Sleep and sleep disorders

Sleep is a physiologically recurring state of rest characterized by relative suspension of consciousness and inaction of voluntary muscles. It is regulated by the circadian rhythm and usually consists of 4–5 sleep cycles that include three stages of non-rapid eye movement sleep (NREM sleep) and one stage of rapid eye movement sleep (REM sleep). Sleep disorders can be grouped into primary (i.e., due to an intrinsic disorder of the sleep-wake cycle) and secondary (i.e., due to an underlying medical condition). Primary sleep disorders are further divided into dyssomnias and parasomnias. Symptoms include difficulty falling asleep, difficulty remaining asleep, or abnormal behavior during sleep. Treatment may include sleep hygiene practice, phototherapy, and sedative pharmacotherapy.

Narcolepsy, restless legs syndrome, and obstructive sleep apnea are discussed in separate articles.

Normal sleep cycle ^[1]

• Sleep latency: the length of time required to fall asleep
• Sleep stages
  • A full night's rest typically consists of 4–5 sleep cycles of 90–120 minutes each.
  • Every cycle consists of 3 NREM sleep stages and one REM sleep stage with the percentage of REM sleep gradually increasing as the night progresses. ^[2]
• Circadian rhythm
  • Definition: a 24-hour cycle of biophysical changes that regulate sleep patterns, feeding patterns, hormone production (e.g., release of melatonin, prolactin, ACTH, norepinephrine), and body temperature
  • Regulation of sleep: photosensitive retinal ganglion cells stimulation by light (dark cues) → retinohypothalamic tract (RHT) stimulation → norepinephrine release from the suprachiasmatic nucleus of the hypothalamus → melatonin release from the pineal gland → sleep induction

Normal sleep phases ^[1][3]

To remember the sequence of brain wave changes during sleep, think: “For BETTER (read “beta”) WAVES, Ask The Silent Surfer Dozing at the Beach” (Beta waves while awake; Alpha waves with eye closure; Theta waves during N1; Sleep spindles during N2; Delta waves during N3; Beta waves during REM sleep).

To remember when teeth grinding (N2 stage) and bedwetting (N3 stage) occur during NREM sleep, think: “I saw the t(w)ooth fairy fleeing and the three little pigs peeing”.

Primary sleep disorders

Dyssomnias

• Definition: : a group of primary sleeping disorders characterized by difficulty falling/staying asleep or hypersomnia (excessive daytime sleepiness)
• Types of dyssomnias
  • Circadian rhythm sleep-wake disorder ^[6]
    • Delayed sleep-wake phase disorder
    • Advanced sleep phase disorder
    • Jet lag disorder
    • Shift-work disorder
    • Non-24 hour sleep-wake disorder
  • Insomnia disorder
  • Hypersomnolence disorder
  • Narcolepsy
  • Central sleep apnea
  • Obstructive sleep apnea

Parasomnias ^[6]

• Definition: : a group of primary sleeping disorders characterized by abnormal behaviors or experiences that occur while falling asleep, during sleep, or while waking up
• Types of parasomnias
  • NREM-related parasomnia: a group of parasomnias characterized by repeated episodes of brief but incomplete awakenings that typically occur during the first third of sleep
    • Sleepwalking disorder
    • Sleep terror disorder
  • REM-related parasomnias: a group of parasomnias characterized by a dissociation between REM sleep and the awake state
    • Nightmare disorder
    • REM sleep behavior disorder
    • Recurrent isolated sleep paralysis
  • Restless legs syndrome

Secondary sleep disorders

• See “Sleep-phase-specific disorders” in “Sleep physiology” section above.

Overview

• Prevalence: ∼ 20% of the population worldwide (most common sleep-wake disorder) ^[10]
• Etiology
  • Poor sleep hygiene
  • Subclinical mood or anxiety disorders
• Classification
  • Acute or transient (< 3 months): associated with stress or a disrupted sleep schedule
  • Chronic (≥ 3 months): associated with an increased risk of psychiatric illness and functional impairment

Clinical features

• Initial or sleep-onset insomnia: difficulty initiating sleep
• Middle or sleep-maintenance insomnia: frequently waking from sleep
• Late or sleep-offset insomnia: awakening early in the morning
• Nonrestorative sleep: feeling fatigued after waking

DSM-5 diagnostic criteria ^[11]

• Problems initiating or maintaining sleep, or awakening early in the morning and being unable to return to sleep
• Symptoms occur ≥ 3 days/week for ≥ 3 months
• Symptoms cause functional impairment or distress
• Symptoms are not caused by an underlying substance or medication use
• Symptoms occur despite having enough time to sleep
• No underlying or coexisting psychiatric or medical disorder that explains symptoms

Treatment

Behavioral therapy

• Sleep hygiene
  • No alcohol 4–6 hours preceding sleep
  • No stimulants: Caffeinated drinks and nicotine should be avoided 3–4 hours before bedtime.
  • Regular exercise is beneficial but should be avoided 6 hours before bedtime.
  • Quiet, dark, pleasantly cool bedroom and a comfortable bed
  • No large meals before bedtime
• Stimulus control therapy: Insomnia disorder may cause the bed and bedroom to become cues for arousal rather than sleep. Stimulus control instructions aim to correct this by re-establishing the association of the bed and bedroom with sleep.
  • Advise waking up at regular times (also during the weekend and holidays).
  • Discourage engaging in other activities in bed such as working or reading.
  • Leave the bedroom when unable to fall asleep within 20 minutes (e.g., to read or listen to music) and return only when sleepy.
  • Advise against afternoon naps; if taken, this should not take place after 3 p.m. and naps should be no longer than 1 hour.
• Sleep restriction therapy
  • A cognitive behavior therapy for patients with chronic insomnia, where the amount of time spent in bed is restricted to their average estimated sleep time.
  • When sleep efficacy (total sleep divided by time spent in bed) is greater than 90%, the amount of time spent in bed is increased.
  • This has been shown to reduce sleep latency.
• Cognitive-behavioral therapy (CBT): preferred treatment for chronic insomnia

Pharmacotherapy

• Benzodiazepines
  • For sleep onset insomnia: short-acting agent (e.g., triazolam)
  • Only for short-term use because of high risk of addiction
  • Decrease sleep latency and number of awakenings during sleep
• Non-benzodiazepine sedatives
  • Zolpidem, eszopiclone, zaleplon
  • Lower risk of daytime sleepiness, although falls and cognitive impairment are still a concern (especially in the elderly and individuals using zolpidem)
• Antidepressants
  • Trazodone (most commonly prescribed antidepressant for chronic insomnia and depressive symptoms)
  • Amitriptyline
• Orexin antagonists: suvorexant

Sleepwalking disorder

• Definition: a NREM-related parasomnia characterized by walking or performing other activites during the first third of the sleep cycle
• Epidemiology: Discrete episodes are common (up to 7% of adults and 30% of children), but the disorder is rare. ^[14][15]
• Etiology: idiopathic or genetic (inherited in 80% of cases)
• Risk factors
  • Sleep deprivation
  • Irregular sleep schedules
  • Stress or fatigue
  • Obstructive sleep apnea
  • Nocturnal seizures
  • Fever
  • Drugs (e.g., benzodiazepines, z-drugs, antidepressants, antipsychotics, β-blockers) ^[16]
• Clinical features
  • Recurrent episodes during the first third of the sleep cycle, including sitting up, walking, or eating
  • Blank stare and difficulty arousing patient during the episode
  • Followed by amnesia of the event
• Treatment
  • Education and reassurance
  • Ensuring safe sleep environment to reduce the risk of physical harm or wandering outdoors
  • In refractory cases, benzodiazepines

Sleep terror disorder

• Definition: a NREM-related parasomnia that occurs during the N3 sleep stage (slow-wave sleep), characterized by episodes of sleep terror
• Epidemiology: : Discrete episodes of sleep terrors are relatively common in children (∼ 20% of children and ∼ 2% of adults), but the disorder is rare.
• Etiology: unknown; presumed to be genetic (family history)
• Risk factors
  • Stress or fatigue
  • Fever
  • Sleep deprivation
  • Obstructive sleep apnea
  • Nocturnal seizures
  • Drugs (e.g., lithium)
• Clinical features
  • Screaming or crying suddenly upon awakening, usually in the first part of the night (rarely during daytime naps) ^[17]
  • Intense fear and agitation
  • Tachypnea, diaphoresis, tachycardia during episodes
  • Difficulty arousing patients during episodes
  • Patients usually return to sleep after the episode.
  • Typically no recollection of the arousal episode (unlike with nightmare disorder)
• Treatment
  • Education and reassurance (disorder usually self-limited)
  • Removal of dangerous objects from bedroom to reduce risk of self-injury
  • In refractory cases, benzodiazepines

Nightmare disorder

• Definition: a REM-related parasomnia characterized by recurrent nightmares
• Epidemiology
  • Prevalence: most common in early adulthood; occurs in 2–5% of the adult population ^[18]
  • Sex: ♀ > ♂
• Risk factors: post-traumatic stress disorder (PTSD)
• Clinical features
  • Recurrent frightening dreams during the second half of sleep cycle (middle of the night or early in the morning)
  • Patient remembers the dream after awakening (unlike in sleep terror disorder).
  • Causes functional impairment or distress
• Treatment
  • Reassurance if the disorder is mild
  • Imagery rehearsal therapy: involves modifying a recurrent nightmare by writing it down and rehearsing new endings that make nightmares less frightening when they occur again
  • Antidepressants or prazosin if associated with PTSD ^[19]

REM sleep behavior disorder

• Definition: a REM-related parasomnia characterized by dream enactment due to loss of REM sleep atonia
• Epidemiology
  • Prevalence: ∼ 1% in the general population ^[20]
  • Sex: ♂ > ♀
  • Usually in older patients (> 50 years)
• Risk factors
  • Narcolepsy
  • Psychiatric medications (e.g., antidepressants)
  • Neurodegenerative disorders (e.g., Parkinson disease, Lewy body dementia)
• Clinical features
  • Physically acting out dreams during sleep (e.g., yelling, moving limbs, walking, punching), sometimes leading to injury to self or others
  • Patient is alert and orientated after awakening, and remembers the dream.
• Treatment
  • Remove dangerous objects from the bedroom to reduce risk of self-injury.
  • If applicable, discontinue causative medications.
  • Pharmacotherapy ^[20]
    • Melatonin receptor agonist (first-line treatment)
    • Benzodiazepines (e.g., clonazepam)

Other parasomnias

• Nocturnal enuresis
• Restless leg syndrome

To remember that nightmare disorder occurs during REM sleep and the experience is remembered, while sleep terror disorder occurs during non-REM sleep and is not remembered, think: I REMember my NIGHTMARE, and there were NO memorable TERRORists.

Normal changes in sleep architecture occur with aging, and include:

• Decreased total sleep time ^[21]
  • Decreased time spent in deep sleep and REM sleep
  • Increased sleep latency
  • More frequent nighttime awakenings that are likely multifactorial (e.g., due to nocturia, pain, and/or less time spent in deeper stages of sleep)
• Advanced circadian rhythms resulting in earlier bedtimes and thus morning awakenings ^[21]