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Insomnia

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Insomnia
Author: Ron A Shatzmiller, MD, MSc; Chief Editor: Selim R Benbadis, MD more...
Updated: Jan 17, 2012

Background
Insomnia is defined as repeated difficulty with the initiation, duration, maintenance, or quality of sleep that occurs
[1]

despite adequate time and opportunity for sleep and results in some form of daytime impairment. Approximately
one third of adults report some difficulty falling asleep and/or staying asleep during the past 12 months, with 17%
reporting this problem as a significant one. As many as 95% of Americans have reported an episode of insomnia at
some point during their lives.

[2]

The 2008 update to the American Academy of Sleep Medicine (AASM) guideline for
[3]

the evaluation and management of chronic insomnia calls insomnia an important public health issue.

Insomnia is usually a transient or short-term condition. In some cases, however, insomnia can become chronic.
Acute insomnia lasts up to 3 months. It is often referred to as adjustment insomnia because it most often occurs in
the context of an acute situational stress, such as a new job or an upcoming deadline or examination. The insomnia
typically resolves when the stressor is no longer present or the individual adapts to the stressor. However, transient
[1]

insomnia often recurs when new or similar stresses arise in the patients life.

Chronic insomnia lasting longer than1 month can be associated with a wide variety of medical and psychiatric
conditions and typically involves conditioned sleep difficulty, but it is believed to occur primarily in patients with an
underlying predisposition to insomnia (see Pathophysiology). The different subtypes of chronic insomnia are
described in Etiology.
Despite inadequate sleep, many patients with insomnia do not complain of excessive daytime sleepiness, such as
involuntary episodes of drowsiness in boring, monotonous, nonstimulating situations. However, they do complain of
feeling tired and fatigued, with poor concentration. This may be related to a physiological state of hyperarousal (see
Pathophysiology). In fact, despite not getting adequate sleep, patients with insomnia oftentimes have difficulty falling
asleep even for daytime naps.
Chronic insomnia also has numerous health consequences (see Prognosis). For example, patients with insomnia
[4]

demonstrate slower response to challenging reaction-time tasks. Moreover, patients with chronic insomnia report
reduced quality of life, comparable to that experienced by patients with such conditions as diabetes, arthritis, and
heart disease. Quality of life improves with treatment but still does not reach the level seen in the general
[5]

population.

In addition, chronic insomnia is associated with impaired occupational and social performance and an elevated
absenteeism rate that is 10-fold greater than controls. Furthermore, insomnia is associated with higher healthcare
use, including a 2-fold increase in hospitalizations and office visits.
Insomnia can also be a risk factor for depression and a symptom of a number of medical, psychiatric, and sleep
disorders. In fact, insomnia appears to be predictive of a number of disorders, including depression, anxiety, alcohol
dependence, drug dependence, and suicide. The annual cost of insomnia is not inconsequential, with the estimated
[6]

annual costs for insomnia at $12 billion dollars for healthcare and $2 billion dollars for sleep-promoting agents.

In 2005, the National Institutes of Health held a State of the Science Conference on the Manifestations of Chronic
[7]

Insomnia in Adults. This conference focused on the definition, classification, etiology, prevalence, risk factors,
consequences, comorbidities, public health consequences and the available treatments and evidence for their
efficacy. A summary of this conference can be obtained at the NIH Consensus Development Program Web site.
Prior to this conference, it was widely believed that most cases of chronic insomnia are secondary to another
medical or psychiatric condition and that effective treatment of the primary condition would effectively address
secondary insomnia.
In fact, insomnia often persists despite treatment of the underlying medical or psychiatric condition, and, in certain

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cases, the persistence of insomnia can increase the risk of relapse of the primary condition. In this regard, the
clinician needs to understand that insomnia is a condition in its own right that requires prompt recognition and
treatment to prevent morbidity and improve quality of life for their patients.
The conference report concluded, based on review of the literature and the panel experts, that the limited
understanding of the mechanistic pathways precludes drawing firm conclusions about the nature of the associations
between other conditions and insomnia, or the directions of causality. Furthermore, the conference members
expressed concern that the term secondary insomnia may promote undertreatment. Therefore, they proposed the
term comorbid insomnia.
Management of insomnia may involve further challenges. If sleep difficulties are not the presenting complaint, there
is often too little time to address them at an office visit.
Physicians receive very little training in medical school on sleep disorders and their impact on patients overall health
and quality of life. In fact, most providers rate their knowledge of sleep medicine as only fair. Finally, many providers
are not aware of the safety issues, efficacy of cognitive behavioral and pharmacologic therapies, or when to refer a
patient to a sleep medicine specialist.
A patient's report of insomnia is nonspecific and can encompass a variety of concerns, including difficulty falling
asleep, awakening early or easily, problems with returning to sleep after awakening, or a general poor quality of
sleep. Therefore, the clinician must determine what the patient means by insomnia.
In order to be considered a disorder, the insomnia should be accompanied by daytime sleepiness, loss of
concentration, irritability, worries about sleep, loss of motivation, or other evidence of daytime impairment that is
associated with the sleep difficulty (see Clinical Presentation).
The management of insomnia varies depending on the underlying etiology. If the patient has a medical, neurologic,
or sleep disorder, treatment is directed at the disorder. Even when comorbid causes of insomnia (ie, medical,
psychiatric) are treated, however, variable degrees of insomnia persist that require additional interventions. These
[8]

patients can benefit from cognitive behavioral therapy (CBT) and a short course of a sedative-hypnotic or
melatonin receptor agonist (see Treatment and Management).
The treatment of primary (psychophysiologic) insomnia begins with education about the sleep problem and
appropriate sleep hygiene measures. CBT is now considered the most appropriate treatment for patients with
primary insomnia.

[9, 10, 11]

For related information, see Primary Insomnia.

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.

Promotion of wakefulness
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.
There includes histaminergic cells in the tuberomammillary nucleus (TMN) in the posterior hypothalamus,
norepinephrine-producing neurons in the locus coeruleus (LC) (norepinephrine), serotonergic neurons in the dorsal
raphe nuclei (DRN), dopaminergic neurons in the ventral tegmental area (VTA), and cholinergic neurons of the basal
forebrain (acetylcholine).
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.

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The ascending arousal system. Adapted from Saper et al. Hypothalamic Regulation of Sleep and Circadian Rhythms. Nature
2005;437:1257-1263.

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

Ventrolateral pre-optic nucleus inhibitory projections to main components of the arousal system to promote sleep.

The homeostatic and circadian processes


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. (See the image below.)

Sleep-wake cycle.

Melatonin and the circadian process


The suprachiasmatic nucleus (SCN) is entrained to the external environment by the cycle of light and darkness. The
retinal ganglion cells transmit light signals via the retinohypothalamic tract to stimulate the SCN. A multisynaptic
pathway from the SCN projects to the pineal gland, which produces melatonin.
Melatonin synthesis is inhibited by light and stimulated by darkness. The nocturnal rise in melatonin increases
[12]

between 8 and 10 am and peaks between 2 and 4 am, then declines gradually over the morning.
Melatonin acts
via 2 specific melatonin receptors: MT1 attenuates the alerting signal and MT2 phase shifts the SCN clock. The
novel sleep-promoting drug ramelteon acts specifically at the MT1 and MT2 receptors to promote sleep.

The flip-flop switch model


[13]

This flip-flop circuit consists of


Saper and colleagues proposed the flip-flop switch model of sleep-wake regulation.
2 sets of mutually inhibitory components. The sleep side is the VLPO and the arousal side includes TMN
histaminergic neurons and brainstem arousal regions (the DRN serotonergic neurons, VTA dopaminergic neurons,

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and LC noradrenergic neurons).


Each side of the switch inhibits the other. For example, when activation of one side is slightly stronger, the weaker
side has increased inhibition, thus further tipping the balance toward the stronger side. This flip-flop switch allows for
rapid state transitions. (See the schematic flip-flop switch model in the image below.)

Schematic flip-flop switch model. Adapted from Saper C et al. Hypothalamic regulation of sleep and circadian rhythms. Nature
2005;437:1257-1263.

Hypocretin neurons in the posterolateral hypothalamus are active during wakefulness and project to all of the
wakefulness arousal systems described above. Hypocretin neurons interact with both the sleep-active and the sleeppromoting systems and act as stabilizers between wakefulness-maintaining and sleep-promoting systems to prevent
[14]

sudden and inappropriate transitions between the 2 systems.

Narcolepsy with cataplexy illustrates the disruption of this system. These patients have a greater than 90% loss of
[15]

hypocretin neurons, and they have sleep-wake state instability with bouts of sleep intruding into wakefulness.

Mechanisms of action of insomnia medication


Benzodiazepines and benzodiazepine receptor agonists
Benzodiazepine receptor agonists (BzRAs) work through GABA receptors to promote sleep by inhibiting brainstem
A

monoaminergic arousal pathways, through facilitation of VLPO inhibitory GABAergic projections to arousal centers
such as the anterior hypothalamus TMN, the posterolateral hypothalamic hypocretin neurons, and the brainstem
arousal regions.
The GABA receptor consists of 5 protein subunits arranged in a ring around a central pore. Most GABA receptors
A

consist of 2 alpha, 2 beta, and 1 gamma subunits. Upon GABA receptor activation, chloride ions flow into the cell,
A

resulting in neuronal hyperpolarization.

[16, 17]

Benzodiazepine receptor agonists (BZRAs) enhance the effect of GABA by lowering the concentration of GABA
required to open the GABA channel. BZRAs bind to a modulatory site on the GABA receptors that is distinct from
A

the GABA binding site and changes the receptor complex allosterically to increase the affinity of the receptor to
GABA, thus producing a larger postsynaptic current prolonging inhibition. Although BZRAs do not directly open the
chloride channel, they modulate the ability of GABA to do so, thus enhancing its inhibitory effect.

GABAA receptor complex subunits and schematic representation of agonist binding sites.

Synaptic GABA receptors typically contain a in combination with an , , and subunit. Most GABA receptors
A

expressed in the CNS are , , , .


1

2 2

3 2

3 2

3 2

While GABA binds at the junction between subunits and , BZRAs bind at the interface between and . The
alpha subunits of the GABA receptor mediate sedative, amnestic, anxiolytic, myorelaxant, ataxic, and sedative
A

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effects. GABA receptors containing the subunit mediate the sedative-hypnotic and amnestic effects and, to some
A

degree, the anticonvulsant effects of BZRAs.


For example, studies of knockout mice that express a benzodiazepine insensitive subunit fail to show the
1

sedative, amnestic effects of diazepam. The nonbenzodiazepine receptor agonists (ie, zaleplon, zolpidem,
eszopiclone) have relative selectivity for GABA receptors containing the subunit, thereby producing fewer
A

adverse effects (ie, ataxia, anxiolytic, myorelaxation properties) than nonselective BZRAs. (See the image below
outlinining the GABA receptor subunit functions.)
A

GABAA receptor subunit function(s).

Melatonin and melatonin receptor agonists


Melatonin is a hormone produced by the pineal gland during the period of sundown to sunrise. It exerts sleeppromoting effects through MT1/MT2 receptors via an unknown mechanism. Ramelteon is an agonist at MT1 and
MT2 receptors, approved by the US Food and Drug Administration (FDA) for the treatment of sleep-onset
[18]

difficulty.

Sedating antidepressants
This class of medicines includes amitriptyline, trimipramine, doxepin, trazodone, and mirtazapine. They were
identified as therapeutic agents for the treatment of insomnia when patients treated for depression reported sedating
side effects. They exert their effects by blocking the receptors of wake-promoting neurotransmitters, namely
[18]

serotonin, norepinephrine, and histamine.


Antihistamines

Diphenhydramine and doxylamine are commonly used in over-the-counter insomnia medications. They exert their
effect by disrupting wake-promoting histaminergic neurotransmission from the tuberomammillary nucleus via the
antagonism of the H1 receptor. Doxepin, mirtazapine, olanzapine, and quetiapine also exert sleep-promoting effects
via this mechanism.

Pathophysiology
Insomnia usually results from an interaction of biological, physical, psychological, and environmental factors. While
transient insomnia can occur in any person, chronic insomnia appears to develop only in a subset of persons who
[19]

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
[20]

Increased 24-hour metabolic rates


Greater night-to-night variability in their sleep
More encephalographic 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

[21]

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. In an experimental model in which
healthy subjects were given caffeine, causing a state of hyperarousal, the healthy subjects had changes in

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[22]

metabolism, daytime sleepiness, and personality similar to the subjects with insomnia.

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.
The Spielman model of chronic insomnia posits 3 components: predisposing factors, precipitating factors, and
[23]

perpetuating factors.

According to this model (see the image below), 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 or other life stress) occurs.
Then, the person experiences 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. This theory is illustrated in
the image below.

Theoretical model of the factors causing chronic insomnia. Chronic insomnia is believed to primarily occur in patients with
predisposing or constitutional factors. These factors may cause the occasional night of poor sleep but not chronic insomnia. A
precipitating factor, such as a major life event, causes the patient to have acute insomnia. If poor sleep habits or other
perpetuating factors occur in the following weeks to months, chronic insomnia develops despite the removal of the precipitating
factor. Adapted from Spielman AJ, Caruso LS, Glovinsky PB: A behavioral perspective on insomnia treatment. Psychiatr Clin
North Am. 1987 Dec;10(4):541-53.

Predisposing factors
Psychosocial, medical, or psychiatric conditions may precipitate insomnia. Only a fraction of patients with medical or
psychiatric conditions develop insomnia, however, which suggests that those individuals have an inherent
susceptibility to develop insomnia in the context of a stressful event. These factors are likely to be genetic and
neurobiologic in nature.
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.

[24]

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
[25]

sensitivity to caffeines effect on sleep.


The ADORA2A 1083T>C genotype determined how closely the caffeineinduced changes in brain electrical activity (ie, increased beta activity) during sleep resembled the alterations
observed in patients with insomnia.
[26]

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
advance 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 GABA beta 3 subunit in a patient with chronic
A

[27]

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.
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 nonrapid 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
[28, 29]

secretion, and adrenocorticotropic hormone (ACTH) levels than patients with normal sleep.

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sleepers demonstrated that these changes were not due to sleep deprivation.

Precipitating factors
In retrospective studies, a large proportion of patients with insomnia (78%) can identify a precipitating trigger for their
insomnia. Morin and colleagues showed that these patients demonstrate an increased response to stress as
[30]

compared with controls. A number of factors can trigger insomnia in vulnerable individuals.
These factors include
depression, anxiety, sleep-wake schedule changes, medications, other sleep disorders, and medical conditions. In
addition, positive or negative family, work-related, and health events are common insomnia precipitants.

Perpetuating factors
Regardless of how insomnia was triggered, cognitive and behavioral mechanisms are generally accepted to be the
factors that perpetuate it. Cognitive mechanisms include misconceptions about normal sleep requirements and
excessive worry about the ramifications of the daytime effects of inadequate sleep.
As a result, these patients often become obsessive about their sleep or try too hard to fall asleep. These
dysfunctional beliefs often produce sleep disruptive behaviors such as trying to catch up on lost sleep with daytime
naps or sleeping in late, which in turn reduces the patients natural homeostatic drive to sleep at their habitual
bedtime. Learned sleep-preventing associations are characterized by over-concern about inability to fall asleep.
Consequently, these patients develop conditioned arousal to stimuli that would normally be associated with sleep (ie,
heightened anxiety and ruminations about going to sleep in their bedroom). A cycle then develops in which the more
the patients strive to sleep, the more agitated they become, and the less they are able to fall asleep. They also have
ruminative thoughts or clock watching as they are trying to fall asleep in their bedroom.
Thus, conditioned environmental cues causing insomnia develop from the continued association of sleeplessness
with situations and behaviors that are typically related to sleep.

Etiology
Many clinicians assume that insomnia is often secondary to a psychiatric disorder, However, a large epidemiologic
[31]

survey showed that half of insomnia diagnoses were not related to a primary psychiatric disorder.
A diagnosis of
insomnia does, however, increase the future risk for depression or anxiety. (See the frequency of causes of insomnia
in the image below.)

Frequency of insomnia causes.


[32]

The International Classification of Sleep Disorders, 2nd Edition (ICSD-2)


follows:

classifies insomnia into 11 categories, as

Adjustment insomnia (acute insomnia)


Psychophysiologic insomnia (primary insomnia)
Paradoxical insomnia
Insomnia due to medical condition
Insomnia due to mental disorder
Insomnia due to drug or substance abuse
Insomnia not due to substance or known physiological condition, unspecified
Inadequate sleep hygiene
Idiopathic insomnia
Behavioral insomnia of childhood
Primary sleep disorders causing insomnia

Adjustment insomnia (acute insomnia)

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Adjustment insomnia is also known as transient, short-term, or acute insomnia. Causes can be divided into 2 broad
categories: environmental and stress-related. Environmental etiologies result from an unfamiliar or nonconducive
sleep environment due to factors such as too much noise or light, extremes of temperature, or an uncomfortable bed
or mattress. Stress-related etiologies primarily involve life events such as new job or school, deadlines or
examinations, or deaths of relatives and close friends.
Adjustment insomnia typically lasts 3 months or less. The insomnia resolves when the stressor is no longer present
or the individual adapts to the stressor .

Psychophysiologic insomnia (primary insomnia)


This type of insomnia begins with a prolonged period of stress in a person with previously adequate sleep. The
patient responds to stress with somatized tension and agitation.
In a person experiencing normal sleep, as the initial stress abates, the bad sleep habits are gradually extinguished
because they are not reinforced nightly. However, in a patient with a tendency toward occasional poor nights of
sleep, the bad habits are reinforced, the patient "learns" to worry about his or her sleep, and chronic insomnia
follows.
The patient will have evidence of conditioned sleep difficulty and or/heightened arousal in bed, as indicated by one or
more of the following:
Excessive focus on and heightened anxiety about sleep
Difficulty falling asleep at the desired bedtime or during planned naps, but no difficulty falling asleep during
other monotonous activities when not intending to sleep
Ability to sleep better away from home than at home
Mental arousal in bed characterized either by intrusive thoughts or a perceived inability to volitionally cease
sleep-preventing mental activity
Heightened somatic tension in bed reflected by a perceived inability to relax the body sufficiently to allow the
onset of sleep
The sleep disturbance is not better explained by another sleep disorder, medical or neurologic disorder, medication
use, or substance abuse disorder.

Paradoxical insomnia
One or more of the following criteria apply:
The patient reports a chronic pattern of little or no sleep most nights, with rare nights during which relatively
normal amounts of sleep are obtained
Sleep log data from one or more weeks of monitoring show an average sleep time often with no sleep at all
indicated for several nights each week; typically, daytime naps are absent following such nights
There is typically a mismatch between objective findings from polysomnography or actigraphy and subjective
sleep estimates from self-reported sleep diary
At least one of the following is observed:
The patient reports constant or near constant awareness of environmental stimuli throughout most nights
The patient reports a pattern of conscious thoughts or rumination throughout most nights while maintaining a
recumbent posture
The daytime impairment reported is consistent with that reported by other insomnia subtypes but is much less severe
than expected given the extreme level of sleep deprivation reported.
The sleep disturbance is not better explained by another sleep disorder, medical or neurologic disorder, medication
use, or substance abuse disorder.

Insomnia due to medical condition


The patient has a coexisting medical condition known to disrupt sleep. Medical disorders may include the following:
Chronic pain syndromes from any cause (eg, arthritis, cancer)
Advanced chronic obstructive lung disease
Benign prostatic hypertrophy (because of nocturia)
Chronic renal disease (especially if on hemodialysis)
Chronic fatigue syndrome

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Fibromyalgia
Neurologic disorders may include Parkinson disease, other movement disorders, and headache syndromes,
particularly cluster headaches, which may be triggered by sleep.
In a retrospective community-based study, people with the following medical problems reported more chronic
[33]

insomnia than did those without those medical problems

Heart disease (44.1% vs 22.8%)


Cancer (41.4% vs 24.6%)
High blood pressure (44% vs 19.3%)
Neurologic disease (66.7% vs 24.3%)
Breathing problems (59.6% vs 21.4%)
Urinary problems (41.5% vs 23.3%)
Chronic pain (48.6% vs 17.2%)
Gastrointestinal problems (55.4% vs 20.0%)
[33]

Conversely, people with chronic insomnia self-reported more of the following than did people without insomnia

Heart disease (21.9% vs 9.5%)


High blood pressure (43.1% vs 18.7%)
Neurologic disease (7.3% vs 1.2%)
Breathing problems (24.8% vs 5.7%)
Urinary problems (19.7% vs 9.5%)
Chronic pain (50.4% vs 18.2%)
Gastrointestinal problems (33.6% vs 9.2%)
In this category, the insomnia is clearly associated with the medical condition. The insomnia began near the time of
onset or with significant progression of the medical condition and waxes and wanes with the severity of this
condition.
The sleep disturbance is not better explained by another sleep disorder, medical or neurologic disorder, medication
use, or substance abuse disorder.

Insomnia due to mental disorder


Most chronic psychiatric disorders are associated with sleep disturbances.
Depression is most commonly associated with early morning awakenings and an inability to fall back asleep.
Conversely, studies have also demonstrated that insomnia can lead to depression: insomnia of more than 1-year
duration is associated with an increased risk of depression.
Schizophrenia and the manic phase of bipolar illness are frequently associated with sleep-onset insomnia. Anxiety
disorders (including nocturnal panic disorder and posttraumatic stress disorder) are associated with both sleep-onset
and sleep-maintenance complaints.
A mental disorder must be diagnosed according to the criteria of the Diagnostic and Statistical Manual 4th Edition,
Text Revision (DSM-IV-TR). The insomnia is temporally associated with the mental disorder; however, in some
cases, insomnia may appear a few days or weeks before the emergence of the underlying mental disorder.
The insomnia is more prominent than that typically associated with the mental disorders, as indicated by causing
marked distress or constituting an independent focus of treatment.
The sleep disturbance is not better explained by another sleep disorder, medical or neurologic disorder, medication
use, or substance abuse disorder.

Insomnia due to drug or substance abuse


Sleep disruption is common with the excessive use of stimulants, alcohol, or sedative-hypnotics. One of the following
applies:
The patient has current ongoing dependence on or abuse of a drug or substance known to have sleep
disruptive properties either during periods of use or intoxication or during periods of withdrawal
The patient has current ongoing use of or exposure to a medication, food, or toxin known to have sleepdisruptive properties in susceptible individuals

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The insomnia is temporally associated with the substance exposure, use, or abuse, or acute withdrawal.
The sleep disturbance is not better explained by another sleep disorder, medical or neurologic disorder, medication
use, or substance abuse disorder.

Insomnia not due to substance or known physiological condition, unspecified


This diagnosis is used for forms of insomnia that cannot be classified elsewhere in ICSD-2, but are suspected to be
due to an underlying mental disorder, psychological factors, or sleep disruptive processes. This diagnosis can be
used on a temporary basis until further information is obtained to determine the specific mental condition or
psychological or behavioral factors responsible for the sleep difficulty.

Inadequate sleep hygiene


Inadequate sleep hygiene practices are evident by the presence of at least 1 of the following:
Improper sleep scheduling consisting of frequent daytime napping, selecting highly variable bed or rising
times or spending excessive amounts of time in bed
Routine use of products containing alcohol, nicotine, or caffeine, especially in the period preceding bedtime
Engagement in mentally stimulating, physically activating, or emotionally upsetting activities too close to
bedtime
Frequent use of the bed for activities other than sleep (eg, television watching, reading, studying, snacking,
thinking, planning)
Failure to maintain a comfortable sleeping environment
The sleep disturbance is not better explained by another sleep disorder, medical or neurologic disorder, medication
use, or substance abuse disorder.

Idiopathic insomnia
This sleep disturbance is a longstanding complaint of insomnia with insidious onset in infancy or childhood. No
precipitant or cause is identifiable. There is a persistent course with no sustained periods of remission. This condition
[34]

is present in 0.7% of adolescents and 1% of very young adults.

Behavioral insomnia of childhood


A child's symptoms meet the criteria for insomnia based on parents or other adult caregivers observations. Two
types of this sleep disturbance are recognized: sleep-onset association and limit-setting.
The sleep-onset association type is characterized by the following:
Falling asleep is an extended process that requires special conditions
Sleep onset associations are highly problematic or demanding
In the absence of associated conditions, sleep onset is significantly delayed or sleep is otherwise disrupted
Nighttime awakenings require caregiver intervention for the child to return to sleep
The limit-setting type is characterized by the following:
The individual has difficulty initiating or maintaining sleep
The individual stalls or refuses to go to bed at an appropriate time or refuses to return to bed following a
nighttime awakening
The caregiver demonstrates insufficient or inappropriate limit-setting to establish appropriate sleeping
behavior in the child

Primary sleep disorders causing insomnia


Included in this category are restless legs syndrome (RLS), obstructive sleep apnea/hypopnea syndrome, and
circadian rhythm disorders.
RLS is a sleep disorder characterized by the following:
An urge to move the legs, usually accompanied by uncomfortable and unpleasant physical sensations in the
legs
Symptoms begin or worsen during periods of rest or inactivity such as lying or sitting
Symptoms are partially or totally relieved by moving, such as walking or stretching, at least as long as the

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activity continues
Symptoms are worse or occur only in the evening or the night
RLS may be associated with periodic limb movement disorder (PLMD), which is characterized by repetitive periodic
leg movements that occur during sleep. If RLS is predominant, sleep-onset insomnia is generally present; if PLMD is
predominant, sleep-maintenance insomnia is more likely.
A minority of patients with obstructive sleep apnea/hypopnea syndrome complain of insomnia rather than
hypersomnolence. Often, these patients complain of multiple awakenings or sleep-maintenance difficulties. They
may also have frequent nocturnal awakenings because of nocturia.
Circadian disorders include the following:
Advanced sleep phase syndrome
Delayed sleep phase syndrome
Shiftwork sleep disorder
Irregular sleep-wake rhythm
In advanced sleep phase syndrome, patients feel sleepy earlier than their desired bedtime (ie, 8 pm) and they wake
up earlier than they would like (ie, 4-5 am). This condition is more common in the elderly. These patients typically
complain of sleep maintenance insomnia.
In delayed sleep phase syndrome, patients do not feel sleepy until much later than the desired bedtime, and they
wake up later than desired or socially acceptable. On sleep diaries or actigraphy, these patients show a consistent
sleep time with earlier wake times that correspond to school or work days and delayed wake times on weekends,
time off, and vacations.
Delayed sleep phase syndrome often begins in adolescence and may be associated with a family history in up to
40% of patients. These patients report difficulty falling asleep at usually socially desired bedtimes, and complain of
excessive daytime sleepiness during the school or work week.
Shift work sleep disorder is a complaint of insomnia or excessive sleepiness that typically is temporally related to a
recurring work schedule that overlaps the usual sleep time. This can occur with early morning shifts (ie, starting at
4-6 am), where the patient is anxious about waking up in time for their early shift, particularly when they have a
rotating shift schedule. Evening shifts that end at 11 pm can result in insomnia in that the patient may need some
time to wind down from work before retiring to bed.
Night shift work can be associated with both sleep onset and maintenance insomnia due to exposure to sunlight on
the drive home from work, daylight exposure in the bedroom, and social and environmental cues (eg, picking up
children at school, paying bills, household chores).
Irregular sleep-wake rhythm is typically seen in patients with poor sleep hygiene, particularly patients who live or
work alone with minimal exposure to light, activity, and social cues. These patients randomly nap throughout the day
making it difficult, if not impossible, to fall asleep at a habitual bedtime with a consolidated sleep period.

Epidemiology
In a 1991 survey, 30-35% of American adults reported difficulty sleeping in the past year and 10% reported the
insomnia to be chronic and/or severe. Despite the high prevalence, only 5% of persons with chronic insomnia visited
their physician specifically to discuss their insomnia. Only 26% discussed their insomnia during a visit made for
another problem.

[35]

In an epidemiologic study from Quebec, 29.9% of 2001 respondents reported insomnia symptoms and 9.5% met
[36]

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 rate of approximately 27% for patients reporting
"difficulty sleeping."

Sex and age demographics


[37]

Women are 1.4 times as likely as men to report insomnia symptoms.

Epidemiologic data indicate that 40% of


[38]

women between age 40 and 55 years report recent sleep difficulty resembling insomnia.

One study by Strine and colleagues indicated that women who have menstrual-related problems are more likely to
[39]

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

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times as likely to report insomnia than women without such problems.


Chronic insomnia increases in frequency with age and is more common in the elderly. This is presumed due to
greater psychosocial stressors, losses, and medical illnesses. Recent epidemiologic data indicate that the
prevalence of chronic insomnia increases from 25% in the adult population to nearly 50% in the elderly
[40]

population.

Prognosis
[41]

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

Consequences of

Individuals with insomnia report an impaired ability to concentrate, poor memory, difficulty coping with minor
irritations, and decreased ability to enjoy family and social relationships
Quality of life is reduced in insomnia patients, often preceding depression or associated with depression
and/or anxiety
Individuals with insomnia are more than twice as likely to have a fatigue-related motor vehicle accident
The mortality rate appears to be higher in patients who sleep fewer than 5 hours each night.
A prospective cohort study among ethnic Chinese in Taiwan demonstrated that sleep duration and insomnia severity
[42]

were associated with all-cause death and cardiovascular disease events.

Study results conflict regarding the cardiovascular consequences of insomnia. A 2009 prospective cohort study over
a 6-year period of follow-up did not find an association between the development of hypertension and insomnia.

[43]

[44, 45]

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
[46]

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
[47]

dipping.

Knutson et al found that the quantity and quality of sleep correlate with future blood pressure. In an ancillary 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
[48]

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). Patients with insomnia are more than twice as likely as the
general population to have a fatigue-related motor vehicle accident.

Associations of insomnia with depression and anxiety


One of the early descriptions of an association between insomnia and depression and anxiety was by Ford and
[31]

Kamerow.
What is still unknown is the nature of the association. For example, insomnia may presage the
development of an incipient mood disorder, and/or mood disorders may independently predispose to insomnia.
After adjusting for medical disorders, ethnicity, and sex, patients with insomnia were 9.8 times more likely to have
clinically significant depression and 17.3 times more likely to have clinically significant anxiety than persons who did
not have insomnia.
Ohayon and Roth found that symptoms of insomnia were reported to occur before the first episode of an anxiety
disorder 18% of the time, simultaneously 39% of the time, and after the onset of an anxiety disorder 44% of the
[49]

time.

In contrast, insomnia symptoms were reported to occur before a first episode of a mood disorder 41% of the time,
simultaneously 29% of the time, and after the onset of a mood disorder 29% of the time.

Patient Education
All patients with insomnia, whether transient or chronic, should be educated about sleep and the elements of good
sleep hygiene. Sleep hygiene refers to daily activities and habits that are consistent with and/or promote the
maintenance of good quality sleep and full daytime alertness.

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Educate patients on the following elements of good sleep hygiene:


Develop regular sleep habits; this means keeping a regular sleep and wake time, sleeping as much as
needed to feel refreshed the following day, but not spending more time in bed than needed
Avoid staying in bed in the morning to catch up on sleep
Avoid daytime naps; if a nap is necessary, keep it short (less than 1 hour) and avoid napping after 3 pm
Keep a regular schedule; regular times for meals, medications, chores, and other activities helps keep the
inner body clock running smoothly
Do not read, write, eat, watch TV, talk on the phone, or play cards in bed
Avoid caffeine after lunch; avoid alcohol within 6 hours of bedtime; avoid nicotine before bedtime
Do not go to bed hungry, but do not eat a big meal near bedtime either
Avoid sleeping pills, particularly over-the-counter remedies
Slow down and unwind before bed (beginning at least 30 minutes before bedtime (a light snack may be
helpful); create a bedtime ritual such as getting ready for bed, wearing night clothes, listening to relaxing
music, or reading a magazine, newspaper, or book
Avoid watching TV in the bedroom or sleeping on the sofa and then going to bed later in the night
Avoid stimulating activities prior to bedtime (eg, vigorous exercise, discussing or reviewing finances, or
discussing stressful issues with a spouse or partner or ruminating about them with oneself)
Keep the bedroom dark, quiet, and at a comfortable temperature
Exercise daily; this is best performed in the late afternoon or early evening (but not later than 6-7 pm)
Do not force yourself to sleep; if you are unable to fall asleep within 15-30 minutes, get up and do something
relaxing until sleepy (eg, read a book in a dimly lit room, watch a nonstimulating TV program); avoid watching
the clock or worrying about the perceived consequences of not getting enough sleep
See the American Academy of Sleep Medicine Sleep Education site for valuable information.
For patient education information, see the Mental Health and Behavior Center and Sleep Disorders Center, as well
as Insomnia, Primary Insomnia, Understanding Insomnia Medications, Sleep Disorders in Women, Sleep Disorders
and Aging, and Sleeplessness and Circadian Rhythm Disorder.

Contributor Information and Disclosures


Author
Ron A Shatzmiller, MD, MSc Assistant Clinical Professor, Department of Neurology, Keck School of Medicine of
the University of Southern California; Specialty Lead Physician, Healthcare Partners Medical Group, Arcadia,
California
Ron A Shatzmiller, MD, MSc is a member of the following medical societies: American Academy of Neurology and
American Academy of Sleep Medicine
Disclosure: Nothing to disclose.
Coauthor(s)
Erasmo A Passaro, MD, FAAN Director, Comprehensive Epilepsy Program/Clinical Neurophysiology Lab,
Bayfront Medical Center, Florida Center for Neurology
Erasmo A Passaro, MD, FAAN is a member of the following medical societies: American Academy of Neurology,
American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society,
American Medical Association, and American Society of Neuroimaging
Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; UCB Honoraria Speaking and teaching; Pfizer
Honoraria Speaking and teaching; Forest Honoraria Speaking and teaching
Chief Editor
Selim R Benbadis, MD Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and
Neurosurgery, Tampa General Hospital, University of South Florida College of Medicine
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology,
American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society,
and American Medical Association
Disclosure: UCB Pharma Honoraria Speaking, consulting; Lundbeck Honoraria Speaking, consulting; Cyberonics
Honoraria Speaking, consulting; Glaxo Smith Kline Honoraria Speaking, consulting; Pfizer Honoraria Speaking,
consulting; Sleepmed/DigiTrace Honoraria Speaking, consulting
Additional Contributors

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Carmel Armon, MD, MSc, MHS Professor of Neurology, Tufts University School of Medicine; Chief, Division of
Neurology, Baystate Medical Center
Carmel Armon, MD, MSc, MHS is a member of the following medical societies: American Academy of Neurology,
American Academy of Sleep Medicine, American Association of Neuromuscular and Electrodiagnostic Medicine,
American Clinical Neurophysiology Society, American College of Physicians, American Epilepsy Society,
American Medical Association, American Neurological Association, American Stroke Association, Massachusetts
Medical Society, Movement Disorders Society, and Sigma Xi
Disclosure: Avanir Pharmaceuticals Consulting fee Consulting
Kendra Becker, MD, MPH Sleep Medicine Department, Kaiser Permanente Fontana Medical Center
Kendra Becker, MD, MPH is a member of the following medical societies: American Academy of Sleep Medicine,
American College of Physicians, and American Medical Association
Disclosure: Nothing to disclose.
Jose E Cavazos, MD, PhD, FAAN Associate Professor with Tenure, Departments of Neurology, Pharmacology,
and Physiology, Program Director of the Clinical Neurophysiology Fellowship, University of Texas School of
Medicine at San Antonio; Co-Director, South Texas Comprehensive Epilepsy Center, University Hospital System;
Director of the San Antonio Veterans Affairs Epilepsy Center of Excellence and Neurodiagnostic Centers, Audie L
Murphy Veterans Affairs Medical Center
Jose E Cavazos, MD, PhD, FAAN is a member of the following medical societies: American Academy of
Neurology, American Clinical Neurophysiology Society, American Epilepsy Society, and American Neurological
Association
Disclosure: GXC Global, Inc. Intellectual property rights Medical Director - company is to develop a seizure
detecting device. No conflict with any of the eMedicine articles that I wrote or edited.
Zab Mosenifar, MD Director, Division of Pulmonary and Critical Care Medicine, Director, Women's Guild
Pulmonary Disease Institute, Professor and Executive Vice Chair, Department of Medicine, Cedars Sinai Medical
Center, University of California, Los Angeles, David Geffen School of Medicine
Zab Mosenifar, MD is a member of the following medical societies: American College of Chest Physicians,
American College of Physicians, American Federation for Medical Research, and American Thoracic Society
Disclosure: Nothing to disclose.
Daniel R Ouellette, MD, FCCP Associate Professor of Medicine, Wayne State University School of Medicine;
Consulting Staff, Pulmonary Disease and Critical Care Medicine Service, Henry Ford Health System
Daniel R Ouellette, MD, FCCP is a member of the following medical societies: American College of Chest
Physicians and American Thoracic Society
Disclosure: Nothing to disclose.
James A Rowley, MD Professor, Fellowship Program Director, Department of Medicine, Division of Pulmonary,
Critical Care and Sleep Medicine, Wayne State University School of Medicine
James A Rowley, MD is a member of the following medical societies: American Academy of Sleep Medicine,
American College of Chest Physicians, American College of Physicians, and American Thoracic Society
Disclosure: Nothing to disclose.
Silverio M Santiago, MD Clinical Professor of Medicine, University of California at Los Angeles School of
Medicine; Chief, Department of Pulmonary and Critical Care Medicine, Medical Director, Sleep Disorders Center,
Veterans Affairs Medical Center of West Los Angeles
Silverio M Santiago, MD is a member of the following medical societies: American Academy of Sleep Medicine,
American College of Chest Physicians, and American Thoracic Society
Disclosure: Nothing to disclose.
Peter Smethurst, MD Attending Physician, Pulmonary, Critical Care and Sleep Medicine, St Joseph's Medical
Center
Disclosure: Nothing to disclose.

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Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College
of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Medscape Salary Employment
Gregory Tino, MD Director of Pulmonary Outpatient Practices, Associate Professor, Department of Medicine,
Division of Pulmonary, Allergy, and Critical Care, University of Pennsylvania Medical Center and Hospital
Gregory Tino, MD is a member of the following medical societies: American College of Chest Physicians,
American College of Physicians, and American Thoracic Society
Disclosure: Nothing to disclose.

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