Treatment algorithm

Your Organisational Guidance

ebpracticenet urges you to prioritise the following organisational guidance:

Aanpak van slaapklachten en insomnie (slapeloosheid) bij volwassenen in de eerste lijnPublished by: Werkgroep Ontwikkeling Richtlijnen Eerste Lijn (Worel)Last published: 2018Prise en charge des problèmes de sommeil et de l’insomnie chez l’adulte en première lignePublished by: Groupe de Travail Développement de recommmandations de première ligneLast published: 2018

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

acute insomnia

1st line – reassurance and management of precipitating factors

Back
ACUTE
|
acute insomnia
|
sleep-onset difficulties
1st line – 

reassurance and management of precipitating factors

Acute insomnia lasts less than 3 months and often occurs in response to an identifiable stressor.[1][2]​ Acute insomnia is very common and often transient, and does not always require treatment.[106]​ Note that current diagnostic classifications do not have quantitative severity criteria for insomnia disorder; it is up to the clinician to judge what is severe enough to treat.[7]

In the first instance, identify potential stressors that may be disturbing sleep (e.g., work-related stress or relationship difficulties) and encourage the patient to address these where possible. Enquire about maladaptive coping strategies such as daytime napping or use of stimulants, and offer advice on avoidance of these as well as on general sleep hygiene measures.[106]

Review the patient's usual medications to establish whether they include drugs that may cause or worsen insomnia, such as stimulants, antidepressants, corticosteroids, diuretics, or sedatives; if so, consider whether it is possible to lower the dosage and/or utilise the medication at another time of the day in order to reduce the impact on sleep.

Aims of short-term treatment for acute insomnia include reducing alarming thoughts associated with sleeplessness, in order to protect against the development of counterproductive cognitive, emotional, and behavioural responses to sleeplessness that are risk factors for developing chronic insomnia.

Follow up patients with acute insomnia after 2-4 weeks to establish whether insomnia is persistent; for persistent insomnia meeting diagnostic criteria for chronic insomnia, follow guidance on management of chronic insomnia.[126]

Consider – sleep hygiene and relaxation techniques

Back
ACUTE
|
acute insomnia
|
sleep-onset difficulties
Consider – 

sleep hygiene and relaxation techniques

Additional treatment recommended for SOME patients in selected patient group

Sleep hygiene and relaxation techniques are appropriate non-pharmacological treatment options for acute insomnia.[112][113][114][115][116][117][118][119][120][121][122][123]

Sleep hygiene involves developing habits conducive to sleep, such as: avoiding stimulants, including nicotine and caffeine (as well as foods containing caffeine), for several hours before bedtime; avoiding alcohol around bedtime; avoiding blue-light-emitting digital devices (e.g., smart-phones/computers) close to bedtime; establishing a regular bedtime and rise time; avoiding excessive time in bed trying to sleep; avoiding extended daytime naps; accepting that sleep onset is involuntary and out of a person's control; adopting a more permissive approach to sleep by controlling and removing impediments but accepting that sleep will happen but not on demand, only trying to sleep when sleepy; taking regular exercise, especially in the late afternoon or early evening; allowing adequate time to unwind before going to bed; ensuring that the environment is conducive to sleep - making certain the bed and bedding are comfortable, the room is dark and quiet, and temperature and humidity are controlled; and avoiding clock-watching during the sleep period. Evidence for most non-pharmacological therapies for insomnia (excluding CBT-I) is limited, and insufficient to determine the relative efficacy of different non-pharmacological treatments.[124]​ There is insufficient evidence that sleep hygiene techniques alone are an effective treatment for insomnia, although they may be helpful when combined with other specific interventions.[125]

Relaxation techniques include progressive relaxation, guided imagery and meditation, and biofeedback. Progressive relaxation therapy involves the tensing and relaxation of muscles systematically from head to toe. Guided imagery and meditation instructs the patient to replace anxiety-ridden thoughts with pleasant, restful imagery. Biofeedback involves giving the patient immediate input as to their stress level and instructions on methods to reduce stress.

1st line – cognitive behavioural therapy for insomnia (CBT-I)

Back
ACUTE
|
acute insomnia
|
sleep-onset difficulties
1st line – 

cognitive behavioural therapy for insomnia (CBT-I)

Acute insomnia lasts less than 3 months and often occurs in response to an identifiable stressor.[1][2]​ Note that current diagnostic classifications do not have quantitative severity criteria for insomnia disorder; it is up to the clinician to judge what is severe enough to treat.[7]​ Treatment for acute insomnia may be required if insomnia is severe and causing significant distress.

CBT-I is a first-line approach for acute insomnia. CBT-I has been shown to be effective for chronic insomnia.[107]​ Evidence for its use in acute insomnia is limited but promising.[4][5][6]​​​​ One randomised controlled trial investigated the effect of a 1-week internet-delivered course of CBT-I on patients with acute insomnia. After 12 weeks, the incidence of progression to chronic insomnia was significantly lower in the CBT-I group compared with controls (33.3% vs. 65.8%).[4] Further small trials have suggested that a single 60- to 70-minute session of CBT-I for acute insomnia is effective in reducing insomnia severity.[5][6]

The core principles of CBT-I are: learning to down-regulate arousal and induce relaxation; accepting the reality that sleep is out of control and surrendering to whatever happens regarding sleep; avoiding time cues; reducing time spent in bed not sleeping; sleep restriction if the person spends excessive time in bed without sleeping; and changing maladaptive beliefs about sleep.[108][109][110][111]

CBT-I is effective when employed under the guidance of a clinician, either in face-to-face individual or group settings, or via internet-based CBT-I (sometimes called digital CBT-I or dCBT-I). There is an increasing evidence base in favour of dCBT-I suggesting that it is comparable to in-person CBT-I in effectiveness.[107][112][139]​​[140]

For insomnia during pregnancy (when the risk:benefit ratio typically shifts in favour of non-pharmacological options where possible), there is a limited evidence base for treatment; CBT-I (both face-to-face and online) appears to be a safe, effective, and acceptable first-line option during pregnancy.[131][132]

Follow up patients with acute insomnia after 2-4 weeks to establish whether insomnia is persistent; for persistent insomnia, follow guidance on management of chronic insomnia.[126]

Consider – sleep hygiene and relaxation techniques

Back
ACUTE
|
acute insomnia
|
sleep-onset difficulties
Consider – 

sleep hygiene and relaxation techniques

Additional treatment recommended for SOME patients in selected patient group

Sleep hygiene and relaxation techniques are appropriate non-pharmacological treatment options for acute insomnia.[112][113][114][115][116][117][118][119][120][121][122][123]

Sleep hygiene involves developing habits conducive to sleep, such as: avoiding stimulants, including nicotine and caffeine (as well as foods containing caffeine), for several hours before bedtime; avoiding alcohol around bedtime; avoiding blue-light-emitting digital devices (e.g., smart-phones/computers) close to bedtime; establishing a regular bedtime and rise time; avoiding excessive time in bed trying to sleep; avoiding extended daytime naps; accepting that sleep onset is involuntary and out of a person's control; adopting a more permissive approach to sleep by controlling and removing impediments but accepting that sleep will happen but not on demand, only trying to sleep when sleepy; taking regular exercise, especially in the late afternoon or early evening; allowing adequate time to unwind before going to bed; ensuring that the environment is conducive to sleep - making certain the bed and bedding are comfortable, the room is dark and quiet, and temperature and humidity are controlled; and avoiding clock-watching during the sleep period. Evidence for most non-pharmacological therapies for insomnia (excluding CBT-I) is limited, and insufficient to determine the relative efficacy of different non-pharmacological treatments.[124]​ There is insufficient evidence that sleep hygiene techniques alone are an effective treatment for insomnia, although they may be helpful when combined with other specific interventions.[125]

Relaxation techniques include progressive relaxation, guided imagery and meditation, and biofeedback. Progressive relaxation therapy involves the tensing and relaxation of muscles systematically from head to toe. Guided imagery and meditation instructs the patient to replace anxiety-ridden thoughts with pleasant, restful imagery. Biofeedback involves giving the patient immediate input as to their stress level and instructions on methods to reduce stress.

2nd line – hypnotic

Back
ACUTE
|
acute insomnia
|
sleep-onset difficulties
2nd line – 

hypnotic

Acute insomnia lasts less than 3 months and often occurs in response to an identifiable stressor.[1][2]​ Note that current diagnostic classifications do not have quantitative severity criteria for insomnia disorder; it is up to the clinician to judge what is severe enough to treat.[7]

Short-term use of a hypnotic is an appropriate option to consider in patients with acute insomnia that is severe or associated with substantial distress when a rapid amelioration of symptoms is desirable, and/or in settings where there is limited or no access to behavioural treatments, if the patient is unable or unwilling to participate in behavioural therapy, or if behavioural therapy is ineffective.​[104][126]​​

For patients with sleep-onset difficulties, non-benzodiazepine benzodiazepine receptor agonists (e.g., zolpidem, zaleplon, eszopiclone), dual orexin receptor antagonists (e.g., suvorexant, lemborexant, daridorexant), and ramelteon (a melatonin receptor agonist) are all reasonable first-line choices.[104][127][128]​​ For patients experiencing both sleep onset and sleep maintenance difficulty, zolpidem, eszopiclone, and dual orexin receptor antagonists appear to be effective.

All non-benzodiazepine benzodiazepine receptor agonists show established efficacy in reducing sleep onset latency (SOL), and for zolpidem and eszopiclone, in reducing wakefulness after sleep onset (WASO), and increasing total sleep time (TST) and sleep quality (SQ), based on both objective (polysomnography [PSG]) and subjective (sleep diary) measures in short-term studies.[104] Accumulating evidence supports the efficacy of dual orexin receptor antagonists in decreasing SOL, WASO, and TST based on objective (PSG) and subjective measures.[127][128][163][164][165][166]​​​ However, longer-term studies are lacking for these agents. Ramelteon has been shown to reduce SOL but is probably ineffective for sleep maintenance.[104][171][172]​​ There exists no clear evidence to support the superiority of one recommended class of hypnotic over another.[173][174]​​ Choice of drug should be tailored to the insomnia phenotype and consideration of its safety and tolerability.

No hypnotics are indicated for use in pregnant women. For patients with insomnia during pregnancy, the risk:benefit ratio typically shifts in favour of non-pharmacological options where possible. Clinicians considering offering a pharmacological treatment for insomnia during pregnancy should seek specialist input (e.g., from a psychiatrist with expertise in prescribing during pregnancy, or from an obstetrician) due to the risks associated with common hypnotics during pregnancy.

Treating older patients with hypnotics presents a challenge because older patients are more prone to medication-related adverse events, yet there exists little quality evidence to support acceptable harm versus efficacy profiles in choosing between agents. The American Geriatric Society BEERs criteria for potentially inappropriate medication prescribing in older adults places all benzodiazepines and non-benzodiazepine benzodiazepine receptor agonists on its list of medications to avoid due to an increased risk of accidents and falls.[179]​ Current data are insufficient to determine whether dual orexin receptor antagonists offer a more favourable risk:benefit profile in older adults than non-benzodiazepine benzodiazepine receptor agonists. No definitive evidence supports an increased risk for one recommended class of hypnotic over the other. The authors do not recommend avoiding non-benzodiazepine benzodiazepine receptor agonists as a class for older adults. An individualised risk versus benefit profile should be determined that takes into account pertinent clinical factors, including co-existing comorbidity, medications, potential for drug-drug interactions, psychosocial factors, and patient values and preferences.

Discuss safety considerations with patients when prescribing hypnotics. Adverse events may include: complex sleep-related behaviours; central nervous system depressant effects; sleep paralysis, cataplexy, and excessive daytime sleepiness; hypnagogic or hypnopompic hallucinations; worsening of depression, suicidality, and impulsivity; misuse or abuse; dependence, tolerance, withdrawal, and rebound; and respiratory suppression. For a detailed discussion of safety considerations, contraindications, and cautions, see Management approach.

Doses should typically be taken immediately before bedtime or within 30 minutes of bedtime (depending on the drug), and more than 7 hours before planned awakening, due to the risk of next-day impairment. Higher doses may increase the risk of next-day impairment; use the lowest effective dose for the shortest possible treatment duration. Lower doses are recommended in older or debilitated patients.

Follow up patients with acute insomnia after 2-4 weeks to establish whether insomnia is persistent; for persistent insomnia meeting diagnostic criteria for chronic insomnia, follow guidance on management of chronic insomnia.[126]

Primary options

zolpidem: 5 mg orally (immediate-release)/sublingually once daily at bedtime when required initially, increase dose according to response, maximum 10 mg/day; 6.25 mg orally (extended-release) once daily at bedtime when required initially, increase dose according to response, maximum 12.5 mg/day

More

OR

zaleplon: 5 mg orally once daily at bedtime when required initially, increase dose according to response, maximum 10-20 mg/day

OR

eszopiclone: 1 mg orally once daily at bedtime when required initially, increase dose according to response, maximum 3 mg/day

OR

ramelteon: 8 mg orally once daily at bedtime when required

OR

suvorexant: 10 mg orally once daily at bedtime when required initially, increase dose according to response, maximum 20 mg/day

OR

lemborexant: 5 mg orally once daily at bedtime when required initially, increase dose according to response, maximum 10 mg/day

OR

daridorexant: 25 mg orally once daily at bedtime when required initially, increase dose according to response, maximum 50 mg/day

Consider – sleep hygiene and relaxation techniques

Back
ACUTE
|
acute insomnia
|
sleep-onset difficulties
Consider – 

sleep hygiene and relaxation techniques

Additional treatment recommended for SOME patients in selected patient group

Sleep hygiene and relaxation techniques are appropriate non-pharmacological treatment options for acute insomnia, especially in patients who prefer not to use medications, or who have suboptimal response to hypnotics.[112][113][114][115][116][117][118][119][120][121][122][123]

Sleep hygiene involves developing habits conducive to sleep, such as: avoiding stimulants, including nicotine and caffeine (as well as foods containing caffeine), for several hours before bedtime; avoiding alcohol around bedtime; avoiding blue-light-emitting digital devices (e.g., smart-phones/computers) close to bedtime; establishing a regular bedtime and rise time; avoiding excessive time in bed trying to sleep; avoiding extended daytime naps; accepting that sleep onset is involuntary and out of a person's control; adopting a more permissive approach to sleep by controlling and removing impediments but accepting that sleep will happen but not on demand, only trying to sleep when sleepy; taking regular exercise, especially in the late afternoon or early evening; allowing adequate time to unwind before going to bed; ensuring that the environment is conducive to sleep - making certain the bed and bedding are comfortable, the room is dark and quiet, and temperature and humidity are controlled; and avoiding clock-watching during the sleep period. Evidence for most non-pharmacological therapies for insomnia (excluding CBT-I) is limited, and insufficient to determine the relative efficacy of different non-pharmacological treatments.[124]​ There is insufficient evidence that sleep hygiene techniques alone are an effective treatment for insomnia, although they may be helpful when combined with other specific interventions.[125]

Relaxation techniques include progressive relaxation, guided imagery and meditation, and biofeedback. Progressive relaxation therapy involves the tensing and relaxation of muscles systematically from head to toe. Guided imagery and meditation instructs the patient to replace anxiety-ridden thoughts with pleasant, restful imagery. Biofeedback involves giving the patient immediate input as to their stress level and instructions on methods to reduce stress.

1st line – reassurance and management of precipitating factors

Back
ACUTE
|
acute insomnia
|
difficulty maintaining sleep or early awakening
1st line – 

reassurance and management of precipitating factors

Acute insomnia lasts less than 3 months and often occurs in response to an identifiable stressor.[1][2]​​ Acute insomnia is very common and often transient, and does not always require treatment.[106]​ Note that current diagnostic classifications do not have quantitative severity criteria for insomnia disorder; it is up to the clinician to judge what is severe enough to treat.[7]

In the first instance, identify potential stressors that may be disturbing sleep (e.g., work-related stress or relationship difficulties) and encourage the patient to address these where possible. Enquire about maladaptive coping strategies such as daytime napping or use of stimulants, and offer advice on avoidance of these as well as on general sleep hygiene measures.[106]

Review the patient's usual medications to establish whether they include drugs that may cause or worsen insomnia, such as stimulants, antidepressants, corticosteroids, diuretics, or sedatives; if so, consider whether it is possible to lower the dosage and/or utilise the medication at another time of the day in order to reduce the impact on sleep.

Aims of short-term treatment for acute insomnia include reducing alarming thoughts associated with sleeplessness, in order to protect against the development of counterproductive cognitive, emotional, and behavioural responses to sleeplessness that are risk factors for developing chronic insomnia.

Follow up patients with acute insomnia after 2-4 weeks to establish whether insomnia is persistent; for persistent insomnia meeting diagnostic criteria for chronic insomnia, follow guidance on management of chronic insomnia.[126]

Consider – sleep hygiene and relaxation techniques

Back
ACUTE
|
acute insomnia
|
difficulty maintaining sleep or early awakening
Consider – 

sleep hygiene and relaxation techniques

Additional treatment recommended for SOME patients in selected patient group

Sleep hygiene and relaxation techniques are appropriate non-pharmacological treatment options for acute insomnia.[112][113][114][115][116][117][118][119][120][121][122][123]

Sleep hygiene involves developing habits conducive to sleep, such as: avoiding stimulants, including nicotine and caffeine (as well as foods containing caffeine), for several hours before bedtime; avoiding alcohol around bedtime; avoiding blue-light-emitting digital devices (e.g., smart-phones/computers) close to bedtime; establishing a regular bedtime and rise time; avoiding excessive time in bed trying to sleep; avoiding extended daytime naps; accepting that sleep onset is involuntary and out of a person's control; adopting a more permissive approach to sleep by controlling and removing impediments but accepting that sleep will happen but not on demand, only trying to sleep when sleepy; taking regular exercise, especially in the late afternoon or early evening; allowing adequate time to unwind before going to bed; ensuring that the environment is conducive to sleep - making certain the bed and bedding are comfortable, the room is dark and quiet, and temperature and humidity are controlled; and avoiding clock-watching during the sleep period. Evidence for most non-pharmacological therapies for insomnia (excluding CBT-I) is limited, and insufficient to determine the relative efficacy of different non-pharmacological treatments.[124]​ There is insufficient evidence that sleep hygiene techniques alone are an effective treatment for insomnia, although they may be helpful when combined with other specific interventions.[125]

Relaxation techniques include progressive relaxation, guided imagery and meditation, and biofeedback. Progressive relaxation therapy involves the tensing and relaxation of muscles systematically from head to toe. Guided imagery and meditation instructs the patient to replace anxiety-ridden thoughts with pleasant, restful imagery. Biofeedback involves giving the patient immediate input as to their stress level and instructions on methods to reduce stress.

1st line – cognitive behavioural therapy for insomnia (CBT-I)

Back
ACUTE
|
acute insomnia
|
difficulty maintaining sleep or early awakening
1st line – 

cognitive behavioural therapy for insomnia (CBT-I)

Acute insomnia lasts less than 3 months and often occurs in response to an identifiable stressor.[1][2]​​ Note that current diagnostic classifications do not have quantitative severity criteria for insomnia disorder; it is up to the clinician to judge what is severe enough to treat.[7]​ Treatment for acute insomnia may be required if insomnia is severe and causing significant distress.

CBT-I is a first-line approach for acute insomnia. CBT-I has been shown to be effective for chronic insomnia.[107]​ Evidence for its use in acute insomnia is limited but promising.[4][5][6]​​​​ One randomised controlled trial investigated the effect of a 1-week internet-delivered course of CBT-I on patients with acute insomnia. After 12 weeks, the incidence of progression to chronic insomnia was significantly lower in the CBT-I group compared with controls (33.3% vs. 65.8%).[4] Further small trials have suggested that a single 60- to 70-minute session of CBT-I for acute insomnia is effective in reducing insomnia severity.[5][6]

The core principles of CBT-I are: learning to down-regulate arousal and induce relaxation; accepting the reality that sleep is out of control and surrendering to whatever happens regarding sleep; avoiding time cues; reducing time spent in bed not sleeping; sleep restriction if the person spends excessive time in bed without sleeping; and changing maladaptive beliefs about sleep.[108][109][110][111]

CBT-I is effective when employed under the guidance of a clinician, either in face-to-face individual or group settings, or via internet-based CBT-I (sometimes called digital CBT-I or dCBT-I). There is an increasing evidence base in favour of dCBT-I suggesting that it is comparable to in-person CBT-I in effectiveness.[107][112][139]​​[140]

For insomnia during pregnancy (when the risk:benefit ratio typically shifts in favour of non-pharmacological options where possible) there is a limited evidence base for treatment; CBT-I (both face-to-face and online) appears to be a safe, effective, and acceptable first-line option.[131][132]

Follow up patients with acute insomnia after 2-4 weeks to establish whether insomnia is persistent; for persistent insomnia meeting diagnostic criteria for chronic insomnia, follow guidance on management of chronic insomnia.[126]

Consider – sleep hygiene and relaxation techniques

Back
ACUTE
|
acute insomnia
|
difficulty maintaining sleep or early awakening
Consider – 

sleep hygiene and relaxation techniques

Additional treatment recommended for SOME patients in selected patient group

Sleep hygiene and relaxation techniques are appropriate non-pharmacological treatment options for acute insomnia.[112][113][114][115][116][117][118][119][120][121][122][123]

Sleep hygiene involves developing habits conducive to sleep, such as: avoiding stimulants, including nicotine and caffeine (as well as foods containing caffeine), for several hours before bedtime; avoiding alcohol around bedtime; avoiding blue-light-emitting digital devices (e.g., smart-phones/computers) close to bedtime; establishing a regular bedtime and rise time; avoiding excessive time in bed trying to sleep; avoiding extended daytime naps; accepting that sleep onset is involuntary and out of a person's control; adopting a more permissive approach to sleep by controlling and removing impediments but accepting that sleep will happen but not on demand, only trying to sleep when sleepy; taking regular exercise, especially in the late afternoon or early evening; allowing adequate time to unwind before going to bed; ensuring that the environment is conducive to sleep - making certain the bed and bedding are comfortable, the room is dark and quiet, and temperature and humidity are controlled; and avoiding clock-watching during the sleep period. Evidence for most non-pharmacological therapies for insomnia (excluding CBT-I) is limited, and insufficient to determine the relative efficacy of different non-pharmacological treatments.[124] There is insufficient evidence that sleep hygiene techniques alone are an effective treatment for insomnia, although they may be helpful when combined with other specific interventions.[125]

Relaxation techniques include progressive relaxation, guided imagery and meditation, and biofeedback. Progressive relaxation therapy involves the tensing and relaxation of muscles systematically from head to toe. Guided imagery and meditation instructs the patient to replace anxiety-ridden thoughts with pleasant, restful imagery. Biofeedback involves giving the patient immediate input as to their stress level and instructions on methods to reduce stress.

2nd line – hypnotic

Back
ACUTE
|
acute insomnia
|
difficulty maintaining sleep or early awakening
2nd line – 

hypnotic

Acute insomnia lasts less than 3 months and often occurs in response to an identifiable stressor.[1][2]​ Note that current diagnostic classifications do not have quantitative severity criteria for insomnia disorder; it is up to the clinician to judge what is severe enough to treat.[7]

Short-term use of a hypnotic is an appropriate option to consider in patients with acute insomnia that is severe or associated with substantial distress, when a rapid amelioration of symptoms is desirable, and/or in settings where there is limited or no access to behavioural treatments, if the patient is unable or unwilling to participate in behavioural therapy, or if behavioural therapy is ineffective.​[104][126]​​

For patients with difficulty maintaining sleep or early awakening, first-line choices include the non-benzodiazepine benzodiazepine receptor agonists with longer half-lives (i.e., zolpidem and eszopiclone), doxepin (a tricyclic antidepressant with antihistamine properties), or a dual orexin receptor antagonist (e.g., suvorexant, lemborexant, daridorexant).[104]​ These drugs all have capacity to decrease wake after sleep onset and increase total sleep time.[104] For patients experiencing both sleep onset and sleep maintenance difficulty, zolpidem, eszopiclone, and dual orexin receptor antagonists appear to be effective.

Zolpidem and eszopiclone have demonstrated reducing wakefulness after sleep onset (WASO), and increasing total sleep time (TST) and sleep quality (SQ), based on both objective (polysomnography [PSG]) and subjective (sleep diary) measures in short-term studies.[104] Accumulating evidence supports the efficacy of dual orexin receptor antagonists in decreasing sleep onset latency (SOL), WASO, and TST based on objective (PSG) and subjective measures.[127][128][163][164][165][166]​​​ However, longer-term studies are lacking for these agents. Evidence supports the efficacy of doxepin in decreasing WASO, increasing sleep efficiency (SE), and increasing TST.[104] There exists no clear evidence to support the superiority of one recommended class of hypnotic over another.[173][174]​​ Choice of drug should be tailored to the insomnia phenotype and consideration of its safety and tolerability.

No hypnotics are indicated for use in pregnant women. For patients with insomnia during pregnancy, the risk:benefit ratio typically shifts in favour of non-pharmacological options where possible. Clinicians considering offering a pharmacological treatment for insomnia during pregnancy should seek specialist input (e.g., from a psychiatrist with expertise in prescribing during pregnancy, or from an obstetrician) due to the risks associated with common hypnotics during pregnancy.

Treating older patients with hypnotics presents a challenge because older patients are more prone to medication-related adverse events, yet there exists little quality evidence to support acceptable harm versus efficacy profiles in choosing between agents. The American Geriatric Society BEERs criteria for potentially inappropriate medication prescribing in older adults places all benzodiazepines and non-benzodiazepine benzodiazepine receptor agonists on its list of medications to avoid due to an increased risk of accidents and falls.[179]​ Current data are insufficient to determine whether dual orexin receptor antagonists offer a more favourable risk:benefit profile in older adults than non-benzodiazepine benzodiazepine receptor agonists. No definitive evidence supports an increased risk for one recommended class of hypnotic over the other. The authors do not recommend avoiding non-benzodiazepine benzodiazepine receptor agonists as a class for older adults. An individualised risk versus benefit profile should be determined that takes into account pertinent clinical factors, including co-existing comorbidity, medications, potential for drug-drug interactions, psychosocial factors, and patient values and preferences.

Discuss safety considerations with patients when prescribing hypnotics. Adverse events may include: complex sleep-related behaviours; central nervous system depressant effects; sleep paralysis, cataplexy, and excessive daytime sleepiness; hypnagogic or hypnopompic hallucinations; worsening of depression, suicidality, and impulsivity; misuse or abuse; dependence, tolerance, withdrawal, and rebound; and respiratory suppression. For a detailed discussion of safety considerations, contraindications, and cautions, see Management approach.

Doses should typically be taken immediately before bedtime or within 30 minutes of bedtime (depending on the drug), and more than 7 hours before planned awakening, due to the risk of next-day impairment. Higher doses may increase the risk of next-day impairment; use the lowest effective dose for the shortest possible treatment duration. Lower doses are recommended in older or debilitated patients.

Follow up patients with acute insomnia after 2-4 weeks to establish whether insomnia is persistent; for persistent insomnia meeting diagnostic criteria for chronic insomnia, follow guidance on management of chronic insomnia.[126]

Primary options

zolpidem: 6.25 mg orally (extended-release) once daily at bedtime when required initially, increase dose according to response, maximum 12.5 mg/day

More

OR

eszopiclone: 1 mg orally once daily at bedtime when required initially, increase dose according to response, maximum 3 mg/day

OR

suvorexant: 10 mg orally once daily at bedtime when required initially, increase dose according to response, maximum 20 mg/day

OR

lemborexant: 5 mg orally once daily at bedtime when required initially, increase dose according to response, maximum 10 mg/day

OR

daridorexant: 25 mg orally once daily at bedtime when required initially, increase dose according to response, maximum 50 mg/day

OR

doxepin: 3-6 mg orally once daily at bedtime when required

Consider – sleep hygiene and relaxation techniques

Back
ACUTE
|
acute insomnia
|
difficulty maintaining sleep or early awakening
Consider – 

sleep hygiene and relaxation techniques

Additional treatment recommended for SOME patients in selected patient group

Sleep hygiene and relaxation techniques are appropriate non-pharmacological treatment options for acute insomnia, especially in patients who prefer not to use medications, or who have suboptimal response to hypnotics.[112][113][114][115][116][117][118][119][120][121][122][123]

Sleep hygiene involves developing habits conducive to sleep, such as: avoiding stimulants, including nicotine and caffeine (as well as foods containing caffeine), for several hours before bedtime; avoiding alcohol around bedtime; avoiding blue-light-emitting digital devices (e.g., smart-phones/computers) close to bedtime; establishing a regular bedtime and rise time; avoiding excessive time in bed trying to sleep; avoiding extended daytime naps; accepting that sleep onset is involuntary and out of a person's control; adopting a more permissive approach to sleep by controlling and removing impediments but accepting that sleep will happen but not on demand, only trying to sleep when sleepy; taking regular exercise, especially in the late afternoon or early evening; allowing adequate time to unwind before going to bed; ensuring that the environment is conducive to sleep - making certain the bed and bedding are comfortable, the room is dark and quiet, and temperature and humidity are controlled; and avoiding clock-watching during the sleep period. Evidence for most non-pharmacological therapies for insomnia (excluding CBT-I) is limited, and insufficient to determine the relative efficacy of different non-pharmacological treatments.[124]​ There is insufficient evidence that sleep hygiene techniques alone are an effective treatment for insomnia, although they may be helpful when combined with other specific interventions.[125]

Relaxation techniques include progressive relaxation, guided imagery and meditation, and biofeedback. Progressive relaxation therapy involves the tensing and relaxation of muscles systematically from head to toe. Guided imagery and meditation instructs the patient to replace anxiety-ridden thoughts with pleasant, restful imagery. Biofeedback involves giving the patient immediate input as to their stress level and instructions on methods to reduce stress.

ONGOING

chronic insomnia

1st line – cognitive behavioural therapy for insomnia (CBT-I)

Back
ONGOING
|
chronic insomnia
|
sleep-onset difficulties
1st line – 

cognitive behavioural therapy for insomnia (CBT-I)

Insomnia lasting 3 months or longer is considered chronic.[1][2]​​

CBT-I is a first-line therapy for chronic insomnia.​[124][129][130]​​​​ It has been shown to effectively treat insomnia long term but requires patient commitment, sustained adherence, and practitioner training.[112][124][133][134][135]​​​​ Treating insomnia using CBT-I has been shown to improve quality of life, prevent depression, and possibly improve cardiometabolic biomarkers such as C-reactive protein and glycosylated haemoglobin (HbA1c).​[29][148][149]

The core principles of CBT-I are: learning to down-regulate arousal and induce relaxation; accepting the reality that sleep is out of control and surrendering to whatever happens regarding sleep; avoiding time cues; reducing time spent in bed not sleeping; sleep restriction if the person spends excessive time in bed without sleeping; and changing maladaptive beliefs about sleep.[108][109][110][111]

CBT-I is effective when employed under the guidance of a clinician, either in face-to-face individual or group settings, or via internet-based CBT-I (sometimes called digital CBT-I or dCBT-I). There is an increasing evidence base in favour of dCBT-I suggesting that it is comparable to in-person CBT-I in effectiveness.[107][112][139]​​[140]​​​ dCBT-I has the potential to increase patient access to CBT-I, thus offering patients and clinicians an increased choice among evidence-based treatments (CBT-I or pharmacotherapy) for insomnia.[129][141]

For insomnia during pregnancy (when the risk:benefit ratio typically shifts in favour of non-pharmacological options where possible) there is a limited evidence base for treatment; CBT-I (both face-to-face and online) appears to be a safe, effective, and acceptable first-line option.[131][132]

Consider – sleep hygiene and relaxation techniques

Back
ONGOING
|
chronic insomnia
|
sleep-onset difficulties
Consider – 

sleep hygiene and relaxation techniques

Additional treatment recommended for SOME patients in selected patient group

Sleep hygiene and relaxation techniques are appropriate non-pharmacological treatment options for insomnia.[112][113][114][115][116][117][118][119][120][121][122][123]

Sleep hygiene involves developing habits conducive to sleep, such as: avoiding stimulants, including nicotine and caffeine (as well as foods containing caffeine), for several hours before bedtime; avoiding alcohol around bedtime; avoiding blue-light-emitting digital devices (e.g., smart-phones/computers) close to bedtime; establishing a regular bedtime and rise time; avoiding excessive time in bed trying to sleep; avoiding extended daytime naps; accepting that sleep onset is involuntary and out of a person's control; adopting a more permissive approach to sleep by controlling and removing impediments but accepting that sleep will happen but not on demand, only trying to sleep when sleepy; taking regular exercise, especially in the late afternoon or early evening; allowing adequate time to unwind before going to bed; ensuring that the environment is conducive to sleep - making certain the bed and bedding are comfortable, the room is dark and quiet, and temperature and humidity are controlled; and avoiding clock-watching during the sleep period. Evidence for most non-pharmacological therapies for insomnia (excluding CBT-I) is limited, and insufficient to determine the relative efficacy of different non-pharmacological treatments.[124] There is insufficient evidence that sleep hygiene techniques alone are an effective treatment for insomnia, although they may be helpful when combined with other specific interventions.[125]

Relaxation techniques include progressive relaxation, guided imagery and meditation, and biofeedback. Progressive relaxation therapy involves the tensing and relaxation of muscles systematically from head to toe. Guided imagery and meditation instructs the patient to replace anxiety-ridden thoughts with pleasant, restful imagery. Biofeedback involves giving the patient immediate input as to their stress level and instructions on methods to reduce stress.

Consider – management of comorbid conditions

Back
ONGOING
|
chronic insomnia
|
sleep-onset difficulties
Consider – 

management of comorbid conditions

Additional treatment recommended for SOME patients in selected patient group

It is important to identify and optimise management of any comorbid medical conditions (e.g., chronic pain, hot flushes, hyperthyroidism, bladder disturbance, obstructive sleep apnoea, periodic limb movement disorder, or restless legs syndrome) or psychiatric disorders (e.g., mood disorders, anxiety disorders, substance use disorder, acute stress, or trauma) that may be contributing to chronic insomnia.[78]

Review the patient's usual medications to establish whether they include drugs that may cause or worsen insomnia, such as stimulants, antidepressants, corticosteroids, diuretics, or sedatives; if so, consider whether it is possible to lower the dosage and/or utilise the medication at another time of the day in order to reduce the impact on sleep.

Comorbid depression or anxiety: sedating antidepressants, such as mirtazapine or paroxetine, may be an appropriate choice for those with active depression and insomnia.[189]​ The efficacy and safety of mirtazapine (a tetracyclic antidepressant) for insomnia has not been established, and there is a risk of daytime sedation and metabolic adverse effects. Paroxetine, a selective serotonin-reuptake inhibitor (SSRI), confers potentially anticholinergic adverse effects and a substantial potential for drug-drug interactions due to its potent ability to inhibit cytochrome CYP2D6. Clinical judgement regarding the use of mirtazapine or paroxetine monotherapy for patients with depression, versus combined treatment with a non-sedating antidepressant and a hypnotic, must be made on an individualised case-by-case basis, which includes consideration of patient preference. Consult a specialist for guidance on selecting a suitable antidepressant or anxiolytic in these patients. One controlled study demonstrated that effective treatment of major depressive disorder with an SSRI allowed for seamless discontinuation of co-administered eszopiclone within 8 weeks.[190]

Comorbid dementia: little evidence exists to help guide pharmacological treatment options for patients with dementia and comorbid insomnia.[191]​ The authors recommend a similar approach to that recommended for hypnotic prescribing in older adults, first considering behavioural options for insomnia. Treating Alzheimer's disease optimally with a combination of an acetylcholinesterase inhibitor and memantine can help to alleviate sleep disturbance.[193][194]​ Behavioural and environmental modifications that allow for circadian realignment may be most helpful.[195][196]

2nd line – hypnotic

Back
ONGOING
|
chronic insomnia
|
sleep-onset difficulties
2nd line – 

hypnotic

Short-term and potentially longer-term provision of a hypnotic is an appropriate second-line option for patients with chronic insomnia. CBT-I should be offered first line but if the insomnia has become severe and the patient is in distress, or they are unable or unwilling to accept CBT-I, or have not responded to CBT-I, consider prescribing a hypnotic.

For patients experiencing sleep onset difficulty alone, hypnotics demonstrating established capacity to reduce sleep onset latency and confer reasonable safety include non-benzodiazepine benzodiazepine receptor agonists (e.g., zolpidem, zaleplon, eszopiclone), and ramelteon (a melatonin receptor agonist).[104]​ Dual orexin receptor antagonists (e.g., suvorexant, lemborexant, daridorexant) are also reasonable choices, based on phase 3 trials.[127][128][163][164][165][166][167]​​ For patients experiencing both sleep onset and sleep maintenance difficulty, zolpidem, eszopiclone, and dual orexin receptor antagonists appear to be effective.

All non-benzodiazepine benzodiazepine receptor agonists show established efficacy in reducing sleep onset latency (SOL), and for zolpidem and eszopiclone, in reducing wakefulness after sleep onset (WASO), and increasing total sleep time (TST) and sleep quality (SQ), based on both objective (polysomnography [PSG]) and subjective (sleep diary) measures in short-term studies.[104] Accumulating evidence supports the efficacy of dual orexin receptor antagonists in decreasing SOL, WASO, and TST based on objective (PSG) and subjective measures.[127][128][163][164][165][166]​ However, longer-term studies are lacking for these agents. Ramelteon has been shown to reduce sleep onset latency but is probably ineffective for sleep maintenance.[104][171][172]​​ There exists no clear evidence to support the superiority of one recommended class of hypnotic over another.[173][174]​​ Choice of drug should be tailored to the insomnia phenotype and consideration of its safety and tolerability.

No hypnotics are indicated for use in pregnant women. For patients with insomnia during pregnancy, the risk:benefit ratio typically shifts in favour of non-pharmacological options where possible. Clinicians considering offering a pharmacological treatment for insomnia during pregnancy should seek specialist input (e.g., from a psychiatrist with expertise in prescribing during pregnancy, or from an obstetrician) due to the risks associated with common hypnotics during pregnancy.

Treating older patients with hypnotics presents a challenge because older patients are more prone to medication-related adverse events, yet there exists little quality evidence to support acceptable harm versus efficacy profiles in choosing between agents. The American Geriatric Society BEERs criteria for potentially inappropriate medication prescribing in older adults places all benzodiazepines and non-benzodiazepine benzodiazepine receptor agonists on its list of medications to avoid due to an increased risk of accidents and falls.[179]​ Current data are insufficient to determine whether dual orexin receptor antagonists offer a more favourable risk:benefit profile in older adults than non-benzodiazepine benzodiazepine receptor agonists. No definitive evidence supports an increased risk for one recommended class of hypnotic over the other. The authors do not recommend avoiding non-benzodiazepine benzodiazepine receptor agonists as a class for older adults. An individualised risk versus benefit profile should be determined that takes into account pertinent clinical factors, including co-existing comorbidity, medications, potential for drug-drug interactions, psychosocial factors, and patient values and preferences.

Discuss safety considerations with patients when prescribing hypnotics. Adverse events may include: complex sleep-related behaviours; central nervous system depressant effects; sleep paralysis, cataplexy, and excessive daytime sleepiness; hypnagogic or hypnopompic hallucinations; worsening of depression, suicidality, and impulsivity; misuse or abuse; dependence, tolerance, withdrawal, and rebound; and respiratory suppression. For a detailed discussion of safety considerations, contraindications, and cautions, see Management approach.

Doses should typically be taken immediately before bedtime or within 30 minutes of bedtime (depending on the drug), and more than 7 hours before planned awakening, due to the risk of next-day impairment. Higher doses may increase the risk of next-day impairment; use the lowest effective dose for the shortest possible treatment duration. Lower doses are recommended in older or debilitated patients.

The safety of long-term hypnotic use is unclear. Some guidelines (e.g., those from the American College of Physicians [APA]) recommend limiting treatment with hypnotics to the short term (4-5 weeks).[124] However, other guidelines do not suggest this limitation.[104] The US Food and Drug Administration (FDA) has approved all hypnotics since 2004 without limitation on the duration of treatment. If symptoms of insomnia recur following tapering down of the hypnotic (note that 1-2 days' worsening post discontinuation may represent rebound and will resolve) and the insomnia has not responded to behavioural treatments such as CBT-I, reinstitution of the previous hypnotic that was well tolerated should be considered. Intermittent dosing strategies for the long-term pharmacological treatment of insomnia can be considered.[210]​​ Specialist consultation (sleep medicine, psychiatrist, or insomnia specialist) and a collaborative care approach can assist with making such decisions and managing patients taking hypnotics over the longer term.

Primary options

zolpidem: 5 mg orally (immediate-release)/sublingually once daily at bedtime when required initially, increase dose according to response, maximum 10 mg/day; 6.25 mg orally (extended-release) once daily at bedtime when required initially, increase dose according to response, maximum 12.5 mg/day

More

OR

zaleplon: 5 mg orally once daily at bedtime when required initially, increase dose according to response, maximum 10-20 mg/day

OR

eszopiclone: 1 mg orally once daily at bedtime when required initially, increase dose according to response, maximum 3 mg/day

OR

ramelteon: 8 mg orally once daily at bedtime when required

OR

suvorexant: 10 mg orally once daily at bedtime when required initially, increase dose according to response, maximum 20 mg/day

OR

lemborexant: 5 mg orally once daily at bedtime when required initially, increase dose according to response, maximum 10 mg/day

OR

daridorexant: 25 mg orally once daily at bedtime when required initially, increase dose according to response, maximum 50 mg/day

Consider – sleep hygiene and relaxation techniques

Back
ONGOING
|
chronic insomnia
|
sleep-onset difficulties
Consider – 

sleep hygiene and relaxation techniques

Additional treatment recommended for SOME patients in selected patient group

Sleep hygiene and relaxation techniques are appropriate non-pharmacological treatment options for insomnia, especially in patients who prefer not to use medications, or who have suboptimal response to hypnotics.[112][113][114][115][116][117][118][119][120][121][122][123]

Sleep hygiene involves developing habits conducive to sleep, such as: avoiding stimulants, including nicotine and caffeine (as well as foods containing caffeine), for several hours before bedtime; avoiding alcohol around bedtime; avoiding blue-light-emitting digital devices (e.g., smart-phones/computers) close to bedtime; establishing a regular bedtime and rise time; avoiding excessive time in bed trying to sleep; avoiding extended daytime naps; accepting that sleep onset is involuntary and out of a person's control; adopting a more permissive approach to sleep by controlling and removing impediments but accepting that sleep will happen but not on demand, only trying to sleep when sleepy; taking regular exercise, especially in the late afternoon or early evening; allowing adequate time to unwind before going to bed; ensuring that the environment is conducive to sleep - making certain the bed and bedding are comfortable, the room is dark and quiet, and temperature and humidity are controlled; and avoiding clock-watching during the sleep period. Evidence for most non-pharmacological therapies for insomnia (excluding CBT-I) is limited, and insufficient to determine the relative efficacy of different non-pharmacological treatments.[124] There is insufficient evidence that sleep hygiene techniques alone are an effective treatment for insomnia, although they may be helpful when combined with other specific interventions.[125]

Relaxation techniques include progressive relaxation, guided imagery and meditation, and biofeedback. Progressive relaxation therapy involves the tensing and relaxation of muscles systematically from head to toe. Guided imagery and meditation instructs the patient to replace anxiety-ridden thoughts with pleasant, restful imagery. Biofeedback involves giving the patient immediate input as to their stress level and instructions on methods to reduce stress.

Consider – management of comorbid conditions

Back
ONGOING
|
chronic insomnia
|
sleep-onset difficulties
Consider – 

management of comorbid conditions

Additional treatment recommended for SOME patients in selected patient group

It is important to identify and optimise management of any comorbid medical conditions (e.g., chronic pain, hot flushes, hyperthyroidism, bladder disturbance, obstructive sleep apnoea, periodic limb movement disorder, or restless legs syndrome) or psychiatric disorders (e.g., mood disorders, anxiety disorders, substance use disorder, acute stress, or trauma) that may be contributing to chronic insomnia.[78]

Review the patient's usual medications to establish whether they include drugs that may cause or worsen insomnia, such as stimulants, antidepressants, corticosteroids, diuretics, or sedatives; if so, consider whether it is possible to lower the dosage and/or utilise the medication at another time of the day in order to reduce the impact on sleep.

Comorbid depression or anxiety: sedating antidepressants, such as mirtazapine or paroxetine, may be an appropriate choice for those with active depression and insomnia.[189]​ The efficacy and safety of mirtazapine (a tetracyclic antidepressant) for insomnia has not been established, and there is a risk of daytime sedation and metabolic adverse effects. Paroxetine, a selective serotonin-reuptake inhibitor (SSRI), confers potentially anticholinergic adverse effects and a substantial potential for drug-drug interactions due to its potent ability to inhibit cytochrome CYP2D6. Clinical judgement regarding the use of mirtazapine or paroxetine monotherapy for patients with depression, versus combined treatment with a non-sedating antidepressant and a hypnotic, must be made on an individualised case-by-case basis, which includes consideration of patient preference. Consult a specialist for guidance on selecting a suitable antidepressant or anxiolytic in these patients. One controlled study demonstrated that effective treatment of major depressive disorder with an SSRI allowed for seamless discontinuation of co-administered eszopiclone within 8 weeks.[190]

Comorbid dementia: little evidence exists to help guide pharmacological treatment options for patients with dementia and comorbid insomnia.[191]​ The authors recommend a similar approach to that recommended for hypnotic prescribing in older adults, first considering behavioural options for insomnia. Treating Alzheimer's disease optimally with a combination of an acetylcholinesterase inhibitor and memantine can help to alleviate sleep disturbance.[193][194]​ Behavioural and environmental modifications that allow for circadian realignment may be most helpful.[195][196]

1st line – cognitive behavioural therapy for insomnia (CBT-I)

Back
ONGOING
|
chronic insomnia
|
difficulty maintaining sleep and early awakening
1st line – 

cognitive behavioural therapy for insomnia (CBT-I)

Insomnia lasting 3 months or longer is considered chronic.[1][2]​​

CBT-I is a first-line therapy for chronic insomnia.​[124][129][130]​​​ It has been shown to effectively treat insomnia long term but requires patient commitment, sustained adherence, and practitioner training.[112][124][133][134][135]​​​​ Treating insomnia using CBT-I has been shown to improve quality of life, prevent depression, and possibly improve cardiometabolic biomarkers such as C-reactive protein and glycosylated haemoglobin (HbA1c).​[29][148][149]

The core principles of CBT-I are: learning to down-regulate arousal and induce relaxation; accepting the reality that sleep is out of control and surrendering to whatever happens regarding sleep; avoiding time cues; reducing time spent in bed not sleeping; sleep restriction if the person spends excessive time in bed without sleeping; and changing maladaptive beliefs about sleep.[108][109][110][111]

CBT-I is effective when employed under the guidance of a clinician, either in face-to-face individual or group settings, or via internet-based CBT-I (sometimes called digital CBT-I or dCBT-I). There is an increasing evidence base in favour of dCBT-I suggesting that it is comparable to in-person CBT-I in effectiveness.[107][112][139]​​[140]​​​ dCBT-I has the potential to increase patient access to CBT-I, thus offering patients and clinicians an increased choice among evidence-based treatments (CBT-I or pharmacotherapy) for insomnia.[129][141]

For insomnia during pregnancy (when the risk:benefit ratio typically shifts in favour of non-pharmacological options where possible) there is a limited evidence base for treatment; CBT-I (both face-to-face and online) appears to be a safe, effective, and acceptable first-line option.[131][132]

Consider – sleep hygiene and relaxation techniques

Back
ONGOING
|
chronic insomnia
|
difficulty maintaining sleep and early awakening
Consider – 

sleep hygiene and relaxation techniques

Additional treatment recommended for SOME patients in selected patient group

Sleep hygiene and relaxation techniques are appropriate non-pharmacological treatment options for insomnia.[112][113][114][115][116][117][118][119][120][121][122][123]

Sleep hygiene involves developing habits conducive to sleep, such as: avoiding stimulants, including nicotine and caffeine (as well as foods containing caffeine), for several hours before bedtime; avoiding alcohol around bedtime; avoiding blue-light-emitting digital devices (e.g., smart-phones/computers) close to bedtime; establishing a regular bedtime and rise time; avoiding excessive time in bed trying to sleep; avoiding extended daytime naps; accepting that sleep onset is involuntary and out of a person's control; adopting a more permissive approach to sleep by controlling and removing impediments but accepting that sleep will happen but not on demand, only trying to sleep when sleepy; taking regular exercise, especially in the late afternoon or early evening; allowing adequate time to unwind before going to bed; ensuring that the environment is conducive to sleep - making certain the bed and bedding are comfortable, the room is dark and quiet, and temperature and humidity are controlled; and avoiding clock-watching during the sleep period. Evidence for most non-pharmacological therapies for insomnia (excluding CBT-I) is limited, and insufficient to determine the relative efficacy of different non-pharmacological treatments.[124] There is insufficient evidence that sleep hygiene techniques alone are an effective treatment for insomnia, although they may be helpful when combined with other specific interventions.[125]

Relaxation techniques include progressive relaxation, guided imagery and meditation, and biofeedback. Progressive relaxation therapy involves the tensing and relaxation of muscles systematically from head to toe. Guided imagery and meditation instructs the patient to replace anxiety-ridden thoughts with pleasant, restful imagery. Biofeedback involves giving the patient immediate input as to their stress level and instructions on methods to reduce stress.

Consider – management of comorbid conditions

Back
ONGOING
|
chronic insomnia
|
difficulty maintaining sleep and early awakening
Consider – 

management of comorbid conditions

Additional treatment recommended for SOME patients in selected patient group

It is important to identify and optimise management of any comorbid medical conditions (e.g., chronic pain, hot flushes, hyperthyroidism, bladder disturbance, obstructive sleep apnoea, periodic limb movement disorder, or restless legs syndrome) or psychiatric disorders (e.g., mood disorders, anxiety disorders, substance use disorder, acute stress, or trauma) that may be contributing to chronic insomnia.[78]

Review the patient's usual medications to establish whether they include drugs that may cause or worsen insomnia, such as stimulants, antidepressants, corticosteroids, diuretics, or sedatives; if so, consider whether it is possible to lower the dosage and/or utilise the medication at another time of the day in order to reduce the impact on sleep.

Comorbid depression or anxiety: sedating antidepressants, such as mirtazapine or paroxetine, may be an appropriate choice for those with active depression and insomnia.[189]​ The efficacy and safety of mirtazapine (a tetracyclic antidepressant) for insomnia has not been established, and there is a risk of daytime sedation and metabolic adverse effects. Paroxetine, a selective serotonin-reuptake inhibitor (SSRI), confers potentially anticholinergic adverse effects and a substantial potential for drug-drug interactions due to its potent ability to inhibit cytochrome CYP2D6. Clinical judgement regarding the use of mirtazapine or paroxetine monotherapy for patients with depression, versus combined treatment with a non-sedating antidepressant and a hypnotic, must be made on an individualised case-by-case basis, which includes consideration of patient preference. Consult a specialist for guidance on selecting a suitable antidepressant or anxiolytic in these patients. One controlled study demonstrated that effective treatment of major depressive disorder with an SSRI allowed for seamless discontinuation of co-administered eszopiclone within 8 weeks.[190]

Comorbid dementia: little evidence exists to help guide pharmacological treatment options for patients with dementia and comorbid insomnia.[191]​ The authors recommend a similar approach to that recommended for hypnotic prescribing in older adults, first considering behavioural options for insomnia. Treating Alzheimer's disease optimally with a combination of an acetylcholinesterase inhibitor and memantine can help to alleviate sleep disturbance.[193][194]​ Behavioural and environmental modifications that allow for circadian realignment may be most helpful.[195][196]

2nd line – hypnotic

Back
ONGOING
|
chronic insomnia
|
difficulty maintaining sleep and early awakening
2nd line – 

hypnotic

Short-term and potentially longer-term provision of a hypnotic is an appropriate second-line option for patients with chronic insomnia. CBT-I should be offered first line but if the insomnia has become severe and the patient is in distress, or they are unable or unwilling to accept CBT-I, or have not responded to CBT-I, consider prescribing a hypnotic.

For patients with sleep maintenance difficulty alone, the non-benzodiazepine benzodiazepine receptor agonists with longer half-lives (i.e., zolpidem and eszopiclone), doxepin (a tricyclic antidepressant with antihistamine properties), and the dual orexin receptor agonist suvorexant demonstrate acceptable efficacy and safety.[104]​ Lemborexant and daridorexant show favourable profiles, based on sponsored phase 3 trials. All of these hypnotics have evidence of efficacy in decreasing wakefulness after sleep onset (WASO), increasing sleep efficiency (SE), and increasing total sleep time (TST). For patients experiencing both sleep onset and sleep maintenance difficulty, zolpidem, eszopiclone, and dual orexin receptor antagonists appear to be effective.

Zolpidem and eszopiclone have demonstrated reducing WASO, and increasing TST and sleep quality (SQ), based on both objective (polysomnography [PSG]) and subjective (sleep diary) measures in short-term studies.[104] Accumulating evidence supports the efficacy of dual orexin receptor antagonists in decreasing sleep onset latency (SOL), WASO, and TST based on objective (PSG) and subjective measures.[127][128][163][164][165][166]​​ Longer-term studies are lacking for these agents. Evidence supports the efficacy of doxepin in decreasing WASO, increasing SE, and increasing TST.[104] There exists no clear evidence to support the superiority of one recommended class of hypnotic over another.[173][174]​​ Choice of drug should be tailored to the insomnia phenotype and consideration of its safety and tolerability.

No hypnotics are indicated for use in pregnant women. For patients with insomnia during pregnancy, the risk:benefit ratio typically shifts in favour of non-pharmacological options where possible. Clinicians considering offering a pharmacological treatment for insomnia during pregnancy should seek specialist input (e.g., from a psychiatrist with expertise in prescribing during pregnancy, or from an obstetrician) due to the risks associated with common hypnotics during pregnancy.

Treating older patients with hypnotics presents a challenge because older patients are more prone to medication-related adverse events, yet there exists little quality evidence to support acceptable harm versus efficacy profiles in choosing between agents. The American Geriatric Society BEERs criteria for potentially inappropriate medication prescribing in older adults places all benzodiazepines and non-benzodiazepine benzodiazepine receptor agonists on its list of medications to avoid due to an increased risk of accidents and falls.[179]​ Current data are insufficient to determine whether dual orexin receptor antagonists offer a more favourable risk:benefit profile in older adults than non-benzodiazepine benzodiazepine receptor agonists. No definitive evidence supports an increased risk for one recommended class of hypnotic over the other. The authors do not recommend avoiding non-benzodiazepine benzodiazepine receptor agonists as a class for older adults. An individualised risk versus benefit profile should be determined that takes into account pertinent clinical factors, including co-existing comorbidity, medications, potential for drug-drug interactions, psychosocial factors, and patient values and preferences.

Discuss safety considerations with patients when prescribing hypnotics. Adverse events may include: complex sleep-related behaviours; central nervous system depressant effects; sleep paralysis, cataplexy, and excessive daytime sleepiness; hypnagogic or hypnopompic hallucinations; worsening of depression, suicidality, and impulsivity; misuse or abuse; dependence, tolerance, withdrawal, and rebound; and respiratory suppression. For a detailed discussion of safety considerations, contraindications, and cautions, see Management approach.

Doses should typically be taken immediately before bedtime or within 30 minutes of bedtime (depending on the drug), and more than 7 hours before planned awakening, due to the risk of next-day impairment. Higher doses may increase the risk of next-day impairment; use the lowest effective dose for the shortest possible treatment duration. Lower doses are recommended in older or debilitated patients.

The safety of long-term hypnotic use is unclear. Some guidelines (e.g., those from the American College of Physicians [APA]) recommend limiting treatment with hypnotics to the short term (4-5 weeks).[124] However, other guidelines do not suggest this limitation.[104] The US Food and Drug Administration (FDA) has approved all hypnotics since 2004 without limitation on the duration of treatment. If symptoms of insomnia recur following tapering down of the hypnotic (note that 1-2 days' worsening post discontinuation may represent rebound and will resolve) and the insomnia has not responded to behavioural treatments such as CBT-I, reinstitution of the previous hypnotic that was well tolerated should be considered. Intermittent dosing strategies for the long-term pharmacological treatment of insomnia can be considered.[210]​ Specialist consultation (sleep medicine, psychiatrist, or insomnia specialist) and a collaborative care approach can assist with making such decisions and managing patients taking hypnotics over the longer term.

Primary options

zolpidem: 6.25 mg orally (extended-release) once daily at bedtime when required initially, increase dose according to response, maximum 12.5 mg/day

More

OR

eszopiclone: 1 mg orally once daily at bedtime when required initially, increase dose according to response, maximum 3 mg/day

OR

suvorexant: 10 mg orally once daily at bedtime when required initially, increase dose according to response, maximum 20 mg/day

OR

lemborexant: 5 mg orally once daily at bedtime when required initially, increase dose according to response, maximum 10 mg/day

OR

daridorexant: 25 mg orally once daily at bedtime when required initially, increase dose according to response, maximum 50 mg/day

OR

doxepin: 3-6 mg orally once daily at bedtime when required

Consider – sleep hygiene and relaxation techniques

Back
ONGOING
|
chronic insomnia
|
difficulty maintaining sleep and early awakening
Consider – 

sleep hygiene and relaxation techniques

Additional treatment recommended for SOME patients in selected patient group

Sleep hygiene and relaxation techniques are appropriate non-pharmacological treatment options for insomnia, especially in patients who prefer not to use medications, or who have suboptimal response to hypnotics.[112][113][114][115][116][117][118][119][120][121][122][123]

Sleep hygiene involves developing habits conducive to sleep, such as: avoiding stimulants, including nicotine and caffeine (as well as foods containing caffeine), for several hours before bedtime; avoiding alcohol around bedtime; avoiding blue-light-emitting digital devices (e.g., smart-phones/computers) close to bedtime; establishing a regular bedtime and rise time; avoiding excessive time in bed trying to sleep; avoiding extended daytime naps; accepting that sleep onset is involuntary and out of a person's control; adopting a more permissive approach to sleep by controlling and removing impediments but accepting that sleep will happen but not on demand, only trying to sleep when sleepy; taking regular exercise, especially in the late afternoon or early evening; allowing adequate time to unwind before going to bed; ensuring that the environment is conducive to sleep - making certain the bed and bedding are comfortable, the room is dark and quiet, and temperature and humidity are controlled; and avoiding clock-watching during the sleep period. Evidence for most non-pharmacological therapies for insomnia (excluding CBT-I) is limited, and insufficient to determine the relative efficacy of different non-pharmacological treatments.[124] There is insufficient evidence that sleep hygiene techniques alone are an effective treatment for insomnia, although they may be helpful when combined with other specific interventions.[125]

Relaxation techniques include progressive relaxation, guided imagery and meditation, and biofeedback. Progressive relaxation therapy involves the tensing and relaxation of muscles systematically from head to toe. Guided imagery and meditation instructs the patient to replace anxiety-ridden thoughts with pleasant, restful imagery. Biofeedback involves giving the patient immediate input as to their stress level and instructions on methods to reduce stress.

Consider – management of comorbid conditions

Back
ONGOING
|
chronic insomnia
|
difficulty maintaining sleep and early awakening
Consider – 

management of comorbid conditions

Additional treatment recommended for SOME patients in selected patient group

It is important to identify and optimise management of any comorbid medical conditions (e.g., chronic pain, hot flushes, hyperthyroidism, bladder disturbance, obstructive sleep apnoea, periodic limb movement disorder, or restless legs syndrome) or psychiatric disorders (e.g., mood disorders, anxiety disorders, substance use disorder, acute stress, or trauma) that may be contributing to chronic insomnia.[78]

Review the patient's usual medications to establish whether they include drugs that may cause or worsen insomnia, such as stimulants, antidepressants, corticosteroids, diuretics, or sedatives; if so, consider whether it is possible to lower the dosage and/or utilise the medication at another time of the day in order to reduce the impact on sleep.

Comorbid depression or anxiety: sedating antidepressants, such as mirtazapine or paroxetine, may be an appropriate choice for those with active depression and insomnia.[189]​ The efficacy and safety of mirtazapine (a tetracyclic antidepressant) for insomnia has not been established, and there is a risk of daytime sedation and metabolic adverse effects. Paroxetine, a selective serotonin-reuptake inhibitor (SSRI), confers potentially anticholinergic adverse effects and a substantial potential for drug-drug interactions due to its potent ability to inhibit cytochrome CYP2D6. Clinical judgement regarding the use of mirtazapine or paroxetine monotherapy for patients with depression, versus combined treatment with a non-sedating antidepressant and a hypnotic, must be made on an individualised case-by-case basis, which includes consideration of patient preference. Consult a specialist for guidance on selecting a suitable antidepressant or anxiolytic in these patients. One controlled study demonstrated that effective treatment of major depressive disorder with an SSRI allowed for seamless discontinuation of co-administered eszopiclone within 8 weeks.[190]

Comorbid dementia: little evidence exists to help guide pharmacological treatment options for patients with dementia and comorbid insomnia.[191]​ The authors recommend a similar approach to that recommended for hypnotic prescribing in older adults, first considering behavioural options for insomnia. Treating Alzheimer's disease optimally with a combination of an acetylcholinesterase inhibitor and memantine can help to alleviate sleep disturbance.[193][194]​ Behavioural and environmental modifications that allow for circadian realignment may be most helpful.[195][196]

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