Insomnia

Insomnia is a sleep disorder characterized by difficulty in the initiation, maintenance, and consolidation of sleep, leading to impairment of function. Patients may exhibit symptoms such as difficulty falling asleep, disrupted sleep, trouble going back to sleep, early awakenings, and feeling tired upon waking. The disorder can be acute (< 3 months), which can progress to the chronic form (≥ 3 months). Multiple risk factors contribute to having insomnia, including medical illnesses, psychiatric disorders, medications, and the sleep environment. Diagnosis starts with a detailed history and sleep diagnostic aids (sleep diary, sleep problems questionnaire). The 1st line of management is nonpharmacologic, i.e., identifying the stressor(s), implementing sleep hygiene, and utilizing cognitive behavioral therapy. Medications are used with nonpharmacologic intervention or after initial management has failed.

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Definition and Classifications

Definition

Insomnia is the subjective perception of difficulty with sleep initiation, duration, consolidation, or quality despite adequate opportunity for sleep, resulting in daytime functional impairment.

Classifications

By duration: 

  • Acute insomnia (< 3 months):
    • Transient or short-term insomnia
    • Due to a certain trigger (i.e., sleep environment, illness) and usually associated with anxiety or life change
    • Can evolve to persistent or chronic form
  • Chronic insomnia (≥ 3 months)
    • Includes primary and comorbid insomnia
    • Muscular weakness, hallucinations, and double vision may be present.

By how sleep is impaired:

  • Sleep-onset insomnia: difficulty falling asleep at the beginning of the night
  • Sleep-maintenance insomnia: difficulty staying asleep
  • Early-morning awakening: waking too early and having difficulty getting back to sleep
  • Paradoxical insomnia:
    • Sleep-state misperception
    • Dissociation between patient’s self-reported quality of sleep and the findings from objective polysomnography (which are normal)

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Epidemiology and Etiology

Epidemiology

  • At least 30% of ambulatory patients report symptoms of insomnia.
  • More common in women and older adults
  • Increased prevalence in those who are unemployed, divorced, or widowed

Risk factors

  • Inadequate sleep hygiene: 
    • Irregular bedtime schedule
    • Using bed for work, eating, or watching television
    • Naps, especially after 3 pm
    • Stimulating activities (e.g., exercising) before bedtime
  • Environmental factors such as noise, light, and extreme temperatures
  • Underlying sleep disorder such as restless leg syndrome
  • Behavioral insomnia (alteration of the sleep cycle) such as from jet lag or shift work
  • Medical conditions or illnesses:
    • Diabetes 
    • GERD
    • Hyperthyroidism
    • Asthma 
    • Alzheimer disease 
    • Menopause (vasomotor symptoms)
    • Chronic pain
  • Mental health disorders: 
    • Depression
    • Anxiety disorders 
    • PTSD
  • Substance abuse/medication induced: 
    • Caffeine 
    • Nicotine 
    • Alcohol 
    • Amphetamines
    • Modafinil
    • Benzodiazepine or opioid withdrawal

Pathophysiology

  • In the brain, several structures are involved in controlling wakefulness and sleep.
  • Sleep-promoting cells in the brainstem and hypothalamus (containing the suprachiasmatic nucleus (SCN)) facilitate reduced activity of arousal centers.
  • Neurotransmitters that play major roles in insomnia:
    • Decreased inhibitory neurotransmitter (GABA) in the brainstem 
    • Activation of SCN and inhibition of melatonin produced by the pineal gland
    • Increased level of stress hormones such as cortisol 
  • Hyperarousal theory:
    • Increased brain arousal during non-rapid eye movement (NREM) sleep
    • Activation of key brain areas, which, once activated, cause inhibition of brain pathways that induce sleep
  • Cognitive-behavioral model:
    • Predisposing conditions (e.g., anxiety) interact with precipitating factors such as illness and bereavement, increasing the risk of insomnia.
    • Perpetuating factors (e.g., daytime behaviors, sleep-wake schedule) contribute to maintaining insomnia.
    • The “3P” model: predisposition, precipitation, and perpetuation of chronic insomnia 

Clinical Presentation and Diagnosis

Symptoms

  • Difficulty falling asleep
  • Daytime sleepiness
  • General fatigue and tiredness
  • Problems with concentration or memory
  • Irritability
  • Increased errors or accidents

Diagnostic aids

  • History:
    • Medical and psychiatric history
    • Sleep history
    • Interview of the bed partner about the quantity and quality of sleep
  • Physical and neurologic exam (helps determine comorbid conditions)
  • Self-report screening tools (e.g., sleep problems questionnaire)
  • Sleep diary: kept over 2–4 weeks to assess patterns of sleep  
  • Polysomnography:
    • Not required for diagnosis
    • Utilized to rule out other sleep disorders

DSM-5 criteria for insomnia disorder

  • Difficulty initiating or maintaining sleep, or early-morning awakening without being able to return to sleep
  • Social, occupational, or behavioral impairment 
  • Symptoms for at least 3 nights per week
  • Symptoms noted for at least 3 months
  • Sleep difficulty present despite having ample opportunity for sleep
  • Sleep disturbance cannot be explained by any other sleep-wake disorder.
  • Sleep difficulty is not due to the physiological effect of a substance, mental disorder, or any medical condition.

Management

Nonpharmacologic treatment

  • Short-term or acute insomnia:
    • Identify the stressor(s) and address accordingly.
    • Use of medication(s):
      • If insomnia interferes with daytime function
      • Temporary
  • Chronic Insomnia:
    • Improve sleep hygiene:
      • Avoid alcohol, caffeinated drinks, and large meals at least 4 hours before bedtime.
      • Maintain regular exercise patterns but no exercising too close to bedtime (3 hours). 
      • Avoid napping or daytime sleeping. 
      • Use bed only for sleep/sex (no eating/television/cellphone in bed).
      • Reduce light exposure around bedtime.
    • Cognitive-behavioral therapy:
      • 1st line of treatment 
      • Goal is to increase sleep efficiency, address maladaptive thoughts, and promote a stable routine of sleep/wake times. 
      • Set a time for sleep each day (follow a sleep schedule)
      • Sleep restriction: reduce time in bed to total hours of sleep
      • Stimulus control: if anxious when unable to sleep, should get out of bed 
      • Sleep hygiene
  • Treat any underlying pain, depression, or other comorbidities before intensive sleep treatment.

Pharmacologic treatment

  • Hypnotic benzodiazepine receptor agonists (BZRAs):
    • Mechanism: acts on GABA receptor without specific affinity to different subtypes of GABA
    • High risk of tolerance, abuse, and dependence as well as cognitive impairments linked with long-term use 
    • Examples: temazepam, clonazepam, triazolam 
  • Nonbenzodiazepine BZRAs:
    • Mechanism: 
      • Benzodiazepine receptor agonists that act on GABA receptor (similar to benzodiazepines)
      • Selective affinity (GABA-A subunit subtypes), which reduces side effects
    • Fewer adverse effects and abuse potential than benzodiazepines
    • Examples: zolpidem, zaleplon, eszopiclone 
  • Dual orexin receptor antagonists 
    • Mechanism: 
      • Orexin or hypocretin system promotes arousal or wakefulness.
      • Orexin receptor antagonists counteract the orexin-mediated nighttime awakening. 
    • Examples: lemborexant, suvorexant 
  • Melatonin agonists:
    • Mechanism: Melatonin is a natural hormone associated with the establishment of the circadian rhythm and sleep-wake cycle. 
    • Examples: 
      • Melatonin: natural hormone (over the counter) 
      • Ramelteon: highly selective melatonin receptor agonist with higher affinity and selectivity than melatonin   
  • Histamine receptor antagonist:
    • Mechanism: H1 receptor antagonist producing sedation
    • Example: doxepin
  • Antidepressants with sedative properties: 
    • Exact mechanism unknown but thought to work through antihistamine and serotonin effects 
    • Off-label use  
    • Examples: trazodone, mirtazapine, amitriptyline, doxepin

Differential Diagnosis

  • Narcolepsy: a sleep disorder characterized by excessive daytime sleepiness and falling asleep at inappropriate times. Narcolepsy is associated with hallucinations (hypnagogic and hypnopompic, which occur upon falling and waking from sleep, respectively) and cataplexy (emotionally triggered loss of muscle tone). Narcolepsy must be ruled out via history and sleep study before diagnosis of primary insomnia.
  • Circadian rhythm sleep-wake disorders: a group of conditions marked by recurrent patterns of sleep disruption. These conditions can be due to an alteration of the circadian system or a misalignment between the inner circadian rhythm and the sleep environment. Delayed sleep-wake phase disorder manifests as delayed onset of sleep and awakening. The sleep quality and duration are preserved. In advanced sleep-wake phase disorder, there is early sleep onset and awakening. Diagnosis is generally clinical. Unlike in these disorders, in insomnia, the patient has difficulty falling asleep at any time. 
  • Hyperthyroidism: caused by an excess of thyroid hormones T3 and T4. Clinical features of hyperthyroidism are mostly due to the body’s increased metabolic rate. Sleep disturbance is one of the important manifestations of this disease. Basic laboratory studies (thyroid-stimulating hormone) should rule out this disorder prior to making a diagnosis of primary insomnia
  • Generalized anxiety disorder: chronic multiple worries that are irrational and uncontrollable. The disorder is associated with fatigue, low concentration, restlessness, irritability, and sleep disturbance. Other anxiety disorders (e.g., phobias, social anxiety disorder, PTSD) can also cause sleep disturbance. Full history should exclude anxiety disorders prior to making a diagnosis of primary insomnia.

References

  1. Bonnet M, Arand D. (2021). Risk factors, comorbidities and consequences of insomnia. UpToDate. Retrieved June 6, 2021, from https://www.uptodate.com/contents/risk-factors-comorbidities-and-consequences-of-insomnia-in-adults
  2. Claman D, Okeson K, Singer C. (2019). Sleep disorders. https://accessmedicine.mhmedical.com/content.aspx?bookid=2747&sectionid=230251345
  3. Conroy D. (2021). Paradoxical Insomnia. Medlink. Retrieved June 6, 2021, from https://www.medlink.com/articles/paradoxical-insomnia
  4. Kaur H, Spurling BC, Bollu PC. (2020). Chronic Insomnia. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; https://www.ncbi.nlm.nih.gov/books/NBK526136/
  5. Neubauer, D. (2020). Pharmacotherapy for insomnia in adults. UpToDate. Retrieved March 28, 2021, from https://www.uptodate.com/contents/pharmacotherapy-for-insomnia-in-adults
  6. Sadock BJ, Sadock VA, Ruiz P. (2014). Kaplan and sadock’s synopsis of psychiatry: Behavioral sciences/clinical psychiatry (11th ed.). Chapter 16, Sleep-wake disorders, pages 533-563. Philadelphia, PA: Lippincott Williams and Wilkins.
  7. Williams J, Roth A, Vatthauer K, McCrae CS. (2013). Cognitive behavioral treatment of insomnia. Chest, 143(2), 554–565. https://doi.org/10.1378/chest.12-0731
  8. Winkelman, J. (2021) Overview of the treatment of insomnia in adults. UpToDate. Retrieved June 6, 2021, from https://www.uptodate.com/contents/overview-of-the-treatment-of-insomnia-in-adults

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