Insomnia
Insomnia - Summary
Insomnia is difficulty in getting to sleep, difficulty staying asleep, early wakening, or non-restorative sleep despite adequate time and opportunity to sleep, resulting in impaired daytime functioning, such as poor concentration, mood disturbance, and daytime tiredness.
There is no standard definition of what constitutes normal sleep.
It usually takes less than 30 minutes for a person to fall asleep.
Average total nocturnal sleep time decreases with age from about 8 hours at 15 years of age to less than 6 hours at 80 years of age.
Insomnia can be categorized according to duration or likely duration:
Short-term insomnia lasts less than 4 weeks.
Long-term (or persistent) insomnia lasts for 4 weeks or longer.
Sleep disorders that need to be excluded when making a diagnosis of insomnia are:
Sleep-related breathing disorders, such as sleep apnoea.
Circadian rhythm disorders, such as advanced and delayed sleep phase disorder, shift work, and jet lag.
Sleep-related movement disorders, such as restless legs syndrome and periodic limb movement disorder.
Insomnia may be associated with psychosocial stressors, psychiatric comorbidities, medical comorbidities, drug and substance misuse, or current medication (secondary insomnia). However, in up to 20% of people with persistent insomnia, there is no associated cause or comorbidity (primary insomnia).
A sleep diary can help identify how much someone is actually sleeping each night, and any factors that may exacerbate insomnia. The diary should be kept for at least 2 weeks.
Polysomnography (sleep study) is not indicated for the standard assessment of insomnia.
Good sleep hygiene should be established in all people with insomnia. This aims to make people more aware of behavioural, environmental, and temporal factors that may be detrimental or beneficial to sleep.
For short-term insomnia, a short course (less than 2 weeks) of a hypnotic drug may be considered if daytime impairment is severe. Other sedative drugs, melatonin, complementary and alternative therapies (such as acupuncture, acupressure), and herbal remedies (such as valerian) are not recommended.
For long-term insomnia, cognitive and behavioural interventions are recommended first line.
A short course of a hypnotic drug may be considered for immediate relief or to manage an acute exacerbation of persistent insomnia.
For older people (more than 55 years of age) with persistent insomnia, modified-release melatonin is an option.
Long-term hypnotics and other sedative drugs, complementary and alternative therapies, and herbal remedies are not recommended.
Referral to a sleep clinic or a specialist with expertise in sleep medicine may be required if a primary sleep disorder is suspected, there is doubt regarding the diagnosis, or long-term insomnia has not responded to management in primary care.
Have I got the right topic?
This CKS topic covers the management of insomnia in primary care.
This CKS topic does not cover the management of underlying causes of insomnia or the management of sleep-related breathing disorders (such as sleep apnoea), circadian rhythm disorders (such as advanced and delayed sleep phase disorders, shift work, and jet lag), or sleep-related movement disorders (such as restless legs syndrome and periodic limb movement disorder). This CKS topic does not cover sleep disorders in long-term care settings.
There are separate CKS topics on Benzodiazepine and z-drug withdrawal, Depression, Sleep apnoea, and Sleep disorders - shift work and jet lag.
The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary health care.
How up-to-date is this topic?
How up-to-date is this topic?
Changes
February 2013 — minor update. The 2013 QIPP options for local implementation have been added to this topic [NICE, 2013].
October 2012 — minor update. The 2012 QIPP options for local implementation have been added to this topic [NPC, 2012].
May 2011 — minor update. The 2010/2011 QIPP options for local implementation have been added to this topic [NPC, 2011]. Issued in June 2011.
November to December 2010 — minor update. Modified-release melatonin is now licensed for up to 26 weeks of treatment in elderly people with primary insomnia. Issued in February 2010.
April to July 2009 — converted from CKS guidance to CKS topic structure. The evidence-base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence.
Modified-release melatonin is now licensed for the management of primary insomnia in older adults, the evidence for its efficacy has been reviewed in detail, and recommendations for its use have been added.
Recommendations on the management of sleep disturbances associated with shift work and jet lag have been removed from this topic and have been included in a separate CKS topic on Sleep disorders - shift work and jet lag.
Previous changes
September 2008 — minor correction to the Changes section. Issued in September 2008.
January to March 2006 — reviewed. Validated in June 2006 and issued in July 2006.
October 2005 — minor technical update. Issued in November 2005.
July 2005 — minor correction to references. Issued July 2005
March 2003 — reviewed. Validated in June 2003 and issued in July 2003.
February 1999 — written, replacing CKS guidance on Sleep disturbances, Transient insomnia, and Persistent insomnia. Validated in April 1999 and issued in August 1999.
Update
New evidence
Evidence-based guidelines
Guidelines published since the last revision of this topic:
Bloom, H.G., Ahmed, I., Alessi, C.A., et al. (2009) Evidence-based recommendations for the assessment and management of sleep disorders in older persons. Journal of the American Geriatrics Society 57(5), 761-789. [Abstract] [Free Full-text]
Wilson, S.J, Nutt, D.J., Alford, C., et al. (2010) British Association for Psychopharmacology consensus statement on evidence-based treatment of insomnia, parasomnias and circadian rhythm disorders. Journal of Psychopharmacology 24(11), 1577-1601. [Abstract]
HTAs (Health Technology Assessments)
No new HTAs since 1 March 2009.
Economic appraisals
No new economic appraisals relevant to England since 1 March 2009.
Systematic reviews and meta-analyses
Systematic review published since the last revision of this topic:
Cao, H., Pan, X., Li, H., and Liu, J. (2009) Acupuncture for treatment of insomnia: a systematic review of randomized controlled trials. Journal of Alternative & Complementary Medicine 15(11), 1171-1186. [Abstract] [Free Full-text]
Cheng, S.K., and Dizon, J. (2012) Computerised cognitive behavioural therapy for insomnia: a systematic review and meta-analysis. Psychotherapy and Psychosomatics 81(4), 206-216. [Abstract]
Cooper, K.L. and Relton, C. (2010) Homeopathy for insomnia: a systematic review of research evidence. Sleep Medicine Reviews 14(5), 329-337. [Abstract]
Ernst, E., Lee, M.S. and Choi, T.Y. (2011) Acupuncture for insomnia? An overview of systematic reviews. European Journal of General Practice 17(2), 116-132. [Abstract]
Fernandez-San-Martin, M.I., Masa-Font, R., Palacios-Soler, L., et al. (2010) Effectiveness of Valerian on insomnia: a meta-analysis of randomized placebo-controlled trials. Sleep Medicine 11(6), 505-511. [Abstract]
Huedo-Medina, T.B., Kirsch, I., Middlemass, J., et al. (2012) Effectiveness of non-benzodiazepine hypnotics in treatment of adult insomnia: meta-analysis of data submitted to the Food and Drug Administration. BMJ 345, e8343. [Abstract] [Free Full-text]
Ishak, W.W., Bagot, K., Thomas, S., et al. (2012) Quality of life in patients suffering from insomnia. Innovations in Clinical Neuroscience 9(10), 13-26. [Abstract]
Liu, J. and Wang, L.N. (2012) Ramelteon in the treatment of chronic insomnia: systematic review and meta-analysis. International Journal of Clinical Practice 66(9), 867-873. [Abstract]
Mitchell, M.D., Gehrman, P., Perlis, M., and Umscheid, C.A. (2012) Comparative effectiveness of cognitive behavioural therapy for insomnia: a systematic review. BMC Family Practice 13, 40. [Abstract] [Free Full-text]
Passos, G.S., Poyares, D.L., Santana, M.G., et al. (2012) Is exercise an alternative treatment for chronic insomnia? Clinics 67(6), 653-660. [Abstract] [Free Full-text]
Yeung, W.F., Chung, K.F., Poon, M.M., et al. (2012) Acupressure, reflexology, and auricular acupressure for insomnia: a systematic review of randomized controlled trials. Sleep Medicine 13(8), 971-984. [Abstract]
Primary evidence
Randomized controlled trials published since the last revision of this topic:
Morin, C.M., Vallieres, A., Guay, B., et al. (2009) Cognitive behavioral therapy, singly and combined with medication, for persistent insomnia: a randomized controlled trial. Journal of the American Medical Association 301(9), 2005-2015. [Abstract] [Free Full-text]
Ritterband, L.M., Thorndike, F.P., Gonder-Frederick, L.A., et al. (2009) Efficacy of an internet-based behavioral interventions for adults with insomnia. Archives of General Psychiatry 66(7), 692-698. [Abstract] [Free Full-text]
Observational studies published since the last revision of this topic:
Billioti de Gage, S., Begaud, B., Bazin, F., et al. (2012) Benzodiazepine use and risk of dementia: prospective population based study. BMJ 345, e6231. [Abstract] [Free Full-text]
Buysse, D.J., Germain, A., Moul, D.E., et al. (2011) Efficacy of brief behavioural treatment for chronic insomnia in older adults. Archives of Internal Medicine 171(10), 887-895. [Abstract] [Free Full-text]
New policies
No new national policies or guidelines since 1 March 2009.
New safety alerts
The Medicines and Healthcare products Regulatory Agency (MHRA) has recently reminded prescribers that chloral hydrate and Triclofos® are not first-line options for insomnia.
Welldorm® and Triclofos® are indicated only for the short-term treatment of severe insomnia which is interfering with normal daily life and where other therapies have failed, as an adjunct to non-pharmacological therapies.
The use of hypnotics in children and adolescents is not generally recommended, and if used, should be under the supervision of a specialist. Welldorm® elixir can be used in children aged 2 years or older as an adjunct to behavioural therapy and sleep-hygiene management, usually for less than 2 weeks.
Reference: MHRA (2009) Chloral hydrate (Welldorm) and Triclofos: not first-line options for insomnia. Drug Safety Update 2(11), 3. [Free Full-text]
Changes in product availability
Modified-release melatonin (Circadin®) is now licensed for up to 26 weeks of treatment in elderly people with primary insomnia (November 2010).
Goals and outcome measures
Goals
To accurately diagnose insomnia and rule out other sleeping disorders
To identify and address any underlying causes of insomnia or associated comorbidities
To address behavioural issues that might be causing or exacerbating insomnia
To refer for cognitive and behavioural treatment as appropriate
To reduce the use of hypnotic drugs
QIPP — Options for local implementation
QIPP — Options for local implementation
Hypnotics
Review and, where appropriate, revise prescribing of hypnotics to ensure that it is in line with national guidance.
Background information
Definition
What is it?
Insomnia is difficulty in getting to sleep, difficulty staying asleep, early wakening, or non-restorative sleep despite adequate time and opportunity to sleep, resulting in impaired daytime functioning, such as poor concentration, mood disturbance, and daytime tiredness.
Insomnia can be classified according to cause:
Primary insomnia is insomnia that occurs when no comorbidity is identified. Commonly, the person has conditioned or learned sleep difficulties, with or without heightened arousal in bed.
Typically, primary insomnia has a duration of at least 1 month.
Primary insomnia accounts for about 15–20% of long-term insomnia.
Comorbid (or secondary) insomnia is when insomnia occurs as a symptom of, or is associated with, other conditions, including medical or psychiatric illness, or drug or substance misuse.
Insomnia can be categorized according to duration or likely duration. Definitions of duration of insomnia vary widely in the literature; for the purpose of this topic, insomnia is categorized as:
Short-term if insomnia lasts between 1 and 4 weeks.
Long-term (or persistent) if insomnia lasts for 4 weeks or longer.
[Dündar et al, 2004; Sateia and Nowell, 2004; American Academy of Sleep Medicine, 2005; Budur et al, 2007; Ramakrishnan and Scheid, 2007; Schutte-Rodin et al, 2008]
Other sleep disorders
What other sleep disorders need to be excluded?
Other sleep disorders that need to be excluded include:
Sleep-related breathing disorders, such as sleep apnoea.
Circadian rhythm disorders, such as advanced and delayed sleep phase disorder, shift work, and jet lag.
Sleep-related movement disorders, such as restless legs syndrome and periodic limb movement disorder.
[Sateia and Nowell, 2004; American Academy of Sleep Medicine, 2005; Budur et al, 2007; Ramakrishnan and Scheid, 2007; Schutte-Rodin et al, 2008]
Prognosis
What is the prognosis?
Insomnia frequently persists over many years.
There is a lack of evidence regarding the natural history of insomnia, but in one study symptoms persisted in 50–85% of people over several years of follow up [Schutte-Rodin et al, 2008].
Assessment
Assessment of insomnia
Causes
What are the causes of and comorbidities associated with insomnia?
Primary insomnia
Idiopathic insomnia starts in childhood and has a persistent, unremitting course.
Psychosocial insomnia is due to a conditioned response in which the person associates the sleeping environment with heightened arousal. It often starts in response to a stressful event but continues despite resolution of the event.
Paradoxical insomnia is when the person describes severe insomnia but there is no objective evidence of sleep disturbance.
Psychosocial stressors (usually short term)
Situational stress (for example occupational, interpersonal, financial, academic, medical).
Environmental stress (for example noise).
Death or illness of a loved one.
Psychiatric comorbidities including:
Mood disorders: depression, bipolar disorder, dysthymia.
Anxiety disorders: generalized anxiety disorder, panic disorder, post-traumatic stress disorder.
Psychotic disorders: paranoia, schizophrenia, delusional disorder.
Medical comorbidities including:
Cardiovascular: angina, congestive heart failure.
Respiratory: chronic obstructive pulmonary disease, asthma.
Neurological: Alzheimer's disease, Parkinson's disease.
Endocrine: thyroid dysfunction.
Rheumatological: fibromyalgia, chronic fatigue syndrome, osteoarthritis, rheumatoid arthritis.
Gastrointestinal: gastroesophageal reflux disease, irritable bowel syndrome.
Genito-urinary: incontinence, benign prostatic hypertrophy, nocturia.
Sleep disorders: restless legs syndrome, sleep apnoea, periodic limb movement disorder, circadian rhythm disorders.
Chronic pain.
Drug and substance misuse
Alcohol.
Recreational drugs.
Caffeine.
Nicotine.
Current medication (prescribed or purchased over-the-counter)
Antidepressants: selective serotonin reuptake inhibitors, venlafaxine, bupropion, duloxetine, monoamine oxidase inhibitors.
Antiepileptics: lamotrigine, phenytoin.
Antihypertensives: beta-blockers, calcium-channel blockers.
Hormones: corticosteroids, thyroid hormones.
Nonsteroidal anti-inflammatory drugs.
Stimulants: methylphenidate, modafinil.
Sympathomimetics: salbutamol, salmeterol, theophylline, pseudoephedrine.
Basis for recommendation
Basis for recommendation
These recommendations are based on expert opinion in review articles [Sateia and Nowell, 2004; Silber, 2005; Budur et al, 2007; Ramakrishnan and Scheid, 2007].
Assessment
How should I assess someone with insomnia?
Explore the person's beliefs about sleep, and what they regard as normal sleep (see Normal sleep patterns).
Ask about impairment of daytime functioning — a person who does not experience any impairment of daytime functioning may simply have a reduced need for sleep or an unrealistic expectation of sleep, or incorrect perception of how long they are sleeping for.
Ask about the impact that insomnia has on the person's quality of life, ability to drive, employment, relationships, and mood.
Advise the person not to drive if they feel sleepy (although it is not necessary to inform the Driver and Vehicle Licensing Agency [DVLA] unless a primary sleep disorder is confirmed). See www.dvla.gov.uk.
Determine whether there is an underlying cause of insomnia or an associated comorbid condition.
Ask about recent stressors such as grief, situational stress, illness, mental health problems, and occupational factors (for example shift work).
If initial evaluation identifies an acute stressor, such as grief or noise, further evaluation is not usually necessary.
Excessive daytime sleepiness (rather than fatigue or tiredness) may indicate a primary sleep disorder such as obstructive sleep apnoea syndrome (see the CKS topic on Sleep apnoea).
Take a detailed history and, if indicated, carry out an examination and investigations to identify any coexisting physical conditions that may cause insomnia.
Rule out circadian rhythm sleep disorders, including advanced sleep phase syndrome (ASPS) and delayed sleep phase syndrome (DSPS).
ASPS is common in elderly people — total sleep time is normal, but the person falls asleep mid evening and sleeps in their chair until bedtime. They are then wakeful in the early morning (typically around 4 a.m.).
DSPS is common in adolescents — total sleep time is normal (without intervention), but sleep onset may be delayed until 4–8 a.m. with a corresponding delay in the rising time.
Assess symptoms that could indicate a comorbid disorder.
Take a drug history, including prescription drugs, recreational drugs, caffeine, nicotine, and alcohol.
Take a sleep history from the person and, if possible, their partner or caregiver. This should include sleep and wakefulness patterns (including daytime napping) and frequency of symptoms.
Determine the duration of symptoms and the likelihood of continuing symptoms.
Consider asking the person to keep a sleep diary.
A sleep diary should be kept for a minimum of 2 weeks and should contain information about:
Time of going to bed.
Time taken to get to sleep.
The number of episodes of waking through the night.
Total time awake during the night as a result of night-time awakenings.
The time of getting up.
Episodes of daytime tiredness and naps.
Times of meals, alcohol consumption, caffeine consumption, and significant events during the day, such as exercise or stress.
Rating of sleep quality (ask the person to rate the quality of their sleep each night, from 1 to 5, where 1 is very poor and 5 is very good).
An example of a 2-week sleep diary is available from the American Academy of Sleep Medicine, at http://yoursleep.aasmnet.org/pdf/sleepdiary.pdf (pdf).
Polysomnography (sleep study) is not indicated for the standard assessment of insomnia.
Normal sleep patterns
Normal sleep patterns
There is no standard definition of what constitutes normal sleep.
Normal sleep-onset latency (the time it takes to fall asleep) is usually considered to be less than 30 minutes [Ringdahl et al, 2004; Budur et al, 2007].
Patterns of sleep vary with age; the number of awakenings increases and the total sleep time decreases with increasing age, probably because of physiological changes.
A meta-analysis of studies examining normal age-related sleep trends showed a wide variation with age [Ohayon et al, 2004]. The average amount of sleep for each age category is given in Table 1.
Table 1. Age-related trend for total nocturnal sleep time.| Age | Total sleep time |
|---|---|
| 15 years | 8 hours |
| 20 years | 7.5 hours |
| 40 years | 6.8 hours |
| 60 years | 6.3 hours |
| 80 years | 5.8 hours |
Basis for recommendation
Basis for recommendation
These recommendations are based on expert opinion in review articles [Ringdahl et al, 2004; Sateia and Nowell, 2004; Budur et al, 2007; Ramakrishnan and Scheid, 2007] and from CKS expert reviewers.
Up to 80% of insomnia is associated with a comorbidity, therefore early identification and management of any comorbid disorders is essential.
Management
Management
Scenario: Management: covers the management of people with insomnia in primary care.
Scenario: Management
Scenario: Management of insomnia
Short-term insomnia (< 4 weeks)
How should I manage someone with short-term insomnia (< 4 weeks)?
Identify and address any underlying cause of insomnia or associated comorbidities.
Advise good sleep hygiene.
If daytime impairment is severe, consider a short course of a hypnotic drug. If a hypnotic is prescribed:
Use the lowest effective dose for the shortest period possible. The exact duration will depend on the underlying cause, but treatment should not continue for longer than 2 weeks.
Inform the person that further prescriptions for hypnotics will not usually be given, ensure that the reasons for this are understood, and document this in the person's notes.
Do not issue further prescriptions without seeing the person again.
Review after 2 weeks and consider referral for cognitive behavioural therapy if symptoms persist, see Long-term insomnia (> 4 weeks).
Treatments that are not recommended for short-term insomnia include:
Sedative drugs other than hypnotics (such as antidepressants, antihistamines, choral hydrate, clomethiazole, and barbiturates).
Melatonin.
Complementary and alternative therapies (such as acupuncture, acupressure).
Herbal remedies (such as valerian).
Basis for recommendation
Basis for recommendation
Good sleep hygiene
There is insufficient evidence to assess the effectiveness of sleep hygiene as a single intervention; however its use is widely supported in current literature and guidelines [Morin et al, 2006; Budur et al, 2007; Schutte-Rodin et al, 2008].
Hypnotic drugs
There is good evidence for the efficacy of hypnotic drugs in short-term insomnia; however, their use is associated with adverse effects, such as daytime sedation, poor motor coordination, cognitive impairment, and related concerns about driving accidents and injuries from falls.
In older people in particular, the magnitude of the beneficial effect of hypnotics may not justify the increased risk of adverse effects (such as cognitive impairment and increased risk of falls).
Treatments that are not recommended
Sedative drugs other than hypnotics (such as antidepressants, antihistamines, choral hydrate, clomethiazole, and barbiturates) are not recommended for the management of insomnia. Expert opinion from reviews suggests that there is insufficient evidence to support their use, and that the potential for adverse effects is significant [Budur et al, 2007; Ramakrishnan and Scheid, 2007; Schutte-Rodin et al, 2008].
Modified-release melatonin (Circadin®) is only licensed for the management of primary insomnia (usually defined as more than 4 weeks' duration), and has only been studied in people with long-term insomnia [ABPI Medicines Compendium, 2009].
The evidence on the efficacy of acupuncture is generally of poor methodological quality with inconsistent results. There is some evidence from single studies in a Cochrane systematic review to suggest that acupuncture and its variants (acupressure and transcutaneous electrical stimulation) may improve quality of sleep. Results for other sleep variables were inconsistent.
There is insufficient good quality evidence to make a recommendation regarding the efficacy of valerian, or any other herbal remedies, in the management of insomnia.
Long-term insomnia (> 4 weeks)
How should I manage someone with long-term insomnia (> 4 weeks)?
Manage any underlying cause of insomnia or associated comorbidities.
Cognitive and behavioural interventions are recommended first line.
Advise good sleep hygiene and regular exercise in addition to cognitive and behavioural interventions.
Hypnotics are not generally recommended for the management of long-term insomnia. A short course of a hypnotic drug may be considered for immediate relief or to manage an acute exacerbation of persistent insomnia. If a hypnotic is prescribed:
Use the lowest effective dose for the shortest period possible. The exact duration will depend on the underlying cause but should not continue for longer than 2 weeks. Up to 4 weeks' use may occasionally be required, but continued use should always be re-assessed after 2 weeks.
Inform the person that further prescriptions for hypnotics will not usually be given, ensure that the reasons for this are understood, and document this in the person's notes.
Do not issue further prescriptions without seeing the person again.
Use caution when prescribing hypnotics for older people.
In older people (more than 55 years of age) with persistent insomnia, consider modified-release melatonin.
The recommended initial duration of treatment is 3 weeks. If there is a response to treatment, it can be continued for a further 10 weeks.
If insomnia persists or recurs on stopping melatonin:
Reconsider whether there may be an underlying cause of insomnia or associated comorbidity.
Consider cognitive behavioural therapy (CBT) if this has not already been tried.
Consider a second 13-week course of melatonin only after other causes of insomnia and comorbidities have been investigated and CBT has been tried. Note that melatonin is not licensed for repeated use or use beyond 13 weeks.
Treatments that are not recommended for insomnia include:
Long-term hypnotics.
Sedative drugs other than hypnotics (such as antidepressants, antihistamines, choral hydrate, clomethiazole, and barbiturates).
Complementary and alternative therapies (such as acupuncture, acupressure).
Herbal remedies (such as valerian).
Basis for recommendation
Basis for recommendation
Identify and manage the underlying cause
This recommendation is based on expert opinion in a literature review [Budur et al, 2007].
Sleep hygiene education
There is insufficient evidence to assess the effectiveness of sleep hygiene as a single intervention; however its use is widely supported in current literature and guidelines [Morin et al, 2006; Budur et al, 2007; Schutte-Rodin et al, 2008].
Exercise
Evidence from one small randomized controlled trial suggests that exercise has a beneficial effect on both the quality and quantity of sleep. In addition exercise confers other health benefits.
Cognitive and behavioural treatment
Cognitive and behavioural interventions are widely recommended for the treatment of long-term insomnia [National Institutes of Health, 2005; Morgenthaler et al, 2006; Budur et al, 2007; Ramakrishnan and Scheid, 2007].
There is good evidence that cognitive and behavioural interventions are effective in the treatment of long-term primary and secondary insomnia.
Hypnotic drugs
Hypnotic drugs are not recommended for long-term use; there is a lack of evidence on their use in long-term insomnia, and there are concerns regarding their safety [Holbrook et al, 2000; Sateia and Nowell, 2004; National Institutes of Health, 2005; Ramakrishnan and Scheid, 2007].
Potential adverse effects include daytime sedation, poor coordination, cognitive impairment, and related concerns about the increased risk of driving accidents and falls.
Long-term use of hypnotics can lead to the development of tolerance, physical or behavioural dependence, adverse effects on withdrawal, rebound insomnia, and increased mortality.
Melatonin
There is some evidence to suggest that melatonin may improve some sleep-related parameters in older people with insomnia.
When used at the dose and duration of modified-release melatonin licensed for use in the UK, three randomized controlled trials demonstrated an improvement in quality of sleep and morning alertness, although the clinical significance of the improvement is unclear. In two of the studies, a small improvement in sleep-onset latency (the time taken to get to sleep was also noted with melatonin).
CKS identified no studies comparing modified-release melatonin with hypnotics for the treatment of insomnia.
The recommendation to consider a second 13-week course of melatonin is based on the opinion of expert CKS reviewers. Melatonin has been studied for 26 weeks of use in one randomized controlled trial. Prescribers are reminded that this is an off-label use of melatonin, and they are encouraged to report any adverse effects that may be experienced in a person taking melatonin.
Treatments not recommended
Sedative drugs other than hypnotics (such as antidepressants, antihistamines, choral hydrate, clomethiazole, and barbiturates) are not recommended for the management of insomnia. Expert opinion from reviews suggests that there is insufficient evidence to support their use, and that the potential for adverse effects is significant [Budur et al, 2007; Ramakrishnan and Scheid, 2007; Schutte-Rodin et al, 2008].
There is insufficient good quality evidence to make a recommendation regarding the efficacy of acupuncture in the management of insomnia.
The evidence on the efficacy of acupuncture is generally of poor methodological quality with inconsistent results. There is some evidence from single studies in a Cochrane systematic review to suggest that acupuncture and its variants (acupressure and transcutaneous electrical stimulation) may improve quality of sleep. Results for other sleep variables were inconsistent.
There is insufficient good quality evidence to make a recommendation regarding the efficacy of valerian in the management of insomnia.
The evidence on the efficacy of valerian is generally of poor methodological quality with inconsistent results.
Good sleep hygiene
What advice should I give regarding good sleep hygiene?
Sleep hygiene aims to make people more aware of behavioural, environmental, and temporal factors that may be detrimental or beneficial to sleep.
Advise the person to:
Establish fixed times for going to bed and waking up (and avoid sleeping in after a poor night's sleep).
Try to relax before going to bed.
Maintain a comfortable sleeping environment: not too hot, cold, noisy, or bright.
Avoid napping during the day.
Avoid caffeine, nicotine, and alcohol within 6 hours of going to bed.
Consider complete elimination of caffeine from the diet.
Avoid exercise within 4 hours of bedtime (although exercise earlier in the day is beneficial).
Avoid eating a heavy meal late at night.
Avoid watching or checking the clock throughout the night.
Only use the bedroom for sleep and sexual activity.
Basis for recommendation
Basis for recommendation
The advice regarding good sleep hygiene measures is consistent with expert opinion in literature reviews [Ringdahl et al, 2004; Sateia and Nowell, 2004; Silber, 2005; Budur et al, 2007] and guidelines [Guidelines & Protocols Advisory Committee, 2004; Alberta Medical Association, 2009; Schutte-Rodin et al, 2008], and from CKS expert reviewers.
Cognitive and behavioural interventions
Which cognitive and behavioural interventions are recommended?
The choice of cognitive and behavioural intervention should be guided by clinical judgement, individual preference, and availability.
The following interventions are recommended:
Stimulus control therapy.
Relaxation training.
Sleep restriction therapy.
Paradoxical intention.
Biofeedback.
Cognitive therapy combined with a behavioural intervention (cognitive behavioural therapy).
Delivery of intervention:
This may be undertaken by appropriately trained personnel in primary care.
Referral for cognitive behavioural intervention may be necessary.
Self-help materials may be useful.
Cognitive and behavioural interventions
Cognitive and behavioural interventions
Stimulus-control therapy aims to help the person to re-associate the bed and bedroom with sleep, and to re-establish a consistent sleep/wake pattern.
Sleep restriction therapy involves limiting the amount of time spent in bed to the actual amount of time spent asleep, creating a mild sleep deprivation, and then increasing sleep time as the efficiency of sleep improves.
Relaxation training aims at reducing tension (for example using progressive muscle relaxation) or minimizing intrusive thoughts that may interfere with sleep.
Paradoxical intention involves staying passively awake, avoiding any intention to fall asleep. Its use is limited to people who have trouble getting to sleep (but not maintaining sleep).
Biofeedback provides visual or auditory feedback to help the person control certain physiologic parameters (such as muscle tension).
Cognitive therapy aims to examine and change the person's beliefs and attitudes about insomnia. It is frequently used in combination with a behavioural intervention (such as stimulus control, sleep restriction, or relaxation training); this is cognitive behavioural therapy.
Basis for recommendation
Basis for recommendation
Choice of intervention
There is insufficient evidence to recommend any one therapy over another [Morgenthaler et al, 2006].
There is good evidence that stimulus control therapy, relaxation therapy, and cognitive behavioural therapy (CBT) are effective in the treatment of long-term insomnia [Morgenthaler et al, 2006].
There is moderate evidence that sleep restriction, paradoxical intention, and biofeedback are effective in the treatment of long-term insomnia [Morgenthaler et al, 2006].
There is insufficient evidence to make a recommendation on imagery training (a visualization technique to focus on some pleasant or neutral images to block out unwanted thoughts before sleep) and cognitive therapy (on its own) [Morgenthaler et al, 2006].
Delivery of intervention
In most clinical trials, cognitive and behavioural interventions have been delivered by psychologists; however, there is emerging evidence that they can be successfully delivered by appropriately trained and supervised community health nurses, primary care counsellors, and primary care physicians.
Evidence from a meta-analysis of 10 randomized controlled trials suggests that self-help interventions are more effective than control at improving sleep parameters in people with insomnia.
Choice of hypnotic drugs
Which hypnotics are recommended?
The hypnotics recommended for the treatment of insomnia are:
Short-acting benzodiazepines — temazepam, loprazolam, lormetazepam.
Non-benzodiazepines (the 'z-drugs') — zopiclone, zolpidem, and zaleplon (all are short acting).
Diazepam is not generally recommended, but it can be useful if insomnia is associated with daytime anxiety.
If there has been no response to a particular hypnotic, do not prescribe another.
If the person experiences adverse effects considered to be directly related to an hypnotic, consider switching to another hypnotic.
Basis for recommendation
Basis for recommendation
Hypnotics
The National Institute for Health and Clinical Excellence concluded that there is a lack of compelling evidence to distinguish between these drugs in their efficacy, adverse effects, or risk of dependency [NICE, 2004].
Diazepam, nitrazepam, and flurazepam are not recommended because their long half-life commonly gives rise to next-day residual effects, and repeated doses tend to be cumulative [NICE, 2004].
Referral
When should I refer a person with insomnia?
Refer to a sleep clinic or a specialist with expertise in sleep medicine if a primary sleep disorder is suspected or there is doubt regarding the diagnosis.
Consider referral for people with long-term insomnia that has not responded to management in primary care.
Access to sleep clinics
Access to sleep clinics
Access to a sleep clinic will depend on locality.
Most local sleep clinics specialize in sleep-related respiratory disorders; if primary insomnia is likely then referral to a regional unit may be necessary (often multi-disciplinary with psychiatric input).
Currently there are two private sleep clinics that accept primary care trust-approved referrals for people with insomnia — the London Sleep Centre (www.londonsleepcentre.com) and the Edinburgh Sleep Centre (www.edinburghsleepcentre.com) both provide comprehensive, 8 to 10-session, combined medical and psychological interventions, including full sleep evaluation and cognitive behavioural therapy.
Basis for recommendation
Basis for recommendation
Referral for polysomnography
People with excessive daytime sleepiness should be assessed for potential causes such as sleep apnoea, restless legs syndrome, periodic limb movement disorder, or primary hypersomnolence disorders (such as narcolepsy) [Ringdahl et al, 2004; Sateia and Nowell, 2004].
Referral for long-term insomnia
CKS found no guidelines for the referral of people with persistent primary insomnia.
CKS expert reviewers agreed that referral to a sleep clinic (where available) or a specialist with expertise in sleep disorders was appropriate:
When a primary sleep disorder is suspected, to enable accurate diagnosis.
When insomnia has not responded to management in primary care, for a full review of the diagnosis and consideration of further treatment options.
Evidence
Evidence
Supporting evidence
Non-drug treatment
Evidence on non-drug treatment for insomnia
Cognitive and behavioural therapies
Evidence on cognitive and behavioural therapies for insomnia
Psychological and behavioural treatments for primary and secondary insomnia
A systematic review (search date: 1998–2004) was conducted by a task force commissioned by the American Academy of Sleep Medicine [Morin et al, 2006]; this was an update of a previous systematic review [Morin et al, 1999]. This evidence was used to update the Academy's practice parameters for the psychological and behavioural treatment of insomnia [Morgenthaler et al, 2006]. The original review included 48 trials and two meta-analyses; the updated review included an additional 37 studies (n = 2246). Data from the individual studies were not pooled in the reviews.
Primary insomnia: 17 studies evaluated the effects of treatment on primary insomnia; only five of these were randomized controlled trials (RCTs), four of which used cognitive behavioural therapy (CBT) as the main intervention. The authors concluded that psychological and behavioural interventions are effective in the treatment of chronic primary insomnia.
Secondary insomnia: 12 studies evaluated the effects of treatment on secondary insomnia; only four of these were RCTs. The authors concluded that psychological and behavioural interventions are effective in the treatment of secondary insomnia.
Older adults: nine studies evaluated the effects of treatment in older adults (average age greater than 60 years); all except one were RCTs.
Specific interventions
Stimulus control: 29 studies evaluating the efficacy of stimulus control therapy either as a single intervention (12 studies) or as part of a multi-component intervention (17 studies) were included in the original review.
Sleep parameters improved in all 12 studies with stimulus control therapy as a single intervention, compared with control.
In two meta-analyses, stimulus control reduced the average sleep-onset latency from 64 minutes to 33 minutes, and the total time awake after sleep onset from 84 minutes to 44 minutes.
One additional RCT was included in the updated review, which supported the efficacy of stimulus control therapy.
Sleep restriction: nine studies evaluating the efficacy of sleep restriction were included in the original review; only two of these as a single intervention.
In one case series, the average sleep-onset latency was reduced from 48 minutes to 19 minutes, and the total time awake after sleep onset from 111 minutes to 31 minutes.
In the second study, sleep efficiency was improved by 24% with sleep restriction compared with 4% with progressive relaxation.
Two additional RCTs were included in the updated review, which strengthened the evidence for the efficacy of sleep restriction therapy.
Relaxation training: 17 studies evaluating the efficacy of progressive muscle relaxation training as a single intervention were included in the original review.
In all studies except one, progressive muscle relaxation training was more effective than placebo, wait-list controls, and no-treatment controls.
In two meta-analyses, progressive muscle relaxation training reduced sleep-onset latency and time awake after sleep by an average of 20–30 minutes.
Four additional RCTs were included in the updated review, which strengthened the evidence for the efficacy of sleep restriction therapy.
Paradoxical intention: six studies evaluating the efficacy of paradoxical intention were included in the original review.
In four studies, paradoxical intention was more effective than control in reducing sleep-onset latency; however in two studies there was no evidence of a significant difference between paradoxical intention and placebo or a waiting-list control. Treatment gains with paradoxical intention were smaller than those seen with stimulus control therapy or relaxation training.
One additional RCT was included in the updated review, which supported the efficacy of paradoxical intention.
Biofeedback: nine studies evaluating the efficacy of biofeedback were included in the original review.
All nine studies showed that biofeedback is an effective intervention for insomnia; improvement rates for people receiving biofeedback were comparable with those obtained with standard relaxation techniques.
Most of these studies are more than 20 years old, suggesting that it is a less viable option for the management of insomnia.
Cognitive behavioural therapy (CBT):
Sleep hygiene education: three studies evaluating the efficacy of sleep hygiene education as a single intervention were included in the original review.
Results from these studies indicated that sleep hygiene alone may have limited benefits for people with persistent insomnia.
No additional studies evaluating sleep hygiene education as a single intervention were included in the updated review.
Cognitive therapy: the original review did not identify any controlled studies evaluating the effects of cognitive therapy as a single intervention.
No additional studies evaluating cognitive therapy as a single intervention were included in the updated review.
Imagery training: three studies evaluating the efficacy of imagery training were included in the initial review.
Two studies indicated that it was no more effective than a waiting list control; however, the third study suggested that it was significantly better than progressive muscle relaxation training.
No additional studies evaluating imagery training were included in the updated review.
Meditation: three studies evaluating the efficacy of meditation were included in the initial review.
All three studies reported significant improvements in sleep-onset latency or the total time awake after sleep onset.
Multi-component compared with single interventions: five RCTs have compared the effects of multi-component interventions (without cognitive therapy) with single interventions. The authors concluded that there was moderately good evidence that multi-component interventions are effective in the management of long-term insomnia.
Primary insomnia
A systematic review evaluated the efficacy of CBT for primary insomnia in people between 18 and 65 years of age [Wang et al, 2005]. The review included seven RCTs (n = 396); data from the individual studies were not pooled.
Improvement in sleep efficacy, sleep-onset latency, and waking after sleep onset were the most frequently reported beneficial outcomes.
Two studies reported reduced use of sleep aids: one reported a reduction in the use of sleep aids from 35% of the time to 26% of the time; in the second study, 76% of people who initially used hypnotic medication had stopped completely following treatment.
Follow-up data suggested that the effect of CBT was sustained over time.
Insomnia in older adults
A Cochrane systematic review investigated the effects of cognitive behavioural interventions for sleep problems in adults 60 years of age and older [Montgomery and Dennis, 2003]. The review included six RCTs (n = 282) of cognitive and/or behavioural treatments for primary insomnia where more than 80% of participants were older than 60 years of age and did not have dementia or depression. The interventions assessed were: sleep hygiene, stimulus control, muscle relaxation, sleep restriction, and cognitive therapies. Controls were either waiting-list control groups or placebo groups.
Pooled data from four RCTs (n = 143) found evidence that people in the treatment group had 14.6 minutes more sleep per night than the control group (95% CI –36.13 to –7.01). At 3 months post-treatment, people in the treatment group were sleeping 14.8 minutes less than the control group (95% CI –38.96 to –68.5). However at 1 year post-treatment, people in the treatment group had 32 minutes more sleep each night compared with the control group (95% CI –71.11 to –8.13).
The authors concluded that as there was considerable overlap between many cognitive and behavioural interventions, for example regarding aspects of sleep hygiene which may restrict sleep, they could not determine which parts of these therapies were effective.
Delivery of cognitive and behavioural interventions
Evidence on the delivery of cognitive and behavioural interventions for insomnia in primary care
Cognitive behavioural therapy (CBT) delivered in primary care
In one randomized controlled trial (RCT), 139 people with long-term insomnia were randomized to receive cognitive behavioural therapies (such as education, sleep hygiene, stimulus control, sleep restriction, relaxation, and cognitive therapy) delivered by trained health visitors (primary care nurses) or self-monitoring control [Espie et al, 2001]. The CBT was delivered in a general practice setting in six group meetings (4–6 participants per group) at weekly intervals.
CBT showed significantly greater improvements than control in sleep-onset latency and total time spent awake after sleep onset, with more modest increases in total sleep time. The effects were sustained at the 12-month follow up.
In a second RCT, 209 people with chronic sleep problems were randomized to receive CBT delivered by primary care counsellors (eligible for accreditation by the British Association for Counselling and Psychotherapy) or no additional treatment (control) [Morgan et al, 2004]. The CBT was delivered in a general practice setting and consisted of six 50-minute sessions.
At 3- and 6-month follow up, people in the CBT group showed significantly greater improvements in their global Pittsburgh Sleep Quality Index scores (p < 0.04), and SF-36 dimensions of vitality at 3 months (p < 0.01), and physical functioning (p < 0.04) and mental health (p < 0.02) at 6 months.
People in the CBT group reported significant reductions in the frequency of hypnotic drug use compared with the control group (p < 0.001), with 29% of people reporting zero drug use at 3 months and 33% at 6 months.
Clinical improvements were maintained within the CBT group at the 12-month follow-up appointment.
In a third RCT, 201 people with long-term insomnia (duration 6 months or more) were randomized to receive either CBT delivered in small groups by primary care nurses, or treatment as usual [Espie et al, 2007].
CBT was associated with improvements in self-reported sleep-onset latency (average reduction 23.3 minutes), total time awake after sleep onset (average reduction 35.8 minutes), and sleep efficiency (average increase 9.1%). Usual treatment was not associated with changes in self-reported sleep parameters.
Improvements were partly sustained at the 6-month follow-up appointment.
Self-help interventions
A meta-analysis of self-help interventions for insomnia (search date: to January 2007) included 10 RCTs (n = 1000) [van Straten and Cuijpers, 2009]. Self-help intervention included all different formats of self-help interventions (for example, books, internet resources, or audio) and support, as long as it was limited in time and directed at helping people master the self-help strategies.
When data from the studies were pooled:
Sleep-onset latency was significantly improved in the self-help group compared with control; effect size (d) 0.29 (95% CI 0.15 to 0.43, p < 0.05).
Sleep efficiency was significantly improved in the self-help group compared with control; d 0.42 (95% CI 0.14 to 0.69, p < 0.05).
Total time awake after sleep onset was significantly improved in the self-help group compared with control; d 0.44 (95% CI 0.12 to 0.76, p < 0.05).
Sleep quality was significantly improved in the self-help group compared with control; d 0.33 (95% CI 0.09 to 0.57, p < 0.05).
Total sleep time was not significantly different between the two groups.
Symptoms of anxiety and depression were significantly reduced in the self-help group compared with the control group.
Exercise
Evidence on exercise for insomnia
One small community-based randomized controlled trial (RCT) in older people with primary insomnia found that 16 weeks of moderate intensity exercise significantly improved quality of sleep, reduced the time taken to fall to sleep, and increased the time spent asleep, compared with a waiting list control.
A Cochrane systematic review (search date: January 2002) assessed the efficacy of exercise in people 60 years of age and older [Montgomery and Dennis, 2002a]. The review included one RCT that compared 16 weeks of regular moderate intensity exercise (30–40 minutes of walking or low impact aerobics four times a week) with no treatment in 43 older people with primary insomnia. The mean age of participants was 62 years of age. The main outcome measure was sleep quality, measured by the change from baseline in Pittsburgh Sleep Quality Index (PSQI).
PSQI score:
After 16 weeks, people in the exercise group showed significantly greater improvements in the PSQI score compared with those receiving no treatment.
The mean scores after treatment were 5.4 with exercise therapy and 8.8 with no treatment. The mean post-test difference between groups was 3.4 (95% CI 1.9 to 5.4, p < 0.001).
Sleep-onset latency:
After 16 weeks, people in the exercise group showed a significant reduction in the time taken to get to sleep compared with those receiving no treatment.
The mean time to get to sleep after treatment was 15 minutes with exercise therapy and 24 minutes with no treatment. The mean post-test difference between groups was 9.2 minutes (p = 0.007).
Average sleep duration:
After 16 weeks, people in the exercise group showed a significant increase in sleep duration compared with those receiving no treatment.
The mean duration of sleep after treatment was 6.8 hours with exercise therapy and 6.0 hours with no treatment. The mean post-test difference between groups was 0.8 hours (p = 0.047).
Light therapy
Evidence on light therapy for insomnia
A Cochrane systematic review (search date: 2001) found no randomized controlled trials comparing the effects of timed bright light treatment with other treatments or no treatment in the management of insomnia [Montgomery and Dennis, 2002b].
Hypnotics
Evidence on hypnotics for insomnia
Benzodiazepines
A meta-analysis (search date: December 1998) compared the efficacy and safety of benzodiazepines with placebo for the management of insomnia [Holbrook et al, 2000]. The meta-analysis included 45 randomized controlled trials (RCTs) (n = 2672 people with primary insomnia); treatment duration was for a mean of 7.7 days.
Sleep-onset latency:
Data were pooled from four RCTs (n = 159) that compared a benzodiazepine with placebo for sleep-onset latency. The time to fall asleep for people receiving a benzodiazepine was 4.2 minutes shorter than for those receiving placebo (95% CI –0.7 to +9.2).
Total sleep duration:
Pooled data from two RCTs (n = 35) that compared a benzodiazepine with placebo found that people in the benzodiazepine group slept for an average of 61.8 minutes longer than those in the placebo group (95% CI 37.4 to 86.2).
Daytime drowsiness:
Pooled data from eight RCTs (n = 889) found that benzodiazepines were more likely than placebo to be associated with complaints of daytime drowsiness (odds ratio 2.4, 95% CI 1.8 to 3.4).
Z-drugs
A Health Technology Assessment reviewed the effectiveness of zaleplon, zolpidem, and zopiclone for the short-term management of insomnia [Dündar et al, 2004]. This systematic review included data from 24 RCTs that compared the z-drugs with either a benzodiazepine or with another z-drug in people with insomnia. In total, 11 different comparisons were made between benzodiazepines (temazepam, lormetazepam, or nitrazepam) and zolpidem (four RCTs) or zopiclone (13 RCTs). No RCTs were identified that compared zaleplon with a benzodiazepine. Six RCTs were reviewed that compared zaleplon with zolpidem and one that compared zolpidem with zopiclone.
Studies:
The duration of the studies ranged from one night to 6 weeks. Ten studies included a follow-up period (3–11 days). The number of participants included in the trials was 10–615. The most common comparator used in the RCTs was nitrazepam, which has a prolonged duration of action and may give rise to residual effects on the following day. None of the trials compared the z-drugs with temazepam 10 mg or loprazolam 1 mg. One of the 10 studies used objective polysomnography (PSG) recordings; the remaining nine collected data from post-sleep questionnaires and sleep diaries.
Five RCTs restricted their inclusion criteria to people 60 years of age or older. Although it is recommended that the doses of both the z-drugs and the benzodiazepine hypnotics should be reduced in older people, only three of the five RCTs used recommended doses for this age group. People older than 60 years of age were amongst the population enrolled in a further 12 of the included RCTs. In these studies, standard dose hypnotics (benzodiazepines and z-drugs) were used with no reported dose reductions for those people older than 60 years of age.
Results:
Although in the individual RCTs there were some statistically significant differences between the z-drugs and the benzodiazepines for some of the efficacy outcome measures, the differences were not consistent across the trials. In addition, in most cases the absolute difference was small and the clinical significance of the differences was difficult to ascertain.
Six RCTs compared zaleplon with zolpidem. One RCT found that zaleplon 10 mg per night resulted in statistically significant shorter sleep-onset latency than zolpidem 5 mg (median time 31 minutes versus 42 minutes).
Pooled data from three RCTs indicated the sleep was of lower quality (odds ratio [OR] 0.66, 95% CI 0.51 to 0.87) and the median sleep time was statistically significantly less with zaleplon 5 mg per night compared with zopiclone 5 mg (291 minutes versus 309 minutes). Compared with zopiclone 7.5 mg, zolpidem 10 mg per night was associated with shorter sleep-onset latency (OR 1.72, 95% CI 1.04 to 2.84) in a 2-week trial. In a crossover study, there were no statistically significant differences between zaleplon 10 mg and zolpidem in the patient's global impression of treatment (38% versus 62%).
Adverse effects:
There was little consistency in the reporting of adverse events, which prevented comparison of individual event rates or meta-analysis. There were no statistically significant differences in the rates of treatment-emergent adverse events associated with any of the comparisons of z-drugs compared with benzodiazepines. There were no consistent differences between the z-drugs and the benzodiazepines in the incidence of next-day residual effects.
Withdrawal or dependency:
In the RCT comparisons between the z-drugs and benzodiazepines in people with insomnia, no data were identified on the frequencies of symptoms associated with withdrawal or dependency. In their submissions, the manufacturers also referenced a number of other studies that examined the rates of tolerance and dependency associated with the z-drugs. The studies were not considered to be methodologically robust and there were no direct comparisons between the z-drugs and the benzodiazepines used in the NHS.
Effects in older people
One meta-analysis (search date: 2003) examined the risks and benefits of hypnotics in older people with insomnia [Glass et al, 2005]. The review included 24 RCTs in 2417 people 60 years of age or older with primary insomnia.
Sleep quality (eight RCTs, n = 719):
Reported sleep quality was significantly better with hypnotic use than with placebo (mean effect size 0.14, 95% CI 0.05 to 0.23; p < 0.005).
Thirteen people would need to be treated with a sedative for one to have a improvement in sleep quality (NNT 13, 95% CI 6.7 to 62.9; n = 1072).
Total sleep time (eight RCTs, n = 601):
There was a significant increase in total sleep time with any sedative, compared with placebo (mean increase 25.2 minutes, 95% CI 12.8 to 37.8; p = 0.001).
Night time awakenings (six RCTs, n = 441):
There was a significant reduction in the mean number of awakenings in people taking a hypnotic, compared with placebo (mean reduction 0.63, 95% CI 0.48 to 0.77; p < 0.0001).
Adverse effects:
Six people would need to be treated with a hypnotic for one to experience any adverse effect (NNT 6, 95% CI 4.7 to 7.1).
Cognitive effects were significantly more common with hypnotic use than with placebo (odds ratio [OR] 4.78, 95% CI 1.47 to 15.47; p < 0.01, n = 712).
Psychomotor-type adverse effects, such as dizziness or loss of balance, were more common with hypnotic use than with placebo, but this did not reach significance (OR 2.25, 95% CI 0.93 to 5.41; p = 0.07, n = 1016).
Melatonin for primary insomnia
Evidence on melatonin for primary insomnia
At the dose of modified-release melatonin licensed for use in the UK, three randomized controlled trials (RCTs) reported an improvement in the quality of sleep and morning alertness, although the clinical significance of the improvement is unclear. In two of the studies, a small improvement in sleep-onset latency (time taken to get to sleep) was also noted with melatonin. CKS identified no studies comparing modified-release melatonin with hypnotics for the treatment of insomnia.
Melatonin compared with placebo
CKS identified three RCTs investigating the efficacy of modified-release melatonin (compared with placebo) at the dose and indication licensed in the UK.
All RCTs had a similar design: following a 2-week placebo run-in to wash-out any previous treatments, people with primary insomnia (that is, insomnia lasting for at least 1 month, with no identified underlying cause) were randomized to receive modified-release melatonin 2 mg (Circadin®) or placebo, followed by a 2-week, single-blind, placebo run-out period. Study medication was to be taken once a day, after the evening meal, 1–2 hours before bedtime.
In the first RCT, 170 people 55 years of age or older were randomized to treatment for 3 weeks [Lemoine et al, 2007].
Description of study methods
Sleep and daytime effects were evaluated using the Leeds Sleep Evaluation Questionnaire (LSEQ; a series of 10 visual analogue scales that measures four domains of sleep and morning behaviour: ease of getting to sleep [GTS], quality of sleep [QOS], hangover on awakening from sleep [AFS], and alertness and behavioural integrity the following morning [BFW]), and a sleep diary on the last 3 days of each period (placebo run-in, double-blind treatment, and placebo run-out).
Withdrawal effects were assessed by change in the Tyrer Benzodiazepine Withdrawal Symptom Questionnaire (BWSQ), which measures the presence or absence of withdrawal symptoms experienced in the previous 24 hours.
Results
A total of six people discontinued treatment during the treatment phase of the study; four (4.9%) in the melatonin group (one for lack of efficacy, one for failing screening criteria, one on request, and one for taking forbidden medication), and two (2.3%) in the placebo group (one for an adverse event [somnolence] and one for poor compliance).
Quality of sleep (LSEQ): people treated with melatonin reported a significant improvement in sleep quality after 3 weeks of treatment compared with sleep quality at run-in (42.8 mm versus 65.5 mm on a 100 mm visual analogue scale; p < 0.0001). The mean improvement from baseline was significantly greater in the melatonin group than in the placebo group (–22.5 mm versus –16.5 mm; p = 0.047), although the clinical significance of a 6 mm difference is questionable (a change of 10 mm or more on the 100 mm visual analogue scale indicates a clinically relevant effect).
Morning alertness: people treated with melatonin reported a significant improvement in morning alertness after 3 weeks of treatment compared with alertness at run-in (44.6 mm versus 60.1 mm on a 100 mm visual analogue scale; p < 0.0001). The mean improvement from baseline was significantly greater in the melatonin group than in the placebo group (–15.7 mm versus –6.8 mm; p = 0.002), although the clinical significance of an 8.9 mm difference is questionable.
Ease of getting to sleep and hangover on awakening from sleep: results were not significantly different between treatments.
Quality of sleep (sleep diary): people treated with melatonin reported a significant improvement in quality of sleep after 3 weeks of treatment compared with at run-in (3.2 versus 2.3 on a 5-point rating scale; p < 0.0001). The mean improvement from baseline was significantly greater in the melatonin group than in the placebo group (0.9 versus 0.5; p = 0.003). The clinical significance of a 0.4-point difference on the 5-point rating scale is not clear.
Run-out period: once treatment had been stopped, a decline was noted in the improvement experienced by people in the melatonin group. However, by the end of the 2-week run-out period, quality of sleep, and alertness and behavioural integrity the following morning, were still better than at baseline.
Withdrawal: there was no evidence of a difference between the two groups for new symptoms experienced during the run-out period compared with the double-blind period; 29% of people in each group experienced new symptoms. In the melatonin group, the most common symptoms at run-out were muscle pain, widespread tingling and prickling, and an unusual taste in the mouth. In the placebo group, the most common symptoms at run-out were muscle spasms, muscle pains, tremors, feeling of unreality, depression, memory lapses, and nausea.
Adverse effects: during the treatment period, 18 people reported treatment-related adverse events (nine in each treatment group). Most adverse events were mild. The most commonly reported were diarrhoea (one person in each group), haematuria, and urinary tract infection (each occurring in two people in the placebo group). One severe adverse event (anxiety) occurred in a person randomized to receive placebo.
In the second RCT, 354 people between 55 and 80 years of age were randomized to treatment for 3 weeks [Wade et al, 2007].
Description of study methods
The primary outcome was the number of people showing an improvement of at least 10 mm in the QOS and BFW domains of the LSEQ.
Secondary outcomes were: change from baseline in the LSEQ domain scores GTS, QOS, AFS, and BFW; the global score from the Pittsburgh Sleep Quality Index (PSQI); the quality of night and quality of day scores derived from a sleep diary; the Clinical Global Improvement (CGI) score, assessed by the clinician; and the quality of life, derived from the World Health Organization (WHO)-5 Wellbeing index.
Results
A total of 20 people discontinued treatment during the treatment phase of the study; eight (3.5%) in the melatonin group (one for an adverse event, four on request, two lost to follow up, and one for taking forbidden medication), and 12 (5.3%) in the placebo group (three for an adverse event, four on request, one for failing screening criteria, two lost to follow up, and two for other reasons).
Quality of sleep and morning alertness: using intention to treat analysis, 25% of people in the melatonin group showed an improvement of at least 10 mm on both the QOS and BFW scales of the LSEQ, compared with 14% of people in the placebo group (odds ratio [OR] 2.01, 95% CI 1.17 to 3.46, p = 0.011).
LSEQ scores: people in the melatonin group showed significantly greater improvements in QOS, BFW, and GTS than people in the placebo group.
PSQI scores: there were significantly greater improvements in sleep quality and sleep latency in the melatonin group compared with the placebo group, but not in total sleep time. On average, people in the melatonin group got to sleep 8.8 minutes sooner than people in the placebo group (95% CI 1.0 to 16.7, p = 0.028).
Sleep diary: there were no significant differences between the two groups in the quality of night and quality of day scores derived from the sleep diary.
CGI score: there were no significant differences between the two groups in the CGI score.
WHO-5 Wellbeing index: the melatonin group showed significantly greater improvements in the WHO-5 Wellbeing index than the placebo group (p = 0.034).
Adverse effects: during the study period and for 30 days following the active treatment phase, 43 people (24%) in the melatonin group and 37 people (21%) in the placebo group reported adverse effects. The most commonly reported adverse effects were nasopharyngitis (reported by five people in the melatonin group and four people in the placebo group) and headache or migraine (reported by four people in the melatonin group and 11 people in the placebo group).
In the third RCT, 791 people with primary insomnia were randomized to modified-release melatonin or placebo for 26 weeks [Wade et al, 2010].
Description of study methods
All people were treated with a placebo run-in for 2 weeks and then randomized double blind to 3 weeks treatment with modified-release melatonin or placebo at night. The group taking modified-release melatonin continued this treatment for 26 weeks. The placebo group were re-randomized to either modified-release melatonin or placebo for 26 weeks, with 2 weeks of single-blind run-out. Double-blinding was maintained by using a centralized randomization system to keep both the participants and study personnel blind to treatment allocation.
The primary outcome was the comparison of sleep latency (measured by the sleep diary) at 3 weeks in two pre-defined subgroups: people of any age who were low excretors of melatonin, and people aged 65–80 years.
Secondary outcomes were: the global score from the Pittsburgh Sleep Quality Index (PSQI); the quality of night and quality of day scores derived from a sleep diary; the Clinical Global Improvement (CGI) score, assessed by the clinician; and the quality of life, derived from the World Health Organization (WHO)-5 Wellbeing index.
Results after 3 weeks' treatment
A total of 43 people (5%) discontinued treatment during the treatment period of the study; 21 in the modified-release melatonin group (three for an adverse event, five lost to follow-up, 11 unwilling to continue, two consent withdrawn) and 22 in the placebo group (two for an adverse event, four lost to follow-up, three ineligible to continue, eight unwilling to continue, one consent withdrawn, and four for other reasons).
Sleep latency, PSQI variables, CGI-I, and WHO-5 Index were not significantly different between groups for low-excretors of melatonin except for sleep disturbances and quality of life.
Sleep latency (assessed by sleep diary) was shorter in the group assigned to melatonin compared with placebo in people aged 65–80 years: –15.6 minutes, 95% CI –25.3 to –6.0, p = 0.002.
PSQI scores: there were greater improvements in sleep quality, sleep latency, and time going to bed in the melatonin group compared with the placebo group, but not in total sleep time (in people aged 65–80 years).
CGI score: there were no significant differences between the two groups in the CGI score in people aged 65–80 years
WHO-5 Wellbeing index: there was a significantly greater improvement in the WHO–5 Wellbeing index with the melatonin group compared with the placebo group in people aged 65–80 years
Results after 26 weeks' treatment
Sleep latency (assessed by sleep diary) was shorter in the group assigned to melatonin compared with placebo in people aged 65–80 years: –14.5 minutes, 95% CI –21.4 to –7.7, p < 0.001.
Morning alertness (assessed by sleep diary): people in the melatonin group were significantly more alert in the morning than those taking placebo in people aged 65–80 years: –0.10, 95% CI –0.19 to –0.01, p = 0.032. There was a trend towards a greater effect on morning alertness with duration of treatment.
PSQI scores: there were significantly greater improvements in sleep quality, sleep latency, time going to bed, and total sleep time in the melatonin group compared with the placebo group in people aged 65–80 years.
CGI score: there was a significantly greater improvement in the CGI score with the melatonin group compared with the placebo group in people aged 65–80 years
WHO-5 Wellbeing index: there was a significantly greater improvement in the WHO–5 Wellbeing index with the melatonin group compared with the placebo group in people aged 65–80 years.
Adverse effects
About 35% of 789 participants had an adverse event during the 3–week study period, 75% during the 26–week extension period, and 15% during the run-out period.
Nasopharyngitis, arthralgia, diarrhoea, lower and upper respiratory tract infections, and headache were the most commonly reported adverse events reported in both groups, and the incidence of these adverse effects was similar in both groups.
Melatonin compared with hypnotics
CKS identified no studies comparing melatonin with hypnotics for the management of primary insomnia.
Complementary and alternative treatments
Evidence on complementary and alternative treatments for insomnia
Acupuncture
Evidence on acupuncture for insomnia
The evidence on the efficacy of acupuncture is generally of poor methodological quality with inconsistent results. There is some evidence from single studies in a Cochrane systematic review to suggest that acupuncture and its variants (acupressure and transcutaneous electrical stimulation) may improve quality of sleep. Results for other sleep variables were inconsistent.
One Cochrane systematic review (search date: to 2006) investigated the efficacy and safety of acupuncture in people with insomnia [Cheuk et al, 2007]. The review included randomized controlled trials (RCTs) evaluating any form of acupuncture in people of all ages with any type of insomnia. Comparisons included placebo, sham acupuncture, or no treatment; comparisons with other treatments were not included. The review included seven RCTs (n = 590); the duration of the trials ranged from 6 months to 19 years.
In general, the methodological quality of the studies was poor and there was significant heterogeneity between them. Meta-analysis was limited because of considerable heterogeneity between comparison groups and between outcome measures.
Sleep quality: there were significant improvements in sleep quality scores with acupuncture compared with placebo (one RCT: standardized mean difference [SMD] –1.08, 95% CI –1.86 to –0.31, p = 0.006), acupressure compared with no treatment (two RCTs: SMD –0.55, 95% CI –0.89 to –0.21, p = 0.002), and transcutaneous electrical acupoint stimulation compared with no treatment (one RCT: SMD –0.74, 95% CI –1.22 to –0.26, p = 0.003).
Other sleep parameters: the efficacy of acupuncture or its variants was inconsistent between studies for other sleep parameters, such as sleep-onset latency, total sleep duration, and waking after sleep onset.
Subjective improvement in insomnia: after pooling data from three RCTS, there was no evidence of a subjective improvement in insomnia with acupuncture or its variants (risk ratio 1.66, 95% CI 0.68 to 4.03).
Adverse effects: only one study reported adverse effects of treatment. In this study, one person (6.3%) in the acupuncture group withdrew because of pain induced by the acupuncture needle.
A slightly more recent systematic review (search date: to 2007) included five additional RCTs [Huang et al, 2009]. Results from this review highlights the poor quality and heterogeneity of the studies.
Herbal remedies
Evidence on herbal remedies for insomnia
There is insufficient good quality evidence to make a recommendation regarding the efficacy of valerian, or any other herbal remedies, in the management of insomnia.
CKS identified three systematic reviews of valerian for the management of insomnia [Stevinson and Ernst, 2000; Bent et al, 2006; Taibi et al, 2007]. The methodological quality of the studies included was generally poor, and the valerian doses, preparations, and length of treatment varied considerably.
Two systematic reviews concluded that the evidence for valerian as a treatment for insomnia is inconclusive [Stevinson and Ernst, 2000; Bent et al, 2006].
The most recent systematic review concluded that, while supporting that valerian is a associated with only rare adverse events, current evidence does not support its efficacy as a treatment for insomnia [Taibi et al, 2007].
Search strategy
Scope of search
A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on primary care management of Insomnia, with additional searches for evidence in the following areas:
self-help techniques: sleep hygiene, relaxation, exercise
drug management: benzodiazepines, 'z-drugs', sedative antihistamines
behavioural treatment
complementary and alternative therapy
melatonin
Search dates
Guidelines: January 2006 – March 2008
Databases: Dates not restricted
Key search terms
Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline and these were adapted for other databases. Further details are available on request.
exp "sleep initiation and maintenance disorders"/, insomnia.tw, sleep$.tw
sleep hygiene.tw, hygiene/, relaxation/, relaxation therapy/, relax$.tw. exercise/, exercise therapy, exercise.tw.
exp benzodiazepines/, benzo$.tw, zopliclone.tw, zolpidem.tw, zaleplom.tw
cognitive therapy/, cognitive behav$ therapy.tw, cbt.tw
exp complementary therapies/ exp acupuncture therapy/ accup$.tw valerian/, valerian.tw
melatonin/ melatonin.tw
Table 1. Key to search terms.| Search commands | Explanation |
|---|---|
| / | indicates a MeSH subject heading with all subheadings selected |
| .tw | indicates a search for a term in the title or abstract |
| exp | indicates that the MeSH subject heading was exploded to include the narrower, more specific terms beneath it in the MeSH tree |
| $ | indicates that the search term was truncated (e.g. wart$ searches for wart and warts) |
Topic specific literature search sources
American Academy of Sleep Medicine
Sources of guidelines
National Institute for Health and Clinical Excellence (NICE)
Scottish Intercollegiate Guidelines Network (SIGN)
National Guidelines Clearinghouse
British Columbia Medical Association
Institute for Clinical Systems Improvement
Guidelines International Network
National Library of Guidelines
National Health and Medical Research Council (Australia)
Royal Australian College of General Practitioners
University of Michigan Medical School
Michigan Quality Improvement Consortium
National Resource for Infection Control
NHS Scotland National Patient Pathways
Agency for Healthcare Research and Quality
UK Ambulance Service Clinical Practice Guidelines
RefHELP NHS Lothian Referral Guidelines
Medline (with guideline filter)
Sources of systematic reviews and meta-analyses
Systematic reviews
Protocols
Database of Abstracts of Reviews of Effects
Medline (with systematic review filter)
EMBASE (with systematic review filter)
Sources of health technology assessments and economic appraisals
NIHR Health Technology Assessment programme
NHS Economic Evaluations
Health Technology Assessments
Canadian Agency for Drugs and Technologies in Health
International Network of Agencies for Health Technology Assessment
Sources of randomized controlled trials
Central Register of Controlled Trials
Medline (with randomized controlled trial filter)
EMBASE (with randomized controlled trial filter)
Sources of evidence based reviews and evidence summaries
DynaMed
Central Services Agency COMPASS Therapeutic Notes
Sources of national policy
Health Management Information Consortium (HMIC)
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