Insomnia

What is insomnia?

Normal sleep requirements vary widely, and there is no standard definition of what is normal. The amount of sleep required tends to decrease with age. Insomnia is a condition of unsatisfactory sleep, either in terms of sleep onset, sleep maintenance or early waking.

Because it is a disorder that subsequently impairs daytime well-being and subjective abilities and functioning, it has been termed a '24-hour disorder'. It is a subjective condition. Insomnia may be associated with fatigue, mood disturbances, problems with interpersonal relationships, occupational difficulties and a reduced quality of life. It has a negative impact on both physical and mental health.

How common is insomnia? (Epidemiology)

• Estimates of prevalence of insomnia vary according to the definition used.

• In one recent study, 29% of UK Biobank participants self-reported insomnia symptoms, but only 10% of those individuals had a Read code for insomnia in their GP records.¹

• The prevalence of insomnia is around 1.5 times higher in women than in men.²

• Insomnia is a long-term disorder and many people have had insomnia for more than two years.

• Approximately half of all people with diagnosed insomnia also have a comorbid psychiatric disorder.³

• The incidence increases in men and women as they get older. A UK GP cohort study of approximately 100,000 patients carried out between 2014 and 2015 found that the mean percentage of registered patients prescribed benzodiazepines or Z drugs for more than a year in the survey sample was 0.69%.⁴

• Benzodiazepine prescribing rates are particularly high amongst older people.⁵⁶⁷

Causes of insomnia (aetiology)

Insomnia may be classified as:

• Short-term - under four weeks in duration.

• Long-term or persistent - lasting over four weeks.

It may also be classified as:

• Primary - no identifiable underlying cause. A diagnosis of exclusion. Accounts for 15-20% of long-term insomnia.

• Secondary - when it is a symptom of, or associated with, other conditions.

Secondary insomnia may be caused by:

Other sleep disorders

• Sleep apnoea.

• Circadian rhythm disorders: sleep disorders caused by a mismatch between circadian rhythms and required sleep-wake cycle. These may sometimes be due to a lifestyle which conflicts with one's internal clock. Shift work and jet lag are common causes.⁸

• Parasomnias - unusual episodes, behaviours or disorders occurring during sleep which disturb the patient or others - eg, nightmares, night terrors, sleepwalking, sleep talking, limb movement disorders, restless legs syndrome.

• Narcolepsy.

Stress

• Situational stress:

  • Relationships - insomnia is associated with declining social support in the elderly.⁹

  • Financial problems.

  • Academic stress.

  • Job-related stress.

  • Medical worries.

• Noise stress.

Psychiatric comorbidity

• Depression and bipolar disorder.

• Generalised anxiety disorder.

• Panic disorder.

• Post-traumatic stress disorder.

• Paranoia and schizophrenia.

Medication and substance abuse

• Alcohol.

• Caffeine.

• Recreational drugs.

• Nicotine.

• Drug withdrawal - eg, hypnotics, alcohol (reduces the time to onset of sleep, but disrupts it later in the night).

• Chronic benzodiazepine misuse.

• Some antidepressants, especially selective serotonin reuptake inhibitors (SSRIs) and monoamine-oxidase inhibitors (MAOIs).

• Sympathomimetics - salbutamol, salmeterol, theophylline, pseudoephedrine.

• Corticosteroids (agitation).

• Anti-hypertensives, beta-blockers, calcium-channel blockers.

• Non-steroidal anti-inflammatory drugs (NSAIDs).

Medical comorbidity

• Movement disorders - eg, restless legs syndrome, Parkinson's disease, cerebrovascular disease.

• Respiratory and cardiac disorders - eg, angina, congestive cardiac failure, chronic obstructive pulmonary disease (COPD), asthma; due to pain, dyspnoea, or cough.

• Pain - eg, osteoarthritis, rheumatoid arthritis, injury, headaches, fibromyalgia.

• Gastrointestinal disease - eg, reflux, irritable bowel syndrome (IBS).

• Nocturia - eg, benign prostatic hyperplasia, diabetes mellitus or diabetes insipidus, diuretics.

• Incontinence.

• Alzheimer's disease.

• Endocrine - eg, hyperthyroidism (sweats).

• Perimenopausal symptoms.

• Other physical symptoms - eg, pruritus, leg cramps.

Physiological factors

• Poor sleep hygiene - eg, caffeine, daytime naps, stimulation prior to bedtime.

• Poor sleeping environment - eg, noise, light.

Assessment

• Careful history to establish a possible underlying cause.

• Physical and psychological examination may be useful to identify a possible underlying cause. Further investigations may also be indicated - eg, blood tests for hyperthyroidism and low ferritin levels, which may be associated with restless legs syndrome.

• Sleep diaries: these provide a record of the sleep pattern and should be kept for at least two weeks. Patients should record time of going to bed and getting up, time it takes for them to get to sleep, number of times they wake in the night, daytime tiredness and naps, mealtimes, alcohol and caffeine intake, and a rating of sleep quality. Sleep diaries can often identify sleep trends or predominant sleep patterns. Sleep diaries can be used as a starting point for managing insomnia and for monitoring progress.

• Polysomnography (overnight sleep study): this measures brain and muscle activity and assesses oxygen saturation overnight. It can be used to confirm sleep apnoea and limb movement disorders or restless legs syndrome.

Management of insomnia

Treatment is appropriate when insomnia causes significant personal distress or marked impairment. Those affected commonly consult doctors, often with the expectation of a 'sleeping tablet'.

Attitudes towards pharmacological treatment of insomnia in guidelines and consensus documents have changed over the years,¹⁰ and now recommend that CBT-I is the first-line, and most effective, treatment for chronic insomnia.¹⁰¹¹

The Committee on Safety of Medicines (now part of the Commission on Human Medicines), the Medicines and Healthcare products Regulatory Agency (MHRA), and the Royal College of Psychiatrists have long advised that hypnotic drugs should be limited to the lowest effective dose for the shortest time possible, with a maximum two-week treatment period, and avoided where possible in the elderly.¹¹

Manage the underlying cause where one has been identified. If any uncertainty exists about the diagnosis or if any safety concerns have been identified (eg, excessive daytime sleepiness or parasomnias causing injuries), patient referral for an assessment by a sleep specialist is indicated.

Sleep hygiene advice

Poor sleep hygiene habits are associated with insomnia. However, provision of sleep hygiene education as a sole intervention has a relatively weak evidence base as a treatment for chronic insomnia.¹²¹³ Recent guidelines from the American Academy of Sleep Medicine state that the evidence does not support the use of sleep hygiene advice as a stand-alone therapy for chronic insomnia, instead favouring CBT-I (in which sleep hygiene education is one of multiple interventions).¹⁴ However, advice about sleep hygiene remains in most guidelines, and it may potentially be useful in acute insomnia, or where CBT-I is not available or not desired.¹⁵

Sleep hygiene principles include:

• Limit caffeine to one cup of coffee in the morning, avoid alcohol and cigarettes at night, and reduce or avoid any other substances that can affect sleep.

• Avoid napping during the day.

• Regular daily exercise can help improve sleep, but exercise late in the evening should be avoided.

• Advise to do only quiet, relaxing activities before bedtime. Heavy meals just before bedtime should be avoided but a light snack may be helpful.

• Ensure that the bedtime environment is comfortable and conducive to sleep.

• Using computers: looking at a computer screen in the hours before bed may delay sleep onset.

• Looking at a clock during awakenings can increase frustration at being awake and so further delay sleep.

• Advise restricting their total time in bed to their estimated total sleep time.

• Use the bed/bedroom only for sleep and sexual activity.

• Get up from bed at the same time each day. Avoid a 'lie-in' after a restless night's sleep.

Cognitive behavioural therapy for insomnia (CBT-I)

• CBT-based treatment for chronic insomnia, including sleep restriction and stimulus control, is effective and should be offered to patients as a first-line treatment, either individually or in small groups.¹⁰ Patients should be referred to psychological services via Improving Access to Psychological Therapies (IAPT).

• CBT-I involves a multimodal 'package' of interventions, usually including sleep hygiene, relaxation therapy, sleep restriction therapy, stimulus control therapy, and cognitive therapeutics.¹⁰

• There is also good evidence for the effectiveness of digitally delivered CBT-I.¹⁶

• CBT-I is thought to directly tackle the cognitive and behavioural factors that maintain insomnia, unlike hypnotic drugs.¹¹

• CBT-I has few side-effects, and benefits persist at medium-to-long-term follow-up.¹¹

• The main limitation of CBT-I, however, is its availability, with potentially long waiting lists for face-to-face therapy.¹¹

• Digital CBT-I interventions may be easier and quicker to access than face-to-face therapy.

  • The National Institute for Health and Care Excellence (NICE) recommended the use of Sleepio, a digital CBT-I service, in 2022.¹⁷

  • Sleepio is available on the NHS in some areas, depending on local commissioning arrangements; alternative digital CBT-I services may also be commissioned and available locally.

Pharmacological treatments

Pharmacological treatments for insomnia can produce short-term improvements in symptoms, but have unclear long-term efficacy. Some, particularly benzodiazepines and Z drugs, have significant long-term risks including tolerance, dependence, over-sedation, hangover effects, nighttime confusion and falls.

Hypnotic drugs are also symptomatic treatments, rather than disease-modifying ones, and insomnia symptoms typically recur in chronic insomnia upon cessation.¹⁰

They should therefore be used cautiously, and ideally as a second-line treatment if non-pharmacological approaches have not worked, or are unsuitable.

Benzodiazepines and 'Z drugs'

• Currently marketed hypnotic drugs are effective in promoting sleep in the short term but there is little good evidence for their long-term efficacy and there are serious concerns regarding the risk of dependence when these drugs are used in this way.

• Z drugs (zopiclone, zaleplon, zolpidem) and short-acting benzodiazepines (nitrazepam, loprazolam, lormetazepam, temazepam) are effective for insomnia.

• Problems relating to safety (adverse events and carry-over effects) are fewer and less serious using drugs with short half-lives. Nitrazepam is longer-acting compared to loprazolam, lormetazepam and temazepam and so is more likely to give rise to 'hangover' effects the next day, and repeated doses may become cumulative. However, they are less likely to cause withdrawal phenomena than the short-acting benzodiazepines. Diazepam (long-acting) is sometimes used as a single nocturnal dose to treat daytime anxiety associated with insomnia.

• NICE recommends that there is little compelling evidence to distinguish between the Z drugs and shorter-acting benzodiazepines clinically, so that the cheapest drug should be used. Only if side-effects specific to that drug develop does NICE suggest switching to a different hypnotic. There is no evidence of benefit of switching between Z-class drugs.

Melatonin
Melatonin is a pineal gland hormone that helps to regulate the sleep-wake cycle.

Melatonin is freely available without prescription in the USA and some other countries,¹⁸ but is a prescription-only medication in the UK. Some people in the UK may, however, obtain melatonin by purchasing it other countries, including via the internet.

There are several different licensed forms of melatonin in the UK, of which the most commonly-prescribed is prolonged-release melatonin (Circadin®). This is licensed as monotherapy for the short-term treatment of primary insomnia characterised by poor quality of sleep in people aged 55 years or over, for a maximum duration of 13 weeks of treatment.¹⁹

Instant-release melatonin may be helpful for circadian rhythm disorders, such as jet lag,¹¹ but there is a lack of evidence supporting its efficacy in chronic insomnia of other causes.¹⁰

Prolonged-release melatonin can produce modest improvements in sleep in older adults. If hypnotics are indicated in patients over 55 years, melatonin should usually be tried first, especially over Z drugs and benzodiazepines.¹⁰

The available data on long-term use of melatonin are generally reassuring, but this area has been insufficiently studied, and further research is required.²⁰

Melatonin is also increasingly used by specialists in children with disturbed sleep where non-pharmacological measures have failed, particularly with autistic children and children with ADHD.¹¹ Existing data have not shown significant harms arising from melatonin use, but long-term safety data are scarce.²¹

Daridorexant

Daridorexant is a dual orexin receptor antagonist. It was approved by NICE as an option for the treatment of long-term insomnia in 2023.²²

In two controlled phase-III studies, daridorexant produced small to moderate improvements in sleep parameters, with mild adverse effects only. It was initially studied up to 3 months' of use, but an extension study up to 1 year demonstrated a maintained efficacy over that period, with no hangover effects, no withdrawal-related symptoms, or rebound insomnia after treatment discontinuation.¹⁰

NICE has advised that it can be considered in adults with insomnia symptoms on 3 or more nights a week, lasting for at least 3 months, and whose daytime function is severely impaired, if:²²

• CBT-I has been tried but not worked, or;

• CBT-I is not available.

NICE recommends that treatment duration should be as short as possible. Treatment should be re-assessed within 3 months after starting and stopped in people whose insomnia has not responded adequately. If treatment is continued, it should be assessed regularly as to whether it is still working.

Antidepressants
There is limited evidence for efficacy of antidepressants in insomnia. Antidepressants may affect a wide range of brain receptors and have longer-lasting carry-over effects than traditional hypnotic drugs - antidepressants are associated with increased risks of road accidents especially early in treatment in depression. Sedating antidepressants, such as amitriptyline, mirtazapine, and trazodone are not licensed for insomnia, but are commonly used off-label, and particularly if insomnia is comorbid with another mental health condition.¹⁰

There is very limited evidence to support their use in insomnia.¹⁰ They may be suitable in some patients, but only after a careful consideration and discussion of the risks and benefits, including the potential side-effects.

Antipsychotics
In the past, sedative antipsychotics were used for insomnia, but concerns over their cardiac safety prevents their use. Atypical antipsychotics, particularly olanzapine and quetiapine, are occasionally used to improve sleep but data on efficacy are inconclusive. Side-effects are common. The current body of evidence does not support the use of antipsychotics to treat insomnia.¹⁰

Sedating antihistamines
These have a limited role in psychiatric and primary care practice for the management of insomnia. Hydroxyzine and promethazine can be the most sedative but long half-lives may result in a hangover effect. Diphenhydramine is widely purchased over the counter but good evidence of efficacy is lacking, and rebound insomnia can occur after prolonged use.

Overall, evidence does not support the use of sedating antihistamines for insomnia treatment.¹⁰

Herbal remedies
Valerian and other herbal remedies have very little evidence of efficacy and are not recommended.¹⁰

Cautions

• Hypnotic drugs: are associated with tolerance, dependence, and withdrawal syndrome, and with rebound insomnia on cessation. However, studies suggest that dependence (tolerance/withdrawal) is not inevitable with hypnotic therapy up to one year with some drugs, including zolpidem.¹¹ Brief interventions in primary care, such as a single letter or consultation, have been shown to have impact on reducing long-term use of hypnotics. See the separate Benzodiazepine dependence article.

• Older people: are most at risk of developing ataxia, becoming confused and/or falling due to hypnotic treatment, as they eliminate the drugs more slowly, are more susceptible to CNS depression and are more likely to be using potentially interacting drugs. The use of long-acting benzodiazepines and some Z drugs seems to be associated with an increased risk of falls and hip fractures in older adults.²³ Past benzodiazepine use is associated with an increased risk of Alzheimer's disease, although the existing evidence is insufficient to demonstrate a causal relationship.²⁴

• Potential for abuse: all hypnotics have the potential for abuse. Temazepam is the most commonly abused of these drugs, but other benzodiazepines and, more recently, zopiclone, have all been implicated in illicit drug use.

• Driving: hypnotics impair judgement and increase reaction times, so affecting the ability to drive or operate machinery, and increasing risk of road traffic accidents. Patients must be aware of this and the fact that hangover effects of a night dose may still manifest themselves the following day. The Driver and Vehicle Licensing Agency (DVLA) advises that any patient suffering from excessive awake-time sleepiness, regardless of cause (including due to the insomnia itself), should cease to drive until there is satisfactory control of symptoms. People who take British National Formulary-recommended doses of prescribed benzodiazepines and have no impairment do not need to inform the DVLA, but persistent non-prescribed misuse or dependency on benzodiazepines will lead to licence refusal or revocation for a minimum of one year.

Complications of insomnia

• Quality of life is impaired in insomnia.

• There is an increased risk of subsequent first episode or relapse of depression and anxiety disorder in those with a pre-existing persistent insomnia.

• Primary insomnia is associated with poor objective sleep and impaired objectively measured daytime performance.

• There is an increased risk of hypertension in insomnia with objectively measured short sleep duration.

• Absenteeism, accidents at work and road accidents are increased in insomnia.

• Insomnia is associated with physiological hyperarousal, and as a result persistent objective short duration of sleep may be associated with an increased risk of cardiometabolic and neurocognitive morbidity and mortality.