Sleep and sleep disorders
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Transcript of Sleep and sleep disorders
Sleep and sleep disorders
Andy Montgomery
Talk Outline
• Normal Sleep• Diagnosing sleep disorders• Insomnia• Hypersomnia• Parasomnias• Circadian sleep rhythm disorders• Psychiatric disorders and sleep• Pharmacology and sleep
Normal sleep
• 1/3 of adult lives asleep
• Role poorly understood
• Sleep deprivation consequences– Cognitive impairment– Hormonal rhythm disturbance– Rebound after deprivation
Normal sleep
• Quantity– 7-8 hours– <6 increased reports dissatisfaction
• Control by 2 processes– Circadian process– Homeostatic process
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
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
Physiology of sleep control
• Orexin (hypocretin)– Peptide hormone– Promotes wakefulness
• Wakefulness– Ascending arousal system dominant
• Sleep– Inhibition of arousal systems
Sleep structure
• Polysomnography– Simultaneous record
• EEG• Muscle activity• Eye movements
• 4-5 cycles – Quiet sleep alternating with REM
• Increased duration through night
Hypnogram
Sleep structure:quiet sleep
• 4 stages• 1: dozing “just resting eyes”• 2: deeper, occasional jerks, reduced HR &RR• 3&4: slow HR & RR
• EEG• Progressive slow synchronous activity
– Reduced cortical arousal– Increased thalamo-cortical synchrony
Sleep structure:REM
• Rapid onset
• EEG “awake”
• Jerky eye movements
• Muscle paralysis
• Autonomic arousal
• Usually several short wakenings
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
Age variants
• 24 hour rhythm– Develops at 3/12
• High levels REM in childhood
• Aging– Time awake increases– Slow wave reduces– GH release reduces
Dreaming
• Only remembered if REM followed by wakefulness
• Occurs in – REM
• Bizarre, storyline
– Slow wave
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
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
Questions to ask
• Time:– Bed, getting up, ?regular pattern– Falling asleep
• Waking episodes
• Quality (Pittsburgh Sleep Quality Index)
• How many bad nights/week?
Questions to ask
• Naps during day• Mood• Motor activity during sleep• Behaviour during sleep• Day-time somnolence (Epworth sleepiness
scale)• Snoring• Use of drugs
Investigations
• Actigraphy– Monitors movement via wrist band– Can be used over days- weeks– Sleep- less movement
• Overnight video recording
Actigraphy
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
Insomnia
• Major public health problem
• 10-15% adults persistent insomnia– Low quality of life– Increased absenteeism– Physical illness– Mental illness
Insomnia
• Symptoms– Too little– Too long to go to sleep– Poor quality– Unrefreshing– Impaired daytime function
• Daytime sleepiness uncommon (circadian rhythm disorder)
Insomnia
• Two main types:– Sleep onset insomnia– Sleep maintenance insomnia
Insomnia - precipitating factors
Sleep wake cycle•jet lag•Shift work•Irregular routine
Psychological stress•Bereavement•Increased arousal•Worry about alarm•Noise•children
Psychiatric disorder•Depression •anxiety
Pharmacological-blocker•AD•Caffeine•Alcohol•Stimulants•Withdrawal
Physical•Pain•Pregnancy•Illness (cardio/resp)•Urinary
Short term insomnia
Insomnia- perpetuation
Short term insomnia
Long term insomnia
Anxiety about sleep
Good sleep
Poor sleep habitsGood sleep habits
Insomnia- treatment
• Establish primary diagnosis
• Acknowledge distress
• Treat precipitating factors/primary cause
• Educate about trigger factors and reassure
• Establish good sleep habits
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
Insomnia- other drugs
• Sedative AD– Mirtazapine– Agomelatine
• Melatonin
• Anti-histamines
Psychological treatments
• Sleep hygiene– Regular hours– Daytime exercise– Morning daylight exposure– Reduced daytime napping– Avoid stimulants– Bed-time routine
Psychological treatments
• Behavioural techniques– Stimulus control
• Avoid clock watching• Don’t watch TV• Don’t stay in bed if awake
– Sleep restriction– Relaxation training
Psychological treatments
• Cognitive techniques– CBT
• Avoid negative thoughts associated with not sleeping
– Rehearsal and planning session– Paradoxical intent
Sleep restriction
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.
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 >25
Obstructive sleep apnoea: treatment
• Weight loss
• Continuous positive pressure ventilation
• Consider modafinil if remain sleepy during day
Narcolepsy
• 3-4/10,000
• HLA DQB1*0602 (18-35% in controls)
• Symptoms– Sudden onset sleep– Sleepiness– Cataplexy– Hypnogogic/pompic hallucinations– Poor nocturnal sleep
Narcolepsy
• Cause– Lack of orexin neurones/release in
hypothalamus– Possible cross-reaction autoimmune disorder
after infection in adolescence
• Diagnosis– Clinical picture– Reduced REM latency
Narcolepsy
• Treatment– Education– Day-time naps– Drugs
• Daytime sleepiness– Modafinil/dexamphetamine
• Cataplexy– 5HT enhancing drug: SSRI, clomipramine
• Night-time sleep disruption– Sodium oxybate
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
Parasomnias
• Unusual behaviours occurring during sleep
• Exacerbated by anxiety
• Variable drug treatments
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
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
Night terrors
• Cause– Genetic component– Incomplete arousals from SW sleep
• Treatment– Clonazepam– Paroxetine (immediate effect)
Night terrors hypnogram
Parasomnias -SWS
• Sleep walking– Automatic behaviour– No recall– 15-20% lifetime prevalence
• Confusional arousals– Semi-purposeful movements
• Sleep bruxism• Sleep talking
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
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
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
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
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 15;262(11):1479-84.
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)
Subjective effects of AD on sleep
• Few good studies– Mismatch between subjective sleep and
objective measure– AD may affect subjective sleep
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
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 62:33-
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
BPAD & dysthymia
• BPAD– Similar findings to MDD (depressed & manic)
• Dysthymia– Minimal changes
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 Apr;154(4):502-9.
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
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
TCA effects
• REM: similar to SSRI
• SWS: – imipramine, clomipramine, desipramine:
increased sleep fragmentation– Amitriptyline: improve sleep healthy
volunteers, not in MDD • ? 5HT2 antagonism effect
MAOI
• REM– Phenelzine complete REM suppression
• 5HT mechanism- reversed by tryp. depl.• ?MAOB effect
– Moclobemide: minimal effect
• SWS– Increased sleep fragmentation
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
Other AD
• Agomelatine– 5HT2c antagonist
– MT1/ MT2 agonist
– Effective AD (antidepressant efficacy of agomelatine: meta-analysis of published
and unpublished studies BMJ 2014;348:g1888)
– 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.
Effects of AD on HAM-D sleep items
Drugs. 2005;65(7):927-47.
Change in perception of sleep quality with nefazadone
Psychiatry Res. 2003 Sep 30;120(2):179-90.
AD adverse effects on sleep
• Restless legs
• Eye-movements in SWS
• Bruxism
• Nightmares
• Withdrawal nightmares
Sleep deprivation effects
• One study– [123I]IBZM SPET– Increased DA release after sleep deprivation
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
Unmedicated patients
• Stage 2 latency increased
• Increased nocturnal wakenings
• Reduced sleep efficiency
• ? REM latency reduced
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
Medicated patients- atypical antipsychotics I
• Olanzapine– Increased total sleep– Increased sleep efficiency– Reduced stage 2 latency– Reduced total REM
• Risperidone– Minimal data– Increased SWS
Medicated patients- atypical antipsychotics II
• Clozapine– Increased total sleep– Increased sleep efficiency– No effect on REM– ? Rebound insomnia after abrupt stop