Highlights & Basics
- Insomnia is one of the most common complaints reported in primary care.
- Diagnosis is made primarily by patient interview. Sleep diaries, actigraphy, and polysomnography may assist in confirming diagnosis.
- Identification of the correct etiology is essential, as interventions differ and may be harmful in some cases if the diagnosis is incorrect.
- The significant morbidity of insomnia indicates that it is a condition that warrants treatment.
- Take an individualized approach to treatment, based on the patient's preferences, the severity of their insomnia, the risks versus benefits of treatment, and the availability of specialist treatment options such as cognitive behavioral therapy.
- For most patients, initial treatment with a behavioral therapy such as cognitive behavioral therapy for insomnia (CBT-I) is likely to provide the best balance between efficacy and safety.
Quick Reference
History & Exam
Key Factors
sleep partner complaints
delayed sleep onset
multiple or long awakenings
Other Factors
impairment of functioning
accidents
decreased sleep time
daytime napping
thyrotoxicosis
chronic pain
restless leg syndrome
enlarged tonsils or tongue
micrognathia and retrognathia
lateral narrowing of oropharynx
Diagnostics Tests
1st Tests to Order
Pittsburgh Sleep Quality Index (PSQI)
Insomnia Severity Index (ISI)
Stanford Sleepiness Scale (SSS)
Epworth Sleepiness Scale
Athens Insomnia Scale (AIS)
Other Tests to consider
polysomnography (PSG)
actigraphy
sleep diary
thyroid-stimulating hormone (TSH)
Treatment Options
acute
acute insomnia
sleep-onset difficulties
difficulty maintaining sleep or early awakening
ongoing
chronic insomnia
sleep-onset difficulties
difficulty maintaining sleep and early awakening
Definition
Classifications
International Classification of Sleep Disorders, third edition, text revision (ICSD-3-TR)
- Chronic insomnia disorder
- Short-term insomnia disorder
- Other insomnia disorder.
Vignette
Common Vignette 1
Common Vignette 2
Epidemiology
Etiology
Pathophysiology
Diagnostic Approach
History and risk factors
Physical exam
Sleep diary
Polysomnography (PSG)
Actigraphy
Laboratory studies
Risk Factors
History & Exam
Tests
Differential Diagnosis
Restless legs syndrome
Differentiating Signs/Symptoms
- Difficulty sleeping may occur due to discomfort or irresistible movements of the legs.
Differentiating Tests
- No differentiating tests. Diagnosis is based on clinical history.
Periodic limb movement disorder (PLMD)
Differentiating Signs/Symptoms
- PLMD is characterized by rhythmic movements of the limbs during sleep, which often disturbs sleep.
Differentiating Tests
- Polysomnography and electromyogram results help differentiate insomnia from PLMD.
Obstructive sleep apnea (OSA)
Differentiating Signs/Symptoms
- OSA is a sleep-related breathing disorder characterized by reductions in airflow during sleep.
Differentiating Tests
- Polysomnography with measures of nasal/oral airflow, respiratory effort, oxygen saturation, body position, and snoring sounds.
Circadian rhythm disorders
Differentiating Signs/Symptoms
- Circadian rhythm disorders are disorders of sleep timing, such as advanced sleep phase syndrome and delayed sleep phase syndrome.
Differentiating Tests
- Sleep history.
Differentiating Signs/Symptoms
- Habitual duration of sleep <5 hours nightly with normal sleep onset, continuity, and quality, and not associated with daytime impairment.
Differentiating Tests
- Sleep history.
Differentiating Signs/Symptoms
- Sleep disturbance due to behaviors that are not conducive to sleep (caffeine, alcohol use, or irregular sleep habits).
Differentiating Tests
- Sleep history.
Criteria
- Difficulty initiating or maintaining sleep or early-morning awakening that leads to dissatisfaction with sleep quantity or quality.
- Resulting sleep disturbance leads to impairment in social, occupational, educational, academic, behavioral, or other important areas of functioning, as well as causing significant distress.
- Patients experience this even with adequate opportunity to sleep, at least 3 nights per week and for at least 3 months.
- Insomnia is not explained by the presence of mental disorders, substance use, or medical conditions and is not associated with another sleep-wake disorder.
Treatment Approach
Management of acute insomnia
Management of chronic insomnia
Nonpharmacologic therapies for chronic insomnia
Pharmacologic therapies for chronic insomnia
- Hypnotics may be used alone or in conjunction with nonpharmacologic therapies.
- Newer nonbenzodiazepine benzodiazepine-receptor agonists such as eszopiclone, zaleplon, and zolpidem, and the melatonin MT1/MT2 receptor agonist ramelteon, appear to be safer for long-term use and are preferred over traditional benzodiazepines.[140]
- For patients with sleep-onset difficulty, hypnotics known to reduce sleep latency may be the first-line approach. These drugs include zolpidem, eszopiclone, zaleplon, and ramelteon.
- For patients with difficulty maintaining sleep, hypnotics known to reduce wakefulness after sleep onset are appropriate, including those with longer half-lives and formulations that extend the drug's duration of action. These include zolpidem (extended-release oral and sublingual formulations) and eszopiclone.
- Dual orexin receptor antagonists block both orexin receptors (OX1R and OX2R) and promote sleep through the binding inhibition of orexin A and B (neuropeptides that promote wakefulness).[141] They are indicated for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance in adults. Suvorexant has been shown to improve global and sleep outcomes compared with placebo.[98] [142] [143] [144] Phase 3 trials showed lemborexant improved total sleep time compared with placebo and similar improved sleep outcomes with daridorexant.[101] [102]
- Suvorexant is a dual orexin receptor antagonist that blocks both orexin receptors (OX1R and OX2R) and promotes sleep through the binding inhibition of orexin A and B (neuropeptides that promote wakefulness).[141] It has been shown to improve global and sleep outcomes compared with placebo.[98] [142] [143] [144] It is indicated for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance in adults.
- There is low-quality evidence that short‐term use of doxepin (a selective H1 receptor antagonist approved for treating sleep maintenance difficulties) at low doses results in a small improvement in sleep quality compared with placebo.[145]
- Both the therapeutic benefits and adverse effects of benzodiazepine and nonbenzodiazepine hypnotics are related to their shared binding to the same receptors, so distinctions based on the chemical structure are less important than their effective half-lives.
- There is currently a lack of evidence to guide pharmacologic treatment options in patients with dementia with comorbid insomnia.[154] Several treatments are in common clinical use for this indication, including sedating antidepressants and antipsychotic medications, despite considerable uncertainty about the risks versus benefits of treatment in this patient group. Due to their potential for adverse effects and unclear evidence for efficacy, some guidelines (e.g., the College of Family Physicians of Canada) recommend discontinuing antipsychotics after 3 months of use when used solely to manage negative behavioral/psychological symptoms associated with dementia. They also recommend discontinuing antipsychotics for adults with primary insomnia treated for any duration, or secondary insomnia in which underlying comorbidities are managed.[155] One Cochrane review looking into pharmacologic treatment for sleep disturbance in dementia found that, of the drugs examined, there was some evidence to support the use of low-dose trazodone, although more trial evidence is needed on the risks versus benefits of this drug.[156]
Safety information for common hypnotics
- Nonbenzodiazepine benzodiazepine-receptor agonists such as zaleplon, zolpidem, and eszopiclone are contraindicated in patients with a history of drug-induced complex sleep-related behaviors.
- Dual orexin receptor antagonists are contraindicated in patients with narcolepsy.
- Hypnotics should be used with caution in patients with a history of alcohol or substance misuse. They should also be avoided in pregnant women if possible; however, they may be used under specialist guidance only when the benefits outweigh the risks.
- There is significant ambiguity and overlap regarding adverse effects of hypnotics for particular patient groups. Adverse effects common to all classes of drug include:[157] [158] [159]
- Daytime sleepiness and sedation
- Dizziness and lightheadedness
- Motor incoordination
- Dependence
- Respiratory depression (e.g., worsening of obstructive sleep apnea).
- The risk of next-morning drowsiness applies to all drugs taken for insomnia, and the lowest dose that treats the patient's symptoms should be prescribed.
- The Food and Drug Administration (FDA) recommended lowering bedtime doses of zolpidem as data showed that blood levels in some patients may be high enough the morning after use to impair activities requiring alertness, including driving. The risk was highest in patients taking the extended-release formulation, and women appear to be more susceptible because they eliminate zolpidem more slowly from their bodies than men.[160]
- The FDA also warned that eszopiclone can cause next-day impairment of driving and other activities that require alertness, and the recommended starting dose has been lowered as a result.
- Higher doses of dual orexin receptor antagonists are also associated with drowsiness the following day, which could interfere with daily activities.
- Observational study and some case control evidence suggests that the use of hypnotics in general for insomnia is associated with increased risk for dementia, fractures, and major injury, particularly in older adults.[142] [161] [162] Confounding by indication may explain part of this risk, although there is some evidence to suggest that hypnotics may increase baseline risk further. Dose and half-life of the drug may also play a role in this risk.[163] [164] [165] [166] [167] It is sensible to offer nonpharmacologic treatments for older adults with insomnia wherever possible. If hypnotics are required for an older adult, this should be done with caution and preferably under specialist advice (e.g., from a geriatrician or psychiatrist); advise the patient and any caregivers about the increased risk of falls and fractures, and explore practical measures they can put in place to decrease this risk.[161]
- There have been several reports of rare, but serious, injuries and deaths resulting from complex sleep behaviors in people who have taken zolpidem, zaleplon, or eszopiclone. These may include sleepwalking, sleep driving, and carrying out other activities while not fully awake, such as turning on a stove or using a gun.[168]
- The safety of long-term hypnotic use is unclear. For this reason, some guidelines (e.g., those from the American College of Physicians [APA]) recommend limiting treatment with hypnotics to the short term (4-5 weeks).[103] However, other guidelines do not suggest this limitation.[100] The 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 after 4-5 weeks (and the insomnia has not responded to behavioral treatments such as CBT-I), the patient may require specialist review (e.g., sleep disorders center evaluation) before consideration of longer-term treatment with a hypnotic.
- Intermittent dosing strategies for the long-term pharmacologic treatment of insomnia can be considered.[169]
Treatment Options
acute insomnia
sleep-onset difficulties
cognitive behavioral therapy for insomnia (CBT-I)
Comments
- Acute insomnia may be considered to be insomnia lasting less than 4 weeks, occurring in response to an identifiable stressor; note that diagnostic criteria allow for symptoms lasting up to 3 months.[2]
- Treatment for acute insomnia may be required if insomnia is severe and causing significant distress. CBT-I is a first-line therapy for acute insomnia, although the evidence base for acute insomnia is limited compared with that for chronic insomnia.[85] There is RCT evidence that a single session of CBT-I is effective compared with treatment as usual for acute insomnia.[87]
- CBT 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 or dCBT). There is an increasing evidence base in favor of dCBT suggesting that it is comparable to in-person CBT in effectiveness.[88] [113] [114] [115] dCBT has the potential to increase patient access to CBT-I, thus offering patients and clinicians an increased choice amongst evidence based treatments (CBT or pharmacotherapy) for insomnia.[56] [116]
- For insomnia during pregnancy (when the risk:benefit ratio typically shifts in favor of nonpharmacologic 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.[105] [106]
- 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.[85]
sleep hygiene and relaxation techniques
Comments
- If CBT-I is unavailable or not wanted, sleep hygiene and relaxation techniques are appropriate nonpharmacologic treatment options for acute insomnia, especially in patients who prefer not to use medications, or have suboptimal response to hypnotics.[88] [89] [90] [91] [92] [93] [94] [95] [96] [97] [98] [99]
- 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.[124]
- Sleep hygiene involves the development of habits conducive to sleep, such as maintaining regular bedtimes and rise times, avoiding daytime naps, avoiding alcohol and electronic devices before bedtime, and avoiding caffeine.[123]
- 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.
- Stimulus control therapy involves some of the sleep hygiene preventive techniques working to create a less agitating environment. The bed is used for sexual activity or sleeping only. Additionally, if the patient has difficulty going to sleep within 15-20 minutes, they are to get out of bed and do a relaxing activity until tired. Then they may return to bed. If the activity is unsuccessful, they may get up again to repeat the exercise. Additionally, sitting in bed should be kept to a minimum, and only when they are ready for sleep and tired should they lie in bed.
- Sleep restriction therapy allows only minimal amounts of time in bed at nighttime at first, increasing time in bed as the days and nights pass. The idea is to create a consolidated, efficient sleep time.
- 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.[85]
hypnotic
Primary Options
- zolpidem
5-10 mg orally (immediate-release) once daily at bedtime when required; 5-10 mg sublingually once daily at bedtime when required; 6.25 to 12.5 mg orally (extended-release) once daily at bedtime when required
- zolpidem
- zaleplon
5-10 mg orally once daily at bedtime when required, maximum 20 mg/day
- zaleplon
- eszopiclone
1 mg orally once daily at bedtime when required initially, dose may be increased to 2-3 mg once daily at bedtime
- eszopiclone
- ramelteon
8 mg orally once daily at bedtime when required
- ramelteon
- suvorexant
10-20 mg orally once daily at bedtime when required
- suvorexant
- lemborexant
5-10 mg orally once daily at bedtime when required
- lemborexant
- daridorexant
25-50 mg orally once daily at bedtime when required
- daridorexant
Comments
- Short-term use of a hypnotic may be an option to consider in patients with acute insomnia that is severe or associated with substantial distress, for example in settings where there is limited or no access to behavioral treatments, if the patient is unable to participate in behavioral therapy, or if behavioral therapy is ineffective.[85][100]
- For patients with insomnia during pregnancy, the risk:benefit ratio typically shifts in favor of nonpharmacologic options where possible. Clinicians considering offering a pharmacologic 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.
- Given the potential for increased risk associated with hypnotics in older adults (e.g., dementia, fractures, and major injury), it is sensible to offer nonpharmacologic treatments for older adults with insomnia wherever possible.[142] [161] [162] If hypnotics are required for an older adult, this should be done with caution and preferably under specialist advice (e.g., from a geriatrician or psychiatrist); advise the patient and any caregivers about the increased risk of falls and fractures, and explore practical measures they can put in place to decrease this risk.[161]
- There is a risk of next-morning drowsiness with all drugs taken for insomnia, and the lowest dose that treats the patient's symptoms should be prescribed.
- There have been several reports of rare, but serious, injuries and deaths resulting from complex sleep behaviors in people who have taken zolpidem, zaleplon, or eszopiclone. These may include sleepwalking, sleep driving, and carrying out other activities while not fully awake, such as turning on a stove or using a gun.[168] Nonbenzodiazepine benzodiazepine-receptor agonists such as zaleplon, zolpidem, and eszopiclone are contraindicated in patients with a history of drug-induced complex sleep-related behaviors.
- Zolpidem (extended-release formulation) has been shown to significantly reduce latency to persistent sleep and increase total sleep time in older patients with insomnia.[170]
- The Food and Drug Administration (FDA) recommended lowering bedtime doses of zolpidem as data showed that blood levels in some patients may be high enough the morning after use to impair activities that require alertness, including driving. The risk was highest in patients taking the extended-release formulation, and women appear to be more susceptible because they eliminate zolpidem more slowly from their bodies than men.[160]
- The FDA also warned that eszopiclone can cause next-day impairment of driving and other activities that require alertness, and the recommended starting dose has been lowered as a result.
- Dual orexin receptor antagonists (e.g., suvorexant, lemborexant, daridorexant) block both orexin receptors (OX1R and OX2R) and promote sleep through the binding inhibition of orexin A and B (neuropeptides that promote wakefulness).[141] They are indicated for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance in adults. Suvorexant has been shown to improve global and sleep outcomes compared with placebo.[98] [142] [143] [144] Phase 3 trials showed lemborexant improved total sleep time compared with placebo and similar improved sleep outcomes with daridorexant.[101] [102] Higher doses may be associated with drowsiness the following day, which could interfere with daily activities. Dual orexin receptor antagonists are contraindicated in patients with narcolepsy.
- 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.[85]
sleep hygiene and relaxation techniques
Comments
- Evidence for most nonpharmacologic therapies for insomnia (excluding CBT-I) is limited, and insufficient to determine the relative efficacy of different nonpharmacologic treatments.[103] If CBT-I is unavailable or not wanted, sleep hygiene and relaxation techniques are appropriate nonpharmacologic treatment options for acute insomnia, especially in patients who prefer not to use medications, or have suboptimal response to hypnotics.[88] [89] [90] [91] [92] [93] [94] [95] [96] [97] [98] [99]
- 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.[124]
- Sleep hygiene involves the development of habits conducive to sleep, such as maintaining regular bedtimes and rise times, avoiding daytime naps, avoiding alcohol and electronic devices before bedtime, and avoiding caffeine.[123]
- 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.
- Stimulus control therapy involves some of the sleep hygiene preventive techniques working to create a less agitating environment. The bed is used for sexual activity or sleeping only. Additionally, if the patient has difficulty going to sleep within 15-20 minutes, they are to get out of bed and do a relaxing activity until tired. Then they may return to bed. If the activity is unsuccessful, they may get up again to repeat the exercise. Additionally, sitting in bed should be kept to a minimum, and only when they are ready for sleep and tired should they lie in bed.
- Sleep restriction therapy allows only minimal amounts of time in bed at nighttime at first, increasing time in bed as the days and nights pass. The idea is to create a consolidated, efficient sleep time.
- 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.[85]
difficulty maintaining sleep or early awakening
cognitive behavioral therapy for insomnia (CBT-I)
Comments
- Acute insomnia may be considered to be insomnia lasting less than 4 weeks, occurring in response to an identifiable stressor; note that diagnostic criteria allow for symptoms lasting up to 3 months.[2]
- Treatment for acute insomnia may be required if insomnia is severe and causing significant distress. CBT-I is a first-line therapy for acute insomnia, although the evidence base for its efficacy is relatively limited compared with that for chronic insomnia.[85] There is RCT evidence that a single session of CBT-I is effective compared with treatment as usual for acute insomnia.[87]
- CBT 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 or dCBT). There is an increasing evidence base in favor of dCBT suggesting that it is comparable to in-person CBT in effectiveness.[88] [113] [114] [115] dCBT has the potential to increase patient access to CBT-I, thus offering patients and clinicians an increased choice amongst evidence based treatments (CBT or pharmacotherapy) for insomnia.[56] [116]
- 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.[85]
sleep hygiene and relaxation techniques
Comments
- Evidence for most nonpharmacologic therapies for insomnia (excluding CBT-I) is limited, and insufficient to determine the relative efficacy of different nonpharmacologic treatments.[103] If CBT-I is unavailable or not wanted, sleep hygiene and relaxation techniques are appropriate nonpharmacologic treatment options for acute insomnia, especially in patients who prefer not to use medications, or have suboptimal response to hypnotics.[88] [89] [90] [91] [92] [93] [94] [95] [96] [97] [98] [99]
- 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.[124]
- Sleep hygiene involves the development of habits conducive to sleep, such as maintaining regular bedtimes and rise times, avoiding daytime naps, avoiding alcohol and electronic devices before bedtime, and avoiding caffeine.[123]
- 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.
- Stimulus control therapy involves some of the sleep hygiene preventive techniques working to create a less agitating environment. The bed is used for sexual activity or sleeping only. Additionally, if the patient has difficulty going to sleep within 15-20 minutes, they are to get out of bed and do a relaxing activity until tired. Then they may return to bed. If the activity is unsuccessful, they may get up again to repeat the exercise. Additionally, sitting in bed should be kept to a minimum, and only when they are ready for sleep and tired should they lie in bed.
- Sleep restriction therapy allows only minimal amounts of time in bed at nighttime at first, increasing time in bed as the days and nights pass. The idea is to create a consolidated, efficient sleep time.
- 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.[85]
hypnotic
Primary Options
- zolpidem
6.25 to 12.5 mg orally (extended-release) once daily at bedtime when required; 1.75 to 3.5 mg sublingually once daily at bedtime when required
- zolpidem
- eszopiclone
1 mg orally once daily at bedtime when required initially, dose may be increased to 2-3 mg once daily at bedtime
- eszopiclone
- suvorexant
10-20 mg orally once daily at bedtime when required
- suvorexant
- lemborexant
5-10 mg orally once daily at bedtime when required
- lemborexant
- daridorexant
25-50 mg orally once daily at bedtime when required
- daridorexant
Secondary Options
- doxepin
3-6 mg orally once daily at bedtime when required
- doxepin
Comments
- Short-term use of a hypnotic may be an option to consider in patients with acute insomnia is severe or associated with substantial distress, for example in settings where there is limited or no access to behavioral treatments, if the patient is unable to participate in behavioral therapy, or if behavioral therapy is ineffective.[85][100]
- For patients with insomnia during pregnancy, the risk:benefit ratio typically shifts in favor of nonpharmacologic 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.
- Given the potential for increased risk associated with hypnotics in older adults (e.g., dementia, fractures, and major injury), it is sensible to offer nonpharmacologic treatments for older adults with insomnia wherever possible.[142] [161] [162] If hypnotics are required for an older adult, this should be done with caution and preferably under specialist advice (e.g., from a geriatrician or psychiatrist); advise the patient and any caregivers about the increased risk of falls and fractures, and explore practical measures they can put in place to decrease this risk.[161]
- There is a risk of next-morning drowsiness with all drugs taken for insomnia, and the lowest dose that treats the patient's symptoms should be prescribed.
- There have been several reports of rare, but serious, injuries and deaths resulting from complex sleep behaviors in people who have taken zolpidem or eszopiclone. These may include sleepwalking, sleep driving, and carrying out other activities while not fully awake, such as turning on a stove or using a gun.[168] Nonbenzodiazepine benzodiazepine-receptor agonists such as zolpidem and eszopiclone are contraindicated in patients with a history of drug-induced complex sleep-related behaviors.
- The Food and Drug Administration (FDA) recommended lowering bedtime doses of zolpidem as data showed that blood levels in some patients may be high enough the morning after use to impair activities that require alertness, including driving. The risk was highest in patients taking the extended-release formulation, and women appear to be more susceptible because they eliminate zolpidem more slowly from their bodies than men.[160]
- The FDA also warned that eszopiclone can cause next-day impairment of driving and other activities that require alertness, and the recommended starting dose has been lowered as a result.
- Dual orexin receptor antagonists (e.g., suvorexant, lemborexant, daridorexant) block both orexin receptors (OX1R and OX2R) and promote sleep through the binding inhibition of orexin A and B (neuropeptides that promote wakefulness).[141] They are indicated for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance in adults. Suvorexant has been shown to improve global and sleep outcomes compared with placebo.[98] [142] [143] [144] Phase 3 trials showed lemborexant improved total sleep time compared with placebo and similar improved sleep outcomes with daridorexant.[101] [102] Higher doses may be associated with drowsiness the following day, which could interfere with daily activities. Dual orexin receptor antagonists are contraindicated in patients with narcolepsy.
- There is low-quality evidence that short‐term use of doxepin (a selective H1 receptor antagonist approved for treating sleep maintenance difficulties) at low doses results in a small improvement in sleep quality compared with placebo.[145]
- 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.[85]
sleep hygiene and relaxation techniques
Comments
- Evidence for most nonpharmacologic therapies for insomnia (excluding CBT-I) is limited, and insufficient to determine the relative efficacy of different nonpharmacologic treatments.[103] If CBT-I is unavailable or not wanted, sleep hygiene and relaxation techniques are appropriate nonpharmacologic treatment options for acute insomnia, especially in patients who prefer not to use medications, or have suboptimal response to hypnotics.[88] [89] [90] [91] [92] [93] [94] [95] [96] [97] [98] [99]
- 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.[124]
- Sleep hygiene involves the development of habits conducive to sleep, such as maintaining regular bedtimes and rise times, avoiding daytime naps, avoiding alcohol and electronic devices before bedtime, and avoiding caffeine.[123]
- 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.
- Stimulus control therapy involves some of the sleep hygiene preventive techniques working to create a less agitating environment. The bed is used for sexual activity or sleeping only. Additionally, if the patient has difficulty going to sleep within 15-20 minutes, they are to get out of bed and do a relaxing activity until tired. Then they may return to bed. If the activity is unsuccessful, they may get up again to repeat the exercise. Additionally, sitting in bed should be kept to a minimum, and only when they are ready for sleep and tired should they lie in bed.
- Sleep restriction therapy allows only minimal amounts of time in bed at nighttime at first, increasing time in bed as the days and nights pass. The idea is to create a consolidated, efficient sleep time.
- 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.[85]
chronic insomnia
sleep-onset difficulties
cognitive behavioral therapy for insomnia (CBT-I)
Comments
- Chronic insomnia may be considered to be insomnia lasting 4 weeks or more, although diagnostic criteria stipulate a duration of 3 months of symptoms.[2]
- CBT-I is a first-line therapy for chronic insomnia.[103]
- It has been shown to effectively treat insomnia long term but requires patient commitment and practitioner training.[88] [103] [107] [108] [109] CBT 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 or dCBT). There is an increasing evidence base in favor of dCBT suggesting that it is comparable to in-person CBT in effectiveness.[88] [113] [114] [115] dCBT has the potential to increase patient access to CBT-I, thus offering patients and clinicians an increased choice amongst evidence based treatments (CBT or pharmacotherapy) for insomnia.[56] [116]
sleep hygiene and relaxation techniques
Comments
- Evidence for most nonpharmacologic therapies for insomnia (excluding CBT-I) is limited, and insufficient to determine the relative efficacy of different nonpharmacologic treatments.[103] If CBT-I is unavailable or not wanted, sleep hygiene and relaxation techniques are appropriate nonpharmacologic treatment options for insomnia, especially in patients who prefer not to use medications, or have suboptimal response to hypnotics.[88] [89] [90] [91] [92] [93] [94] [95] [96] [97] [98] [99]
- 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.[124]
- Sleep hygiene involves the development of habits conducive to sleep, such as maintaining regular bedtimes and rise times, avoiding daytime naps, avoiding alcohol and electronic devices before bedtime, and avoiding caffeine.[123]
- 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.
- Stimulus control therapy involves some of the sleep hygiene preventive techniques working to create a less agitating environment. The bed is used for sexual activity or sleeping only. Additionally, if the patient has difficulty going to sleep within 15-20 minutes, they are to get out of bed and do a relaxing activity until tired. Then they may return to bed. If the activity is unsuccessful, they may get up again to repeat the exercise. Additionally, sitting in bed should be kept to a minimum, and only when they are ready for sleep and tired should they lie in bed.
- Sleep restriction therapy allows only minimal amounts of time in bed at nighttime at first, increasing time in bed as the days and nights pass. The idea is to create a consolidated, efficient sleep time.
hypnotic
Primary Options
- zolpidem
5-10 mg orally (immediate-release) once daily at bedtime when required; 5-10 mg sublingually once daily at bedtime when required; 6.25 to 12.5 mg orally (extended-release) once daily at bedtime when required
- zolpidem
- eszopiclone
1 mg orally once daily at bedtime when required initially, dose may be increased to 2-3 mg once daily at bedtime
- eszopiclone
- zaleplon
5-10 mg orally once daily at bedtime when required, maximum 20 mg/day
- zaleplon
- ramelteon
8 mg orally once daily at bedtime when required
- ramelteon
- suvorexant
10-20 mg orally once daily at bedtime when required
- suvorexant
- lemborexant
5-10 mg orally once daily at bedtime when required
- lemborexant
- daridorexant
25-50 mg orally once daily at bedtime when required
- daridorexant
Secondary Options
- trazodone
25-150 mg orally once daily at bedtime when required
- trazodone
Comments
- Hypnotics are an alternative option for insomnia in settings where there is limited or no access to behavioral treatments, if the patient is unable to participate in behavioral therapy, or if behavioral therapy is ineffective.[100]
- For patients with insomnia during pregnancy, the risk:benefit ratio typically shifts in favor of nonpharmacologic 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.
- Given the potential for increased risk associated with hypnotics in older adults (e.g., dementia, fractures, and major injury), it is sensible to offer nonpharmacologic treatments for older adults with insomnia wherever possible.[142] [161] [162] If hypnotics are required for an older adult, this should be done with caution and preferably under specialist advice (e.g., from a geriatrician or psychiatrist); advise the patient and any caregivers about the increased risk of falls and fractures, and explore practical measures they can put in place to decrease this risk.[161]
- There is a risk of next-morning drowsiness with all drugs taken for insomnia, and the lowest dose that treats the patient's symptoms should be prescribed.
- There have been several reports of rare, but serious, injuries and deaths resulting from complex sleep behaviors in people who have taken zolpidem, zaleplon, or eszopiclone. These may include sleepwalking, sleep driving, and carrying out other activities while not fully awake, such as turning on a stove or using a gun.[168]
- The Food and Drug Administration (FDA) recommended lowering bedtime doses of zolpidem as data showed that blood levels in some patients may be high enough the morning after use to impair activities that require alertness, including driving. The risk was highest in patients taking the extended-release formulation, and women appear to be more susceptible because they eliminate zolpidem more slowly from their bodies than men.[160]
- The FDA also warned that eszopiclone can cause next-day impairment of driving and other activities that require alertness, and the recommended starting dose has been lowered as a result.
- Dual orexin receptor antagonists (e.g., suvorexant, lemborexant, daridorexant) block both orexin receptors (OX1R and OX2R) and promote sleep through the binding inhibition of orexin A and B (neuropeptides that promote wakefulness).[141] They are indicated for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance in adults. Suvorexant has been shown to improve global and sleep outcomes compared with placebo.[98] [142] [143] [144] Phase 3 trials showed lemborexant improved total sleep time compared with placebo and similar improved sleep outcomes with daridorexant.[101] [102] Higher doses may be associated with drowsiness the following day, which could interfere with daily activities. Dual orexin receptor antagonists are contraindicated in patients with narcolepsy.
- 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).[103] However, other guidelines do not suggest this limitation.[100] The 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 after 4-5 weeks (and the insomnia has not responded to behavioral treatments such as cognitive behavioral therapy for insomnia), the patient may require specialist review (e.g., sleep disorders center evaluation) before consideration of longer-term treatment with a hypnotic. Intermittent dosing strategies for the long-term pharmacologic treatment of insomnia can be considered.[169]
sleep hygiene and relaxation techniques
Comments
- Evidence for most nonpharmacologic therapies for insomnia (excluding CBT-I) is limited, and insufficient to determine the relative efficacy of different nonpharmacologic treatments.[103] If CBT-I is unavailable or not wanted, sleep hygiene and relaxation techniques are appropriate nonpharmacologic treatment options for insomnia, especially in patients who prefer not to use medications, or have suboptimal response to hypnotics.[88] [89] [90] [91] [92] [93] [94] [95] [96] [97] [98] [99]
- 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.[124]
- Sleep hygiene involves the development of habits conducive to sleep, such as maintaining regular bedtimes and rise times, avoiding daytime naps, avoiding alcohol and electronic devices before bedtime, and avoiding caffeine.[123]
- 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.
- Stimulus control therapy involves some of the sleep hygiene preventive techniques working to create a less agitating environment. The bed is used for sexual activity or sleeping only. Additionally, if the patient has difficulty going to sleep within 15-20 minutes, they are to get out of bed and do a relaxing activity until tired. Then they may return to bed. If the activity is unsuccessful, they may get up again to repeat the exercise. Additionally, sitting in bed should be kept to a minimum, and only when they are ready for sleep and tired should they lie in bed.
- Sleep restriction therapy allows only minimal amounts of time in bed at nighttime at first, increasing time in bed as the days and nights pass. The idea is to create a consolidated, efficient sleep time.
antidepressant or anxiolytic
Comments
- In patients with comorbid depression, hypnotics have been shown to be efficacious when used in combination with an antidepressant.[149]
- Consult a specialist for guidance on selecting a suitable antidepressant or anxiolytic in these patients.
difficulty maintaining sleep and early awakening
cognitive behavioral therapy for insomnia (CBT-I)
Comments
- Chronic insomnia may be considered to be insomnia lasting 4 weeks or more, although diagnostic criteria stipulate a duration of 3 months of symptoms.[2]
- CBT-I is a first-line therapy for chronic insomnia.[103]
- Has been shown to effectively treat insomnia long term but requires patient commitment and practitioner training.[88] [103] [107] [108] [109] CBT 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 or dCBT). There is an increasing evidence base in favor of dCBT suggesting that it is comparable to in-person CBT in effectiveness.[88] [113] [114] [115] dCBT has the potential to increase patient access to CBT-I, thus offering patients and clinicians an increased choice amongst evidence based treatments (CBT or pharmacotherapy) for insomnia.[56] [116]
sleep hygiene and relaxation techniques
Comments
- Evidence for most nonpharmacologic therapies for insomnia (excluding CBT-I) is limited, and insufficient to determine the relative efficacy of different nonpharmacologic treatments.[103] If CBT-I is unavailable or not wanted, sleep hygiene and relaxation techniques are appropriate nonpharmacologic treatment options for insomnia, especially in patients who prefer not to use medications, or have suboptimal response to hypnotics.[88] [89] [90] [91] [92] [93] [94] [95] [96] [97] [98] [99]
- 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.[124]
- Sleep hygiene involves the development of habits conducive to sleep, such as maintaining regular bedtimes and rise times, avoiding daytime naps, avoiding alcohol and electronic devices before bedtime, and avoiding caffeine.[123]
- 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.
- Stimulus control therapy involves some of the sleep hygiene preventive techniques working to create a less agitating environment. The bed is used for sexual activity or sleeping only. Additionally, if the patient has difficulty going to sleep within 15-20 minutes, they are to get out of bed and do a relaxing activity until tired. Then they may return to bed. If the activity is unsuccessful, they may get up again to repeat the exercise. Additionally, sitting in bed should be kept to a minimum, and only when they are ready for sleep and tired should they lie in bed.
- Sleep restriction therapy allows only minimal amounts of time in bed at nighttime at first, increasing time in bed as the days and nights pass. The idea is to create a consolidated, efficient sleep time.
hypnotic
Primary Options
- zolpidem
6.25 to 12.5 mg orally (extended-release) once daily at bedtime when required; 1.75 to 3.5 mg sublingually once daily at bedtime when required
- zolpidem
- eszopiclone
1 mg orally once daily at bedtime when required initially, dose may be increased to 2-3 mg once daily at bedtime
- eszopiclone
- suvorexant
10-20 mg orally once daily at bedtime when required
- suvorexant
- lemborexant
5-10 mg orally once daily at bedtime when required
- lemborexant
- daridorexant
25-50 mg orally once daily at bedtime when required
- daridorexant
Secondary Options
- doxepin
3-6 mg orally once daily at bedtime when required
- doxepin
- trazodone
25-150 mg orally once daily at bedtime when required
- trazodone
Comments
- Hypnotics are an alternative option for insomnia in settings where there is limited or no access to behavioral treatments, if the patient is unable to participate in behavioral therapy, or if behavioral therapy is ineffective.[100]
- For patients with insomnia during pregnancy, the risk:benefit ratio typically shifts in favor of nonpharmacologic 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.
- Given the potential for increased risk associated with hypnotics in older adults (e.g., dementia, fractures, and major injury), it is sensible to offer nonpharmacologic treatments for older adults with insomnia wherever possible.[142] [161] [162] If hypnotics are required for an older adult, this should be done with caution and preferably under specialist advice (e.g., from a geriatrician or psychiatrist); advise the patient and any caregivers about the increased risk of falls and fractures, and explore practical measures they can put in place to decrease this risk.[161]
- There is a risk of next-morning drowsiness with all drugs taken for insomnia, and the lowest dose that treats the patient's symptoms should be prescribed.
- There have been several reports of rare, but serious, injuries and deaths resulting from complex sleep behaviors in people who have taken zolpidem or eszopiclone. These may include sleepwalking, sleep driving, and carrying out other activities while not fully awake, such as turning on a stove or using a gun.[168]
- The Food and Drug Administration (FDA) recommended lowering bedtime doses of zolpidem as data showed that blood levels in some patients may be high enough the morning after use to impair activities that require alertness, including driving. The risk was highest in patients taking the extended-release formulation, and women appear to be more susceptible because they eliminate zolpidem more slowly from their bodies than men.[160]
- The FDA also warned that eszopiclone can cause next-day impairment of driving and other activities that require alertness, and the recommended starting dose has been lowered as a result.
- Dual orexin receptor antagonists (e.g., suvorexant, lemborexant, daridorexant) block both orexin receptors (OX1R and OX2R) and promote sleep through the binding inhibition of orexin A and B (neuropeptides that promote wakefulness).[141] They are indicated for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance in adults. Suvorexant has been shown to improve global and sleep outcomes compared with placebo.[98] [142] [143] [144] Phase 3 trials showed lemborexant improved total sleep time compared with placebo and similar improved sleep outcomes with daridorexant.[101] [102] Higher doses may be associated with drowsiness the following day, which could interfere with daily activities. Dual orexin receptor antagonists are contraindicated in patients with narcolepsy.
- There is low-quality evidence that short‐term use of doxepin (a selective H1 receptor antagonist approved for treating sleep maintenance difficulties) at low doses results in a small improvement in sleep quality compared with placebo.[145]
- 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).[103] However, other guidelines do not suggest this limitation.[100] The 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 after 4-5 weeks (and the insomnia has not responded to behavioral treatments such as cognitive behavioral therapy for insomnia), the patient may require specialist review (e.g., sleep disorders center evaluation) before consideration of longer-term treatment with a hypnotic. Intermittent dosing strategies for the long-term pharmacologic treatment of insomnia can be considered.[169]
sleep hygiene and relaxation techniques
Comments
- Evidence for most nonpharmacologic therapies for insomnia (excluding CBT-I) is limited, and insufficient to determine the relative efficacy of different nonpharmacologic treatments.[103] If CBT-I is unavailable or not wanted, sleep hygiene and relaxation techniques are appropriate nonpharmacologic treatment options for insomnia, especially in patients who prefer not to use medications, or have suboptimal response to hypnotics.[88] [89] [90] [91] [92] [93] [94] [95] [96] [97] [98] [99]
- 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.[124]
- Sleep hygiene involves the development of habits conducive to sleep, such as maintaining regular bedtimes and rise times, avoiding daytime naps, avoiding alcohol and electronic devices before bedtime, and avoiding caffeine.[123]
- 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.
- Stimulus control therapy involves some of the sleep hygiene preventive techniques working to create a less agitating environment. The bed is used for sexual activity or sleeping only. Additionally, if the patient has difficulty going to sleep within 15-20 minutes, they are to get out of bed and do a relaxing activity until tired. Then they may return to bed. If the activity is unsuccessful, they may get up again to repeat the exercise. Additionally, sitting in bed should be kept to a minimum, and only when they are ready for sleep and tired should they lie in bed.
- Sleep restriction therapy allows only minimal amounts of time in bed at nighttime at first, increasing time in bed as the days and nights pass. The idea is to create a consolidated, efficient sleep time.
antidepressant or anxiolytic
Comments
- In patients with comorbid depression, hypnotics have been shown to be efficacious when used in combination with an antidepressant.[149]
- Consult a specialist for guidance on selecting a suitable antidepressant or anxiolytic in these patients.
Emerging Tx
Melatonin
5HT2A antagonists
Anticonvulsants
Prevention
Primary Prevention
Follow-Up Overview
Prognosis
Monitoring
Complications
Citations
American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 5th ed., text revision (DSM-5-TR). Washington, DC: American Psychiatric Publishing; 2022.[Full Text]
Ford DE, Kamerow DB. Epidemiologic study of sleep disturbances and psychiatric disorders: an opportunity for prevention? JAMA. 1989 Sep 15;262(11):1479-84.[Abstract]
Sun J, Kang J, Wang P, et al. Self-relaxation training can improve sleep quality and cognitive functions in the older: a one-year randomised controlled trial. J Clin Nurs. 2013 May;22(9-10):1270-80.[Abstract]
Brasure M, Fuchs E, MacDonald R, et al. Psychological and behavioral interventions for managing insomnia disorder: an evidence report for a clinical practice guideline by the American College of Physicians. Ann Intern Med. 2016 Jul 19;165(2):113-24.[Abstract]
Sateia MJ, Buysse DJ, Krystal AD, et al. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2017 Feb 15;13(2):307-49.[Abstract][Full Text]
Qaseem A, Kansagara D, Forciea MA, et al. Management of chronic insomnia disorder in adults: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2016 Jul 19;165(2):125-33.[Abstract][Full Text]
Deschenes CL, McCurry SM. Current treatments for sleep disturbances in individuals with dementia. Curr Psychiatry Rep. 2009 Feb;11(1):20-6.[Abstract][Full Text]
Sin CW, Ho JS, Chung JW. Systematic review on the effectiveness of caffeine abstinence on the quality of sleep. J Clin Nurs. 2009 Jan;18(1):13-21.[Abstract]
Edinger JD, Arnedt JT, Bertisch SM, et al. Behavioral and psychological treatments for chronic insomnia disorder in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2021 Feb 1;17(2):255-62.[Abstract][Full Text]
Wilt TJ, MacDonald R, Brasure M, et al. Pharmacologic treatment of insomnia disorder: an evidence report for a clinical practice guideline by the American College of Physicians. Ann Intern Med. 2016 Jul 19;165(2):103-12.[Abstract]
Krystal AD, Erman M, Zammit GK, et al. Long-term efficacy and safety of zolpidem extended-release 12.5 mg, administered 3 to 7 nights per week for 24 weeks, in patients with chronic primary insomnia: a 6-month, randomized, double-blind, placebo-controlled, parallel-group, multicenter study. Sleep. 2008 Jan;31(1):79-90.[Abstract][Full Text]
Mayer G, Wang-Weigand S, Roth-Schechter B, et al. Efficacy and safety of 6-month nightly ramelteon administration in adults with chronic primary insomnia. Sleep. 2009 Mar;32(3):351-60.[Abstract][Full Text]
Sateia MJ, Buysse DJ, Krystal AD, et al. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2017 Feb 15;13(2):307-49.[Abstract][Full Text]
Inagaki T, Miyaoka T, Tsuji S, et al. Adverse reactions to zolpidem: case reports and a review of the literature. Prim Care Companion J Clin Psychiatry. 2010;12(6):PCC.09r00849.[Abstract][Full Text]
1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 5th ed., text revision (DSM-5-TR). Washington, DC: American Psychiatric Publishing; 2022.[Full Text]
2. American Academy of Sleep Medicine. The AASM international classification of sleep disorders - third edition, text revision (ICSD-3-TR). Jun 2023 [internet publication].[Full Text]
3. Ohayon MM. Epidemiology of insomnia: what we know and what we still need to learn. Sleep Med Rev. 2002 Apr;6(2):97-111.[Abstract]
4. Johnson EO, Roehrs T, Roth T, et al. Epidemiology of alcohol and medication as aids to sleep in early adulthood. Sleep. 1998 Mar 15;21(2):178-86.[Abstract]
5. Ford ES, Wheaton AG, Cunningham TJ, et al. Trends in outpatient visits for insomnia, sleep apnea, and prescriptions for sleep medications among US adults: findings from the National Ambulatory Medical Care survey 1999-2010. Sleep. 2014 Aug 1;37(8):1283-93.[Abstract][Full Text]
6. Breslau N, Roth T, Rosenthal L, et al. Sleep disturbance and psychiatric disorders: a longitudinal epidemiological study of young adults. Biol Psychiatry. 1996 Mar 15;39(6):411-8.[Abstract]
7. Mellinger GD, Balter MB, Uhlenhuth EH. Insomnia and its treatment: prevalence and correlates. Arch Gen Psychiatry. 1985 Mar;42(3):225-32.[Abstract]
8. Lindberg E, Janson C, Gislason T, et al. Sleep disturbances in a young adult population: can gender differences be explained by differences in psychological status? Sleep. 1997 Jun;20(6):381-7.[Abstract]
9. Wickwire EM, Shaya FT, Scharf SM. Health economics of insomnia treatments: the return on investment for a good night's sleep. Sleep Med Rev. 2016 Dec;30:72-82.[Abstract]
10. Benca RM, Ancoli-Israel S, Moldofsky H. Special considerations in insomnia diagnosis and management: depressed, elderly, and chronic pain populations. J Clin Psychiatry. 2004;65(suppl 8):26-35.[Abstract]
11. Cochen V, Arbus C, Soto ME, et al. Sleep disorders and their impacts on healthy, dependent, and frail older adults. J Nutr Health Aging. 2009 Apr;13(4):322-9.[Abstract]
12. Ford DE, Kamerow DB. Epidemiologic study of sleep disturbances and psychiatric disorders: an opportunity for prevention? JAMA. 1989 Sep 15;262(11):1479-84.[Abstract]
13. Pigeon WR, Bishop TM, Krueger KM. Insomnia as a precipitating factor in new onset mental illness: a systematic review of recent findings. Curr Psychiatry Rep. 2017 Aug;19(8):44.[Abstract]
14. Li L, Wu C, Gan Y, et al. Insomnia and the risk of depression: a meta-analysis of prospective cohort studies. BMC Psychiatry. 2016 Nov 5;16(1):375.[Abstract][Full Text]
15. Richardson JD, Thompson A, King L, et al. Insomnia, psychiatric disorders and suicidal ideation in a National Representative Sample of active Canadian Forces members. BMC Psychiatry. 2017 Jun 6;17(1):211.[Abstract][Full Text]
16. Baglioni C, Battagliese G, Feige B, et al. Insomnia as a predictor of depression: a meta-analytic evaluation of longitudinal epidemiological studies. J Affect Disord. 2011 Dec;135(1-3):10-9.[Abstract]
17. Ancoli-Israel S, Roth T. Characteristics of insomnia in the United States: results of the 1991 National Sleep Foundation Survey. I. Sleep. 1999 May 1;22(suppl 2):S347-53.[Abstract]
18. Ohayon MM, Roth T. What are the contributing factors for insomnia in the general population? J Psychosom Res. 2001 Dec;51(6):745-55.[Abstract]
19. Katz DA, McHorney CA. Clinical correlates of insomnia in patients with chronic illness. Arch Intern Med. 1998 May 25;158(10):1099-107.[Abstract][Full Text]
20. Mallon L, Broman JE, Hetta J. Sleep complaints predict coronary artery disease mortality in males: a 12-year follow-up study of a middle-aged Swedish population. J Intern Med. 2002 Mar;251(3):207-16.[Abstract][Full Text]
21. McCracken LM, Iverson GL. Disrupted sleep patterns and daily functioning in patients with chronic pain. Pain Res Manag. 2002 Summer;7(2):75-9.[Abstract]
22. Mathias JL, Cant ML, Burke ALJ. Sleep disturbances and sleep disorders in adults living with chronic pain: a meta-analysis. Sleep Med. 2018 Dec;52:198-210.[Abstract]
23. Nicassio PM, Wallston KA. Longitudinal relationships among pain, sleep problems, and depression in rheumatoid arthritis. J Abnorm Psychol. 1992 Aug;101(3):514-20.[Abstract]
24. Roth T. Insomnia: definition, prevalence, etiology, and consequences. J Clin Sleep Med. 2007 Aug 15;3(5 suppl):S7-10.[Abstract][Full Text]
25. Harvey AG. A cognitive model of insomnia. Behav Res Ther. 2002 Aug;40(8):869-93.[Abstract]
26. Reeve S, Sheaves B, Freeman D. The role of sleep dysfunction in the occurrence of delusions and hallucinations: a systematic review. Clin Psychol Rev. 2015 Dec;42:96-115.[Abstract][Full Text]
27. Gates P, Albertella L, Copeland J. Cannabis withdrawal and sleep: a systematic review of human studies. Subst Abus. 2016;37(1):255-69.[Abstract]
28. Perney P, Lehert P. Insomnia in alcohol-dependent patients: prevalence, risk factors and acamprosate effect: an individual patient data meta-analysis. Alcohol Alcohol. 2018 Sep 1;53(5):611-8.[Abstract][Full Text]
29. Nierenberg AA, Pava JA, Clancy K, et al. Are neurovegetative symptoms stable in relapsing or recurrent atypical depressive episodes? Biol Psychiatry. 1996 Oct 15;40(8):691-6.[Abstract]
30. Krystal AD, Thase ME, Tucker VL, et al. Bupropion HCL and sleep in patients with depression. Curr Psych Rev. 2007;3(2):123-8.
31. Doufas AG, Panagiotou OA, Panousis P, et al. Insomnia from drug treatments: evidence from meta-analyses of randomized trials and concordance with prescribing information. Mayo Clin Proc. 2017 Jan;92(1):72-87.[Abstract]
32. Blanken TF, Benjamins JS, Borsboom D, et al. Insomnia disorder subtypes derived from life history and traits of affect and personality. Lancet Psychiatry. 2019 Feb;6(2):151-63.[Abstract]
33. Bonnet MH, Arand DL. 24-hour metabolic rate in insomniacs and matched normal sleepers. Sleep. 1995 Sep;18(7):581-8.[Abstract]
34. Bonnet MH, Arand DL. Physiological activation in patients with sleep state misperception. Psychosom Med. 1997 Sep-Oct;59(5):533-40.[Abstract]
35. Bonnet MH, Arand DL. Heart rate variability in insomniacs and matched normal sleepers. Psychosom Med. 1998 Sep-Oct;60(5):610-5.[Abstract]
36. Dodds KL, Miller CB, Kyle SD, et al. Heart rate variability in insomnia patients: a critical review of the literature. Sleep Med Rev. 2017 Jun;33:88-100.[Abstract]
37. Vgontzas AN, Bixler EO, Lin HM, et al. Chronic insomnia is associated with nyctohemeral activation of the hypothalamic-pituitary-adrenal axis: clinical implications. J Clin Endocrinol Metab. 2001 Aug;86(8):3787-94.[Abstract][Full Text]
38. Vgontzas AN, Tsigos C, Bixler EO, et al. Chronic insomnia and activity of the stress system: a preliminary study. J Psychosom Res. J Psychosom Res. 1998 Jul;45(1):21-31.[Abstract]
39. Riemann D, Klein T, Rodenbeck A, et al. Nocturnal cortisol and melatonin secretion in primary insomnia. Psychiatry Res. 2002 Dec 15;113(1-2):17-27.[Abstract]
40. Sánchez-Ortuño MM, Carney CE, Edinger JD, et al. Moving beyond average values: assessing the night-to-night instability of sleep and arousal in DSM-IV-TR insomnia subtypes. Sleep. 2011 Apr 1;34(4):531-9.[Abstract][Full Text]
41. Katz DA, McHorney CA. The relationship between insomnia and health-related quality of life in patients with chronic illness. J Fam Pract. 2002 Mar;51(3):229-35.[Abstract]
42. Hertenstein E, Feige B, Gmeiner T, et al. Insomnia as a predictor of mental disorders: a systematic review and meta-analysis. Sleep Med Rev. 2019 Feb;43:96-105.[Abstract]
43. Léger D, Massuel MA, Metlaine A; SISYPHE Study Group. Professional correlates of insomnia. Sleep. 2006 Feb;29(2):171-8.[Abstract]
44. He Q, Zhang P, Li G, et al. The association between insomnia symptoms and risk of cardio-cerebral vascular events: a meta-analysis of prospective cohort studies. Eur J Prev Cardiol. 2017 Jul;24(10):1071-82.[Abstract]
45. Fernandez-Mendoza J, Vgontzas AN, Liao D, et al. Insomnia with objective short sleep duration and incident hypertension: the Penn State Cohort. Hypertension. 2012 Oct;60(4):929-35.[Abstract][Full Text]
46. Suka M, Yoshida K, Sugimori H. Persistent insomnia is a predictor of hypertension in Japanese male workers. J Occup Health. 2003 Nov;45(6):344-50.[Abstract]
47. Vgontzas AN, Liao D, Pejovic S, et al. Insomnia with objective short sleep duration is associated with type 2 diabetes: a population-based study. Diabetes Care. 2009 Nov;32(11):1980-5.[Abstract][Full Text]
48. Li Y, Zhang X, Winkelman JW, et al. Association between insomnia symptoms and mortality: a prospective study of US men. Circulation. 2014 Feb 18;129(7):737-46.[Abstract][Full Text]
49. Parthasarathy S, Vasquez MM, Halonen M, et al. Persistent insomnia is associated with mortality risk. Am J Med. 2015 Mar;128(3):268-75.[Abstract][Full Text]
50. Jarrin DC, Alvaro PK, Bouchard MA, et al. Insomnia and hypertension: a systematic review. Sleep Med Rev. 2018 Oct;41:3-38.[Abstract]
51. Zheng B, Yu C, Lv J, et al; China Kadoorie Biobank Collaborative Group. Insomnia symptoms and risk of cardiovascular diseases among 0.5 million adults: a 10-year cohort. Neurology. 2019 Dec 3;93(23):e2110-20.[Abstract]
52. Lovato N, Lack L. Insomnia and mortality: a meta-analysis. Sleep Med Rev. 2019 Feb;43:71-83.[Abstract]
53. de Almondes KM, Costa MV, Malloy-Diniz LF, et al. Insomnia and risk of dementia in older adults: systematic review and meta-analysis. J Psychiatr Res. 2016 Jun;77:109-15.[Abstract]
54. Shi L, Chen SJ, Ma MY, et al. Sleep disturbances increase the risk of dementia: a systematic review and meta-analysis. Sleep Med Rev. 2018 Aug;40:4-16.[Abstract]
55. Gottesman RF, Lutsey PL, Benveniste H, et al. Impact of sleep disorders and disturbed sleep on brain health: a scientific statement from the American Heart Association. Stroke. 2024 Mar;55(3):e61-76.[Abstract][Full Text]
56. Wilson S, Anderson K, Baldwin D, et al. British Association for Psychopharmacology consensus statement on evidence-based treatment of insomnia, parasomnias and circadian rhythm disorders: an update. J Psychopharmacol. 2019 Aug;33(8):923-47.[Abstract][Full Text]
57. Boyd JH, Weissman MM. Epidemiology of affective disorders: a reexamination and future directions. Arch Gen Psychiatry. 1981 Sep;38(9):1039-46.[Abstract]
58. Johnson EO, Roth T, Schultz L, et al. Epidemiology of DSM-IV insomnia in adolescence: lifetime prevalence, chronicity, and an emergent gender difference. Pediatrics. 2006 Feb;117(2):e247-56.[Abstract][Full Text]
59. Manber R, Bootzin RR. Sleep and the menstrual cycle. Health Psychol. 1997 May;16(3):209-14.[Abstract]
60. Smagula SF, Stone KL, Fabio A, et al. Risk factors for sleep disturbances in older adults: evidence from prospective studies. Sleep Med Rev. 2016 Feb;25:21-30.[Abstract][Full Text]
61. Gislason T, Reynisdottir H, Kristbjarnarson H, et al. Sleep habits and sleep disturbances among the elderly: an epidemiological survey. J Intern Med. 1993 Jul;234(1):31-9.[Abstract]
62. Janson C, Lindberg E, Gislason T, et al. Insomnia in men: a 10-year prospective population based study. Sleep. 2001 Jun 15;24(4):425-30.[Abstract]
63. Leysen L, Lahousse A, Nijs J, et al. Prevalence and risk factors of sleep disturbances in breast cancersurvivors: systematic review and meta-analyses. Support Care Cancer. 2019 Dec;27(12):4401-33.[Abstract]
64. Lobo LL, Tufik S. Effects of alcohol on sleep parameters of sleep-deprived healthy volunteers. Sleep. 1997 Jan;20(1):52-9.[Abstract]
65. Curatolo PW, Robertson D. The health consequences of caffeine. Ann Intern Med. 1983 May;98(5 Pt 1):641-53.[Abstract]
66. Clark I, Landolt HP. Coffee, caffeine, and sleep: a systematic review of epidemiological studies and randomized controlled trials. Sleep Med Rev. 2017 Feb;31:70-8. [Abstract]
67. Soldatos CR, Kales JD, Scharf MB, et al. Cigarette smoking associated with sleep difficulty. Science. 1980 Feb 1;207(4430):551-3.[Abstract]
68. Sandsmark DK, Elliott JE, Lim MM. Sleep-wake disturbances after traumatic brain injury: synthesis of human and animal studies. Sleep. 2017 May 1;40(5).[Abstract][Full Text]
69. Cingi C, Emre IE, Muluk NB. Jetlag related sleep problems and their management: A review. Travel Med Infect Dis. 2018 Jul - Aug;24:59-64.[Abstract][Full Text]
70. Richardson GS, Miner JD, Czeisler CA. Impaired driving performance in shiftworkers: the role of the circadian system in a multifactorial model. Alcohol Drugs Driving. 1989-1990;5-6(4-1):265-73.[Abstract]
71. Ohayon MM, Lemoine P, Arnaud-Briant V, et al. Prevalence and consequences of sleep disorders in a shift worker population. J Psychosom Res. 2002 Jul;53(1):577-83.[Abstract]
72. Booker LA, Magee M, Rajaratnam SMW, et al. Individual vulnerability to insomnia, excessive sleepiness and shift work disorder amongst healthcare shift workers. A systematic review. Sleep Med Rev. 2018 Oct;41:220-33.[Abstract][Full Text]
73. Gupta L, Morgan K, Gilchrist S. Does elite sport degrade sleep quality? A systematic review. Sports Med. 2017 Jul;47(7):1317-33.[Abstract][Full Text]
74. Yang Y, Shin JC, Li D, et al. Sedentary behavior and sleep problems: a systematic review and meta-analysis. Int J Behav Med. 2017 Aug;24(4):481-92.[Abstract]
75. Herscovitch J, Broughton R. Sensitivity of the Stanford sleepiness scale to the effects of cumulative partial sleep deprivation and recovery oversleeping. Sleep. 1981;4(1):83-91.[Abstract]
76. Schutte-Rodin S, Broch L, Buysse D, et al. Clinical guideline for the evaluation and management of chronic insomnia in adults. J Clin Sleep Med. 2008 Oct 15;4(5):487-504.[Abstract][Full Text]
77. Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991 Dec;14(6):540-5.[Abstract]
78. Soldatos CR, Dikeos DG, Paparrigopoulos TJ. The diagnostic validity of the Athens Insomnia Scale. J Psychosom Res. 2003 Sep;55(3):263-7.[Abstract]
79. Buysse DJ, Reynolds CF 3rd, Monk TH, et al. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989 May;28(2):193-213.[Abstract]
80. Bastien CH, Vallieres A, Morin CM. Validation of the Insomnia Severity Index as an outcome measure for insomnia research. Sleep Med. 2001 Jul;2(4):297-307.[Abstract]
81. American Academy of Sleep Medicine. The AASM manual for the scoring of sleep and associated events. Feb 2023 [internet publication].[Full Text]
82. Krahn LE, Arand DL, Avidan AY, et al. Recommended protocols for the Multiple Sleep Latency Test and Maintenance of Wakefulness Test in adults: guidance from the American Academy of Sleep Medicine. J Clin Sleep Med. 2021 Dec 1;17(12):2489-98.[Abstract][Full Text]
83. Smith MT, McCrae CS, Cheung J, et al. Use of actigraphy for the evaluation of sleep disorders and circadian rhythm sleep-wake disorders: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2018 Jul 15;14(7):1231-7.[Abstract][Full Text]
84. Khosla S, Deak MC, Gault D, et al. Consumer sleep technology: an American Academy of Sleep Medicine position statement. J Clin Sleep Med. 2018 May 15;14(5):877-80.[Abstract][Full Text]
85. Toward Optimized Practice. Assessment to management of adult insomnia. Dec 2015 [internet publication].[Full Text]
86. Riemann D, Baglioni C, Bassetti C, et al. European guideline for the diagnosis and treatment of insomnia. J Sleep Res. 2017 Dec;26(6):675-700.[Abstract][Full Text]
87. Ellis JG, Cushing T, Germain A. Treating acute insomnia: a randomized controlled trial of a "single-shot" of cognitive behavioral therapy for insomnia. Sleep. 2015 Jun 1;38(6):971-8.[Abstract][Full Text]
88. Cheng SK, Dizon J. Computerised cognitive behavioural therapy for insomnia: a systematic review and meta-analysis. Psychother Psychosom. 2012;81(4):206-16.[Abstract]
89. Morin CM, Vallières A, Guay B, et al. Cognitive behavioral therapy, singly and combined with medication, for persistent insomnia: a randomized controlled trial. JAMA. 2009 May 20;301(19):2005-15.[Abstract][Full Text]
90. Morin CM, Bootzin RR, Buysse DJ, et al. Psychological and behavioral treatment of insomnia: update of the recent evidence (1998-2004). Sleep. 2006 Nov;29(11):1398-414.[Abstract]
91. Mitchell MD, Gehrman P, Perlis M, et al. Comparative effectiveness of cognitive behavioral therapy for insomnia: a systematic review. BMC Fam Pract. 2012 May 25;13:40.[Abstract][Full Text]
92. Buysse DJ. Insomnia. JAMA. 2013 Feb 20;309(7):706-16.[Abstract][Full Text]
93. Sun J, Kang J, Wang P, et al. Self-relaxation training can improve sleep quality and cognitive functions in the older: a one-year randomised controlled trial. J Clin Nurs. 2013 May;22(9-10):1270-80.[Abstract]
94. Vitiello MV, McCurry SM, Shortreed SM, et al. Cognitive-behavioral treatment for comorbid insomnia and osteoarthritis pain in primary care: the lifestyles randomized controlled trial. J Am Geriatr Soc. 2013 Jun;61(6):947-56.[Abstract][Full Text]
95. Black DS, O'Reilly GA, Olmstead R, et al. Mindfulness meditation and improvement in sleep quality and daytime impairment among older adults with sleep disturbances: a randomized clinical trial. JAMA Intern Med. 2015 Apr;175(4):494-501.[Abstract][Full Text]
96. Wu JQ, Appleman ER, Salazar RD, et al. Cognitive behavioral therapy for insomnia comorbid with psychiatric and medical conditions: a meta-analysis. JAMA Intern Med. 2015 Sep;175(9):1461-72.[Abstract]
97. Brasure M, Fuchs E, MacDonald R, et al. Psychological and behavioral interventions for managing insomnia disorder: an evidence report for a clinical practice guideline by the American College of Physicians. Ann Intern Med. 2016 Jul 19;165(2):113-24.[Abstract]
98. Brasure M, MacDonald R, Fuchs E, et al; Agency for Healthcare Research and Quality. Management of insomnia disorder. Dec 2015 [internet publication].[Abstract][Full Text]
99. Rash JA, Kavanagh VAJ, Garland SN. A meta-analysis of mindfulness-based therapies for insomnia and sleep disturbance: moving towards processes of change. Sleep Med Clin. 2019 Jun;14(2):209-33.[Abstract]
100. Sateia MJ, Buysse DJ, Krystal AD, et al. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2017 Feb 15;13(2):307-49.[Abstract][Full Text]
101. Editorial Executive Committee. Lemborexant for insomnia. Aust Prescr. 2022 Feb;45(1):29-30.[Abstract][Full Text]
102. Mignot E, Mayleben D, Fietze I, et al. Safety and efficacy of daridorexant in patients with insomnia disorder: results from two multicentre, randomised, double-blind, placebo-controlled, phase 3 trials. Lancet Neurol. 2022 Feb;21(2):125-39.[Abstract]
103. Qaseem A, Kansagara D, Forciea MA, et al. Management of chronic insomnia disorder in adults: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2016 Jul 19;165(2):125-33.[Abstract][Full Text]
104. Ree M, Junge M, Cunnington D. Australasian Sleep Association position statement regarding the use of psychological/behavioral treatments in the management of insomnia in adults. Sleep Med. 2017 Aug;36(suppl 1):S43-7.[Abstract]
105. Manber R, Bei B, Simpson N, et al. Cognitive behavioral therapy for prenatal insomnia: a randomized controlled trial. Obstet Gynecol. 2019 May;133(5):911-9.[Abstract][Full Text]
106. Felder JN, Epel ES, Neuhaus J, et al. Efficacy of digital cognitive behavioral therapy for the treatment of insomnia symptoms among pregnant women: a randomized clinical trial. JAMA Psychiatry. 2020 May 1;77(5):484-92.[Abstract][Full Text]
107. Riemann D, Perlis ML. The treatments of chronic insomnia: a review of benzodiazepine receptor agonists and psychological and behavioral therapies. Sleep Med Rev. 2009 Jun;13(3):205-14.[Abstract]
108. Morin CM, Culbert JP, Schwartz SM. Nonpharmacological interventions for insomnia: a meta-analysis of treatment efficacy. Am J Psychiatry. 1994 Aug;151(8):1172-80.[Abstract]
109. Johnson JA, Rash JA, Campbell TS, et al. A systematic review and meta-analysis of randomized controlled trials of cognitive behavior therapy for insomnia (CBT-I) in cancer survivors. Sleep Med Rev. 2016 Jun;27:20-8.[Abstract]
110. Cheung JMY, Jarrin DC, Ballot O, et al. A systematic review of cognitive behavioral therapy for insomnia implemented in primary care and community settings. Sleep Medicine Reviews. 2019 Apr;44:23-36.[Abstract]
111. Davidson JR, Dickson C, Han H. Cognitive behavioural treatment for insomnia in primary care: a systematic review of sleep outcomes. Br J Gen Pract. 2019 Sep;69(686):e657-64.[Abstract][Full Text]
112. Koffel E, Bramoweth AD, Ulmer CS. Increasing access to and utilization of cognitive behavioral therapy for insomnia (CBT-I): a narrative review. J Gen Intern Med. 2018 Jun;33(6):955-62.[Abstract][Full Text]
113. Seyffert M, Lagisetty P, Landgraf J, et al. Internet-delivered cognitive behavioral therapy to treat insomnia: a systematic review and meta-analysis. PLoS One. 2016 Feb 11;11(2):e0149139.[Abstract]
114. van Straten A, van der Zweerde T, Kleiboer A, et al. Cognitive and behavioral therapies in the treatment of insomnia: a meta-analysis. Sleep Med Rev. 2018 Apr;38:3-16.[Abstract]
115. Zachariae R, Lyby MS, Ritterband LM, et al. Efficacy of internet-delivered cognitive-behavioral therapy for insomnia: a systematic review and meta-analysis of randomized controlled trials. Sleep Med Rev. 2016 Dec;30:1-10.[Abstract]
116. National Institute for Health and Care Excellence. Sleepio to treat insomnia and insomnia symptoms. May 2022 [internet publication].[Full Text]
117. Deschenes CL, McCurry SM. Current treatments for sleep disturbances in individuals with dementia. Curr Psychiatry Rep. 2009 Feb;11(1):20-6.[Abstract][Full Text]
118. McCurry SM, Gibbons LE, Logsdon RG, et al. Nighttime insomnia treatment and education for Alzheimer's disease: a randomized, controlled trial. J Am Geriatr Soc. 2005 May;53(5):793-802.[Abstract]
119. Lamarche LJ, De Koninck J. Sleep disturbance in adults with posttraumatic stress disorder: a review. J Clin Psychiatry. 2007 Aug;68(8):1257-70.[Abstract]
120. Ballesio A, Aquino M, Feige B, et al. The effectiveness of behavioural and cognitive behavioural therapies for insomnia on depressive and fatigue symptoms: a systematic review and network meta-analysis. Sleep Med Rev. 2018 Feb;37: 114-29.[Abstract]
121. Cunningham JEA, Shapiro CM. Cognitive behavioural therapy for insomnia (CBT-I) to treat depression: a systematic review. J Psychosom Res. 2018 Mar;106:1-12.[Abstract]
122. Gebara MA, Siripong N, DiNapoli EA, et al. Effect of insomnia treatments on depression: a systematic review and meta-analysis. Depress Anxiety. 2018 Aug;35(8):717-31.[Abstract]
123. Sin CW, Ho JS, Chung JW. Systematic review on the effectiveness of caffeine abstinence on the quality of sleep. J Clin Nurs. 2009 Jan;18(1):13-21.[Abstract]
124. Edinger JD, Arnedt JT, Bertisch SM, et al. Behavioral and psychological treatments for chronic insomnia disorder in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2021 Feb 1;17(2):255-62.[Abstract][Full Text]
125. Chung KF, Lee CT, Yeung WF, et al. Sleep hygiene education as a treatment of insomnia: a systematic review and meta-analysis. Fam Pract. 2018 Jul 23;35(4):365-75.[Abstract]
126. Feng F, Zhang Y, Hou J, et al. Can music improve sleep quality in adults with primary insomnia? A systematic review and network meta-analysis. Int J Nurs Stud. 2018 Jan;77:189-96.[Abstract]
127. Jespersen KV, Pando-Naude V, Koenig J, et al. Listening to music for insomnia in adults. Cochrane Database Syst Rev. 2022 Aug 24;(8):CD010459.[Abstract][Full Text]
128. van Straten A, Cuijpers P. Self-help therapy for insomnia: a meta-analysis. Sleep Med Rev. 2009 Feb;13(1):61-71.[Abstract]
129. Yang PY, Ho KH, Chen HC, et al. Exercise training improves sleep quality in middle-aged and older adults with sleep problems: a systematic review. J Physiother. 2012;58(3):157-63.[Abstract][Full Text]
130. Rubio-Arias JÁ, Marín-Cascales E, Ramos-Campo DJ, et al. Effect of exercise on sleep quality and insomnia in middle-aged women: a systematic review and meta-analysis of randomized controlled trials. Maturitas. 2017 Jun;100:49-56.[Abstract]
131. Taibi DM, Landis CA, Petry H, et al. A systematic review of valerian as a sleep aid: safe but not effective. Sleep Med Rev. 2007 Jun;11(3):209-30.[Abstract]
132. Meolie AL, Rosen C, Kristo D, et al. Oral nonprescription treatment for insomnia: an evaluation of products with limited evidence. J Clin Sleep Med. 2005 Apr 15;1(2):173-87.[Abstract]
133. Cooper KL, Relton C. Homeopathy for insomnia: a systematic review of research evidence. Sleep Med Rev. 2010 Oct;14(5):329-37.[Abstract]
134. Cooper KL, Relton C. Homeopathy for insomnia: summary of additional RCT published since systematic review. Sleep Med Rev. 2010 Dec;14(6):411.[Abstract]
135. Kalavapalli R, Singareddy R. Role of acupuncture in the treatment of insomnia: a comprehensive review. Complement Ther Clin Pract. 2007 Aug;13(3):184-93.[Abstract]
136. Lee SH, Lim SM. Acupuncture for insomnia after stroke: a systematic review and meta-analysis. BMC Complement Altern Med. 2016 Jul 19;16:228.[Abstract][Full Text]
137. Cao HJ, Yu ML, Wang LQ, et al. Acupuncture for primary insomnia: an updated systematic review of randomized controlled trials. J Altern Complement Med. 2019 May;25(5):451-74.[Abstract]
138. He W, Li M, Zuo L, et al. Acupuncture for treatment of insomnia: an overview of systematic reviews. Complement Ther Med. 2019 Feb;42:407-16.[Abstract][Full Text]
139. Cheuk DK, Yeung WF, Chung KF, et al. Acupuncture for insomnia. Cochrane Database Syst Rev. 2012 Sep 12;(9):CD005472.[Abstract][Full Text]
140. Rösner S, Englbrecht C, Wehrle R, et al. Eszopiclone for insomnia. Cochrane Database Syst Rev. 2018 Oct 10;(10):CD010703.[Abstract][Full Text]
141. Herring WJ, Snyder E, Budd K, et al. Orexin receptor antagonism for treatment of insomnia: a randomized clinical trial of suvorexant. Neurology. 2012 Dec 4;79(23):2265-74.[Abstract]
142. Wilt TJ, MacDonald R, Brasure M, et al. Pharmacologic treatment of insomnia disorder: an evidence report for a clinical practice guideline by the American College of Physicians. Ann Intern Med. 2016 Jul 19;165(2):103-12.[Abstract]
143. Herring WJ, Connor KM, Snyder E, et al. Suvorexant in elderly patients with insomnia: pooled analyses of data from phase III randomized controlled clinical trials. Am J Geriatr Psychiatry. 2017 Jul;25(7):791-802.[Abstract]
144. Kuriyama A, Tabata H. Suvorexant for the treatment of primary insomnia: a systematic review and meta-analysis. Sleep Med Rev. 2017 Oct;35:1-7.[Abstract]
145. Everitt H, Baldwin DS, Stuart B, et al. Antidepressants for insomnia in adults. Cochrane Database Syst Rev. 2018 May 14;(5):CD010753.[Abstract][Full Text]
146. Jaffer KY, Chang T, Vanle B, et al. Trazodone for insomnia: a systematic review. Innov Clin Neurosci. 2017 Aug 1;14(7-8):24-34.[Abstract][Full Text]
147. Yi XY, Ni SF, Ghadami MR, et al. Trazodone for the treatment of insomnia: a meta-analysis of randomized placebo-controlled trials. Sleep Med. 2018 May;45:25-32.[Abstract]
148. Pollack M, Kinrys G, Krystal A, et al. Eszopiclone coadministered with escitalopram in patients with insomnia and comorbid generalized anxiety disorder. Arch Gen Psychiatry. 2008 May;65(5):551-62.[Abstract]
149. Ji JL, Liu WJ, Zhang N, et al. Effects of paroxetine with or without zolpidem on depression with insomnia: a multi-center randomized comparative study [in Chinese]. Zhonghua Yi Xue Za Zhi. 2007 Jun 19;87(23):1585-9.[Abstract]
150. Fava M, Asnis GM, Shrivastava R, et al. Zolpidem extended-release improves sleep and next-day symptoms in comorbid insomnia and generalized anxiety disorder. J Clin Psychopharmacol. 2009 Jun;29(3):222-30.[Abstract]
151. Ensrud KEJ, Sternfeld BL. Effect of escitalopram on insomnia symptoms and subjective sleep quality in healthy perimenopausal and postmenopausal women with hot flashes: a randomized controlled trial. Menopause. 2012 Aug;19(8):848-55.[Abstract][Full Text]
152. Stein DJ, Lopez AG, Stein DJ, et al. Effects of escitalopram on sleep problems in patients with major depression or generalized anxiety disorder. Adv Ther. 2011 Nov;28(11):1021-37.[Abstract]
153. Fava M, Asnis GM, Shrivastava RK, et al. Improved insomnia symptoms and sleep-related next-day functioning in patients with comorbid major depressive disorder and insomnia following concomitant zolpidem extended-release 12.5 mg and escitalopram treatment: a randomized controlled trial. J Clin Psychiatry. 2011 Jul;72(7):914-28.[Abstract]
154. Kinnunen KM, Vikhanova A, Livingston G. The management of sleep disorders in dementia: an update. Curr Opin Psychiatry. 2017 Nov;30(6):491-97.[Abstract]
155. Bjerre LM, Farrell B, Hogel M, et al. Deprescribing antipsychotics for behavioural and psychological symptoms of dementia and insomnia: evidence-based clinical practice guideline. Can Fam Physician. 2018 Jan;64(1):17-27.[Abstract]
156. McCleery J, Sharpley AL. Pharmacotherapies for sleep disturbances in dementia. Cochrane Database Syst Rev. 2020 Nov 15;(11):CD009178.[Abstract][Full Text]
157. Buscemi N, Vandermeer B, Friesen C, et al. The efficacy and safety of drug treatments for chronic insomnia in adults: a meta-analysis of RCTs. J Gen Intern Med. 2007 Sep;22(9):1335-50.[Abstract][Full Text]
158. Nowell PD, Mazumdar S, Buysse DJ, et al. Benzodiazepines and zolpidem for chronic insomnia: a meta-analysis of treatment efficacy. JAMA. 1997 Dec 24-31;278(24):2170-7.[Abstract]
159. Glass J, Lanctôt KL, Herrmann N, et al. Sedative hypnotics in older people with insomnia: meta-analysis of risks and benefits. BMJ. 2005 Nov 19;331(7526):1169.[Abstract][Full Text]
160. Moore TJ, Mattison DR. Assessment of patterns of potentially unsafe use of zolpidem. JAMA Intern Med. 2018 Sep 1;178(9):1275-7.[Abstract][Full Text]
161. Andrade C. Sedative hypnotics and the risk of falls and fractures in the elderly. J Clin Psychiatry. 2018 May/Jun;79(3):18f12340.[Abstract][Full Text]
162. Treves N, Perlman A, Kolenberg Geron L, et al. Z-drugs and risk for falls and fractures in older adults-a systematic review and meta-analysis. Age Ageing. 2018 Mar 1;47(2):201-8.[Abstract][Full Text]
163. Ray WA, Griffin MR, Downey W. Benzodiazepines of long and short elimination half-life and the risk of hip fracture. JAMA. 1989 Dec 15;262(23):3303-7.[Abstract]
164. Hanlon JT, Boudreau RM, Roumani YF, et al. Number and dosage of central nervous system medications on recurrent falls in community elders: the Health, Aging and Body Composition study. J Gerontol A Biol Sci Med Sci. 2009 Apr;64(4):492-8.[Abstract][Full Text]
165. Gray SL, Dublin S, Yu O, et al. Benzodiazepine use and risk of incident dementia or cognitive decline: prospective population based study. BMJ. 2016 Feb 2;352:i90.[Abstract][Full Text]
166. Neutel CI, Johansen HL. Association between hypnotics use and increased mortality: causation or confounding? Eur J Clin Pharmacol. 2015 May;71(5):637-42.[Abstract]
167. Patorno E, Glynn RJ, Levin R, et al. Benzodiazepines and risk of all cause mortality in adults: cohort study. BMJ. 2017 Jul 6;358:j2941.[Abstract][Full Text]
168. Dyer O. FDA issues black box warnings on common insomnia drugs. BMJ. 2019 May 10;365:l2165.[Abstract]
169. Perlis M, Gehrman P, Riemann D. Intermittent and long-term use of sedative hypnotics. Curr Pharm Des. 2008;14(32):3456-65.[Abstract]
170. Walsh JK, Soubrane C, Roth T. Efficacy and safety of zolpidem extended release in elderly primary insomnia patients. Am J Geriatr Psychiatry. 2008 Jan;16(1):44-57.[Abstract]
171. Zammit G, Schwartz H, Roth T, et al. The effects of ramelteon in a first-night model of transient insomnia. Sleep Med. 2009 Jan;10(1):55-9.[Abstract]
172. Reynoldson JN, Elliott E Sr, Nelson LA. Ramelteon: a novel approach in the treatment of insomnia. Ann Pharmacother. 2008 Sep;42(9):1262-71.[Abstract]
173. Uchimura N, Ogawa A, Hamamura M, et al. Efficacy and safety of ramelteon in Japanese adults with chronic insomnia: a randomized, double-blind, placebo-controlled study. Expert Rev Neurother. 2011 Feb;11(2):215-24.[Abstract]
174. Uchiyama M, Hamamura M, Kuwano T, et al. Evaluation of subjective efficacy and safety of ramelteon in Japanese subjects with chronic insomnia. Sleep Med. 2011 Feb;12(2):119-26.[Abstract]
175. Liu J, Wang LN. Ramelteon in the treatment of chronic insomnia: systematic review and meta-analysis. Int J Clin Pract. 2012 Sep;66(9):867-73.[Abstract][Full Text]
176. Krystal AD, Erman M, Zammit GK, et al. Long-term efficacy and safety of zolpidem extended-release 12.5 mg, administered 3 to 7 nights per week for 24 weeks, in patients with chronic primary insomnia: a 6-month, randomized, double-blind, placebo-controlled, parallel-group, multicenter study. Sleep. 2008 Jan;31(1):79-90.[Abstract][Full Text]
177. Erman M, Guiraud A, Joish VN, et al. Zolpidem extended-release 12.5 mg associated with improvements in work performance in a 6-month randomized, placebo-controlled trial. Sleep. 2008 Oct;31(10):1371-8.[Abstract][Full Text]
178. Mayer G, Wang-Weigand S, Roth-Schechter B, et al. Efficacy and safety of 6-month nightly ramelteon administration in adults with chronic primary insomnia. Sleep. 2009 Mar;32(3):351-60.[Abstract][Full Text]
179. Auld F, Maschauer EL, Morrison I, et al. Evidence for the efficacy of melatonin in the treatment of primary adult sleep disorders. Sleep Med Rev. 2017 Aug;34:10-22.[Abstract]
180. Hoyer D, Allen A, Jacobson LH. Hypnotics with novel modes of action. Br J Clin Pharmacol. 2020 Feb;86(2):244-9.[Abstract][Full Text]
181. Lo HS, Yang CM, Lo HG, et al. Treatment effects of gabapentin for primary insomnia. Clin Neuropharmacol. 2010 Mar-Apr;33(2):84-90.[Abstract]
182. Department of Veterans Affairs; Department of Defense. VA/DoD clinical practice guideline for the management of chronic insomnia disorder and obstructive sleep apnea. 2019 [internet publication].[Full Text]
183. National Institute for Health and Care Excellence. Medicines associated with dependence or withdrawal symptoms: safe prescribing and withdrawal management for adults. Apr 2022 [internet publication].[Full Text]
184. Sateia MJ, Buysse DJ, Krystal AD, et al. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2017 Feb 15;13(2):307-49.[Abstract][Full Text]
185. Inagaki T, Miyaoka T, Tsuji S, et al. Adverse reactions to zolpidem: case reports and a review of the literature. Prim Care Companion J Clin Psychiatry. 2010;12(6):PCC.09r00849.[Abstract][Full Text]
186. Lemoine P, Zisapel N. Prolonged-release formulation of melatonin (Circadin) for the treatment of insomnia. Expert Opin Pharmacother. 2012 Apr;13(6):895-905.[Abstract]
187. Richardson G, Wang-Weigand S. Effects of long-term exposure to ramelteon, a melatonin receptor agonist, on endocrine function in adults with chronic insomnia. Hum Psychopharmacol. 2009 Mar;24(2):103-11.[Abstract]
Key Articles
Referenced Articles
Guidelines
Diagnostic
Summary
Reference for the scoring of polysomnography (PSG) and home sleep apnea tests (HSATs).Published by
American Academy of Sleep Medicine
Published
2023
Summary
Classification and diagnostic tool.Published by
American Psychiatric Association
Published
2022
Summary
Evidence-based practice parameters on the multiple sleep latency test (MSLT) and maintenance of wakefulness test (MWT) and their indications, including recommendations on MSLT and MWT protocols.Published by
American Academy of Sleep Medicine
Published
2021
Summary
Provides recommendations for use of actigraphy, which has been shown to be useful as an outcome measure in patients with circadian rhythm disorders and insomnia.Published by
American Academy of Sleep Medicine
Published
2018
Summary
This American Academy of Sleep Medicine position statement details the disadvantages and potential benefits of consumer sleep technologies (CSTs) and provides guidance when approaching patient-generated health data from CSTs in a clinical setting.Published by
American Academy of Sleep Medicine
Published
2018
Summary
Systematically developed recommendations to assist physicians in the assessment of insomnia in adults.Published by
Toward Optimized Practice (Canada)
Published
2015
Summary
Evidence-based European guidelines based on a systematic review of meta-analyses published before June 2016. The target audience for this guideline includes all clinicians involved in the diagnosis of patients with chronic insomnia.Published by
European Sleep Research Society
Published
2017
Treatment
Summary
Clinical practice recommendations for the use of behavioral and psychological treatments for chronic insomnia in adults.Published by
American Academy of Sleep Medicine
Published
2021
Summary
The guideline describes the decision points in the management of chronic insomnia disorder and obstructive sleep apnea (insomnia/OSA) and provides evidence-based recommendations incorporating current information and practices for practitioners throughout the DoD and VA Health Care systems.Published by
US Department of Veterans Affairs; Department of Defense
Published
2019
Summary
Clinical practice recommendations for the pharmacologic treatment of chronic insomnia in adults. The guideline focuses on individual drugs commonly used to treat insomnia, taking into account the evidence regarding their benefits and harms, and offers recommendations on which drugs should and should not be used to treat insomnia.Published by
American Academy of Sleep Medicine
Published
2017
Summary
Systematically developed recommendations to assist physicians in the management of primary insomnia in adults.Published by
Toward Optimized Practice (Canada)
Published
2015
Summary
Evidence-based European guidelines based on a systematic review of meta-analyses published before June 2016. The target audience for this guideline includes all clinicians involved in the management of patients with chronic insomnia.Published by
European Sleep Research Society
Published
2017
Summary
Guidance covering the general principles for prescribing and managing withdrawal from opioids, benzodiazepines, gabapentinoids, Z-drugs and antidepressants in primary and secondary care.Published by
National Institute for Health and Care Excellence
Published
2022
Summary
Evidence-based guidance on the treatment of insomnia, parasomnias, and circadian rhythm disorders.Published by
British Association for Psychopharmacology
Published
2019
Credits
Patient Instructions
- They should avoid stimulants (e.g., caffeine, nicotine) and alcohol for several hours before bedtime, and avoid using blue-light emitting electronic devices (e.g., smartphones) in the hour before bedtime
- They should allow adequate time to relax before bed, creating an environment conducive to sleep
- Their mattress and bedding should be comfortable and the noise level minimal, with lighting, temperature, and humidity controlled
- It is best to avoid clock-watching, which can lead to hyperarousal
- Most importantly, they should attempt to maintain a regular sleep schedule, with consistent bedtime and rise times, and avoid daytime naps.
- Complex sleep-related behaviors, such as sleepwalking, sleep driving, and cooking. On rare occasions, these may lead to serious injury or even death. If they experience these behaviors, they should stop taking the drug and contact their healthcare professional right away.
- Anaphylaxis or angioedema, which can occur as early as the first time the drug is taken.