Studies

Active Not Recruiting

Number of studies: 54

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Completed

Number of studies: 625

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Enrolling by Invitation

Number of studies: 22

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Not Yet Recruiting

Number of studies: 57

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Recruiting

Number of studies: 172

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Results Available

Number of studies: 149

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Results Not available

Number of studies: 936

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Suspended

Number of studies: 3

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Terminated

Number of studies: 49

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Withdrawn

Number of studies: 19

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Typical Test

Insomnia is a clinical diagnosis. Diagnostic studies are indicated principally for the clarification of comorbid disorders.

Before therapy is instituted, most patients are asked to keep a sleep log for 2-4 weeks. This log, in which the patient records bed and wake times, sleep duration, and daytime naps and activities, gives a clearer picture of the degree of sleep disturbance and allows development of a tailored treatment.

Studies for Hypoxemia

Patients with a history suggestive of chronic obstructive pulmonary disease (COPD) and insomnia should have oximetry or an arterial blood gas (ABG) test performed to determine whether they are hypoxemic. Insomnia in COPD frequently begins with the development of nocturnal hypoxemia, although nocturnal hypoxemia is not required for insomnia to occur. Oxygen therapy may improve insomnia but rarely eliminates it.

Nocturnal hypoxemia is present if the patient has daytime hypoxemia or, frequently, exercise-related hypoxemia. If the oximetry or ABG result is negative for hypoxemia, an exercise desaturation study or overnight oximetry may be helpful to determine whether the patient needs oxygen.

Polysomnography

Polysomnography and daytime multiple sleep latency testing (MSLT) are not routinely indicated for the workup of insomnia. However, patients with a history suggestive of sleep apnea should be referred to a sleep center for polysomnography, as should patients who have precipitous arousals with violent or injurious behavior, as well as some patients with restless legs syndrome (RLS)/periodic limb movement disorder (PLMD). Treatment failure may also be an indication for polysomnography.

Actigraphy

For actigraphy, a portable device is worn around the wrist to record gross motor activity and light/darkness over extended periods. This study provides an indirect objective measure of sleep and wake time. Actigraphy has shown concordance with polysomnography in the assessment of total sleep time. The role of actigraphy in insomnia evaluation has not been well established, but actigraphy can help document sleep patterns and circadian rhythms.

Distinguishing primary insomnia from circadian-rhythm disorders and identifying paradoxical insomnia is useful, particularly with insomnia that is refractory to treatment.

Genetic Testing

If a patient with rapidly progressing insomnia has any first-degree relatives who died with insomnia, there may be concern for fatal familial insomnia (FFI). Genetic testing for this rare condition is available and consists of sequencing the PRNP gene. Brain imaging—specifically, positron-emission tomography (PET) to look for hypometabolism in the thalamus and cingulated cortex—may also assist in the diagnosis of FFI.