Prevalence of Insomnia

Insomnia, or inability to sleep, is the most

commonly reported sleep problem in the

industrialized world.1 Estimates suggest that

between 40 and 70 million Americans are

affected by either intermittent or chronic sleep

problems, representing approximately 20 percent

of the population.2 The Sleep in America Poll,

conducted by the National Sleep Foundation,

revealed that almost 50 percent of people

surveyed had complaints of frequent insomnia,

but only 6 percent were formally diagnosed.3

Moreover, approximately, 30 to 35 percent of

respondents complained of nightly insomnia.3

The most prevalent symptoms of insomnia,

experienced at least a few nights a week by

people with insomnia, include waking up feeling

unrefreshed (34 percent) and being awake often

during the night (32 percent).3 The symptoms

of difficulty falling asleep and waking up too

early are less common, but still experienced at

least a few nights a week by about one-fourth of

adults with insomnia (23 to 24 percent).3

Risk Factors for Insomnia

Although some risk factors and etiologies of

insomnia have been identified, the nature of the

relationships has not been fully elucidated. Some

risk factors for insomnia that have emerged from

data related to insomnia include female gender3

and old age.4 Additional risks factors include less

education, unemployment, separation or divorce,

and medical illness.1 Insomnia may be primary

or secondary to other sleep problems and may be

associated with a number of co-morbidities. An

association has been found between insomnia

and psychiatric (depression and anxiety) and

psychological disorders.4 There is increasing

evidence that chronic insomnia may predispose

individuals to the development of psychiatric

disorders.5-6 Persistent insomnia increases the risk

of depression, substance abuse, and anxiety

disorders. Environmental factors such as

irregular sleep schedules, use of caffeine or other

stimulants, co-morbid medical conditions,

and/or shift work may also predispose vulnerable

individuals to insomnia. 

Consequences of Insomnia

Insomnia has significant direct and indirect

effects on the health and wellness of affected

individuals. Insomnia has been correlated with

frequent use of medical services,7-8 chronic health

problems, 9-10 increased drug use,7-8 and perceived

poor health,11 and has been associated with

medical problems including heart disease,12

hypertension,13 and musculoskeletal problems.12

The daytime consequences of chronic insomnia

often include increased healthcare utilization,

increased risk of depression,14 poor memory,

reduced concentration, poor work performance,

and perceived or real risk of failure at work.15

The economic implications of insomnia and

Evidence Report/Technology Assessment

Number 125

Manifestations and Management of Chronic

Insomnia in Adults

Summary

Authors: Buscemi N, Vandermeer B, Friesen C, Bialy L, Tubman M, Ospina M, 

Klassen TP, Witmans M

Agency for Healthcare Research and Quality

Advancing Excellence in Health Care • www.ahrq.gov

Agency for Healthcare Research and Quality Evidence-Based

Practice
2

associated morbidity have been described.7,3 The direct costs of

insomnia (insomnia treatments, healthcare services, hospital

and nursing home care) are estimated to be nearly $14

billion.16-17 The indirect costs of insomnia, such as time lost

from work and loss of productivity, are estimated to be nearly

$28 billion. A National Sleep Foundation survey found that

lost productivity from insomnia alone was over $18 billion. 

Management of Insomnia

Management of acute insomnia has traditionally involved

pharmacotherapy. The use of such agents is common practice

for both acute and chronic insomnia, despite the fact that the

Food and Drug Administration (FDA) has approved none of

them for chronic insomnia. Another medication, eszopiclone

(Lunesta), was recently approved by the FDA for treatment of

insomnia, but the duration of use is not explicitly stated. An

estimated 0.5 percent of the population takes sedative

medications for insomnia for more than 1 year.3 More than 1

in 10 people (11 percent) report using prescription (6 percent)

and/or over-the-counter (OTC) medications (6 percent), at

least a few nights a month, to help them sleep, according to a

Sleep in America Poll.3 Individuals reporting symptoms of

medical conditions are more likely to take sleep aids, both

prescription and OTC medications. For example, 14 percent

of people with symptoms of depression report using

prescription medication, and 12 percent of people with

symptoms of depression report using OTC sleep aids.3

Medications commonly used to treat insomnia include

sedating antidepressants,18 antihistamines, anticholinergics,

benzodiazepines, and non-benzodiazepine hypnotics. A side

effect of all hypnotics is to reduce slow wave sleep. Other side

effects of concern are possible daytime residual effects related

to sedation, rebound insomnia, and tolerance, along with

minor side effects specific to each drug class. Many questions

and challenges related to pharmacological therapy for chronic

insomnia remains, such as the appropriate treatment for

different types of primary and secondary insomnia, and the

long-term side effects and daytime consequences of

pharmacotherapy. The evidence for management of chronic

insomnia with pharmacotherapy has not been systematically

evaluated. 

Cognitive/behavioral therapy has been recognized as a valid

and successful treatment approach for insomnia. Cognitive/

behavioral therapy can include any combination of sleep

restriction, sleep hygiene, stimulus control, paradoxical

intention, and cognitive restructuring. Many of these

commonly used clinical tools have not undergone rigorous

testing to determine their efficacy and long-term safety. The

efficacy of these treatments has been evaluated in some

studies,4,19 but differences in the definition of insomnia and

outcome measures make it difficult to compare study results. 

In summary, insomnia is a common complaint with

significant consequences. Significant advancements have been

made in sleep research over the past three decades, yet many

questions related to the treatment of chronic insomnia remain.

Our goal was to review the evidence and state of research in

the area of chronic insomnia.

Objectives

The objectives of this report are to conduct a systematic

review of (1) the prevalence, natural history, incidence, risk

factors, and consequences of chronic insomnia in adults and

(2) the efficacy and safety of treatments used in the

management of chronic insomnia in adults. A population was

considered to suffer from chronic insomnia if the sleep

disturbance persisted for at least 4 weeks, regardless of severity

of symptoms. 

Methods

Literature Search

The research librarian, in collaboration with the TEP

(Technical Expert Panel), developed and implemented search

strategies designed to identify relevant evidence for key

questions of the review. A systematic search of 21 electronic

databases was conducted. We searched MEDLINE®,

EMBASE, CINAHL®, Ovid MEDLINE® In-Process &

Other Non-Indexed Citations, Ovid OLDMEDLINE®,

PsycINFO®, EBM Reviews-Cochrane Central Register of

Controlled Trials, International Pharmaceutical Abstracts,

AMED (Allied and Complementary Medicine) ,

HealthSTAR/Ovid Healthstar, EBM Reviews-Cochrane

Database of Systematic Reviews (CDSR), ACP Journal Club

(ACPJC), Database of Abstracts of Reviews of Effects

(DARE), Science Citation Index ExpandedTM, Biological

Abstracts, Cochrane Complementary Medicine Field Registry,

CAB Abstracts, SIGLE, OCLC Proceedings First, Dissertation

Abstracts, Alt HealthWatch, NLM Gateway, and PubMed®.

Most of the searches were limited to humans, and no age

restrictions were applied to any of the searches. 

For Question 1, which relates to the definition,

classification, diagnosis, and aetiology of chronic insomnia in

adults, we searched for narrative and systematic reviews, book
chapters, diagnostic manuals and standards of practice

parameters, and applied English-language restrictions. For

Question 2, which relates to the prevalence, natural history,

incidence, and risk factors for chronic insomnia in adults, and

Question 3, which relates to the consequences, morbidities,

co-morbidities and public health burden associated with

chronic insomnia in adults, we searched for observational

studies, encompassing a range of designs including crosssectional, case-control, and cohort studies, and applied

English-language restrictions. For Question 4, which relates to

the treatments for chronic insomnia in adults, and the

evidence regarding their safety, efficacy, and effectiveness, we

searched for randomized controlled trials, and no language

restrictions were applied. 

Inclusion Criteria

We did not develop formal inclusion criteria for the

question pertaining to the definition, classification, diagnosis,

and etiology of chronic insomnia (Question 1), nor for the

question pertaining to the future direction of insomnia-related

research (Question 5). The former question was answered by

providing an overview of the literature, and the latter question

was answered by assessing the limitations in the evidence for

the other questions of the review.

Inclusion criteria were developed for three questions of the

review (Questions 2-4). Question-specific inclusion criteria

appear below. In the interest of clarity, questions 2 and 3 will

be referred to as the questions on manifestations of chronic

insomnia, while question 4 will be referred to as the question

on management of chronic insomnia.

2. What are the prevalence, natural history, incidence,

and risk factors for chronic insomnia? Specific risk

factors of interest include age, gender, race/ethnicity,

psychiatric illness and psychological problems, medical

disease, socioeconomic status, and shift work.

A study was considered to be relevant to the portion of

Question 2 pertaining to the prevalence, natural history, and

incidence of chronic insomnia, if it met the following criteria:

• The report was written in English

• Participants were at least 15 years old

• It examined chronic insomnia

• It had a cross-sectional or cohort design

• It assessed the prevalence, natural history, or incidence

of chronic insomnia

A study was considered to be relevant to the portion of

Question 2 pertaining to risk factors for chronic insomnia, if it

met the first three criteria listed above as well as the following:

• It had a cohort, case-control, or cross-sectional design

• It assessed one of the risk factors of interest

3. What are the consequences, morbidities, comorbidities, and public health burden associated with

chronic insomnia? Specific outcomes of interest include

healthcare utilization, psychiatric illness, absenteeism,

work performance, accidents, falls in the elderly, quality

of life and social relationships, memory, cognitive

function, mood, and direct and indirect costs.

A study was considered to be relevant to this question of the

review, if it met the first three criteria outlined for Question 2 as

well as the following:

• It had a cohort or cross-sectional design

• It assessed one of the consequences of interest

For Questions 2 and 3, a study was considered to examine

chronic insomnia if this condition was defined as a sleep

disturbance of four weeks or more or the report explicitly

mentioned that chronic sleep disturbance was examined.

4. What treatments are used for the management of

chronic insomnia and what is the evidence regarding

their safety, efficacy, and effectiveness? Specific

treatments of interest include prescription medication,

over-the-counter medication, alcohol, behavioral therapy,

combination therapy, and complementary and alternative

care.

A study was considered to be relevant to this question of the

review, if it met the following criteria:

• The report was written in English

• Participants were at least 15 years old, and the

majority were at least 18 years old

• Participants suffered from chronic insomnia

• Participants were randomized to intervention or

placebo

• Participants and assessors were blind to treatment

received

• It assessed at least one of the following outcomes,

listed in order of importance in deriving conclusions

of the review:

• sleep onset latency

• wakefulness after sleep onset 

• sleep efficiency

• total sleep time

3
4

• sleep quality

• quality of life

Sleep onset latency was defined as the amount of time

between the participant laying down to sleep and the onset of

sleep; wakefulness after sleep onset was defined as the amount

of time spent awake in bed following the attainment of sleep;

sleep efficiency was defined as the amount of time spent asleep

as a percentage of the total time spent in bed; and total sleep

time was defined as the total time spent asleep while in bed.

Sleep onset latency and wakefulness after sleep onset were

given the highest priority in deriving conclusions from the

review, since they were considered the best indices of sleep

initiation and sleep maintenance, respectively. However,

subgroup analyses were conducted only on data relevant to

sleep onset latency, since this outcome was the most highly

reported outcome across studies.

If the majority of participants met one of the following

criteria, the study population was considered to suffer from

chronic insomnia:

• Participants suffered from a sleep disturbance of four

weeks or more.

• Participants were described as having a chronic/longstanding/persistent sleep disturbance.

• Participants were selected from a sleep disorders clinic.

In the case of combination therapy, the combined treatment

could be compared to either placebo or single treatment.

We acknowledged the fact that double-blinding is often not

feasible in studies of psychological treatments by not requiring

double-blinding in these studies for inclusion in the review.

The placebo treatment for relaxation therapy and cognitive/

behavioral therapy was minimal treatment, such as sleep

hygiene recommendations or minimal instruction. We

required that the placebo resemble the intervention of the

study except that it was known to produce either no effect or

only a minimal effect. 

Study Selection

In the first stage of study selection, two reviewers screened

the titles and abstracts of all potentially relevant articles,

independently. Each reviewer noted the titles and abstracts

that were potentially relevant to the review, and these articles

were retrieved. In the second stage of study selection, two

reviewers appraised the potentially relevant articles,

independently, using pre-determined, question-specific,

inclusion criteria. Disagreements between reviewers were

resolved by discussion and consensus. The rate of

disagreement between reviewers and the primary reason for

exclusion of potentially relevant articles were noted.

Data Extraction

Data relevant to study design, population, interventions,

and outcomes were extracted from studies, as appropriate,

using standardized data extraction forms. A trained reviewer

extracted relevant data, and a second reviewer verified the data

extracted for accuracy and completeness.

Assessment of Study Quality 

The quality of studies relevant to the questions on

manifestations of chronic insomnia was assessed using one of

three instruments; studies on prevalence and incidence were

assessed using a scale designed specifically for this purpose.20

All other studies relevant to manifestations of chronic

insomnia were assessed using one of two Newcastle-Ottawa

scales (unpublished), each scale specific to either cohort or

case-control studies.

The quality of studies relevant to management of chronic

insomnia was assessed using the Jadad scale.21 The

concealment of allocation of participants to treatment groups

was also assessed.22

Data Analysis

Data relevant to manifestations of chronic insomnia were

analyzed qualitatively, while data relevant to management of

chronic insomnia were analyzed quantitatively.

Manifestations of Chronic Insomnia

For the questions on prevalence, natural history, incidence,

risk factors, and consequences of chronic insomnia, data

relevant to each variable were analyzed separately, except for

data relevant to potential risk factors and potential

consequences of chronic insomnia, which were analyzed

together as associated factors of chronic insomnia. The data

were synthesized to provide a description of the methods and

results of the studies relevant to a given variable. 

Management of Chronic Insomnia

For continuous outcomes (e.g., sleep onset latency and sleep

efficiency), studies were combined using a mean difference

(MD), with the exception of sleep quality and quality of life,

where studies were combined using a standardized mean

difference (SMD). Dichotomous outcomes (i.e., safety

outcomes) were combined using a risk difference (RD). A
number needed to harm (NNH) was also reported for any

safety outcomes that were found to be statistically significant.

The Inverse Variance Method23 was used to weight the studies.

An efficacy estimate, with corresponding 95% confidence

interval, was computed for each outcome. All meta-analyses

were performed using a Random Effects Model.24

For some outcomes (sleep onset latency and number of

adverse events), treatment categories were compared indirectly,

via their relationship to placebo. Differences of differences

with 95% confidence intervals (CI) were computed. 

All estimates of efficacy were assessed for heterogeneity

using the I-squared statistic.25 For our primary outcome (sleep

onset latency), heterogeneity was explored in subgroup and

sensitivity analyses using a number of variables (treatment,

presence/absence of psychiatric illness, length of treatment,

age, gender and study quality). Deeks’ chi-square statistic26

was used to test for significant heterogeneity reduction in

partitioned subgroups.

We tested for publication bias visually using the Funnel

Plot27 and quantitatively using the Rank Correlation Test,28 the

Graphical Test,29 and the Trim and Fill Method.30

Main Results

Prevalence of Chronic Insomnia

In general populations: Interquartile Range (IQR): 8.5-

24.3 percent. There was evidence of an association between

female gender and chronic insomnia.

• In clinical populations: IQR: 27.8-43.0 percent.

• In outpatients of general practice: IQR: 19.8-53.7

percent.

• The majority of studies were either of moderate or high

quality.

Natural History of Chronic Insomnia

• Only one study provided evidence on natural history of

chronic insomnia: the remission rate was 13.1 percent

after a 4-month followup period in a population suffering

from insomnia for 1 month or more.

• The study was of moderate quality.

Incidence of Chronic Insomnia

• No studies were identified that provided evidence on

incidence of chronic insomnia.

Factors Associated with Chronic

Insomnia

Potential Risk Factors

• Age. Eleven studies found evidence of an association

between age and chronic insomnia, whereas seven studies

found no evidence of an association between these

variables. Of the studies that found an association, all,

except one,31 found evidence that chronic insomnia is

associated with older age. 

• Gender. Eleven studies found evidence of an association

between gender and chronic insomnia, while seven

studies found no evidence of an association between these

variables. All of the studies that found evidence of an

association between gender and chronic insomnia, found

evidence that chronic insomnia is associated with female

gender.

• Race/ethnicity. Two studies found evidence of an

association between ethnicity and chronic insomnia,32-33

while one study found no evidence of an association

between these variables.34 Bixler et al. found evidence

that chronic insomnia is associated with being a nonCaucasian minority, and Riedel et al. found evidence that

chronic insomnia is associated with being White.

• Psychiatric illness and psychological problems. Thirtyeight studies found evidence of an association between

present or past psychiatric illness or psychological

problems and chronic insomnia. Seven studies did not

find evidence of an association between these variables. 

• Medical conditions. Twelve studies found evidence of an

association between medical conditions or poor general

health and chronic insomnia, while one study35 did not

find evidence of an association between these variables. 

• Socioeconomic status. Six studies found evidence of an

association between socioeconomic status and chronic

insomnia. Nine studies did not find evidence of an

association between these variables. 

• Shift work. Only 2 studies provided evidence regarding

the relationship between shift-work and chronic

insomnia.31,36 The study by Kageyama et al. provided

evidence that chronic insomnia is associated with three or

less night shifts per month within the preceding three

months in hospital nurses. The study by Martikainen et

al. found no evidence of an association between shift

work and chronic insomnia.

5
Potential Consequences

• Healthcare utilization. Five studies provided evidence of

an association between increased healthcare utilization

and chronic insomnia. One study did not find evidence

of an association between chronic insomnia and

undergoing medical treatment in hospital nurses.31

• Absenteeism and work performance. Only two studies

provided evidence regarding the relationship between

work performance or absenteeism and chronic

insomnia;37-38 both studies found evidence of an

association between chronic insomnia and absenteeism.

The study by Zammit et al. also found evidence of an

association between chronic insomnia and impaired work

performance.

• Quality of life and quality of social relationships. Five

studies examined the relationship between either quality

of life (from a global perspective) or quality of social

relationships and chronic insomnia. All studies found

evidence of an association between chronic insomnia and

either lower quality of life or lower quality of social

relationships; one of these studies found evidence that

both quality of life and quality of social relationships are

impaired in chronic insomniacs.39

• Memory, cognitive function, and mood. Fifteen studies

found evidence of an association between decrements in

memory, mood or cognitive function and chronic

insomnia. One study40 found evidence of increased recall

of presentations made just before sleep onset in chronic

insomniacs. Eleven studies found no evidence of an

association between mood, memory, or cognitive function

and chronic insomnia. 

We did not identify any studies that provided data relevant

to the relationship between accidents or falls in the elderly and

chronic insomnia or direct and indirect costs of the disorder.

The majority of studies were of either moderate or high

quality.

Efficacy and Safety of the Six Main

Categories of Interventions Identified in

the Literature

The efficacy estimates are provided as mean differences

(MDs) in the effect of intervention and placebo on sleep onset

latency (SOL) or wakefulness after sleep onset (WASO). The

safety estimates are provided as risk differences (RDs) between

intervention and placebo.

• Benzodiazepines. MD (SOL): -16.5, 95% CI: (-20.5, -

12.5); MD (WASO): -23.1, 95% CI: (-35.7, -10.5); RD:

0.15, 95% CI: (0.10, 0.20); number needed to harm was

eight.

• Non-benzodiazepines. MD (SOL): -18.1, 95% CI: (-

22.5, -13.7); MD (WASO): -12.6, 95% CI: (-23.0, -2.3);

RD: 0.05, 95% CI: (0.01, 0.09); number needed to

harm was 20.

• Antidepressants. MD (SOL): -7.4, 95% CI (-10.5, -4.4);

MD (WASO): -11.4, 95% CI: (-16.2, -6.6); RD: 0.09,

95% CI (0.01, 0.18); number needed to harm was 12.

• L-Tryptophan. MD (SOL): -11.0, 95% CI: (-33.0,

11.1)

• Melatonin. MD (SOL): -8.3, 95% CI: (-14.5, -2.0);

MD (WASO): -9.7, 95% CI: (-33.6, 14.3); RD: 0.09,

95% CI: (-0.11, 0.29)

• Valerian. MD (SOL): -1.3, 95% CI: (-21.4, 18.9); MD

(WASO): -8.4, 95% CI: (-15.9, -1.0); RD: -0.06, 95%

CI: (-0.48, 0.35) 

• Relaxation therapy. MD (SOL): -14.6, 95% CI: (-29.3,

0.2); MD (WASO): -1.6, 95% CI: (-14.1, 10.8). No

adverse event data was provided.

• Cognitive/behavioral therapy. MD (SOL): -4.6, 95%

CI: (-9.8, 0.6); MD (WASO): -18.2, 95% CI: (-30.4, -

6.0). No adverse event data was provided.

Most studies were of moderate or high quality.

Discussion

Prevalence, Natural History, Incidence, and

Factors Associated with Chronic Insomnia

The interquartile range of prevalence varied from 8.5-24.3

percent across high-quality studies of general populations, to

19.8-53.7 percent across moderate-quality studies of

outpatient populations, to 27.8-43.0 percent across moderatequality studies of clinical populations. Therefore, the

prevalence estimates for chronic insomnia in outpatient and

clinical populations appear to be significantly higher than

those for the general population, a finding that is consistent

with evidence of an association between chronic insomnia and

6
medical conditions, poor general health, and increased

healthcare utilization. 

Only one study provided data on the natural history of

chronic insomnia; the remission rate was 13.1 percent after a

4-month followup. More research is necessary to determine

the course of chronic insomnia in various populations. We did

not identify any studies that provided evidence regarding the

incidence of chronic insomnia; more research is needed in this

area as well.

We found evidence to suggest that chronic insomnia is

associated with older age, female gender, present or past

psychiatric illness and psychological problems, medical

conditions and poor general health, increased healthcare

utilization, lower quality of life and social relationships,

socioeconomic status (marital separation, unemployment,

poorer working conditions, and lower social status), and

decrements in memory, mood, and cognitive function. Some

of the factors that are thought to contribute to insomnia in the

elderly include multiple medical problems, polypharmacy, and

environmental factors such as absence of zeitgebers

(time/schedule cues).11,41 Similarly, factors such as stress,

pregnancy, menopause, medical conditions, and complex

home life may explain the higher prevalence of insomnia in

females. 

Efficacy and Safety of Treatments for

Chronic Insomnia

The interventions for chronic insomnia that were

investigated in included studies may be categorized as either

benzodiazepines, non-benzodiazepines, antidepressants,

complementary and alternative care (L-tryptophan, melatonin

and valerian), relaxation therapy, cognitive/behavioral therapy,

barbiturates, hormone therapy, alcohol, low energy emission

therapy, and combination therapy. The majority of studies

were classified under the first six categories of the preceding

list. 

The review provides evidence that benzodiazepines and

non-benzodiazepines are effective treatments for chronic

insomnia. There is some evidence that antidepressants are

effective treatments for chronic insomnia, although more

research is required in this area. The review provides some

evidence that melatonin is effective in subsets of the chronic

insomnia population; however, more research is required in

this area. There is also evidence that relaxation therapy and

cognitive/behavioral therapy are effective treatments in subsets

of the chronic insomnia population. There were too few

studies of L-tryptophan and valerian to draw conclusions

regarding the efficacy of these treatments in the management

of chronic insomnia: additional large-scale, randomized trials

are needed. Additional large-scale, randomized trials are also

needed in the area of relaxation therapy and cognitive/

behavioral therapy in the management of chronic insomnia to

determine the efficacy of these interventions across subsets of

the chronic insomnia population. The reduction in sleep

onset latency by benzodiazepines and non-benzodiazepines was

significantly greater than that for antidepressants and

melatonin, based on indirect comparisons. However, it should

be noted that there were significantly fewer studies of

antidepressants and melatonin compared to benzodiazepines

and non-benzodiazepines, and additional large-scale,

randomized trials of the former interventions are needed

before firm conclusions can be drawn regarding the relative

efficacy of these interventions. 

The benzodiazepines, non-benzodiazepines, and

antidepressants had a significantly greater risk of harm than

placebo, while melatonin did not. There were too few studies

of L-tryptophan to draw conclusions regarding the safety of

this intervention. Although there was no evidence that

valerian poses a risk of harm, this result was based on only

three studies of relatively small sample size. Therefore, more

studies are needed before firm conclusions can be drawn

regarding the safety of valerian. The risk for benzodiazepines

was significantly greater than for non-benzodiazepines, based

on indirect comparisons. Indeed, benzodiazepine use has been

shown to increase the risk of injury in the elderly,42 and there is

pharmacologic evidence that the non-benzodiazepines have a

better side-effect profile than the benzodiazepines.43-44 Studies

of relaxation therapy and cognitive/behavioral therapy did not

provide adverse event data. 

There was substantial heterogeneity in the pooled estimate

for SOL for benzodiazepines, non-benzodiazepines, Ltryptophan, valerian, and relaxation therapy. Similarly, there

was substantial heterogeneity in the pooled estimate for

WASO for benzodiazepines, non-benzodiazepines, melatonin,

and cognitive/behavioral therapy. The heterogeneity was often

due to differences in the magnitude of the point estimate and

confidence interval across studies, rather than differences in the

directionality of the effect. The exceptions are for estimates of

the efficacy of relaxation therapy with respect to SOL and the

efficacy of melatonin with respect to WASO. The

heterogeneity in the pooled estimates for SOL was explored in

7
8

sensitivity and sub-group analyses. The results indicate that

heterogeneity in the pooled estimate for SOL for relaxation

therapy is at least partially due to type of relaxation therapy,

length of treatment, age and gender distribution of the study

population, and study quality. 

There was strong evidence of publication bias in the pooled

estimates for SOL for the benzodiazepine and nonbenzodiazepine categories of intervention. This finding

suggests that the true estimate of efficacy is lower than the

estimate calculated in the current analysis.

We identified a small sample of studies examining the

efficacy of combination treatments in the management of

chronic insomnia; some of these studies compared a

combination of treatments with placebo, while others

compared them with single treatment. Many comparisons did

not have data for our primary outcome, sleep onset latency,

and the majority of results were non-significant. The latter

finding may reflect the low power of these analyses. None of

the studies provided data on adverse events. We identified

only one study that compared the efficacy of a combined

pharmacological and psychological treatment with these

treatments administered sequentially. The research agenda for

the management of chronic insomnia should include an

evaluation of the efficacy and safety of combination treatments

and sequential treatments.

Our results relating to relaxation therapy and

cognitive/behavioral therapy are somewhat at odds with three

meta-analyses reviewing the efficacy of psychological

treatments in the management of chronic insomnia.45-47 The

difference in the findings may relate to key differences in the

conduct of the reviews. First, we restricted our meta-analysis

to a review of placebo-controlled, randomized trials and

accounted for placebo effects in our estimations of efficacy.

Other meta-analyses have included non-controlled studies, and

for these studies, have not accounted for placebo/control

effects in their estimation of efficacy. Second, we used clearly

defined criteria for chronic insomnia; however, for some

studies the criteria for insomnia was not clear. Third, we

separated predominantly cognitive/behavioral approaches from

predominantly relaxation approaches in management of

insomnia, resulting in distinct meta-analyses for each category

of intervention. These interventions have been grouped under

the broader heading of psychological/non-pharmacological

treatments in other reviews. 

Conclusions

• There is evidence that the prevalence of chronic insomnia

in outpatient and clinical populations is larger than in the

general population.

• There is evidence that chronic insomnia is associated with

older age, female gender, present or past psychiatric illness

and psychological problems, medical conditions and poor

general health, increased healthcare utilization, lower

quality of life and social relationships, socioeconomic

status (marital separation, unemployment, poorer

working conditions and lower social status), and

decrements in memory, mood, and cognitive function.

• Additional studies are needed to determine the incidence

and natural history of chronic insomnia in adults.

Similarly, additional studies are needed to explore the

relationship between chronic insomnia and race/ethnicity,

shift work, absenteeism, work performance, accidents,

falls in the elderly, and the direct and indirect costs of the

disorder. It is necessary that longitudinal studies be

undertaken to explore the risk factors and consequences

of chronic insomnia.

• There is evidence that benzodiazepines and nonbenzodiazepines are effective in the management of

chronic insomnia. There is some evidence that

antidepressants are effective in the management of

chronic insomnia: more research is required in this area.

There is evidence that benzodiazepines, nonbenzodiazepines, and antidepressants pose a risk of harm.

• There is some evidence that melatonin is effective in the

management of chronic insomnia in subsets of the

chronic insomnia population, and there is no evidence

that melatonin poses a risk of harm. However, more

research is required in this area given that the results are

based on a small number of studies. Similarly, additional

large-scale, randomized trials are needed to determine the

efficacy of melatonin across subsets of the chronic

insomnia population. There is insufficient evidence to

conclude on the efficacy and safety of L-tryptophan and

valerian in the management of chronic insomnia.

Additional large-scale, randomized trials are needed in

these areas.

• There is evidence that relaxation therapy and

cognitive/behavioral therapy are effective in the

management of chronic insomnia in subsets of the
chronic insomnia population. Additional large-scale,

randomized trials are needed to determine their efficacy

across subsets of the chronic insomnia population.

• There is evidence that benzodiazepines have a greater risk

of harm than non-benzodiazepines.

• There is insufficient evidence to conclude whether there

are differences between the short- and long-term efficacy

and safety of the various categories of interventions in the

management of chronic insomnia; additional long-term

studies are needed.

• There is insufficient evidence regarding the efficacy and

safety of combined treatments of pharmacological and

psychological interventions, and sequential treatments, in

the management of chronic insomnia; additional studies

are needed in these areas.

Availability of the Full Report

The full evidence report from which this summary was

taken was prepared for the Agency for Healthcare Research

and Quality (AHRQ) by the University of Alberta Evidencebased Practice Center, under Contract No. C400000021. It is

expected to be available in June 2005. At that time, printed

copies may be obtained free of charge from the AHRQ

Publications Clearinghouse by calling 800-358-9295.

Requesters should ask for Evidence Report/Technology

Assessment No. 125, Manifestations and Management of

Chronic Insomnia in Adults. In addition, Internet users will be

able to access the report and this summary online through

AHRQ’s Web site at www.ahrq.gov.

Suggested Citation

Buscemi N, Vandermeer B, Friesen C, Bialy L, Tubman M,

Ospina M, Klassen TP, Witmans M. Manifestations and

Management of Chronic Insomnia in Adults. Summary,

Evidence Report/Technology Assessment No. 125. (Prepared

by the University of Alberta Evidence-based Practice Center,

under Contract No. C400000021.) AHRQ Publication No.

05-E021-1. Rockville, MD: Agency for Healthcare Research

and Quality. June 2005.

References

1. Sateia MJ, Doghramji K, Hauri P, et al. Evaluation of chronic

insomnia. An American Academy of Sleep Medicine Review. Sleep

2000; 23(2):243-308.

2. Trans-NIH Sleep Research Coordinating Committee. 2003 National

Sleep Disorders Research Plan. US Department of Health and

Human Services. National Institute of Health.

http://www.nhlbisupport.com/sleep/research/research-a.htm.

3. National Sleep Foundation. Sleep in America Poll. Data from 1997

and 2001, 2002 sleep poll. http://www.sleepfoundation.org/img/

2002SleepInAmericaPoll.pdf.

4. Zorick FJ, Walsh JK. In Kryger MH, Roth T, Dement WC.

Principles and Practice of Sleep Medicine. 3rd Ed. Philadelphia, PA:

W.B. Saunders Co; 2000. Chapter 53, Evaluation and management

of insomnia. 

5. Sateia MJ, Nowell P. Insomnia. Lancet 2004; 364:1959-73.

6. Breslau N, Roth T, Rosenthal L, et al. Sleep disturbances and

psychiatric disorders: a longitudinal epidemiological study of young

adults. Biol Psychiatry 1996; 39:411-18.

7. Simon GE, VonKorff M. Prevalence, burden, and treatment of

insomnia in primary care. Am J Psychiatry 1997; 154(10):1417-23.

8. Leger D, Guilleminault C, Bader G, et al. Medical and socioprofessional impact of insomnia. Sleep 2002; 25(6):625-9.

9. Ohayon M. Epidemiological study on insomnia in the general

population. Sleep 1996; 19(3 Suppl):S7-15.

10. Roberts RE, Shema SJ, Kaplan GA. Prospective data on sleep

complaints and associated risk factors in an older cohort. Psychosom

Med 1999; 61(2):188-96.

11. Foley DJ, Monjan A, Simonsick EM, et al. Incidence and remission

of insomnia among elderly adults: an epidemiologic study of 6,800

persons over three years. Sleep 1999; 22(Suppl 2):S366-72.

12. Janson C, Lindberg E, Gislason T, et al. Insomnia in men - A 10-year

prospective population based study. Sleep 2001; 24(4):425-30.

13. Gislason T, Reynisdottir H, Kristbjarnarson H, et al. Sleep habits and

sleep disturbances among the elderly—an epidemiological survey. J

Int Med 1993; 234(1):31-9.

14. Riemann D, Voderholzer U. Primary insomnia: a risk factor to

develop depression? J Affect Disord 2003; 76:255-9.

15. Kryger MH, Roth T, Dement WC. Principles and Practice of Sleep

Medicine. 3rd Ed. Philadelphia, PA: W.B. Saunders Co; 2000.

16. Walsh JK, Engelhardt CL. The direct economic costs of insomnia in

the United States for 1995. Sleep 1999; 22(Suppl 2):S386-93.

17. Walsh JK. Clinical and socioeconomic correlates of insomnia. J Clin

Psychiatry 2004; 65 Suppl 8:13-9.

18. Walsh J. Pharmacologic management of insomnia. J Clin Psychiatry

2004; 65(Supp 16):41-5.

19. Morin CM, Colecchi C, Stone J, et al. Behavioral and

pharmacological therapies for late-life insomnia: a randomized

controlled trial. J Am Med Assoc 1999; 281(11):991-9.

20. Loney PL, Chambers LW, Bennett KJ, et al. Critical appraisal of the

health research literature: prevalence or incidence of a health problem

(Review). Chronic Dis Can 1988; 19(4):170-6.

9
21. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of

reports of randomized clinical trials: is blinding necessary? Control

Clin Trials 1996; 17:1-12.

22. Schulz KF, Chalmers I, Hayes RJ, et al. Empirical evidence of bias.

Dimensions of methodological quality associated with estimates of

treatment effects in controlled trials. J Am Med Assoc 1995;

273:408-12.

23. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control

Clin Trials 1986; 7:177-88.

24. Bailey KR. Inter-study differences: How should they influence the

interpretation and analysis of results? Stat Med 1987; 6:351-8.

25. Higgins JPT, Thompson SG. Quantifying heterogeneity in a metaanalysis. Stat Med 2002; 21(11):1539-58.

26. Deeks JJ, Altman DG, Bradburn MJ. Statistical methods for

examining heterogeneity and combining results from several studies

in meta-analysis. In: Egger M, Davey Smith G, and Altman DG.

Systematic reviews in health care. 2nd ed. London, UK: BMJ Books;

2001.

27. Light RJ, Pillemer DB. Summing up. The science of reviewing

research. Cambridge, MA: Harvard University Press; 1984.

28. Begg CB, Mazumdar M. Operating characteristics of a rank

correlation test for publication bias. Biometrics 1994; 50:1088-101.

29. Egger M, Smith GD, Schneider M, et al. Bias in meta-analysis

detected by a simple, graphical test. Br Med J 1997; 315(7109):629-

34.

30. Duval S, Tweedie R. A nonparametric “trim and fill” method of

accounting for publication bias in meta-analysis. J Am Med Assoc

2000; 95(449):89-98.

31. Kageyama T, Nishikido N, Kobayashi T, et al. Cross-sectional survey

on risk factors for insomnia in Japanese female hospital nurses

working rapidly rotating shift systems. J Hum Ergol 2001; 30(1-

2):149-54.

32. Bixler EO, Vgontzas AN, Lin HM, et al. Insomnia in Central

Pennsylvania. J Psychosom Res 2002; 53(1):589-92.

33. Riedel BW, Durrence H, Lichstein KL, et al. The Relation Between

Smoking and Sleep: The Influence of Smoking Level, Health, and

Psychological Variables. Behav Sleep Med 2004; 2(1):63-78.

34. Lopes Rocha F, Guerra HL, Lima-Costa MFF. Prevalence of

insomnia and associated socio-demographic factors in a Brazilian

community: The Bambui study. Sleep Med 2002; 3(2):121-6.

35. Kageyama T, Kabuto M, Nitta H, et al. A population study on risk

factors for insomnia among adult Japanese women: a possible effect

of road traffic volume. Sleep 1997; 20(11):963-71.

36. Martikainen K, Partinen M, Hasan J, et al. The impact of somatic

health problems on insomnia in middle age. Sleep Med 2003;

4(3):201-6.

37. Terzano MG, Parrino L, Cirignotta F, et al. Studio Morfeo: insomnia

in primary care, a survey conducted on the Italian population. Sleep

Med 2004; 5(1):67-75.

38. Zammit GK, Weiner J, Damato N, et al. Quality of life in people

with insomnia. Sleep 1999; 22(Suppl 2):S379-85.

39 Shochat T, Umphress J, Israel AG, et al. Insomnia in primary care

patients. Sleep 1999; 22(Suppl 2):S359-65.

40. Perlis ML, Smith MT, Orff HJ, et al. The mesograde amnesia of

sleep may be attenuated in subjects with primary insomnia. Physiol

Behav 2001; 74(1-2):71-6.

41. Benca RM, Ancoli-Israel S, Moldofsky H. Special considerations in

insomnia diagnosis and management: depressed, elderly, and chronic

pain populations. J Clin Psychiatry 2004; 65(Suppl 8):26-35.

42. Panneman MJ, Goettsch WG, Kramarz P, et al. The costs of

benzodiazepine-associated hospital-treated fall Injuries in the EU: a

Pharmo study. Drugs Aging 2003; 20(11):833-9.

43. Drover DR. Comparative pharmacokinetics and pharmacodynamics

of short-acting hypnosedatives: zaleplon, zolpidem and zopiclone.

Clin Pharmacokinet 2004; 43(4):227-38.

44. Roehrs T, Roth T. Hypnotics: an update. Curr Neurol Neurosci Rep

2003; 3(2):181-4.

45. Morin CM, Culbert JP, Schwartz SM. Nonpharmacological

interventions for insomnia: A meta-analysis of treatment efficacy. Am

J Psychiatry 1994; 151(8):1172-80.

46. Murtagh DRR, Greenwood KM. Identifying effective psychological

treatments for insomnia: a meta-analysis. J Consult Clin Psychol

1995; 63(1 ):79-89.

47. Smith MT, Perlis ML, Park A, et al. Comparative meta-analysis of

pharmacotherapy and behavior therapy for persistent insomnia. Am J

Psychiatry 2002; 159:5-11.

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www.ahrq.gov

AHRQ Pub. No. 05-E021-1

June 2005

ISSN 1530-440X