CNS Spectrums A clinical algorithm for diagnosis and treatment

www.cambridge.org/cns
of insomnia in adults: an updated review
Habibolah Khazaie1, Amir Sharafkhaneh2, Ali Zakiei1 and Earl Charles Crew3
1
Sleep Disorders Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran; 2Department of
Guidelines Medicine, Baylor College of Medicine, Houston, TX 77004, USA and 3Psychiatry and Behavioral Sciences, Baylor
Cite this article: Khazaie H, Sharafkhaneh A, College of Medicine, Houston, TX, USA
Zakiei A, and Crew EC (2024). A clinical
algorithm for diagnosis and treatment of Abstract
insomnia in adults: an updated review. CNS
Spectrums 29(5), 463–473. Difficulty falling asleep and/or maintaining sleep are common complaints in patients visiting
https://doi.org/10.1017/S1092852924000385 medical clinics. Insomnia can occur alone or in combination with other medical or psychiatric
disorders. Diagnosis and management of insomnia at times are perplexing. This updated study
Received: 28 September 2023
Accepted: 21 May 2024
review aimed at a clinical algorithm for diagnosis and treatment of insomnia in adults. We
developed an easy-to-apply algorithm to diagnose and manage insomnia that can be used by
Keywords: general practitioners and non-sleep specialists. To this end, our team reviewed the previous
Clinical algorithm; diagnosis; insomnia; review; studies to determine the prevalence, evaluation, and treatment of insomnia. We used the results
sleep disorders; treatment
to develop a clinical algorithm for diagnosing and managing insomnia.
Corresponding author: Insomnia occurs in a short (less than 3 months duration) or chronic form (≥3 months duration).
Ali Zakiei; Insomnia management includes both pharmacological and non-pharmacological interventions.
Email: [email protected] There is ample research evidence for the impact of a variety of non-pharmacological treatments,
but both types of treatments can be used for each patient. If there are any contradictions in the
diagnosis process, therapists should use objective instruments, such as polysomnography, but
they should not be in a hurry to use these instruments.

Introduction
Insomnia is one of the serious concerns related to community health.1 Difficulty with sleep is also
a common complaint in patients visiting medical clinics. These complaints may occur alone or in
combination with other medical or psychiatric conditions.2 An important issue is that insomnia
can impose high direct and indirect economic burden on society.3 The costs of insomnia are high
to the extent that some studies have referred to it as a public health crisis.4 The World Health
Organization (WHO) has also addressed the financial burden and costs of treating insomnia.
Thus, researchers have emphasized that insomnia is a financial and costly burden for care
systems. These costs can occur directly, for example, through treatment costs, or are imposed
indirectly by sick leave or early retirement.5 Insomnia also adversely affects the economy by
reducing productivity in the workplace.6 The available evidence suggests that the financial
burden of insomnia is comparable to the financial burden of other psychiatric disorders such
as depression, anxiety, and substance use disorders.7 Therefore, it is essential to find a suitable
model for the diagnosis and treatment of insomnia. Our primary goal is to propose an easy-to-
apply clinical algorithm that can be used by nonspecialist practitioners to manage patients with
insomnia. Accordingly, this study explores the causes of insomnia, identifies comorbid disorders,
and determines the effective diagnosis and treatment methods. We developed an easy-to-apply
algorithm to diagnose and manage insomnia that can be used by general practitioners and non-
sleep specialists. To this end, our team reviewed previous studies to determine the prevalence,
evaluation, and treatment of insomnia. We used the results to develop a clinical algorithm for
diagnosing and managing insomnia.

Definition of insomnia and its symptoms

Insomnia is generally defined as the lack of sleep satisfaction, including dissatisfaction with both
the quality and quantity of sleep.8 The American Academy of Sleep Medicine also defines
insomnia as the subjective perception of difficulty with sleep initiation, duration, consolidation,
or quality that occurs despite adequate opportunity for sleep, resulting in a complaint of
© The Author(s), 2024. Published by Cambridge insomnia and/or some form of daytime impairment.9 Thus, insomnia is dissatisfaction with
University Press. the duration and quality of sleep, which can lead to distress and disruption/reduction of a
person’s quality of life and performance. It should be noted that daytime dysfunction includes a
wide range of symptoms, including problems with attention, concentration, and memory
impairment, as well as fatigue, weakness, or loss of energy, workplace errors, car accidents, or
any other form of social or occupational dysfunction, headache or gastrointestinal symptoms,

https://doi.org/10.1017/S1092852924000385 Published online by Cambridge University Press

 464 H. Khazaie et al.

daytime drowsiness, and mood dysregulation, including anxiety, explaining the symptoms of insomnia.12 The International Classi-
depression, and irritability.10 Some scholars have focused on inad- fication of Sleep Disorders 3 (ICSD-3) specifies almost the same
equate sleep and even have claimed that this is a public health criteria for diagnosing insomnia.13 The symptoms of insomnia are
concern;11 however, the term insomnia is not only related to sleep divided into daytime and nighttime symptoms. The nighttime
duration but also includes dissatisfaction with sleep and daily symptoms include sleep disturbances, environmental sensitivity,
dysfunction due to insomnia. unsuccessful sleep attempts, presleep arousal, and frequent awak-
The Diagnostic and Statistical Manual of Mental Disorders, enings. The daytime symptoms include cognitive problems, drows-
Fifth Edition (DSM-5) specifies criteria for insomnia, The first iness (sleepiness), and fatigue.
criterion that relates to the patient’s main complaint is dissatisfac- Insomnia occurs in a short (<3 months) or chronic form
tion with the quantity or quality of sleep, along with symptoms (≥3 months):14 If it lasts less than 3 months, it is called short-term
such as difficulty starting sleep, difficulty maintaining sleep insomnia, and if it lasts for at least 3 months, it is called chronic
(frequent awakenings), and waking up early in the morning. The insomnia.15 Following existing theories and previous studies in the
second criterion refers to daily functioning, showing a significant literature, a diagnostic algorithm was developed for insomnia, as
decline in social, occupational, educational, behavioral, and other shown in Figure 1. According to this algorithm and its diagnostic
functions. The third and fourth criteria deal with the duration of criteria presented in Table 1, the clinician must determine if the
the problem. The problem should persist at least 3 nights a week patient is suffering from primary insomnia or insomnia associated
and last for at least 3 months. The fifth criterion emphasizes that with medical and psychological conditions and substance abuse. In
the sleep problem manifests itself despite having enough time to the latter case, the therapist should treat both comorbidity and
sleep. According to the sixth criterion, sleep problems should not insomnia. However, if the patient is suffering from primary insomnia,
be better explained by the presence of other sleep disorders. The it should be specified if the duration of symptoms is less than 3 months
seventh criterion specifies that insomnia is not due to the physio- or more. If the symptoms are present for less than 3 months, the
logical effect of a substance such as the use of drugs or medication patient is diagnosed with short-term insomnia. In such case, the
(ie, the acute or withdrawal effects of these substances are not the causes of insomnia should be examined and treated accordingly.
cause of the problem). The eighth criterion refers to ensuring that Moreover, if the symptoms of insomnia have lasted for more
other mental and/or medical disorders are ruled out as better than 3 months, the patient is diagnosed with chronic insomnia.

Figure 1. The diagnosis and treatment algorithm for insomnia.

https://doi.org/10.1017/S1092852924000385 Published online by Cambridge University Press

 CNS Spectrums 465

Table 1. Criteria for Diagnosing Insomnia

1. The person is mainly complaining about one or more of the following problems:
A. Difficulty in sleep onset: The person cannot fall asleep easily.
B. Difficulty in maintaining sleep: The person may have frequent awakenings.
C. The person wakes up earlier in the morning than the desired time.
D. The person is not satisfied with the quality of their sleep, and does not feel relaxed and refreshed after waking up.
2. Despite the good conditions and opportunities for sleeping, the person cannot fall asleep.
3. The person has problems during the day and may complain about one or more of the following problems:
A. The feeling of lethargy and tiredness
B. Lack of concentration and memory impairment
C. Occupational, academic, and social dysfunction
D. Irritability and mood disorders
E. Having drowsiness during the day
F. Lack of energy or reduced motivation to do daily activities
G. Increased work errors
H. Having headaches and gastrointestinal symptoms
I. Having ruminations and negative thoughts about sleeping

It should be noted that there is no clear boundary for the insomnia in adolescence has been reported to range from 4% to
diagnosis and classification of insomnia subtypes, and such sub- 39%.20 This statistic is higher in older adults, with 57% of older
types have been not recognized in reliable guidelines, such as the adults affected by this disorder.21 It has been claimed that women
DSM-5 and ICSD-3, but paying attention to them can have some are 1.5 times more likely than men to report insomnia.22 The results
benefits. One subtype of insomnia is termed psychophysiological of a study showed that symptoms of insomnia are more common in
insomnia and is characterized by presleep arousal, which can be women than men.23
physical, emotional, or cognitive. Before going to sleep while in bed, Furthermore, the reported prevalence has continuously grown
the affected person may perseverate overs concerns about the over the last 2 decades. A study in 2002 reported a prevalence
consequences of not being able to sleep, or be overly sensitive to between 9% and 15%,24 while one study in 2006 reported insomnia
cues for night/bedtime, which can trigger a “hyperaroused” state varying from 5% to 25%.25 This figure was reported to be
upon getting into bed (even if they reported feeling “sleepy” just between 20% and 40% in 2009.26 A study reported its prevalence
before).16 Another type of insomnia, called idiopathic insomnia, in 2015 at 23.8%,27 and a systematic review study in 2020 showed
affects a person for life. Most patients with this type of insomnia that the prevalence of insomnia is 37.9%.28 However, a study
suffer from sleep disorders since childhood, and such disorders do confirmed a growing trend in the prevalence of insomnia.11 In
not improve or remit during their lifetime.17 The third type of conclusion, insomnia is a common disorder that affects a large
insomnia is known as paradoxical insomnia. This type of insomnia number of people in the community. Its prevalence may be even
is characterized by a discrepancy between subjective and objective higher than reported due to underreporting. Epidemiological stud-
evaluation of sleep, rendering diagnosis and treatment more chal- ies on insomnia are essential for understanding the burden of this
lenging. Typically, polysomnographic (PSG) findings show signif- disorder and developing effective interventions.
icantly longer total sleep time than patients’ self-reported sleep (eg,
on a sleep diary), and the difference between subjective sleep and
PSG is typically greater than that seen in other subtypes of insom- Causes of insomnia
nia.18 Patients with this subtype often complain about insomnia,
but objective studies (via PSG or actigraphic monitoring) do not Causes of insomnia can be divided into 3 categories: Predisposing
support the patient’s complaint. Another type of insomnia is factors, including demographic, biological, psychological, and
attributable primarily to engagement in multiple sleep- social factors; precipitating factors, such as life stressors and med-
incompatible hygiene practices and it is commonly referred to as ical conditions; and perpetuating factors, such as behavioral factors
inadequate sleep hygiene. Example behaviors include irregular and cognitive changes.8,29 For example, genetic influences or per-
sleep patterns, use of alcohol, nicotine, caffeine in close proximity sonality traits such as neuroticism and maladaptive perfectionism
to bedtime, or engaging in sleep-irrelevant activities in the bed- are considered predisposing factors,5 and maladaptive coping strat-
room, all of which can negatively affect sleep at night.16 Inadequate egies are perpetuating factors.5
sleep hygiene in majority of cases of insomnia coexist to some One study listed the variables that can increase the risk for
degree with the main insomnia diagnosis. incident insomnia including having a previous period of insomnia,
having a family history of insomnia, susceptibility to irritability,
poorer general health, and physical pain.30 The findings of another
study highlighted the role of psychological factors, such as emotion
Prevalence of insomnia
regulation, in the development of insomnia.31 Furthermore, mental
Insomnia is a widespread disorder that affects both clinical and health symptoms, poor sleep quality, and obesity have been iden-
general populations. Its epidemiology varies across geographical tified as risk factors for insomnia.23 Alcohol consumption is also
regions around the world and changes over time. The prevalence of implicated as a cause of insomnia. Previous studies have confirmed
insomnia differs in various communities, ranging between 5% and the negative role of alcohol consumption in the development of
40%. An epidemiological review of insomnia shows that its prev- insomnia.32 The results of another study identified factors such as
alence rate has been reported to range from 5% to 40% in different health anxiety, dysfunctional coping strategies, job and income worries,
communities.19 Another study reported its prevalence in European and old age as risk factors for insomnia.33 One of the other factors
countries to be between 5.7% and 19%.5 The prevalence of related to insomnia can be personality traits and temperaments.34

https://doi.org/10.1017/S1092852924000385 Published online by Cambridge University Press

 466 H. Khazaie et al.

A review of the literature shows that there is usually never one Evaluating to diagnose insomnia
primary cause for insomnia, but often multiple physiological,
The most important part of insomnia assessment is a careful
cognitive, and behavioral factors contributing to the development
analysis of the patient history and a complete physical examina-
of clinical symptoms. More recently, an increased attention has
tion.8,64,65 A complete clinical history is often needed to identify the
been paid to psychological and cognitive factors. Cognitive activ-
factors influencing insomnia.1 A general principle in both diagno-
ities can include factors such as worry or anxiety, repetitive
sis and treatment of insomnia is that the person’s sleep history must
thoughts, and a generally “overactive” mind. Most cognitive theo-
be examined as the diagnosis and treatment depend on the person’s
ries have also emphasized these factors. In the last decade, several
sleep history. An analysis of sleep history helps to identify any
cognitive models have been developed to account for cognitive
predisposing factors that increased risk for incident insomnia,
causes of insomnia. These models include Spielman and Glovins-
precipitating factors that directly contribute to insomnia onset,
ky’s (1991) model,35 Morin’s (1993) integrated model,36 Perlis
and perpetuating factors—including maladaptive behaviors-
et al.’s (1997) cognitive model,37 Lundh and Broman’s (2000)
related poor sleep—that maintain the insomnia chronically.66
model,38 Harvey’s (2002) model,39 Espie’s (2007) model,40 Vande-
Thus, it has been claimed that insomnia should be diagnosed based
kerckhove and Cluydts’s (2010) model,41 and Ong, Ulmer, and
on a longitudinal approach.67 Useful information to support the
Manber’s (2012) metacognitive model.42 A theme in all of these
diagnosis of insomnia can be obtained through clinical interviews
models is how cognitive factors contribute to “arousal” that pro-
and the completion of sleep diaries. If this information makes the
duces insomnia, but each varies about specific factors or dynamics
diagnosis possible, there is no need for laboratory diagnostic tests,
that can produce arousal. In summary, the factors that are hypoth-
and these tests may even provide misleading information, since
esized to lead to arousal in these cognitive models include mal-
insomnia is diagnosed based on a pattern of sleep over an extended
adaptive cognitions, dysfunctional attitudes, and beliefs about
time, and no single night of evaluation. Some patients may insist on
sleep, responses to poor sleep that produce irritability, stress,
having polysomnography (PSG), which should be interpreted
anxiety, emotional conflict, or rumination; and metacognitive
based on historical information and questionnaires, and the nature
beliefs, coping styles, and emotion regulation strategies. No com-
of the disorder must be explained to the patient.
prehensive model has been yet proposed for the causes and symp-
Studies conducted using PSG have shown a large difference
toms of insomnia. Besides, there is no consensus among most
between the subjective experience of sleep and the results of PSG
theorists, researchers, and therapists about the proposed models
in insomnia patients, making the use of PSG a challenging tool for
and theories.
diagnosing insomnia. Hence, insomnia should be assessed and
diagnosed based on clinical interviews, sleep questionnaires, and
sleep diaries.67
Consequences of insomnia
Self-report tools collect key and important information to
The negative effects of insomnia are numerous and can vary inform the diagnosis and treatment of insomnia. Although other
person-to-person. These negative effects are more significant in tools developed through scientific advances are used more exten-
vulnerable groups such as those with mental and physical illness, sively, self-report tools still play a key role in most studies on
older adults, and women during menopause.14 Insomnia has been insomnia.68 Instruments used for measuring insomnia symptoms
identified as a risk factor for cardiovascular disease,10,43 and is can be divided into laboratory and non-laboratory instruments.
generally associated with mental health problems, heart disease, The most important laboratory instrument is PSG. It is the most
type 2 diabetes, decreased daily functioning, and reduced quality of widely used method in sleep disorders centers. This test is the gold
life.44 Insomnia is linked with a number of mental health condi- standard for diagnosing many sleep disorders. PSG plays a vital role
tions.45 Various studies have shown that insomnia is a risk factor in diagnosing sleep disorders, including insomnia. Interpreting
for depression.46–49 The results of one meta-analysis reported that PSG data are a challenging task that should be performed by
insomnia is significantly associated with an increased risk of professional staff. All the factors involved should be considered
depression,50 although this outcome is not age-specific. Insomnia when interpreting the data, including the patient’s medical history
in children and adolescents is also associated with depression.20,51 and medications. Besides, the data from observing the patient’s in
Insomnia is also associated with anxiety,52,53 and may be correlated the clinic must be taken into account.69
with increased stress levels.54 Non-laboratory tools can include expert interviews and ques-
The results of a study observed that insomnia increases the risk tionnaires. Questionnaires are useful instruments for assessing
of physical, interpersonal, and psychological problems, and diffi- insomnia. Questionnaires have several advantages; first, they do
culty in daily activities.7 Insomnia has also been identified as a risk not require special facilities and contexts. They can be administered
factor for self-injurious behaviors.55 Research has shown that the quickly and at a specific time and do not require a person with a
symptoms of insomnia can predict self-injurious behaviors.56,57 In specific profession.70 There are several valid questionnaires used to
addition, some researchers have identified insomnia as a key risk measure insomnia. The Pittsburgh Sleep Quality Index is the most
factor for suicide,58 with numerous studies reporting a relationship common tool for measuring sleep quality worldwide. It is a self-
between insomnia and suicide.59–62 Insomnia can also be viewed as assessment tool that assesses sleep quality and sleep disturbances
a major contributor to road accidents and car crashes.63 Accord- over the past month.71 This 19-item tool evaluates 7 components,
ingly, the consequences of insomnia can be summarized into 3 cat- including subjective sleep quality, sleep latency, sleep duration,
egories: health-related consequences, functional consequences, habitual sleep efficiency, sleep disturbances, use of sleeping med-
and economic consequences. Health-related consequences include ication, and daytime dysfunction.71 Another instrument to mea-
experiencing a wide range of physical, mental, and cognitive prob- sure insomnia is the Insomnia Severity Index (ISI), which is a brief
lems. Functional consequences include impaired individual and self-assessment tool36 that measures the patient’s perception of
family functioning, while economic consequences include insomnia insomnia. It also measures subjective symptoms and consequences
costs, treatment costs, and reduced productivity. of insomnia (the degree of anxiety or distress caused by its

https://doi.org/10.1017/S1092852924000385 Published online by Cambridge University Press

 CNS Spectrums 467

problems).72 The content of the instrument corresponds to some their performance has declined psychologically, emotionally, occu-
extent with the diagnostic criteria of insomnia.72 The ISI assesses pationally, socially, and physically. Table 2 provides a short
the severity of 7 components during the last month. The assessed description of the most important instruments used to diagnose
dimensions are the severity of problems with delayed sleep onset, insomnia:
sleep maintenance, and early morning awakenings, as well as the By considering diagnostic criteria, objective evaluations, and the
level of satisfaction with the current sleep pattern, interference with patient’s reports according to the model presented in Figure 2, the
daily functioning, others noticing impairment from the sleep prob- therapist can take diagnostic and therapeutic measures to treat
lem, and worry or distress related to the sleep problem.73 The third insomnia.
instrument used to measure insomnia is the Athens Insomnia Scale
(AIS). It is a self-assessment tool designed to measure sleep prob-
lems according to the ICD-10 criteria. The instrument measures Co-occurrence of other diseases with insomnia
8 sleep characteristics: sleep induction, awakenings at night, final
Depression is a disorder that usually occurs simultaneously as
awakening, sleep duration, sleep quality, and daytime symptoms:
insomnia. Thus, the question is which disorder needs to be treated
well-being, functioning, and sleepiness.74 The first part of this scale
first. A recent study claimed that conceptualizing insomnia as a
assesses the quality of night sleep, and the second part evaluates
secondary symptom of depression should be avoided77 for some
daytime functioning.70 Previously, ISI and AIS have been proposed
reasons: First, insomnia symptoms often appear before mood
as a part of comprehensive sleep assessment to evaluate patients
swings and are independently associated with an increased risk
with suspected insomnia disorder.64
of depression in the future. Second, insomnia symptoms persist
Another instrument that measures insomnia is the Bergen
after treatment for depression; and third, if depression is treated
Insomnia Scale. This scale was developed based on existing clinical
alone and insomnia is not treated, depression will recur77.
diagnosis criteria for insomnia. This 16-item instrument measures
In addition to depression, other mental health problems such as
sleep initiation, sleep maintenance, early morning awakening,
anxiety may be observed in patients with insomnia.78 Other sleep
nonrestorative sleep, and experiencing dysfunction (loss of func-
disorders, such as sleep apnea, may also co-occur with insom-
tion) during the day.75 This scale is a self-report tool that is
nia.79,80 The results of a study showed that diseases such as hyper-
completed in a short time.75 The items are answered based on
tension, diabetes, heart disease, migraine, gastric ulcer, asthma,
the number of nights that the person has experienced insomnia
osteoarthritis, and menstrual problems are also found in patients
syndrome. Thus, the respondent is asked to rate their sleep quality
with insomnia.81 Insomnia may also occur at the same time as other
on a scale of 0–7 based on their experience during the past month.
sleep disorders such as obstructive sleep apnea (OSA).82 It is argued
Another important tool to measure insomnia is the Sleep Diary.
that the association between insomnia and OSA is an important yet
This 11-item instrument determines the respondent’s sleep pattern
unknown area of research that requires in-depth investigations.82
during each night in a week. It measures bedtime and/or lights-out
Furthermore, therapists should consider evaluating the possibility
time, sleep latency, nighttime awakening time, final wake-up time,
of other sleep disorders. Given the possibility of insomnia
and rise time. The instrument also provides information about the
co-occurring with other mental disorders and physical illnesses,
quality of sleep and the feeling of relaxation after sleep. This diary is
therapists should be careful in their assessment and diagnosis and
a useful tool for measuring and assessing the symptoms of insom-
need to evaluate the co-occurrence of other mental disorders such
nia. The instrument contains 11 items that are completed daily by
as depression, anxiety, post-traumatic stress disorder, and bipolar
the patient. It measures components such as sleep duration, sleep
disorder. It is important to note that treating insomnia should not
onset delay, number of night awakenings, sleep efficiency, and
be delayed in the presence of comorbid disorders and the therapist
subjective quality of sleep.19,76 It is worth mentioning that sleep
should treat insomnia at the same time.
assessment tools are not perfect, flawless instruments, but they can
provide some helpful information for therapists that help them
diagnose and treat insomnia.68 Two important things should be
Treatments for insomnia
considered when diagnosing insomnia. The patient is dissatisfied
with the quantity and quality of their sleep, and this dissatisfaction Following the literature, insomnia therapies can be divided into
has caused suffering. The patient reports daytime dysfunction and non-pharmacological treatments and pharmacological treatments:

Table 2. The Most Important Instruments used to Diagnose Insomnia

Year of Number of
Instrument construction items Content (subscales)
Pittsburgh Sleep 1989 19 Subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances,
Quality Index (PSQI) use of sleeping medication, and daytime dysfunction
Insomnia Severity 1993 7 The severity of problems with delayed sleep onset, sleep maintenance, early morning awakenings,
Index (ISI) satisfaction with current sleep pattern, interference with daily functioning, and so forth
Athens Insomnia Scale 2000 8 Measuring sleep problems based on the ICD-10 criteria
(AIS)
Bergen Insomnia Scale 2008 6 Measuring the symptoms of insomnia and diagnosis criteria
(BIS)
Sleep Diary - 11 Bedtime and/or lights-out time, sleep latency, nighttime awakening time, final wake-up time, rise time,
and sleep quality

https://doi.org/10.1017/S1092852924000385 Published online by Cambridge University Press

 468 H. Khazaie et al.

Figure 2. The diagnosis and treatment algorithm of insomnia based on polysomnography data.

Non-pharmacological treatments for patients with disorders occurring with insomnia and can
improve sleep parameters.88 This treatment can also be done
Given the side effects of medications prescribed for the treat-
electronically and has effective outcomes for patients.89
ment of insomnia, as well as uncertainties about the effective-
2. Sleep hygiene education (SHE): SHE is commonly used as a
ness of these medications, therapists are recommended to use
practical treatment for insomnia.90 SHE focuses on things like
non-pharmacological treatments. In fact, in the treatment of
not consuming caffeine, cigarettes, and alcohol, developing a
insomnia, priority is given to non-pharmacological treatments.
sleep–wake schedule, and some nutrition tips. SHE can improve
Following a review of the literature, the most important and
sleep, improve sleep quality, facilitate sleep, rest, and job per-
effective non-pharmacological treatments are introduced as
formance, and also reduce daily sleepiness.91 Need to emphasize
follows:
that effects in chronic insomnia disorder are minimal (SHE is
1. Cognitive-behavioral therapy for insomnia (CBT-I): CBT-I is often a control arm in RCTs for CBT-I).
an evidence-based psychotherapy that uses a range of treat- 3. Mindfulness-based therapy for insomnia (MBT-I): Mindful-
ments such as behavioral interventions to regulate sleep cycles, ness has emerged as a new approach to regulating emotions and
cognitive interventions to address maladaptive thoughts, and reducing stress, and it has several health benefits. Recently,
the reduction of over-reliance on sleeping medication.83. The MBT-I has been proposed92 to help the patient increase their
components of CBT-I usually include stimulus control, sleep awareness of the mental and physical conditions associated with
restriction, cognitive therapy, and relaxation training.84. Studies insomnia, as well as experience ways to adapt to these condi-
have shown that CBT-I is effective in reducing sleep onset tions, which are usually undesirable. It also helps the patient
latency (SOL) and wake time after sleep onset and improving monitor their daily activities and sleep schedule by paying
sleep efficiency.85,86 The results of a meta-analysis study showed attention to insomnia-induced fatigue during the day and
that CBT-I is an effective treatment to improve insomnia that applying strategies for regulating insomnia-related emotions.92
causes significant changes in the indices of the daily insomnia This therapy focuses on mindfulness and sleep, mindfulness of
diary. The results of this study also indicated that the effects of stress, mindfulness for breathing, mindfulness for thoughts and
CBT-I on SOL, wake-up after sleep, and sleep efficiency are emotions, meditation, and the role of mindfulness in dealing
stable over time.87 It should be noted that CBT-I can be effective with future challenges.93

https://doi.org/10.1017/S1092852924000385 Published online by Cambridge University Press

 CNS Spectrums 469

4. Mindfulness-based cognitive behavioral therapy: The combi- effective non-pharmacological treatments for insomnia are intro-
nation of 2 methods of mindfulness and CBTI can be used in the duced in Table 3.
treatment of insomnia. This new treatment technique integrates
CBTI components and mindfulness exercises to reduce sleep-
related arousal and improve sleep.94 The results of a study Pharmacological treatments
showed that this integrative approach can be an effective treat- A wide range of drugs are prescribed for the treatment of insomnia.
ment for insomnia, reduce the symptoms of insomnia, and These drugs can be divided into 7 categories as follows:
produce stable outcomes over time.95
5. Acceptance and Commitment Therapy (ACT): One of the 1. Benzodiazepines (BZD): These drugs are commonly used to
therapies that can be considered for treating insomnia is ACT. treat insomnia and can be effective.98. A meta-analysis study
showed that the use of BZD for treating insomnia is associated
ACT focuses on 6 processes or skills: Acceptance, cognitive
defusion, being at present, self as context, values, and committed with an increase in sleep duration, but no significant effect was
action.19 In the ACT, the main emphasis is on the individual’s on sleep latency.99 However, there are problems with BZD.
desire for inner experiences. Thus, it can help patients with Thus, researchers recommend that due to the high risk of abuse
chronic insomnia to consider dysfunctional beliefs and sleep- and dependence on these drugs, they should be administered
related thoughts as just thoughts.19 This treatment not only with great caution, and if BZD are prescribed, they should be
focuses on sleep problems and symptom control but also taken in the shortest possible time and with the lowest possible
emphasizes the patient as a whole. This focus is vital for increas- dose.100
ing the patient’s quality of life and psychological resilience, 2. A: Antidepressants used to treat insomnia
reducing the severity of insomnia.96 The results of a study include amitriptyline, doxepin, and trazodone. The results of
showed that ACT can improve sleep quality and sleep patterns one study showed that trazodone is a safe and effective drug for
in patients with insomnia, and also this treatment reduces the treatment of insomnia.101 However, another study suggested
dysfunctional sleep beliefs and attitudes in patients.19 Further- that there may be a slight improvement in sleep quality with
short-term use of doxepin and low-dose trazodone compared
more, a meta-analysis study showed that ACT is an effective
treatment for insomnia, reduces the severity of insomnia, and is to the placebo.102 There are some uncertainties about the use
effective in improving sleep patterns.96 The results of another of antidepressants in the treatment of insomnia, and studies
study indicated that ACT reduces the symptoms of insomnia.97 have not definitively indicated their effectiveness.102,103 How-
ever, some researchers recommend the use of these drugs for
An overview of non-pharmacological therapies shows that these the treatment of insomnia should be prescribed only to
therapies focus on presleep thoughts and emotions that cause the patients who, along with insomnia, are also suffering from
person to become aroused and have difficulty starting to sleep. As depression.104
noted earlier, arousal has been addressed as a keyword and effective 3. A: The results of studies have shown that
factor in treatment in cognitive models and theories. taking tiagabine can increase the duration of sleep. Besides,
Given that daytime symptoms are the main problems associ- increased deep sleep has been observed with the use of this drug,
ated with insomnia, an effective treatment should reduce the but it does not have a significant effect on subjective sleep
incidence of these symptoms. Thus, an effective treatment tech- quality.105 Other studies have also confirmed the effect of gaba-
nique for insomnia improves constructs such as functional health, pentin and pregabalin on improving sleep quality.106,107 In
psychological well-being, and quality of life. Accordingly, paying general, it has been claimed that the use of these drugs increases
attention to these constructs can be a very important part of sleep duration and sleep quality, but they should not be taken
satisfactory insomnia treatment.44 The most important and frequently.100

Table 3. Non-pharmacological Treatments for Insomnia

Treatment
Therapy Content Goal(s) duration
Cognitive- Sleep hygiene, sleep restriction, stimulus control, Improving sleep efficiency, increasing sleep duration, regulating Four to
behavioral cognitive therapy, thought challenging, and the sleep–wake cycle, and changing the nature of sleep-related eight
therapy for relaxation training dysfunctional thoughts sessions
insomnia (CBT-I)
Sleep hygiene Teaching proper sleeping habits, dietary and Improving sleep quality, increasing sleep duration, regulating the 4 sessions
education (SHE) nutritional recommendations, teaching healthy sleep–wake cycle
sleep-related lifestyles
Mindfulness Mindfulness exercises Increasing awareness of the mental and physical states associated Six to eight
with insomnia sessions
Adaptation to adverse conditions caused by insomnia
Monitoring activities and sleep schedule
Mindfulness-based Mindfulness meditation, sleep restriction, stimulus Decreasing presleep arousal Reducing nighttime symptoms of Six to eight
cognitive control, sleep education, and sleep hygiene insomnia sessions
behavioral Reducing dysfunctional sleep cognitions
therapy
Acceptance and Acceptance, cognitive defusion, being at present, Accepting dysfunctional beliefs and thoughts related to sleep Six to eight
Commitment self as context, values, and committed action Accepting emotions before going to sleep sessions
Therapy (ACT) Improving sleep quality and regulating sleep patterns

https://doi.org/10.1017/S1092852924000385 Published online by Cambridge University Press

 470 H. Khazaie et al.

4. A: Drugs such as quetiapine, olanzapine, and people with a history of BZD, other classes of drugs may not be
risperidone are some antipsychotics that have been used for responsive, so the process of taking other drugs should not be
treating insomnia. Studies have shown that these drugs can stopped. However, if medication is to be prescribed for the first
improve sleep quality.108 Furthermore, research on the effec- time, it is best to start treatment with other drugs. Another point to
tiveness of these drugs for sleep has confirmed their relative note is that pharmacological treatments are not recommended for
effectiveness.109,110. Another study showed that olanzapine and patients who report symptoms of insomnia for less than 3 months
risperidone have a significant effect on improving sleep qual- (short-term) unless the medication can correct the defective sub-
ity.111 One advantage of these drugs is that they are not addictive jective cycle. Finally, the use of antianxiety drugs and SSRIs can be
and can be used by people who are concerned about substance helpful for patients with psychophysiological insomnia due to
abuse.76 The effects of these drugs on sleep are due to the repetitive thoughts and anxiety. In addition, if preoccupation in
blocking of neurotransmitter receptors such as dopamine and patients with paradoxical insomnia is obsessive, SSRIs and low
serotonin.112 Nevertheless, there is insufficient research evi- doses of antipsychotics can be effective. However, antipsychotics
dence to confirm the effectiveness of these drugs on insomnia. can be used in cases where mental preoccupation has become a
5. Z-drugs: This group of drugs includes eszopiclone, zaleplon, fixed idea that evokes delusions.18
and zolpidem. They have been approved for treating insom-
nia.113 Eszopiclone is an effective and safe drug with a low risk of
dependence. Research has shown that this drug can be effective Suggestions and future directions
in sleep latency and maintenance.114 These drugs can generally In this study, we tried to adhere to the 2 principles of resource
be useful in the short term for people with insomnia.115 How- validity and summarization. Thus, we were very careful in report-
ever, there are some concerns about the side effects of this group ing previous studies in the literature. There were a large number of
of drugs, because they also have side effects similar to BZD, and studies, and we had to select the most important studies and report
can cause anterograde amnesia, sedation, impaired balance, and the most practical results. Following the observations made in this
complex sleep-related behavior.116 study, sleep therapists must be careful in the diagnosis process.
6. Melatonin agonists: One of the drugs used to treat insomnia is Patients may seek prompt treatment and insist on treatment in a
ramelteon. It has minimal side effects and is effective in improv- short time. Thus, therapists should not neglect a thorough exam-
ing SOL and increasing sleep duration, making it a valuable first- ination of the history of the disease and patients’ conditions. If there
line option. It also improves sleep maintenance and has mild are any contradictions in the diagnosis process, therapists should
side effects including drowsiness.104 It is said to be a safe use objective instruments such as PSG, but they should not be in a
drug that can be used in old age.105 These medications can hurry to use these instruments. Figures 1 and 2 provide a simple
reduce SOL. and practical model of diagnosis and treatment. Besides, given the
7. Antihistamines: Antihistamines are commonly used for people high probability of co-occurring insomnia with other mental dis-
with allergic rhinitis,117 but some, such as diphenhydramine, orders and physical illnesses, therapists should be careful in diag-
doxylamine, and hydroxyzine, are used to treat insomnia.112 A nosing comorbid disorders.
study showed that diphenhydramine can improve sleep qual- Future research can focus on both diagnosis and treatment.
ity.118 However, there is no strong empirical evidence to confirm Certainly, comparing the diagnostic power of objective and sub-
the effectiveness of these drugs in the treatment of insomnia.112 jective tools can be useful in the development of this discipline.
Since antihistamines do not have significant potential for abuse, Future studies also need to focus on the parameters of insomnia
they can be used in patients with insomnia prone to substance when seeking effective treatments, and to determine which treat-
abuse. Antihistamines are also suitable for people with insomnia ment is more effective for a given symptom. Sleep therapists are
who have allergy symptoms or upper respiratory tract infec- also recommended to pay attention to third-wave behavioral ther-
tions.100,112 apies, such as ACT. Moreover, analysis of co-occurrence of insom-
8. Dual orexin receptor antagonists: Suvorexant and lemborex- nia with other disorders is an important and practical research area.
ant have recently been considered dual orexin receptor antag- Thus, future studies should focus on the nature and the reasons for
onists for treating insomnia. Studies have shown that these this problem.
2 drugs have a significant effect on the treatment of insom-
nia.119–121 Research data have confirmed that suvorexant has Data availability statement. The datasets used during the current study are
significant effects on sleep onset time, sleep duration, and sleep available from the corresponding author on reasonable request.
quality,122 but it has side effects such as drowsiness, fatigue, and
abnormal dreams.122 The results of a study on lemborexant Acknowledgment. The authors gratefully appreciate Kermanshah University
showed that this drug can have significant effects on sleep onset of Medical Sciences.
time and sleep maintenance.123 Another study suggested that
Author contribution. Habibolah Khazaie: Conceptualization (equal);
lemborexant (2.5–10 mg) was effective in treating insomnia
investigation (equal), methodology (equal), project administration (equal),
while minimizing residual drowsiness the next morning.124 supervision (lead), validation (equal), and visualization (equal). Amir Sharaf-
Overall, it has been claimed that pharmacological treatments have khaneh: Conceptualization (equal); investigation (equal), methodology (equal),
immediate relief effects, but the therapeutic outcomes do not last supervision (equal), validation (equal), visualization (equal), and writing—
over time, and the effects are temporary.125 On the other hand, review and editing (lead). Ali Zakiei: Conceptualization (equal); data curation
(equal), investigation (equal), methodology (equal), project administration
long-term use of sleep medication carries the risk of dependence,
(equal), resources (equal), visualization (equal), writing—review and editing
and people often have difficulty quitting.125 Another issue in (equal), and writing—original draft preparation (equal). Earl Charles Crew:
prescribing sleep medication is the problem of drug interactions Investigation (equal), methodology (equal), project administration (equal),
that may cause problems for patients, so these issues should be resources (equal), validation (equal), visualization (lead), and revised the man-
considered when prescribing such medication. Furthermore, in uscript (equal).

https://doi.org/10.1017/S1092852924000385 Published online by Cambridge University Press

 CNS Spectrums 471

Competing interest. There are no competing interests. 21. Abad VC, Guilleminault C. Insomnia in elderly patients: recommenda-
tions for pharmacological management. Drugs Aging 2018;35(9):791–817.
Ethics approval and consent to participate. The protocol for this study was 22. Suh S, Cho N, Zhang J. Sex differences in insomnia: from
registered in the Sleep Disorders Research Center of Kermanshah University of epidemiology and etiology to intervention. Current Psychiatry Rep.
Medical Sciences in Iran and was approved by the ethics committee of the 2018;20(9):1–12.
university. This study was performed under the ethical principles laid down in 23. Singareddy R, Vgontzas AN, Fernandez-Mendoza J, et al. Risk factors for
the seventh and current edition (2013) of the Declaration of Helsinki. Written incident chronic insomnia: a general population prospective study. Sleep
informed consent was obtained from all subjects and/or their legal guardian(s). Med. 2012;13(4):346–353. doi:10.1016/j.sleep.2011.10.033
24. Ohayon MM. Epidemiology of insomnia: what we know and what we still
need to learn. Sleep Med Rev. 2002;6(2):97–111. doi:10.1053/smrv.2002.0186
25. Morin CM, LeBlanc M, Daley M, Gregoire JP, Mérette C. Epidemiology of
References insomnia: prevalence, self-help treatments, consultations, and determi-
1. Merrigan JM, Buysse DJ, Bird JC, Livingston EH. JAMA patient page. nants of help-seeking behaviors. Sleep Med. 2006;7(2):123–130. doi:
Insomnia. JAMA. 2013;309(7):733. doi:10.1001/jama.2013.524 10.1016/j.sleep.2005.08.008
2. Morin CM, Benca R. Chronic insomnia. Lancet. 2012;379(9821): 26. Moree WJ, Li BF, Jovic F, et al. Characterization of novel selective
1129–1141. doi:10.1016/s0140-6736(11)60750-2 H1-antihistamines for clinical evaluation in the treatment of insomnia. J
3. Bollu PC, Kaur H. Sleep medicine: insomnia and sleep. Missouri Med. Med Chem. 2009;52(17):5307–5310. doi:10.1021/jm900933k
2019;116(1):68. 27. Chaput J-P, Yau J, Rao DP, Morin CM. Prevalence of insomnia for
4. Kraus SS, Rabin LA. Sleep America: managing the crisis of adult chronic Canadians aged 6 to 79. Health Rep. 2018;29(12):16–21.
insomnia and associated conditions. J Affect Disord. 2012;138(3):192–212. 28. Wu T, Jia X, Shi H, et al. Prevalence of mental health problems during the
doi:10.1016/j.jad.2011.05.014 COVID-19 pandemic: a systematic review and meta-analysis. J Affect
5. Riemann D, Baglioni C, Bassetti C, et al. European guideline for the Disord. 2021;281:91–98. doi:10.1016/j.jad.2020.11.117
diagnosis and treatment of insomnia. J Sleep Res. 2017;26(6):675–700. 29. Spielman AJ, Caruso LS, Glovinsky PB. A behavioral perspective on
doi:10.1111/jsr.12594 insomnia treatment. Psychiatric Clinics of North America. 1987;10(4):
6. Qaseem A, Kansagara D, Forciea MA, Cooke M, Denberg TD. Manage- 541–553.
ment of chronic insomnia disorder in adults: a clinical practice guideline 30. LeBlanc M, Mérette C, Savard J, Ivers H, Baillargeon L, Morin CM.
from the American College of physicians. Ann Intern Med. 2016;165(2): Incidence and risk factors of insomnia in a population-based sample.
125–133. doi:10.7326/m15-2175 Sleep. 2009;32(8):1027–1037. doi:10.1093/sleep/32.8.1027
7. Roberts RE, Roberts CR, Duong HT. Chronic insomnia and its negative 31. Zakiei A, Khazaie H, Reshadat S, Rezaei M, Komasi S. The comparison of
consequences for health and functioning of adolescents: a 12-month emotional dysregulation and experiential avoidance in patients with
prospective study. J Adolesc Health. 2008;42(3):294–302. doi:10.1016/j. insomnia and non-clinical population. J Caring Sci. 2020;9(2):87–92.
jadohealth.2007.09.016 doi:10.34172/jcs.2020.013
8. Patel D, Steinberg J, Patel P. Insomnia in the elderly: a review. J Clin Sleep 32. Plescia F, Cirrincione L, Martorana D, et al. Alcohol abuse and insomnia
Med. 2018;14(6):1017–1024. doi:10.5664/jcsm.7172 disorder: Focus on a group of night and day workers. Int J Environ Res
9. Edinger JD, Bonnet MH, Bootzin RR, et al. Derivation of research diag- Public Health. 2021;18(24). doi:10.3390/ijerph182413196
nostic criteria for insomnia: report of an American Academy of Sleep 33. Halsøy Ø, Johnson SU, Hoffart A, Ebrahimi OV. Insomnia symptoms in
Medicine Work Group. Sleep 2004;27(8):1567–1596. doi:10.1093/ the general population during the COVID-19 pandemic. Front Psychiatry.
sleep/27.8.1567 2021;12:762799. doi:10.3389/fpsyt.2021.762799
10. Javaheri S, Redline S. Insomnia and risk of cardiovascular disease. Chest. 34. Komasi S, Rezaei F, Hemmati A, Rahmani K, Amianto F, Miettunen J.
2017;152(2):435–444. doi:10.1016/j.chest.2017.01.026 Comprehensive meta-analysis of associations between temperament and
11. Ford ES, Cunningham TJ, Giles WH, Croft JB. Trends in insomnia and character traits in Cloninger’s psychobiological theory and mental disor-
excessive daytime sleepiness among U.S. adults from 2002 to 2012. Sleep ders. J Int Med Res. 2022;50(1):03000605211070766.
Med. 2015;16(3):372–378. doi:10.1016/j.sleep.2014.12.008 35. Spielman A, Glovinsky P. Introduction: the varied nature of insomnia. In
12. American Psychiatric Association. Diagnostic and statistical manual of Case studies in insomnia. Boston, MA: Springer US, 1991:1–15.
mental disorders: DSM-5; 2013. 36. Morin CM. Insomnia: Psychological Assessment and Management. Guil-
13. Medicine AAoS. The International Classification of Sleep Disorders:(ICSD- ford Press; 1993.
3). American Academy of Sleep Medicine; 2014. 37. Perlis ML, Giles DE, Mendelson WB, Bootzin RR, Wyatt JK. Psychophys-
14. Dopheide JA. Insomnia overview: epidemiology, pathophysiology, diag- iological insomnia: the behavioural model and a neurocognitive perspective.
nosis and monitoring, and nonpharmacologic therapy. Am J Manag Care. J Sleep Res. 1997;6(3):179–188. doi:10.1046/j.1365-2869.1997.00045.x
2020;26(4 Suppl):S76–S84. doi:10.37765/ajmc.2020.42769 38. Lundh LG, Broman JE. Insomnia as an interaction between sleep-
15. Rosenberg R, Citrome L, Drake CL. Advances in the treatment of chronic interfering and sleep-interpreting processes. J Psychosom Res. 2000;49
insomnia: a narrative review of new nonpharmacologic and pharmaco- (5):299–310. doi:10.1016/s0022-3999(00)00150-1
logic therapies. Neuropsychiatr Dis Treat. 2021;17:2549–2566. doi: 39. Harvey AG. A cognitive model of insomnia. Behav Res Ther. 2002;40(8):
10.2147/ndt.S297504 869–893. doi:10.1016/s0005-7967(01)00061-4
16. Schutte-Rodin S, Broch L, Buysse D, Dorsey C, Sateia M. Clinical guideline 40. Espie CA. Understanding insomnia through cognitive modelling. Sleep
for the evaluation and management of chronic insomnia in adults. J Clin Med. 2007;8(Suppl 4):S3–S8. doi:10.1016/s1389-9457(08)70002-9
Sleep Med. 2008;4(5):487–504. 41. Vandekerckhove M, Cluydts R. The emotional brain and sleep: an inti-
17. Sano H, Itoh H. [Idiopathic insomnia]. Nihon Rinsho. 1998;56(2):361–364. mate relationship. Sleep Med Rev. 2010; 14(4):219–226. doi:10.1016/j.
18. Rezaie L, Fobian AD, McCall WV, Khazaie H. Paradoxical insomnia and smrv.2010.01.002
subjective-objective sleep discrepancy: A review. Sleep Med Rev. 2018;40: 42. Ong JC, Ulmer CS, Manber R. Improving sleep with mindfulness and
196–202. doi:10.1016/j.smrv.2018.01.002 acceptance: a metacognitive model of insomnia. Behav Res Ther. 2012;50
19. Zakiei A, Khazaie H, Rostampour M, et al. Acceptance and commitment (11):651–660. doi:10.1016/j.brat.2012.08.001
therapy (ACT) improves sleep quality, experiential avoidance, and emo- 43. Khazaie H, Komasi S, Mehra R, et al. Insomnia and incidence of heart
tion regulation in individuals with insomnia-results from a randomized failure in a sample of half a million people: a meta-analytic review and
interventional study. Life (Basel). 2021;11(2). doi:10.3390/life11020133 meta-regression of prospective studies. Curr Sleep Med Rep. 2023; 9(4):
20. de Zambotti M, Goldstone A, Colrain IM, Baker FC. Insomnia disorder in 281–95.
adolescence: Diagnosis, impact, and treatment. Sleep Med Rev. Jun 2018; 44. Espie CA, Emsley R, Kyle SD, et al. Effect of digital cognitive behavioral
39:12–24. doi:10.1016/j.smrv.2017.06.009 therapy for insomnia on health, psychological well-being, and sleep-

https://doi.org/10.1017/S1092852924000385 Published online by Cambridge University Press

 472 H. Khazaie et al.

related quality of life: a randomized clinical trial. JAMA Psychiatry. 2019; 65. Edinger JD, Arnedt JT, Bertisch SM, et al. Behavioral and psychological
76(1):21–30. treatments for chronic insomnia disorder in adults: an American Acad-
45. Hertenstein E, Feige B, Gmeiner T, et al. Insomnia as a predictor of mental emy of sleep medicine clinical practice guideline. J Clin Sleep Med. 2021;
disorders: a systematic review and meta-analysis. Sleep Med reviews. 2019; 17(2):255–262.
43:96–105. 66. Burman D. Sleep disorders: insomnia. FP Essent. 2017;460:22–28.
46. Riemann D, Voderholzer U. Primary insomnia: a risk factor to develop 67. Riemann D, Spiegelhalder K, Feige B, et al. The hyperarousal model of
depression? J Affect Disord. 2003;76(1–3):255–259. doi:10.1016/s0165- insomnia: a review of the concept and its evidence. Sleep Med Rev. 2010;
0327(02)00072-1 14(1):19–31. doi:10.1016/j.smrv.2009.04.002
47. Baglioni C, Battagliese G, Feige B, et al. Insomnia as a predictor of 68. Moul DE, Hall M, Pilkonis PA, Buysse DJ. Self-report measures of
depression: a meta-analytic evaluation of longitudinal epidemiological stud- insomnia in adults: rationales, choices, and needs. Sleep Med Rev. 2004;
ies. J Affect Disord. 2011;135(1–3):10–19. doi:10.1016/j.jad.2011.01.011 8(3):177–198. doi:10.1016/s1087-0792(03)00060-1
48. Perlis ML, Smith LJ, Lyness JM, et al. Insomnia as a risk factor for onset of 69. Jafari B, Mohsenin V. Polysomnography. Clin Chest Med. 2010;31(2):
depression in the elderly. Behav Sleep Med. 2006; 4 (2):104–113. doi: 287–297.
10.1207/s15402010bsm0402_3 70. Ibáñez V, Silva J, Cauli O. A survey on sleep questionnaires and diaries.
49. Ford DE, Kamerow DB. Epidemiologic study of sleep disturbances and Sleep Med. 2018;42:90–96. doi:10.1016/j.sleep.2017.08.026
psychiatric disorders. An opportunity for prevention? JAMA 1989; 71. Buysse DJ, Reynolds III CF, Monk TH, Berman SR, Kupfer DJ. The
262(11):1479–1484. doi:10.1001/jama.262.11.1479 Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice
50. Li L, Wu C, Gan Y, Qu X, Lu Z. Insomnia and the risk of depression: a and research. Psychiatry Res. 1989;28(2):193–213. doi:10.1016/0165-1781
meta-analysis of prospective cohort studies. BMC Psychiatry. 2016;16(1): (89)90047-4
375. doi:10.1186/s12888-016-1075-3 72. Bastien CH, Vallières A, Morin CM. Validation of the Insomnia Severity
51. Liu X, Buysse DJ, Gentzler AL, et al. Insomnia and hypersomnia associ- Index as an outcome measure for insomnia research. Sleep Med. 2001;2(4):
ated with depressive phenomenology and comorbidity in childhood 297–307. doi:10.1016/s1389-9457(00)00065-4
depression. Sleep. 2007;30(1):83–90. doi:10.1093/sleep/30.1.83 73. Morin CM, Belleville G, Bélanger L, Ivers H. The Insomnia Severity Index:
52. Gillin JC. Are sleep disturbances risk factors for anxiety, depressive and psychometric indicators to detect insomnia cases and evaluate treatment
addictive disorders? Acta Psychiatr Scand Suppl. 1998;393:39–43. doi: response. Sleep. 2011;34(5):601–608. doi:10.1093/sleep/34.5.601
10.1111/j.1600-0447.1998.tb05965.x 74. Soldatos CR, Dikeos DG, Paparrigopoulos TJ. Athens Insomnia Scale:
53. Shanahan L, Copeland WE, Angold A, Bondy CL, Costello EJ. Sleep validation of an instrument based on ICD-10 criteria. J Psychosom Res.
problems predict and are predicted by generalized anxiety/depression 2000;48(6):555–560. doi:10.1016/s0022-3999(00)00095-7
and oppositional defiant disorder. J Am Acad Child Adolesc Psychiatry. 75. Pallesen S, Bjorvatn B, Nordhus IH, Sivertsen B, Hjørnevik M, Morin CM.
2014;53(5):550–558. doi:10.1016/j.jaac.2013.12.029 A new scale for measuring insomnia: the Bergen Insomnia Scale. Percept
54. Średniawa A, Drwiła D, Krotos A, Wojtaś D, Kostecka N, Tomasik T. Mot Skills. 2008;107(3):691–706. doi:10.2466/pms.107.3.691-706
Insomnia and the level of stress among students in Krakow, Poland. 76. Porwal A, Yadav YC, Pathak K, Yadav R. An update on assessment,
Trends in Psychiatry and Psychotherapy 2019;41:60–68. therapeutic management, and patents on insomnia. Biomed Res Int.
55. Latina D, Bauducco S, Tilton-Weaver L. Insomnia symptoms and non- 2021;2021:6068952. doi:10.1155/2021/6068952
suicidal self-injury in adolescence: understanding temporal relations and 77. Sweetman A, Lack L, Van Ryswyk E, et al. Co-occurring depression and
mechanisms. J Sleep Res. 2021;30 (1):e13190. doi:10.1111/jsr.13190 insomnia in Australian primary care: recent scientific evidence. Med J
56. Khazaie H, Khazaie S, Zakiei A, et al. When non-suicidal self-injury Aust. 2021;215(5):230–236. doi:10.5694/mja2.51200
predicts non-suicidal self-injury and poor sleep-results from a larger 78. Blank M, Zhang J, Lamers F, Taylor AD, Hickie IB, Merikangas KR.
cross-sectional and quasi-longitudinal study. Int J Environ Res Public Health correlates of insomnia symptoms and comorbid mental disorders
Health. 2021;18 24). doi:10.3390/ijerph182413011 in a nationally representative sample of US adolescents. Sleep. 2015;38(2):
57. Khazaie H, Zakiei A, McCall WV, et al. Relationship between sleep 197–204. doi:10.5665/sleep.4396
problems and self-injury: a systematic review. Behav Sleep Med. 2021; 79. Appleton SL, Gill TK, Lang CJ, et al. Prevalence and comorbidity of sleep
19(5):689–704. doi:10.1080/15402002.2020.1822360 conditions in Australian adults: 2016 Sleep Health Foundation national
58. Vargas I, Perlis ML, Grandner M, et al. Insomnia symptoms and suicide- survey. Sleep Health. 2018;4(1):13–19. doi:10.1016/j.sleh.2017.10.006
related ideation in U.S. army service members. Behav Sleep Med. 2020;18 80. Benetó A, Gomez-Siurana E, Rubio-Sanchez P. Comorbidity between
(6):820–836. doi:10.1080/15402002.2019.1693373 sleep apnea and insomnia. Sleep Med Rev. 2009;13(4):287–293. doi:
59. Fisher K, Houtsma C, Assavedo BL, Green BA, Anestis MD. Agitation as a 10.1016/j.smrv.2008.09.006
moderator of the relationship between insomnia and current suicidal 81. Budhiraja R, Roth T, Hudgel DW, Budhiraja P, Drake CL. Prevalence and
ideation in the military. Arch Suicide Res. 2017;21(4):531–543. doi: polysomnographic correlates of insomnia comorbid with medical disor-
10.1080/13811118.2016.1193077 ders. Sleep. 2011;34(7):859–867. doi:10.5665/sleep.1114
60. Pigeon WR, Pinquart M, Conner K. Meta-analysis of sleep disturbance 82. Ragnoli B, Pochetti P, Raie A, Malerba M. Comorbid Insomnia and
and suicidal thoughts and behaviors. J Clin Psychiatry. 2012;73(9): Obstructive Sleep Apnea (COMISA): current concepts of patient man-
e1160–e1167. doi:10.4088/JCP.11r07586 agement. Int J Environ Res Public Health. 2021;18(17). doi:10.3390/
61. Pigeon WR, Woosley JA, Lichstein KL. Insomnia and hypnotic medica- ijerph18179248
tions are associated with suicidal ideation in a community population. Arch 83. Koffel E, Bramoweth AD, Ulmer CS. Increasing access to and utilization
Suicide Res. 2014;18(2):170–180. doi:10.1080/13811118.2013.824837 of cognitive behavioral therapy for insomnia (CBT-I): a narrative
62. Dolsen MR, Prather AA, Lamers F, Penninx B. Suicidal ideation and review. J Gen Intern Med. 2018;33(6):955–962. doi:10.1007/s11606-
suicide attempts: associations with sleep duration, insomnia, and inflam- 018-4390-1
mation. Psychol Med. 2020;51(12):2094–103. doi:10.1017/ 84. Davidson JR, Dickson C, Han H. Cognitive behavioural treatment for
s0033291720000860 insomnia in primary care: a systematic review of sleep outcomes. Br J Gen
63. Ohayon MM, Smirne S. Prevalence and consequences of insomnia disor- Pract. 2019;69(686):e657–e664. doi:10.3399/bjgp19X705065
ders in the general population of Italy. Sleep Med. 2002;3(2):115–120. doi: 85. Sivertsen B, Omvik S, Pallesen S, et al. Cognitive behavioral therapy
10.1016/s1389-9457(01)00158-7 vs zopiclone for treatment of chronic primary insomnia in older adults:
64. Martin JL, Mysliwiec V, Chowdhuri S, Ulmer CS. The veterans adminis- a randomized controlled trial. JAMA. 2006;295(24):2851–2858. doi:
tration and department of defense clinical practice guidelines for the 10.1001/jama.295.24.2851
diagnosis and management of sleep disorders: what does this mean for 86. Jacobs GD, Pace-Schott EF, Stickgold R, Otto MW. Cognitive behavior
the practice of sleep medicine? J Clin Sleep Med. 2020;16(8):1377–1381. therapy and pharmacotherapy for insomnia: a randomized controlled trial

https://doi.org/10.1017/S1092852924000385 Published online by Cambridge University Press

 CNS Spectrums 473

and direct comparison. Arch Intern Med. 2004;164(17):1888–1896. doi: 107. Foldvary-Schaefer N, De Leon Sanchez I, Karafa M, Mascha E, Dinner D,
10.1001/archinte.164.17.1888 Morris HH. Gabapentin increases slow-wave sleep in normal adults.
87. Trauer JM, Qian MY, Doyle JS, Rajaratnam SM, Cunnington D. Cognitive Epilepsia. 2002;43(12):1493–1497. doi:10.1046/j.1528-1157.2002.21002.x
behavioral therapy for chronic insomnia: a systematic review and meta- 108. Rios P, Cardoso R, Morra D, et al. Comparative effectiveness and safety of
analysis. Ann Intern Med. 2015;163(3):191–204. doi:10.7326/m14-2841 pharmacological and non-pharmacological interventions for insomnia:
88. Wu JQ, Appleman ER, Salazar RD, Ong JC. Cognitive Behavioral Therapy an overview of reviews. Syst Rev. 2019;8(1):281. doi:10.1186/s13643-019-
for Insomnia Comorbid With Psychiatric and Medical Conditions: A 1163-9
Meta-analysis. JAMA Intern Med. 2015;175(9):1461–1472. doi:10.1001/ 109. Tassniyom K, Paholpak S, Tassniyom S, Kiewyoo J. Quetiapine for
jamainternmed.2015.3006 primary insomnia: a double blind, randomized controlled trial. J Med
89. Ye YY, Chen NK, Chen J, et al. Internet-based cognitive-behavioural Assoc Thai. 2010;93(6):729–734.
therapy for insomnia (ICBT-i): a meta-analysis of randomised controlled 110. Chakravorty S, Hanlon AL, Kuna ST, et al. The effects of quetiapine on sleep
trials. BMJ Open. 2016;6(11):e010707. doi:10.1136/bmjopen-2015-010707 in recovering alcohol-dependent subjects: a pilot study. J Clin Psychophar-
90. Chung KF, Lee CT, Yeung WF, Chan MS, Chung EW, Lin WL. Sleep macol. 2014;34(3):350–354. doi:10.1097/jcp.0000000000000130
hygiene education as a treatment of insomnia: a systematic review and meta- 111. Khazaie H, Rezaie L, Darvishi F, Najafi F, Avis K. Treatment of
analysis. Fam Pract. 2018;35(4):365–375. doi:10.1093/fampra/cmx122 paradoxical insomnia with atypical antipsychotic drugs. A comparison
91. Burton WN, Chen CY, Li X, et al. Evaluation of a workplace-based sleep of olanzapine and risperidone. Neurosciences (Riyadh). 2013;18(1):
education program. J Occup Environ Med. 2016;58(9):911–917. doi: 64–69.
10.1097/jom.0000000000000824 112. Krystal AD, Prather AA, Ashbrook LH. The assessment and management
92. Ong J, Sholtes D. A mindfulness-based approach to the treatment of of insomnia: an update. World Psychiatry. 2019;18(3):337–352.
insomnia. J Clin Psychol. 2010;66(11):1175–1184. doi:10.1002/jclp.20736 113. Brandt J, Leong C. Benzodiazepines and Z-Drugs: an updated review of
93. Pan C, Wang X, Deng Y, et al. Efficacy of mindfulness-based intervention major adverse outcomes reported on in epidemiologic research. Drugs R
(’mindfulness-based joyful sleep’) in young and middle-aged individuals D. 2017;17(4):493–507. doi:10.1007/s40268-017-0207-7
with insomnia using a biomarker of inflammatory responses: a prospec- 114. Rösner S, Englbrecht C, Wehrle R, Hajak G, Soyka M. Eszopiclone for
tive protocol of a randomised controlled trial in China. BMJ Open. 2019; insomnia. Cochrane Database Syst Rev. 2018;10(10):CD010703.
9(7):e027061. doi:10.1136/bmjopen-2018-027061 115. Wilt TJ, MacDonald R, Brasure M, et al. Pharmacologic treatment of
94. Ong JC, Shapiro SL, Manber R. Combining mindfulness meditation with insomnia disorder: an evidence report for a clinical practice guideline
cognitive-behavior therapy for insomnia: a treatment-development study. by the American College of Physicians. Ann Intern Med. 2016;165(2):
Behav Ther. 2008;39(2):171–182. doi:10.1016/j.beth.2007.07.002 103–112. doi:10.7326/m15-1781
95. Ong JC, Shapiro SL, Manber R. Mindfulness meditation and cognitive 116. Dobia A, Ryan K, BaHammam AS, Edwards A. Using benzodiazepines
behavioral therapy for insomnia: a naturalistic 12-month follow-up. and Z-drugs for managing primary insomnia in adults in Saudi Arabia: an
Explore (NY). 2009;5(1):30–36. doi:10.1016/j.explore.2008.10.004 e-Delphi study to aid the development of clinical guidelines. Sleep Breath-
96. Paulos-Guarnieri L, Linares IMP, El Rafihi-Ferreira R. Evidence and ing. 2019;23(4):1133–1139.
characteristics of Acceptance and Commitment Therapy (ACT)-based 117. Kawauchi H, Yanai K, Wang D-Y, Itahashi K, Okubo K. Antihistamines
interventions for insomnia: a systematic review of randomized and non- for allergic rhinitis treatment from the viewpoint of nonsedative proper-
randomized trials. J. Contextual Behav Sci. 2022;23:1–14. ties. Int J Mol Sci 2019;20(1):213.
97. El Rafihi-Ferreira R, Morin CM, Toscanini AC, et al. Acceptance and 118. Morin CM, Koetter U, Bastien C, Ware JC, Wooten V. Valerian-hops
commitment therapy-based behavioral intervention for insomnia: a pilot combination and diphenhydramine for treating insomnia: a randomized
randomized controlled trial. Braz J Psychiatry. 2021;43(5):504–509. doi: placebo-controlled clinical trial. Sleep. 2005;28(11):1465–1471. doi:
10.1590/1516-4446-2020-0947 10.1093/sleep/28.11.1465
98. McCall WV. A psychiatric perspective on insomnia. J Clin Psychiatry. 119. Kishi T, Nomura I, Matsuda Y, et al. Lemborexant vs suvorexant for
2001;62(Suppl 10):27–32. insomnia: a systematic review and network meta-analysis. J Psychiatr Res.
99. Holbrook AM, Crowther R, Lotter A, Cheng C, King D. Meta-analysis of 2020;128:68–74. doi:10.1016/j.jpsychires.2020.05.025
benzodiazepine use in the treatment of insomnia. CMAJ. 2000;162(2): 120. Yardley J, Kärppä M, Inoue Y, et al. Long-term effectiveness and safety of
225–233. lemborexant in adults with insomnia disorder: results from a phase
100. Matheson E, Hainer BL. Insomnia: pharmacologic therapy. Am Fam 3 randomized clinical trial. Sleep Med. 2021;80:333–342. doi:10.1016/j.
Physician. 2017;96(1):29–35. sleep.2021.01.048
101. Jaffer KY, Chang T, Vanle B, et al. Trazodone for insomnia: a systematic 121. Kishi T, Matsunaga S, Iwata N. Suvorexant for primary insomnia: a
review. Innov Clin Neurosci. 2017;14(7–8):24–34. systematic review and meta-analysis of randomized placebo-controlled
102. Everitt H, Baldwin DS, Stuart B, et al. Antidepressants for insomnia in trials. PLoS One. 2015;10(8):e0136910. doi:10.1371/journal.pone.
adults. Cochrane Database Syst Rev. 2018;5(5):Cd010753. doi:10.1002/ 0136910
14651858.CD010753.pub2 122. Kuriyama A, Tabata H. Suvorexant for the treatment of primary insomnia:
103. Wichniak A, Wierzbicka A, Walęcka M, Jernajczyk W. Effects of antide- A systematic review and meta-analysis. Sleep Med Rev. 2017;35:1–7. doi:
pressants on sleep. Curr Psychiatry Rep. 2017;19(9):63. doi:10.1007/ 10.1016/j.smrv.2016.09.004
s11920-017-0816-4 123. Rosenberg R, Murphy P, Zammit G, et al. Comparison of lemborexant
104. Schroeck JL, Ford J, Conway EL, et al. Review of safety and efficacy of sleep with placebo and zolpidem tartrate extended release for the treatment of
medicines in older adults. Clin Ther. 2016;38(11):2340–2372. doi:10.1016/ older adults with insomnia disorder: A phase 3 randomized clinical trial.
j.clinthera.2016.09.010 JAMA Netw Open. 2019;2(12):e1918254. doi:10.1001/jamanetworko-
105. Sys J, Van Cleynenbreugel S, Deschodt M, Van der Linden L, Tournoy J. pen.2019.18254
Efficacy and safety of non-benzodiazepine and non-Z-drug 124. Murphy P, Moline M, Mayleben D, et al. Lemborexant, A Dual Orexin
hypnotic medication for insomnia in older people: a systematic literature Receptor Antagonist (DORA) for the treatment of insomnia disorder:
review. Eur J Clin Pharmacol. 2020;76(3):363–381. doi:10.1007/s00228-019- Results from a Bayesian, adaptive, randomized, double-blind, placebo-
02812-z controlled study. J Clin Sleep Med. 2017;13(11):1289–1299. doi:10.5664/
106. Furey SA, Hull SG, Leibowitz MT, Jayawardena S, Roth T. A randomized, jcsm.6800
double-blind, placebo-controlled, multicenter, 28-day, polysomnographic 125. Cho YW, Song ML. Effects of pregabalin in patients with hypnotic-
study of gabapentin in transient insomnia induced by sleep phase advance. dependent insomnia. J Clin Sleep Med. 2014;10(5):545–550. doi:
J Clin Sleep Med. 2014;10(10):1101–1109. doi:10.5664/jcsm.4110 10.5664/jcsm.3708

https://doi.org/10.1017/S1092852924000385 Published online by Cambridge University Press