Sleep and sleep disorders

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Sleep and sleep disorders

• Andy Montgomery

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Talk Outline

• Normal Sleep
• Diagnosing sleep disorders
• Insomnia
• Hypersomnia
• Parasomnias
• Circadian sleep rhythm disorders
• Psychiatric disorders and sleep
• Pharmacology and sleep

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Normal sleep

• 1/3 of adult lives asleep
• Role poorly understood
• Sleep deprivation consequences
• Cognitive impairment
• Hormonal rhythm disturbance
• Rebound after deprivation

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Normal sleep

• Quantity
• 7-8 hours
• lt6 increased reports dissatisfaction
• Control by 2 processes
• Circadian process
• Homeostatic process

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The Circadian process

• 24 hour cycle
• Many cells and organs
• Principle time-keeper
• Supra-chiasmatic nucleus
• Influenced by light and temperature
• Some sleep disorders associated with genetic
  variant
• Determines owl/lark

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The homeostatic process

• Aka recovery drive to sleep
• Increases in proportion to time awake
• 2 processes interact
• Generates
• Post-lunch dip
• mid-evening activity
• Other influences
• Arousal, relaxation, anxiety

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Physiology of sleep control

• Orexin (hypocretin)
• Peptide hormone
• Promotes wakefulness
• Wakefulness
• Ascending arousal system dominant
• Sleep
• Inhibition of arousal systems

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Sleep structure

• Polysomnography
• Simultaneous record
• EEG
• Muscle activity
• Eye movements
• 4-5 cycles
• Quiet sleep alternating with REM
• Increased duration through night

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Hypnogram
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Sleep structurequiet sleep

• 4 stages
• 1 dozing just resting eyes
• 2 deeper, occasional jerks, reduced HR RR
• 34 slow HR RR
• EEG
• Progressive slow synchronous activity
• Reduced cortical arousal
• Increased thalamo-cortical synchrony

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Sleep structureREM

• Rapid onset
• EEG awake
• Jerky eye movements
• Muscle paralysis
• Autonomic arousal
• Usually several short wakenings

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Stage EEG Eye movt EMG
Wake Low-amp, mixed some alpha Many varied, usually fast High
1 Low amp, mainly irregular theta Slow rolling lateral movt Slightly lowered
2 Sleep spindles, K complexes low amp theta None Lowered
3 High amp delta, K complexes None Low
4 As 3 None Low
REM Low amp irregular, saw-toothed Rapid jerky, lateral absent
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Age variants

• 24 hour rhythm
• Develops at 3/12
• High levels REM in childhood
• Aging
• Time awake increases
• Slow wave reduces
• GH release reduces

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Dreaming

• Only remembered if REM followed by wakefulness
• Occurs in
• REM
• Bizarre, storyline
• Slow wave

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Sleep and cognition

• Sleep enhances memory consolidation
• Transfer from short-term to long-term memory
• Dependent on hippocampal activity
• Sleep deprivation associated with reduced
  hippocampal neurogenesis

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Sleep disorders

• Diagnosis
• Take sleep history
• Questionnaires and diaries can be helpful
• Sleep centres polysomnography, actigraphy, video
  recording
• Classified in ICD 10 and DSM IV
• 3 categories
• Insomnia
• Hypersomnia
• Parasomnia

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Questions to ask

• Time
• Bed, getting up, ?regular pattern
• Falling asleep
• Waking episodes
• Quality (Pittsburgh Sleep Quality Index)
• How many bad nights/week?

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Questions to ask

• Naps during day
• Mood
• Motor activity during sleep
• Behaviour during sleep
• Day-time somnolence (Epworth sleepiness scale)
• Snoring
• Use of drugs

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Investigations

• Actigraphy
• Monitors movement via wrist band
• Can be used over days- weeks
• Sleep- less movement
• Overnight video recording

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Actigraphy
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Polysomnography

• Terms
• Time in bed
• Sleep onset (to stage 1 or 2)
• Sleep onset latency
• Sleep period onset to wake
• Total sleep time
• Number of wakenings
• Sleep efficiency (total sleep/time in bed)
• Wake after sleep onset
• REM onset latency
• Time in each sleep stage

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Insomnia

• Major public health problem
• 10-15 adults persistent insomnia
• Low quality of life
• Increased absenteeism
• Physical illness
• Mental illness

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Insomnia

• Symptoms
• Too little
• Too long to go to sleep
• Poor quality
• Unrefreshing
• Impaired daytime function
• Daytime sleepiness uncommon (circadian rhythm
  disorder)

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Insomnia

• Two main types
• Sleep onset insomnia
• Sleep maintenance insomnia

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Insomnia - precipitating factors

• Psychiatric disorder
• Depression
• anxiety

• Pharmacological
• ?-blocker
• AD
• Caffeine
• Alcohol
• Stimulants
• Withdrawal

• Psychological stress
• Bereavement
• Increased arousal
• Worry about alarm
• Noise
• children

Short term insomnia

• Physical
• Pain
• Pregnancy
• Illness (cardio/resp)
• Urinary

• Sleep wake cycle
• jet lag
• Shift work
• Irregular routine

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Insomnia- perpetuation
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Insomnia- treatment

• Establish primary diagnosis
• Acknowledge distress
• Treat precipitating factors/primary cause
• Educate about trigger factors and reassure
• Establish good sleep habits

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Insomnia- treatmentHypnotics

• Act at GABA-A benzodiazepine receptor
• Generally safe and effective in short term
• SE
• Muscle relaxation
• Memory impairment
• Ataxia
• Potentiated by EtOH
• Avoid long term px

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Insomnia- other drugs

• Sedative AD
• Mirtazapine
• Agomelatine
• Melatonin
• Anti-histamines

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Psychological treatments

• Sleep hygiene
• Regular hours
• Daytime exercise
• Morning daylight exposure
• Reduced daytime napping
• Avoid stimulants
• Bed-time routine

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Psychological treatments

• Behavioural techniques
• Stimulus control
• Avoid clock watching
• Dont watch TV
• Dont stay in bed if awake
• Sleep restriction
• Relaxation training

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Psychological treatments

• Cognitive techniques
• CBT
• Avoid negative thoughts associated with not
  sleeping
• Rehearsal and planning session
• Paradoxical intent

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Sleep restriction
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Hypersomnia

• Feeling sleepy during day
• Distinct from tired
• 37 adults a few days a month
• 16 a few days / week
• Main causes
• Fragmentation of sleep
• Obstructive sleep apnoea
• Intrusion of sleep phenomena into wake
• narcolepsy
• Disturbed circadian rhythm.

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Obstructive sleep apnoea symptoms

• Excessive daytime sleepiness
• Loud snoring
• Interruptions of breathing
• Resumes with loud gasp, violent movement
• Marital problems
• Dry mouth, sore throat, headache
• Depression
• Present in 0.5 men BMI gt25

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Obstructive sleep apnoea treatment

• Weight loss
• Continuous positive pressure ventilation
• Consider modafinil if remain sleepy during day

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Narcolepsy

• 3-4/10,000
• HLA DQB10602 (18-35 in controls)
• Symptoms
• Sudden onset sleep
• Sleepiness
• Cataplexy
• Hypnogogic/pompic hallucinations
• Poor nocturnal sleep

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Narcolepsy

• Cause
• Lack of orexin neurones/release in hypothalamus
• Possible cross-reaction autoimmune disorder after
  infection in adolescence
• Diagnosis
• Clinical picture
• Reduced REM latency

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Narcolepsy

• Treatment
• Education
• Day-time naps
• Drugs
• Daytime sleepiness
• Modafinil/dexamphetamine
• Cataplexy
• 5HT enhancing drug SSRI, clomipramine
• Night-time sleep disruption
• Sodium oxybate

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Other causes of daytime sleepiness

• Idiopathic hypersomnia
• Kleine-Levine syndrome
• Rare, reversible disorder
• Hypersomnia /- excessive eating hypersexuality
• Onset adolescence
• Typical duration 4-8 years
• ? autoimmune

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Parasomnias

• Unusual behaviours occurring during sleep
• Exacerbated by anxiety
• Variable drug treatments

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Night terrors

• Recurrent episodes of abrupt waking usually first
  1/3 of night
• Intense fear and autonomic arousal
• Unresponsive to comforting
• No detailed recall
• Significant distress

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Night terrors

• Occur in 30-40 children
• Generally resolve with aging
• Can recur at times of stress
• Comorbidity with anxiety common
• Often run in families

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Night terrors

• Cause
• Genetic component
• Incomplete arousals from SW sleep
• Treatment
• Clonazepam
• Paroxetine (immediate effect)

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Night terrors hypnogram
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Parasomnias -SWS

• Sleep walking
• Automatic behaviour
• No recall
• 15-20 lifetime prevalence
• Confusional arousals
• Semi-purposeful movements
• Sleep bruxism
• Sleep talking

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Parasomnias -REM

• Nightmares
• Wake oriented (vs night terrors)
• Association with depression and PTSD
• Psychological treatment
• Guided imagery- rehearse happy endings
• Sleep paralysis
• Waking with fear, foreboding, unable to move
• Common-25 experience
• Treatment- good sleep hygiene

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Parasomnias -REM behaviour disorder

• Violent, short duration
• Several episodes/night
• Can wake
• Remembers dream
• Violent unpleasant content
• Strong association with subsequent IPD OR LBD
  (45-85)
• Made worse by AD
• Treat by making sleep environment safe

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Circadian rhythm sleep disorders

• Jet lag
• Worse for travel east (natural clock 24.5hr)
• Melatonin may help
• Delayed sleep phase syndrome
• Unable to sleep before 2-3AM
• Preferred wake time after 10 AM
• Causes insomnia and sleepiness on work days
• Advanced sleep phase disorder
• rare

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Circadian rhythm sleep disorders

• Non 24hr circadian sleep disorder
• Sleep pattern advances daily
• Most common in congenitally blind
• Irregular sleep wake rhythm
• Seen in dementia- ? Loss of melatonin neurons in
  SCN
• Shift work sleep disorder

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Sleep and depression

• Sleep disturbance common in depression
• Almost 100 some disturbance
• Depression common in insomnia
• 14-21 c/o insomnia depressed
• 9 c/o hypersomnia depressed
• 1 no sleep problem depressed
• Depression most common diagnosis associated with
  insomnia

Epidemiologic study of sleep disturbances and
psychiatric disorders. An opportunity for
prevention?JAMA. 1989 Sep 15262(11)1479-84.
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Sleep complaints in mood disorders

• Initial insomnia
• Frequent/extended wakening
• EMW
• Vivid dreams, -ve emotional content
• Lack of adequate rest
• Hypersomnia (BPAD depressed, SAD)
• Reduced sleep (mania)

(MDD)
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Subjective effects of AD on sleep

• Few good studies
• Mismatch between subjective sleep and objective
  measure
• AD may affect subjective sleep

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Polysomnography findings MDD

• Initiation and maintenance
• ?sleep latency
• Frequent awakenings
• EMW
• Reduced SWS
• Absolute and relative
• Fewer delta waves
• REM
• Reduced REM latency
• ?REM in first half night
• More eye movements

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Polysomnography in at-risk population

• Two 1st degree relatives with MDD
• Reduced SWS in first NREM sleep cycle
• Increased REM density first REM period

J Affect Dis 2001 6233-
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Functional imaging depression

• REM
• Increased activation wake vs sleep
• Midbrain reticular formation
• L hemisphere cortical regions (DLPFC, FEF)
• Limbic/paralimbic regions (hipp, basal
  forebrain, ACC, MPFC)
• NREM
• Increased whole brain metabolism

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BPAD dysthymia

• BPAD
• Similar findings to MDD (depressed manic)
• Dysthymia
• Minimal changes

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Treatment effects

• Pharmacological tx most effective in pt with
  sleep architecture disturbance

Which depressed patients will respond to
interpersonal psychotherapy? The role of
abnormal EEG sleep profiles.Am J Psychiatry.
1997 Apr154(4)502-9.
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SSRI effects on REM

• Reduced REM
• Increased REM latency
• Effects within 2-3 days
• effects mediated ? synaptic 5HT
• ?5HT1A
• 1A knockout mice no effect of citalopram on REM
  latency
• 5HT1a agonists reduce REM
• Tryptophan depletion removes SSRI REM effect

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SSRI effects SWS

• Increased time Stage1
• Increased awakenings
• Increased time awake
• Effects diminish over 5/7 (except fluoxetine)
• ?5HT2 mediated
• Agonists disturb sleep
• Antagonists promote sleep

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TCA effects

• REM similar to SSRI
• SWS
• imipramine, clomipramine, desipramine increased
  sleep fragmentation
• Amitriptyline improve sleep healthy volunteers,
  not in MDD
• ? 5HT2 antagonism effect

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MAOI

• REM
• Phenelzine complete REM suppression
• 5HT mechanism- reversed by tryp. depl.
• ?MAOB effect
• Moclobemide minimal effect
• SWS
• Increased sleep fragmentation

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Other AD

• Mianserin
• Suppressed REM
• Reduced SWS fragmentation (?H1 blockade)
• Mirtazepine, trazadone, nefazadone
• Increased REM onset latency
• Reduced fragmentation (5HT2 antagonism)
• Reboxetine
• Minimal effect on REM or SWS
• Venlafaxine
• SSRI like effects

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Other AD

• Agomelatine
• 5HT2c antagonist
• MT1/ MT2 agonist
• Effective AD (antidepressant efficacy of
  agomelatine meta-analysis of published and
  unpublished studies BMJ 2014348g1888)
• Increased SWS, reduced sleep latency
• No effects on REM latency, total REM or REM
  densityThe International Journal of
  Neuropsychopharmacology (Impact Factor 5.64).
  11/2007 10(5)691-6.

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Effects of AD on HAM-D sleep items
Drugs. 200565(7)927-47.
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Change in perception of sleep quality with
nefazadone
Psychiatry Res. 2003 Sep 30120(2)179-90.
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AD adverse effects on sleep

• Restless legs
• Eye-movements in SWS
• Bruxism
• Nightmares
• Withdrawal nightmares

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Sleep deprivation effects

• One study
• 123IIBZM SPET
• Increased DA release after sleep deprivation

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Sleep and schizophrenia

• Rarely predominant complaint
• Disturbance may precede relapse
• Insomnia occasionally very severe
• Studies contradictory
• Variety of definitions of schizophrenia
• Older patients included
• Medicated patients

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Unmedicated patients

• Stage 2 latency increased
• Increased nocturnal wakenings
• Reduced sleep efficiency
• ? REM latency reduced

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Medicated patients- typical antipsychotics

• Stage 2 latency increased
• Reduced stage 2 4
• Total sleep time reduced
• Reduced sleep efficiency
• Reduced REM latency
• Reduced total REM sleep

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Medicated patients- atypical antipsychotics I

• Olanzapine
• Increased total sleep
• Increased sleep efficiency
• Reduced stage 2 latency
• Reduced total REM
• Risperidone
• Minimal data
• Increased SWS

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Medicated patients- atypical antipsychotics II

• Clozapine
• Increased total sleep
• Increased sleep efficiency
• No effect on REM
• ? Rebound insomnia after abrupt stop