Chronic insomnia

doi:10.1016/S0140-6736(11)60750-2

The Lancet

Volume 379, Issue 9821, 24–30 March 2012, Pages 1129-1141

https://doi.org/10.1016/S0140-6736(11)60750-2 Get rights and content

Summary

Insomnia is a prevalent complaint in clinical practice that can present independently or comorbidly with another medical or psychiatric disorder. In either case, it might need treatment of its own. Of the different therapeutic options available, benzodiazepine-receptor agonists (BzRAs) and cognitive-behavioural therapy (CBT) are supported by the best empirical evidence. BzRAs are readily available and effective in the short-term management of insomnia, but evidence of long-term efficacy is scarce and most hypnotic drugs are associated with potential adverse effects. CBT is an effective alternative for chronic insomnia. Although more time consuming than drug management, CBT produces sleep improvements that are sustained over time, and this therapy is accepted by patients. Although CBT is not readily available in most clinical settings, access and delivery can be made easier through use of innovative methods such as telephone consultations, group therapy, and self-help approaches. Combined CBT and drug treatment can optimise outcomes, although evidence to guide clinical practice on the best way to integrate these approaches is scarce.

Introduction

Insomnia is a common complaint that can present independently or comorbidly with another medical disorder (eg, pain) or psychiatric disorder (eg, depression). Insomnia is the most prevalent sleep disorder and affects large proportions of the population on a situational, recurrent, or persistent basis. It carries a heavy burden for both patients and the health-care system as evidenced by its effect on quality of life, and on psychological, occupational, and economic domains.1, 2, 3, 4 Insomnia is often unrecognised and untreated because of barriers to assessment and management.

Section snippets

Clinical presentation and findings

Insomnia is characterised by subjective complaints about dissatisfaction with sleep quality or duration, difficulty falling asleep at bedtime, waking up in the middle of the night or too early in the morning, or non-restorative or poor quality sleep. Insomnia also includes subjective reports of daytime symptoms such as fatigue or low energy, difficulties with cognitive functions (eg, attention, concentration, and memory), and mood disturbances (eg, irritability, dysphoria), all of which can

Prevalence

About 25% of adults are dissatisfied with their sleep, 10–15% report symptoms of insomnia associated with daytime consequences, and 6–10% meet criteria for an insomnia disorder.8, 12, 13, 14 Insomnia is one of the most prevalent complaints in primary care;15, 16, 17 complaints increase with age and are twice as prevalent in women as in men.8, 12

Comorbidity

A high rate of comorbidity exists between chronic insomnia and medical and psychiatric disorders.13, 14, 15, 16, 17, 18 In the 2002 US National Health

Pathophysiological mechanisms

Definitive pathophysiological mechanisms have not been identified, although several neurobiological abnormalities are associated with insomnia. Patients with insomnia show increased activation of the autonomic nervous system, as evidenced by sleep-related elevations in heart rate and heart rate variability, metabolic rate, body temperature, activity of the hypothalamic-pituitary-adrenal axis activity, and norepinephrine secretion.36, 37 In one study, night-time blood pressure was higher in

Assessment and diagnosis

In view of the high prevalence and substantial morbidities of insomnia, patients should routinely be asked about sleep problems by health-care providers.44, 45 Patients who report difficulty sleeping should be questioned about the specific symptoms of insomnia, and their frequency and severity (panel 1). Although no standardised quantitative definitions for insomnia exist, several criteria are suggested: average reported sleep latency of more than 30 min, wakefulness after sleep onset of more

Rationale and indication

Cognitive behavioural therapy (CBT) for insomnia is a brief, sleep-focused, multimodal intervention that includes psychological and behavioural procedures such as sleep restriction, stimulus control, relaxation, cognitive strategies, and education about sleep hygiene (panel 5).51, 52 These therapies can be used singly, although a combined approach is preferred because several dimensions of insomnia can be addressed. The most common approach includes a behavioural (stimulus control, sleep

Pharmacotherapy

Various drugs are used to treat insomnia, including over-the-counter agents (OTCs; antihistamines, melatonin, and herbal preparations), prescription hypnotic drugs for insomnia (BzRAs, chronobiotic agents, and low-dose doxepin hydrochloride), and other prescription agents not specifically indicated for insomnia (antidepressants, antipsychotics, and anticonvulsants) (table).

For agents not approved by the US Food and Drug Administration (FDA), scarce data exist about efficacy for improvement of

Conclusion

Insomnia is a prevalent and costly public health problem. It is associated with substantial long-term effects on psychological, occupational, and physical functioning. Despite advances in diagnosis and management, insomnia is still under-recognised and often goes untreated. Although insomnia often presents with a comorbid medical or psychiatric disorder, it usually warrants separate treatment. Two therapeutic options—CBT and approved hypnotic drugs—have adequate evidence from clinical trials to

Search strategy and selection criteria

We searched PubMed, PsychNet, Embase, CINAHL, and the Cochrane Library from January, 2005, to April, 2010, with the search term “Insomnia”. The search was restricted to human beings and to English and French languages. The main focus was on original contributions, meta-analyses, and systematic reviews reported during this period, but we also cited older publications that were judged to be relevant and to add new information. Because of the large number of citations, we selected those that were

References (136)

M Daley et al.
Insomnia and its relationship to health-care utilization, work absenteeism, productivity and accidents
Sleep Med
(2009)
DJ Buysse et al.
Daytime symptoms in primary insomnia: a prospective analysis using ecological momentary assessment
Sleep Med
(2007)
CM Morin et al.
Epidemiology of insomnia: prevalence, self-help treatments, consultations, and determinants of help-seeking behaviors
Sleep Med
(2006)
JA Shekleton et al.
Searching for the daytime impairments of primary insomnia
Sleep Med Rev
(2010)
MM Ohayon
Epidemiology of insomnia: what we know and what we still need to learn
Sleep Med Rev
(2002)
T Roth et al.
Sleep problems, comorbid mental disorders, and role functioning in the national comorbidity survey replication
Biol Psychiatry
(2006)
MM Ohayon et al.
Epidemiological and clinical relevance of insomnia diagnosis algorithms according to the DSM-IV and the International Classification of Sleep Disorders (ICSD)
Sleep Med
(2009)
MT Smith et al.
How do sleep disturbance and chronic pain inter-relate? Insights from the longitudinal and cognitive-behavioral clinical trials literature
Sleep Med Rev
(2004)
N Breslau et al.
Sleep disturbance and psychiatric disorders: a longitudinal epidemiological study of young adults
Biol Psychiatry
(1996)
M Jansson-Frojmark et al.
A bidirectional relationship between anxiety and depression, and insomnia? A prospective study in the general population
J Psychosom Res
(2008)

ML Perlis et al.

Self-reported sleep disturbance as a prodromal symptom in recurrent depression

J Affect Disord

(1997)

MH Bonnet et al.

Hyperarousal and insomnia: state of the science

Sleep Med Rev

(2010)

D Riemann et al.

The hyperarousal model of insomnia: a review of the concept and its evidence

Sleep Med Rev

(2010)

E Altena et al.

Reduced orbitofrontal and parietal gray matter in chronic insomnia: a voxel-based morphometric study

Biol Psychiatry

(2010)

CM Morin et al.

Are changes in beliefs and attitudes about sleep related to sleep improvements in the treatment of insomnia?

Behav Res Ther

(2002)

MT Smith et al.

Cognitive behavior therapy for chronic insomnia occurring within the context of medical and psychiatric disorders

Clin Psychol Rev

(2005)

DJ Taylor et al.

A pilot study of cognitive-behavioral therapy of insomnia in people with mild depression

Behav Ther

(2007)

MC Ouellet et al.

Efficacy of cognitive-behavioral therapy for insomnia associated with traumatic brain injury: a single-case experimental design

Arch Phys Med Rehabil

(2007)

S Pallesen et al.

Behavioral treatment of insomnia in older adults: An open clinical trial comparing two interventions

Behav Res Ther

(2003)

JP Soeffing et al.

Psychological treatment of insomnia in hypnotic-dependant older adults

Sleep Med

(2008)

A van Straten et al.

Self-help therapy for insomnia: a meta-analysis

Sleep Med Rev

(2009)

D Benke et al.

GABA A receptors as in vivo substrate for the anxiolytic action of valerenic acid, a major constituent of valerian root extracts

Neuropharmacology

(2009)

MI Fernandez-San-Martin et al.

Effectiveness of Valerian on insomnia: a meta-analysis of randomized placebo-controlled trials

Sleep Med

(2010)

M Daley et al.

The economic burden of insomnia: direct and indirect costs for individuals with insomnia syndrome, insomnia symptoms, and good sleepers

Sleep

(2009)

National Institutes of Health state of the science conference statement on manifestations and management of chronic insomnia in adults, June 13–15, 2005

Sleep

(2005)

B Sivertsen et al.

The long-term effect of insomnia on work disability: the HUNT-2 historical cohort study

Am J Epidemiol

(2006)

International classification of sleep disorders: diagnostic and coding manuel

(2005)

JD Edinger et al.

Derivation of research diagnostic criteria for insomnia: report of an American Academy of Sleep Medicine Work Group

Sleep

(2004)

ML Perlis et al.

Beta/Gamma EEG activity in patients with primary and secondary insomnia and good sleeper controls

Sleep

(2001)

E Fortier-Brochu et al.

Insomnia and daytime cognitive performance: a meta-analysis

Sleep Med Rev

(2011)

F Hohagen et al.

Prevalence and treatment of insomnia in general practice. A longitudinal study

Eur Arch Psychiatry Clin Neurosci

(1993)

GE Simon et al.

Prevalence, burden, and treatment of insomnia in primary care

Am J Psychiatry

(1997)

JE Aikens et al.

Help-seeking for insomnia among adult patients in primary care

J Am Board Fam Pract

(2005)

NJ Pearson et al.

Insomnia, trouble sleeping, and complementary and alternative medicine: analysis of the 2002 national health interview survey data

Arch Intern Med

(2006)

PP Chang et al.

Insomnia in young men and subsequent depression. The Johns Hopkins Precursors Study

Am J Epidemiol

(1997)

AA Nierenberg et al.

Residual symptoms after remission of major depressive disorder with citalopram and risk of relapse: a STAR*D report

Psychol Med

(2010)

AA Nierenberg et al.

Residual symptoms in depressed patients who respond acutely to fluoxetine

J Clin Psychiatry

(1999)

CH Bastien et al.

Precipitating factors of insomnia

Behav Sleep Med

(2004)

A Vallieres et al.

Variability and predictability in sleep patterns of chronic insomniacs

J Sleep Res

(2005)

DJ Buysse et al.

Prevalence, course, and comorbidity of insomnia and depression in young adults

Sleep

(2008)

H Morphy et al.

Epidemiology of insomnia: a longitudinal study in a UK population

Sleep

(2007)

CM Morin et al.

The natural history of insomnia: a population-based 3-year longitudinal study

Arch Intern Med

(2009)

M Suka et al.

Persistent insomnia is a predictor of hypertension in Japanese male workers

J Occup Health

(2003)

MA Dew et al.

Healthy older adults' sleep predicts all-cause mortality at 4 to 19 years of follow-up

Psychosom Med

(2003)

AN Vgontzas et al.

Insomnia with short sleep duration and mortality: the Penn State cohort

Sleep

(2010)

AJ Spielman et al.

The varied nature of insomnia

M Deuschle et al.

Association between a serotonin transporter length polymorphism and primary insomnia

Sleep

(2010)

PA Lanfranchi et al.

Nighttime blood pressure in normotensive subjects with chronic insomnia: implications for cardiovascular risk

Sleep

(2009)

RM Benca et al.

Sleep and psychiatric disorders. A meta-analysis

Arch Gen Psychiatry

(1992)

EA Nofzinger et al.

Functional neuroimaging evidence for hyperarousal in insomnia

Am J Psychiatry

(2004)

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SeminarChronic insomnia

Summary

Introduction

Section snippets

Clinical presentation and findings

Prevalence

Comorbidity

Pathophysiological mechanisms

Assessment and diagnosis

Rationale and indication

Pharmacotherapy

Conclusion

Search strategy and selection criteria

Sleep Med

Sleep Med

Sleep Med

Sleep Med Rev

Sleep Med Rev

Biol Psychiatry

Sleep Med

Sleep Med Rev

Biol Psychiatry

J Psychosom Res

J Affect Disord

Sleep Med Rev

Sleep Med Rev

Biol Psychiatry

Behav Res Ther

Clin Psychol Rev

Behav Ther

Arch Phys Med Rehabil

Behav Res Ther

Sleep Med

Sleep Med Rev

Neuropharmacology

Sleep Med

The economic burden of insomnia: direct and indirect costs for individuals with insomnia syndrome, insomnia symptoms, and good sleepers

Sleep

National Institutes of Health state of the science conference statement on manifestations and management of chronic insomnia in adults, June 13–15, 2005

Sleep

The long-term effect of insomnia on work disability: the HUNT-2 historical cohort study

Am J Epidemiol

International classification of sleep disorders: diagnostic and coding manuel

Derivation of research diagnostic criteria for insomnia: report of an American Academy of Sleep Medicine Work Group

Sleep

Beta/Gamma EEG activity in patients with primary and secondary insomnia and good sleeper controls

Sleep

Insomnia and daytime cognitive performance: a meta-analysis

Sleep Med Rev

Prevalence and treatment of insomnia in general practice. A longitudinal study

Eur Arch Psychiatry Clin Neurosci

Prevalence, burden, and treatment of insomnia in primary care

Am J Psychiatry

Help-seeking for insomnia among adult patients in primary care

J Am Board Fam Pract

Insomnia, trouble sleeping, and complementary and alternative medicine: analysis of the 2002 national health interview survey data

Arch Intern Med

Insomnia in young men and subsequent depression. The Johns Hopkins Precursors Study

Am J Epidemiol

Residual symptoms after remission of major depressive disorder with citalopram and risk of relapse: a STAR*D report

Psychol Med

Residual symptoms in depressed patients who respond acutely to fluoxetine

J Clin Psychiatry

Precipitating factors of insomnia

Behav Sleep Med

Variability and predictability in sleep patterns of chronic insomniacs

J Sleep Res

Prevalence, course, and comorbidity of insomnia and depression in young adults

Sleep

Epidemiology of insomnia: a longitudinal study in a UK population

Sleep

The natural history of insomnia: a population-based 3-year longitudinal study

Arch Intern Med

Persistent insomnia is a predictor of hypertension in Japanese male workers

J Occup Health

Healthy older adults' sleep predicts all-cause mortality at 4 to 19 years of follow-up

Psychosom Med

Insomnia with short sleep duration and mortality: the Penn State cohort

Sleep

The varied nature of insomnia

Seminar
Chronic insomnia