Download Sleep & Psychiatr 2011 (Koranyi Lecture) 2011_compressed

Sleep Disorders Medicine
In Psychiatry
Alan B. Douglass
MD, FRCPC, Dip. ABPN, Dip. Amer. Board of Sleep Medicine
Asst. Professor, Dept of Psychiatry, University of Ottawa
Medical Director, Sleep Disorders Service, Royal Ottawa Hospital
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Introduction
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Financial Disclosure:
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Today we will cover:
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Nothing to declare
Basic sleep physiology
Narcolepsy – a disorder of the REM control system
Periodic Limb Movement Disorder
Obstructive Sleep Apnea
Insomnia – diagnosis & treatment
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DSM-IV-TR
Great
clinical
textbook:
(Mayo
Clinic,
2004)
Sleep waveform schematic
Sleep Stage % by Age
Stg%
EEG Frequencies
EEG Type
Hz.
Sleep Stg.
Delta
0.5 - 3
SWS
Theta
3-7
REM
Alpha
8 - 12
Wake
Beta
16 - 25
Wake
Spindle
12 - 14
Stg. 2 - 4
Gamma
20 - 50
REM, wake
10-20
The
“10 – 20”
system of
EEG
electrode
placement
(C3 / C4
in yellow
– where
sleep is
scored).
10 – 20 electrodes
Wake => Sleep Transition
R & K 1968
Wake => Sleep Transition
R & K 1968
Stage 2 Sleep
Stage 4 Sleep
REM sleep onset
Onset of REM
R & K 1968
Sleep Histogram
RL
24-hr Sleepiness Profile
Multiple
Sleep
Latency Test
(MSLT)
Sleep Restriction
MSLT
Narcolepsy: MSLT, SOREMs
Whole
Brain
midsaggital
section.
Netter / CIBA
Neurotransmitters in Sleep
REM: only time of day when monoamines not firing !
REM Control Nuclei
“Biological Clock”
OREXIN
REM induces
muscle
paralysis
SCN
clock
DA
(+)
~
Orexin /
Hypocretin
Histamine
(+)
5HT
(+)
NA
(+)
Monoamines
controlled by
Orexin
REM Trigger: nucleus
reticularis pontis oralis
REM Control
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Orexin-Hypocretin projections
Narcolepsy -- Cataplexy
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Narcolepsy: night sleep
Narcolepsy “Tetrad” (4 symptoms)
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True sleep attacks
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Cataplexy
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Flaccid muscle paralysis; eyes and diaphragm OK; pt.
remains awake but paralyzed.
Hypnagogic / Hypnopompic hallucinations
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Falls asleep without warning, unusual situations
“Multimodal” – visual, tactile, auditory, smell. Often
highly emotional, sexual, frightening
Sleep Paralysis
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Awakes unable to move anything but eyes. Can’t
breathe voluntarily or talk. HH often occur here too.
Narcolepsy: age of onset
Silber 2004, p.97.
Narcolepsy Biology
Orexin / Hypocretin cells
Orexin
receptors
REM intrusion:
(SP, Cataplexy)
HUMAN
DOG
Destroyed by
immune system
Normal
Normal
Genetic
abnormality,
inactive
+
+
Narcolepsy Treatments:
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SLEEPINESS:
Stimulants (noradrenalin receptor agonists):
amphetamine, methylphenidate, modafinil.
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CATPLEXY:
Antidepressants that increase serotonin and
or noradrenaline and block ACh, i.e.
clomipramine, venlafaxine.
Narcolepsy versus Schizophrenia
Narcolepsy
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Apparent
“Schizophrenic”
Hallucinations
Actually
Daytime
REM sleep
intrusion
90% aassociation of narcolepsy with an HLA antigen DNA
fragment (DQB1*0602) allows “inverse” screening of
schizophrenics for narcolepsy
Narcolepsy is detectable in sleep lab (MSLT) but pt. must
be medication-free for at least 3 weeks.
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Worm in
lateral
hypothalamus
causing
narcolepsy.
(neurocysticercosis)
J. Clin. Sleep Med. 1(1)
2005, p. 41.
Obstructive Sleep Apnea
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Normal
Sleep Apnea
OSA Clinical Symptoms
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Clinical Applicability – Apnea
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Sleep apnea and depression share clinical
features; apnea can produce secondary
depression.
Serious sleep apnea can cause sufficient
impairment to suggest dementia; severe
snoring in a “demented” patient could be a
treatable illness.
Apnea or PLMD can cause sleep deprivation
which can cause relapse of mania or
depression.
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Restless Legs Syndrome /
Periodic Limb Movement Disorder
(RLS-PLMD)
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Periodic Limb Movement Disorder
RLS – PLMD: neurochemistry
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Likely due to iron deficiency in basal
ganglia (Fe++ is co-factor for enzymes
that synthesize DA).
May predict onset of “syn-nuclein-
opathies” (REM behaviour disorder,
PSP, Parkinson’s, Lewy Body dementia).
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RLS – PLMD: Sx and Tx
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SYMPTOMS
Late evening / night
Legs cramp, squirm,
move by themselves
Multiple awakenings
“Charley Horses”
Can’t tolerate legs
being immobilized
Worse in elderly
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TREATMENT
Check Fe, ferritin,
B12, folate
Dopamine agonists
(L-DOPA, ropinirole,
pramipexole)
Benzodiazepines or
opiates now 2nd line
Quinine obsolete
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Polysomnographic Abnormalities
In Psychiatric Patients
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Sleep Abnormalities in Psychiatry
Benca, 1992
 Meta-analysis of sleep in all major psychiatric
disorders showed affective disorders had the
largest and most consistent differences from
controls.
Kaneko, 1981
 Extremely short nocturnal REM latency is
common to both psychiatric disorders and
narcolepsy
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Psychiatric Sleep Measurements
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Sleep Latency (SL) – sleep onset defined as first 3
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REM Latency (RL) – time from sleep onset to first
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REM Latency Minus Awake (RLMA) – subtract any
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Eye Movement Density in REM Sleep (REM
contiguous 30-sec. pages of Stage 1 sleep
epoch of REM sleep
interposed pages of waking from the RL
Density, RD) – the actual number of eye movements
divided by minutes spent in REM
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REM Latency (RL & RLMA)
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RL varies inversely with age & is highly
prevalent in affective disorders.
RLMA has statistical properties that are
superior to RL (smaller variance, more
normal distribution).
RL is shortened by cholinergic agonists
(arecoline, pilocarpine, physostigmine).
Prolonged by anticholinergics (benztropine,
trihexyphenidyl, diphenhydramine).
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MDD: sleep features
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Long initial insomnia, early morning wakening
Shallow sleep, easily awakened
Non-refreshing sleep
Short RL & RLMA; normalized by SSRI
(antidepressants are REM suppressants
because they increase neurotransmission in
serotonergic and adrenergic pathways).
High REM density (also a good predictor of
eventual depression in a never-ill person)
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MDD (cont.)
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Some powerful sleep mechanism underlies
the expression of depression
Total sleep deprivation or selective REM
deprivation dramatically improves mood of
severely depressed patients (benefit is lost
after one night’s sleep or even short nap)
Amount of Non-REM sleep in nap predicts
worsening of mood
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Bipolar Disorder vs. MDD
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MDD patients typically have reduced total
night sleep, but normal day alertness
Depressed bipolar patients in often have
excess sleep (up to 18 hours/day), crushing
fatigue when awake, ravenous appetite, &
weight gain: “atypical depression”.
“Switch process” in bipolars often occurs
during sleep.
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Bipolar Disorder vs. MDD
Excessive
sleeping
“Atypical
Depression”
Crushing
fatigue
Extreme
appetite
Actually
Depressed
Phase of
Bipolar
Disorder
DDx: Narcolepsy, Idiopathic Hypersomnolence
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Bipolar Disorder with Narcolepsy
Narcolepsy
+
Bipolar
Disorder
Apparent
Schizophrenic
Hallucinations
Actually
Hypnagogic
Hallucinations
These 2 illnesses when found together give a
misdiagnosis: “psychotic bipolar,” “schizo-affective”
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Alcoholism
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Acute administration of alcohol produces
REM suppression, then:
Withdrawal
after chronic
alcohol
intoxication
Hallucination –
visual,
gustatory,
tactile dreamlike imagery
Actually
REM sleep
without
physiological
paralysis
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Management of Insomnia
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Causes of acute insomnia
 Stressful personal events – child is sick,
financial crisis, fire damages the house,
natural disasters.
 Impending stressors – exams, marriage,
moving away from home, court appearance.
 Acute illness: medical, surgical, especially if
painful.
. . . acute insomnia #2
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Note: all of these conditions are likely to be selflimited, resolving in days to a couple of weeks, and
could occur to almost anyone. This matches the
federal licensing conditions for all marketed hypnotic
drugs (CPS 2009, p. 1132): “Treatment with {Imovane} should usually
not exceed 7 – 10 consecutive days. Use for more than 2 – 3 consecutive
weeks requires a complete reassessment of the patient. Prescriptions
should be written for short-term use (7 – 10 days) and should not be
prescribed in amounts exceeding a 1-month supply. The use of hypnotics
should be restricted to insomnia where disturbed sleep results in impaired
daytime functioning.“
. . . acute insomnia #3
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These conditions also illustrate that a state of stress / hyperarousal is intrinsic in acute insomnia. This has been confirmed
by measured elevations of the following in such patients:
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Whole body metabolic rate
Heart rate variability
Adrenalin & dopamine metabolites
Cortisol, ACTH, and CRF
Cerebral glucose metabolism (via PET scan).
However, some patients have a chronic trait of hyper-arousal
that can lull the doctor into prescribing hypnotics for the long
term. This may or may not amount to a psychiatric illness.
Chronic Insomnia:
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Studies indicate that 45 – 85% of chronic insomnia
(defined as lasting 6 months or more) is due to psychiatric
illness, even if the patient will not endorse or admit it.
DSM-IV diagnoses these patients “Insomnia related to
another mental disorder,” which includes:
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Anxiety Disorders:
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Obsessive compulsive disorder
Panic disorder & PTSD
Generalized anxiety disorder
Hypochondriasis
Substance Abuse (especially alcohol & cocaine)
. . . Chronic insomnia #2
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Mood Disorders:
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Psychoses:
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Bipolar disorder, especially mania or hypomania
Major depression
Dysthymic disorder
Schizophrenia & Schizo-affective disorder
Delusional disorder
Psychotic affective disorders.
Remaining insomnia patients mainly have painful or
disruptive chronic medical conditions (i.e., diarrhea) or a
diagnosable sleep disorder (i.e., sleep apnea).
...
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Chronic insomnia #3
Yet there appears to be a type of patient with chronic
insomnia in whom no psychiatric or physical diagnosis can be
found. These patients often have:
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Erratic sleep-wake schedules
Poor sleep hygiene
Unreasonable expectations about their sleep (“I have to get 9
hours of sleep each night or I’ll get sick”).
A belief that they are not sleeping when sleep recordings show
that they are.
Hyper-vigilance regarding bodily functions
Increased sensitivity to the consequences of reduced night sleep
(I.e., distorted perception of daytime deficits).
. . . Chronic insomnia #4
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In the International Classification of Sleep Disorders (ICSD),
these patients have been variously called “psycho-physiological
/ learned” insomnia, “sleep state misperception”, “idiopathic
insomnia” and “inadequate sleep hygiene.”
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DSM-IV-TR lumps all of these under “Primary Insomnia” &
places the threshold for diagnosis at one month of symptoms or
more.
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Certain patterns of insomnia have diagnostic specificity, I.e.,
early morning awakening in Major Depression, and initial
insomnia in anxiety disorders.
Assessment of Insomnia
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The Interview is critical. It must include:
 Amount of insomnia (at least 31 min. 3x /week).
 When did it begin (recent life events and stressors).
 What time do the lights go out; when does alarm ring in AM?
 Is there napping in the daytime (causes insomnia at night).
 Is there Shiftwork? How long on one shift before rotation?
 In what part of night does insomnia occur?
 Is it associated with physical or environmental causes?
 Is there alcohol consumption after 19:00h?
 Is there caffeine consumption after 14:00h?
 Is there stimulant drug use or abuse?
 If indicated, do a full psychiatric diagnostic screening.
 Consider pain and physical illnesses that could cause it.
Treatment Plan for Insomnia
Is the
Is insomnia
it ACUTE?
acute?
N
Identify & treat
medical, surgical, or
environmental
causes
Y
Does
reassurance
& support
help?
N
Rx benzos
short-term
No better?
Go to next
page
Y
end
Ask psychiatric
questions:
substance abuse,
depression,
anxiety
+
-
Physical sleep
disorders? Refer to
sleep lab if (+).
Ask: sleep
hygiene, naps,
caffeine, shifts
Treat psychiatric
illness or refer
to psychiatrist.
+
+
Counsel pt. yourself
Refer to sleep
psychologist, esp. if
“primary insomnia”
When to refer to sleep clinic
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Symptoms of sleep apnea (obese, snores, HTN, weight
gain, awakens choking, morning headache).
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Symptoms of RLS / PLMD – legs squirm, cramp, tingle
after supper and especially at night
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If nocturnal injuries – could be sleepwalking, REM
Behaviour Disorder, or nocturnal epilepsy.
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Any chronic insomnia that does not have an obvious
cause after reasonable investigations are negative.
Questions ?
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