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SCIENCE OF MEDICINE | SINGLE SERIES
68 | 116:1 | January/February 2019 | Missouri Medicine
Sleep Medicine Single Series
Sleep Medicine: Insomnia and Sleep
by Pradeep C. Bollu, MD & Harleen Kaur, MBBS
Contact: BolluP@health.missouri.edu
Abstract
Insomnia disorder is an
economic burden and public
health concern affecting up to
one-third of the population of
the United States. It is mostly
seen in older age groups, and
often considered a normal aging
phenomenon. The diagnosis and
treatment of insomnia rely mainly
on a thorough sleep history
to address the precipitating
factors as well as maladaptive
behaviors resulting in poor sleep.
It is important for clinicians
to recognize and manage the
symptoms of insomnia to prevent
the morbidity associated with
it. This review aims to highlight
the pathophysiology, associated
comorbidities, clinical evaluation
and effective management
strategies for insomnia disorder.
Introduc on
Insomnia is a public health
concern and one of the most common
complaints in medical practice.
The disorder is characterized by
diffi culty with sleep quality, initiating
or maintaining sleep, along with
substantial distress and impairments
of daytime functioning.1 Studies have
established insomnia to be a very
common condition with symptoms
present in about 33–50% of the adult
population.2 Its prevalence ranges
from 10 to 15% among the general
population, with higher rates seen
among females, divorced or separated
individuals, those with loss of loved
ones, and older people.3 There is
also an increased risk of depression,
anxiety, substance abuse, suicide,
motor vehicle accidents and possible
immune dysfunction with chronic
insomnia.4 Initially considered to be
a symptom, insomnia is now defi ned
as a disorder and classifi ed separately
in DSM-V (Diagnostic and Statistical
Manual of Mental Disorders-5th
edition) and ICSD-3 (International
Classifi cation of Sleep Disorders-3rd
edition).
Pathophysiology
The genetic factors responsible for
insomnia were identifi ed from work
on “insomnia-like Drosophila fl ies”
(ins-l fl ies), which had traits similar to
human insomnia. The genes associated
with insomnia are Apolipoprotein
(Apo) E4, PER3 (Period Circadian
Regulator 3), Clock (Clock Circadian
Regulator) and 5-HTTLPR(Serotonin
Transporter Linked Polymorphic
Region) genes. There is also a close
association between insomnia and
HLA-DQB1*0602.
The molecular factors responsible
for the sleep-wake regulation include
the wake-promoting chemicals
like orexin, norepinephrine, and
histamine, and sleep promoting
chemicals like GABA (Gamma
AminoButyric Acid), adenosine,
melatonin, and prostaglandin D2.
The orexin mediated increased
neuronal fi ring in the wake-promoting
areas (tuberomammillary nucleus,
Chronic insomnia is a rising
public health concern
a ec ng the quality of life
of up to one-third of the
popula on of the United
States. It can be associated
with psychopathology along
with a variety of systemic
disorders.
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SCIENCE OF MEDICINE | SINGLE SERIES
dorsal raphe and locus
coeruleus) and inhibition
of the sleep-promoting
areas (ventrolateral
preoptic nucleus and
median preoptic nucleus)
is one of the possible
mechanisms contributing
to insomnia (sleep switch
model).5 Other possible
mechanisms noted in
the literature are briefly
illustrated in Figure 1.
Classicaon
According to
the International
Classification of Sleep
Disorders-3rd Edition
(ICSD-III), insomnia
disorder can be classified as:
1. Chronic Insomnia Disorder
Patient experiences sleep disturbances for the last
three months affecting the night time sleep for at least
three times a week.
2. Short-term Insomnia Disorder
Sleep disturbances experienced within three months.
3. Other Insomnia Disorder
Sleep disturbances that do not meet the criteria for
chronic insomnia or short-term insomnia disorder are
classified under this category.
The International Classification of Sleep Disorders, 2nd
Edition describes the various subtypes of insomnia as:
1. Psychophysiological Insomnia
It is characterized by increased levels of cognitive
and somatic arousal at bedtime. Such individuals describe
excessive worrying about sleep along with difficulty with
sleeping in their home environment. They may sleep easily
in any other environment or when not planning to sleep.
2. Idiopathic Insomnia
It is characterized by sleep disturbances occurring
early in childhood and persisting over a lifelong period. It
may be associated with congenital or genetic variations in
the sleep-wake cycle.
3. Paradoxical Insomnia
In this type of insomnia, the patients underestimate
the total amount of sleep they obtained. They usually have
a good night sleep which they perceive as the time of
wakefulness. Paradoxical insomnia can be confirmed by
polysomnography or actigraphy.
4. Inadequate Sleep Hygiene
Sleep hygiene highlights the effect of daily activity on
the quality of sleep. Excessive daytime napping, evening
consumption of alcohol or caffeine, watching television
till late at night, working on electronic gadgets just before
bedtime can negatively affect the sleep quality.
5. Behavioral Insomnia of Childhood
Insomnia in children may be affected by
their dependency on certain stimulations, objects,
environmental settings, disruption of which can result in
significant delay in falling asleep (Sleep onset association
type) or may show resistance to go to bed (Limit setting
type) or both (mixed type).
Precipitang Factors
Although insomnia can affect any age group, women
and elderly (>65 years) are the population more
susceptible to the development of insomnia. Psychosocial
factors like the stress of work, shift work, loss of a loved
one, divorce, domestic abuse can lead to significant
sleep disturbances. Developmental issues in children
like delayed milestones, hyperactive behavior, separation
anxiety can precipitate sleep disturbances in children.
Figure 1: Pathophysiology of insomnia
(VLPO: ventrolateral preoptic nucleus; TMN: Tuberomammillary nucleus; DR:
dorsal raphe; LC: Locus coeruleus; GABA: gamma-aminobutyric acid)
INSOMNIA
HYPERAROUSAL
MODEL
-COGNITIVE
-PHYSIOLO GIC
-CORTICAL
GENETIC FACTOR
-Apo ε4
-PER 3
-HLADQBI*0602
-CLOCK Gene
-5HTTLPR
SNP (Single Nucleotide
Polymorphism)
Molecular Mechanism
Sleep suppressing:
-Catecholamine
-Orexin
-Histamine
Sleep Promoting:
-GABA
-Adenosine
-Serotonin
-Melatonin
prostaglandin D2
SLEEP SWITCH MODEL
OREXIN
WAKE
-TMN
-DR
SLEEP -LC
-VLPO
COGNITIVE AND
BEHAVIORAL DOMAIN
3P MODEL:
-PREDISPOSING FA CTOR
-PRECIPITATIN G FACTOR S
-PERPETUATIN G FACTOR S
Sleep Medicine Single Series
Sleep Medicine: Insomnia and Sleep
by Pradeep C. Bollu, MD & Harleen Kaur, MBBS
Jan Feb 2019.indd 69 2/4/2019 4:00:25 PM
SCIENCE OF MEDICINE | SINGLE SERIES
70 | 116:1 | January/February 2019 | Missouri Medicine
Certain personality traits like excessive worrying, repressed
personality, perfectionism, neuroticism can have a
disturbing effect on sleep. Psychiatric comorbidities like
depression, mood, and anxiety disorders, post-traumatic
stress disorder can increase the risk of insomnia. Alcohol
and substance abuse/dependence, excessive caffeine
intake, excessive smoking can potentially affect the sleep-
wake cycle.
Clinical Features
The sleep disturbances in insomnia can manifest
as difficulty in falling asleep (Sleep Onset Insomnia),
maintaining the continuity of sleep (waking up in the
middle of the night and difficulty in returning to sleep)
or waking up too early in the morning well before the
desired time, irrespective of the adequate circumstances
to sleep every night (Early Morning Insomnia). Insomnia
can significantly impact the daytime functioning resulting
in waking up tired in the morning, decreased workplace
productivity, proneness to errors and accidents, inability
to concentrate, frequent daytime naps and poor quality
of life.
In children, insomnia can be reported as frequent
nighttime awakening, resisting to go to bed and sleep
independently. Children may have a dependency on certain
stimulations (rocking, storytelling), objects (bottle feeding,
favorite toy) or room setting (parents in the room) to fall
asleep, and lack of these stimulations can create anxiety
and fear in them and result in sleep disturbances. Insomnia
can affect their school performance, daily activity of
playing, inability to concentrate and behavior problems.
Co-Morbidies Associated with Chronic Insomnia
Chronic insomnia disorder is a considerable risk
factor for cardiovascular disease, hypertension, type 2
diabetes, gastroesophageal reflux (GERD) and asthma, the
details of which are discussed under the following headings
(Figure 2).
Insomnia and Cardiovascular Disease
Insomnia is a risk factor for cardiovascular morbidity
and mortality.6 The underlying pathophysiology that
explains this increased risk is mainly due to dysregulation
of the hypothalamic-pituitary axis with increased release
of adrenocorticotropin hormone, increased sympathetic
nervous system activity, elevation of inflammatory
cytokines and a rise in C-reactive protein level (CRP).7,8
Chronic insomnia is also noted to increase the risk of
hypertension, reduce heart rate variability and increased
atherogenesis.9,10 The HUNT Study noted a 27-45%
increased risk of myocardial infarction in patients with
chronic insomnia.11 Even though the prospective data
suggests a significant association of chronic insomnia with
cardiovascular disease, further research is required to
understand how the management of insomnia can impact
the cardiometabolic health in these patients.
Insomnia and Type-2 Diabetes Mellitus
It is estimated that chronic insomnia increases the
risk of type 2 diabetes mellitus (T2D) by 16%, in the
adult population.12 In a recent study by Lin et al., the risk
of developing T2D was proportional to the duration of
insomnia. They observed that in patients with chronic
insomnia of <4, 4-8 and >8 years, the risk of T2D
Figure 2: Comorbidities associated with chronic insomnia.
CHRONIC
INSOMNIA
HYPTHALAMIC -
PITUITARY -AXIS
IMBALANCE
RELEASE OF
INFLAMMATORY
MEDIATORS
INCREASED
ATHEROGENESIS
CARDIOVASCULAR
DISEASE
HYPERTEN SION
TYPE-2 DIABETES
ASTHMA/ALLERGIC
RHINTIS
THYROID DISORDERS
Figure 2. Comorbidies associated
with chronic insomnia.
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increased by 14%, 38%, and 51% respectively.13 The
multiple mechanisms that might be involved in the
pathogenesis include dysregulation of the hypothalamic-
pituitary axis with an increase in the cortisol level,
impairment in glucose metabolism, an imbalance in the
leptin- ghrelin system that increases the appetite and risk
of obesity resulting in insulin resistance and unstable blood
sugars level. 7,14
Insomnia and Gastroesophageal Reux Disease
A bidirectional association is noted between
Gastroesophageal Reflux Disease (GERD), symptoms and
sleep disturbances.15 In 2009, Mody et al., noted the effect
of GERD on sleep quality. Out of 11,685 individuals with
GERD, 88.9% experienced sleep disturbances, out of
which 49.1% complained of difficulty in initiating sleep,
and 58.3% had difficulty in maintaining sleep.16 In the
same year, a cross-sectional cohort study by Jansson et
al. on 65,333 patients with GERD observed, that there
was three times increase in the risk of GERD in patients
with insomnia.17 Further, the treatment of GERD with
proton pump inhibitor has shown to improve the sleep
disturbances in these patients significantly.18
Insomnia and Asthma
A potential risk of asthma and allergic rhinitis is noted
in patients with chronic insomnia.19 Though the exact
mechanism is not known, the various factors responsible
may include the release of inflammatory mediators like
interleukin 6 (IL-6), nuclear factor kappa-B cell (NF-
ĸβ) in chronic insomnia resulting in allergic airway
inflammation.20,21 It is also noted that chronic insomnia
may reduce interferon-γ production that reduces the
airway epithelial inflammation and thereby increasing the
risk of reactive airway disease in patients with insomnia.
Optimal management of chronic insomnia may prevent the
release of such inflammatory mediators reducing the risk
of airway inflammation.
Insomnia and Thyroid Disorders
The risk of thyroid disorders with chronic insomnia is
not very well known. However, studies have shown that the
dysregulation in the hypothalamic-pituitary axis in chronic
insomnia increases the levels of corticotrophin-releasing
hormone (CRH), thyrotropin-releasing hormone (TRH)
and cortisol, resulting in fluctuation in thyroid hormone
levels. The abnormal levels of TRH and thyroid stimulating
hormone (TSH) are also noted higher in patients with
insomnia with comorbid depression.22
Clinical Assessment
A detailed sleep history is a key to the evaluation
of insomnia. Clinicians should be able to recognize
the sleep disturbances and rule out other sleep-related
disorders like restless leg syndrome, sleep apnea, periodic
limb movements, and nocturnal leg cramps that may
be contributing to the sleep fragmentation. Complete
laboratory workup should be helpful to evaluate any
underlying medical conditions contributing to insomnia.
Furthermore, questionnaires, sleep logs, and actigraphy
can be helpful tools for the assessment of insomnia.
A self-reported questionnaire can be helpful to
evaluate the quality of sleep in chronic insomnia. Epworth
Sleepiness Scale (total score 0-24; score>15 considered
for severe daytime sleepiness) and Pittsburgh Sleep Quality
Index (score > five is considered poor sleep score) are the
two most widely used assessment tools in doctor’s office
visits.23
Sleep diaries are another cost-effective way to evaluate
the sleep-wake disturbances in the patients. It is helpful
to determine the total sleep time (TST), wakefulness after
sleep onset (WASO), sleep efficiency and circadian rhythm
disturbances. They also include information about caffeine
consumption, medications daytime napping and bedtime
activities which are helpful to assess the sleep hygiene in
these patients.24
Wrist actigraphy is a noninvasive tool that records the
gross motor activity during sleep and wakefulness. It is
useful to estimate the sleep parameters like sleep duration,
wakefulness after sleep onset (WASO), sleep latency.
Maintaining sleep diaries along with actigraphy can provide
complementary information.25 Further, actigraphy is not
helpful to asses periodic limb movements or abnormal
breathing patterns for which, polysomnography should
be chosen. However, polysomnography is not routinely
recommended for the initial assessment of insomnia.
Non-Pharmacological Management
1. Sleep Hygiene
Sleep hygiene includes educating the patients about
lifestyle modifications like limiting the daytime naps,
avoiding late night dinner, restricting the use of electronic
gadgets/smartphones during bedtime or evening intake
of alcohol, caffeine, or smoking. Certain practice scales
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like sleep hygiene index and the sleep hygiene awareness
scales are useful to assess the sleep hygiene. However,
sleep hygiene alone is ineffective in managing patients with
chronic insomnia and should be used with other aspects of
cognitive behavior therapy.26
2. Sleep Restriction Therapy
This therapy aims to reduce sleep time by limiting
the number of sleeping hours. Reduced sleep time can
improve the homeostatic sleep drive and result in a more
consolidated sleep. The major limitation of this therapy is
an increased chance of daytime sleepiness due to sleep loss.
3. Stimulus Control Therapy
Stimulus Control involves restriction of maladaptive
behaviors like eating or reading in bed, late night use of
digital devices in bed and promoting the use of bed for
sleeping and only when feeling drowsy.
4. Relaxation Therapy
Regular practice of breathing exercises, meditation or
yoga can help to improve the sleeping pattern and reduce
underlying anxiety and stress. Studies have shown that
management of stress with relaxation and mindfulness
training helps to improve focused attention and reduce
pre-sleep arousal and worry in insomnia patients.27
5. Cognitive Behavioral Therapy for Insomnia
Cognitive behavioral therapy for Insomnia (CBTi) is
the mainstay of management of insomnia. Effective CBTi
can show significant improvement in sleep onset latency
(SOL), wakefulness after sleep onset (WASO) and total
sleep time (TST). Studies have shown CBTi is superior
to pharmacotherapy in the management of chronic
insomnia.28 It is typically delivered in six sessions over
six- to eight-week period by either health care nurse, sleep
therapist, physician assistant, or even a social worker. The
sessions include sleep education, relaxation techniques,
sleep restriction therapy, stimulus control therapy,
cognitive. and behavioral therapy. It can also be provided
through the telehealth (video conferencing) or internet-
based versions that are beneficial for those who are hesitant
to visit a therapist in person. “SHUTi” is an online
internet-based CBTi program proven for insomnia. “Sleep
Ninja” is a smartphone app, that delivers CBTi over the
phone.29 However, the major limitation of these web-based
versions is that a lot of self-encouragement is required to
follow through the entire length of the programs regularly.
Another limitation of the CBTi program is a shortage of
efficient therapists to deliver the therapy effectively along
with a higher out of pocket costs, which further restrict the
patients from the benefits of the program.30
Pharmacological Management
Drugs Acng on GABA-A Receptors
The benzodiazepines (BZD) and benzodiazepine
receptor agonists (BzRA or non-BZD) both act on
the gamma-aminobutyric acid (GABA) receptor sites
thereby exerting sedative, anxiolytic, muscle relaxant,
and hypnotic effects. One significant difference between
the two groups is the affinity for different subtypes of
GABA alpha subunit. While all the BZD have similar
affinity to various subtypes of alpha subunits, BzRA have
a varying affinity to different subtypes of alpha subunits.
For example, zolpidem, zopiclone, and zaleplon have
higher affinity to alpha-1 subunit and lower affinity to
alpha-2 and alpha-3 subunit; whereas, eszopiclone has
higher affinity to alpha-2 and alpha-3 subunit of GABA
receptor.31 The adverse effects associated with BZD like
rapid development of tolerance, the risk of abuse or
dependence, the occurrence of rebound insomnia after
drug discontinuation, and cognitive impairment further
limit the use of BZD over BzRA
BzRA are approved by the Food and drug
administration (FDA) for the management of insomnia.
They are rapidly absorbed, relatively short-acting (as
compared to benzodiazepines) and have better side
effect profiles. They are effective in treating sleep onset
insomnia, sleep maintenance insomnia or both.
Zolpidem binds selectively to the alpha-one subtype
of GABA-A receptor. It has a short half-life of 2.5 hours
and is available in immediate-release (IR) formulation
of 5-mg and 10-mg doses, which are effective for the
treatment of short-term insomnia. The controlled-release
(CR) form is available in 6.25-mg and 12.5-mg dosage for
sleep onset and sleep maintenance insomnia. A sublingual
form (doses in male 3.5 mg and female 1.75 mg) is
available for the treatment of middle of night awakenings
and difficulty in returning to sleep and should be used
if there is a minimum of 4 or more hours of intended
sleep time. The adverse effects associated with zolpidem
are headache, falls, somnolence, and antegrade amnesia.
(Table 1).
Zaleplon has the shortest duration of action with the
half-life of one hour and is available at the doses of 5 mg,
10 mg, 20 mg for the treatment of insomnia. The adverse
effects associated with it are a headache, drowsiness,
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nausea, and worsening of depressive
symptoms in patients with the
comorbid depressive disorder.
Eszopiclone helps to improve
sleep efficiency, daytime functioning
along with a reduction in sleep onset
latency and wakefulness after sleep
onset. It is used for management
of sleep onset insomnia (2 mg)
and sleep maintenance (3 mg)
insomnia. It acts on the alpha-2,
and alpha-3 receptors subtype of the
GABA-A receptors, thereby exerting
anxiolytic and antidepressant effect
respectively, and hence, is effective
in the management of insomnia with
comorbid depression or generalized
anxiety disorder. Common adverse
effects associated with eszopiclone are
unpleasant metallic taste, headache,
dizziness, and somnolence.32
Drugs Acng on Melatonin
Receptors
Melatonin is a natural hormone produced by the
pineal gland. The circadian system in the hypothalamus
and the suprachiasmatic nucleus (SCN) regulates the
levels of this hormone throughout the day and night.
Melatonin is available over the counter and is approved
by FDA for treatment of insomnia, especially in older
adults. A dose range of 2 to 8 mg is effective in treating
circadian rhythm sleep-wake disorders. However, food
can delay the absorption of melatonin, and a gap should
be maintained between the last meal of the day and the
intake of melatonin.
Ramelteon, melatonin receptor agonist decreases the
sleep latency by acting on the melatonin MT1 and MT2
receptors in the SCN with higher affinity than melatonin
itself.33 The FDA recommends a dosage of 8 mg for the
management of sleep onset insomnia. It exerts minimal
adverse effects including somnolence, fatigue, and
dizziness.
Tasimelteon is another melatonin receptor agonist
effective in improving sleep initiation and maintenance
particularly in blind patients with Non-24-hour sleep-
wake circadian rhythm disorders.34
Drugs Acng as Orexin Receptor Antagonist
Suvorexant is a dual orexin receptor antagonist
(OX1 and OX2 receptor) which counteracts the orexin/
hypocretin system that plays an important role in
wakefulness. It is effective in doses of 5 mg, 10 mg, 15
mg, and 20 mg for the management of sleep onset and
sleep maintenance insomnia. A dose of 15 mg and 20
mg has shown improvement in total sleep time and a
reduction in sleep onset latency. However, the FDA does
not recommend a higher dose of 30 mg or 40 mg of
suvorexant because of safety concerns, with an increased
risk of next day driving difficulty, increased daytime
somnolence and narcolepsy-like symptoms (hypnogogic-
hypnopompic hallucinations, cataplexy, and vivid dreams).
Also, suvorexant is contraindicated in patients with
narcolepsy because of possible underlying mechanisms of
orexin antagonism.35
Drugs Acng as Histamine-1 Receptor Antagonist
Doxepin is a tricyclic antidepressant, but at a low
dose of 3 mg and 6 mg, it is effective in the management
of sleep maintenance insomnia. It causes improvement
Drugs acting on various receptors
Elimination half-life(hour)
GABA receptors
Benzodiazepines
Triazolam (Halcion®) 1.5-5.5
Temazepam (Restoril
®
)
3.5-18.4
Estazolam (ProSom®) 10-24
Flurazepam (Dalmane®) 48-120
BzRA
Zolpidem -oral (Ambien
®
)
2.5
Zolpidem-
oral spray
(Zolpimist®) 2.8
Zolpidem-
extended release
(Ambien CR
®
)
2.8(1.6-4.5)
Zolpidem -
Sublingual
(Intermezzo®) 2.5
Eszopiclone (Lunesta
®
)
6-9
Zaleplon (Sonata®) 1
Histamine-1 receptor antagonist
Doxepin (Silenor
®
)
15.3
Melatonin receptor agonist
Ramelteon (Rozerem®) 1-2.6
Orexin receptor antagonist
Suvorexant (Belsomra
®
)
12
Table 1: The table summarizes the drug therapy approved for chronic insomnia along with their
brand names and half-life elimination.
(GABA: gamma-aminobutyric acid; BzRA: Benzodiazepine receptor agonist)
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in total sleep time, wakefulness after
sleep onset and sleep efficiency. At
low doses (3 mg and 6 mg), Doxepin
acts as pure H-1 receptor antagonist
being 800 times more potent than
diphenhydramine for H-1 receptors,
and at high doses of 25 mg to 300 mg
daily (antidepressant dosage), it exerts
antihistaminic, antiserotonergic,
anticholinergic and antiadrenergic
activity. The adverse effects associated
with doxepin at low doses are
headache and somnolence.36
O-Label Drugs
1. Antidepressants:
trazodone, mirtazapine,
and amitriptyline are
most commonly used
antidepressants for the
management of insomnia at
low doses mainly because of
their antihistaminic effect.
Studies have shown a 50 mg
once a day dose of trazodone
has proved to be effective
in improving sleep latency,
wakefulness after sleep onset and duration of
sleep.37
2. Atypical antipsychotics: Olanzapine and
quetiapine can be useful in the treatment of
insomnia with comorbid psychotic conditions.
They exert a sedative effect at low doses mainly
by their antihistaminic, anti-adrenergic and
antidopaminergic properties.38
3. Anticonvulsants: Gabapentin has shown to
improve the sleep efficiency and decrease the
wakefulness after sleep onset. It can be effective
in managing insomnia in patients with alcohol
dependence. Pregabalin increases the total sleep
time, stage N3, sleep efficiency and decreases
sleep onset latency and REM sleep. It is helpful
in improving sleep in patients with generalized
anxiety disorder and fibromyalgia. 39
The American Academy of Sleep Medicine (AASM)
has proposed a PICO (Patient, population, problem,
Intervention, Comparison, and Outcomes) template,
based on the patient-oriented tools to determine
the outcomes in response to the treatment given for
insomnia. The four most critical outcomes useful for
clinical decision-making are sleep latency (SL), wake
after sleep onset (WASO), total sleep time (TST), and
the quality of sleep (QoS) (Figure 3).40
Conclusion
Chronic insomnia is a rising public health concern
affecting the quality of life of up to one-third of the
population of the United States. It can be associated
with psychopathology along with a variety of systemic
disorders. Genetic and environmental factors play a
role in the pathogenesis of this problem. Cognitive
behavioral therapy is still the first line treatment
for insomnia though the scarcity of therapists and
the high costs make it less practical in many cases.
Pharmacotherapy can be effective in many patients
and should always be used in conjunction with sleep
hygiene.
Figure 3: Effect of various pharmacological agents on Total Sleep time (TST), Wakefulness after
sleep onset (WASO), Sleep latency (SL), Quality of Sleep (QOS).
TST
-DOXEPIN
-DIPHENHYDRAMINE
-EZSCOPIC LONE
-SUVOREXANT
-TEMAZEPAM
-TEAGABINE
-TRAZO DONE
-ZALEPLON
-ZOLPIDEM
WASO
-DIPHENHYDRAMINE
-DOXEPIN
-EZSOP ICLONE
- SUVOREXANT
-TEMAZEPAM
-TEAGABINE
-TRAZO DONE
-TRYPTOPHAN
-ZOLPIDEM
SL
- DOXEPIN
-DIPHENHYDRAMINE
-EZSCOPIC LONE
-MELATONIN
-RAMELTEON
SUVOREXANT
-TEMAZEPAM
-TRAZO DONE
-TRIAZOLAM
TRYPTOPHAN
-ZALEPLON
ZOLPIDEM
QOS
-DOXEPIN
-DIPHENHYDR AMINE
-EZSCOPICLONE
-MELATONIN
-RAMELTEON
SUVOREXANT
-TEMAZEPAM
-TRAZO DON
-TRIAZOLAM
-TIAGABINE
-TRIAZOLAM
TRYPTOPHAN
-ZALEPLON
ZOLPIDEM
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Disclosure
None reported. MM
Jan Feb 2019.indd 75 2/4/2019 4:00:26 PM
