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Sleep Disorders MedicineIn Psychiatry
Alan B. DouglassMD, FRCPC, Dip. ABPN, Dip. Amer. Board of Sleep MedicineAsst. Professor, Dept of Psychiatry, University of OttawaMedical Director, Sleep Disorders Service, Royal Ottawa
Hospital
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Introduction
A large proportion of insomnia cases involve elements of:
Depression Anxiety Disorder Bipolar Disorder
Current diagnostic reference – Internat’l Classification of Sleep Disorders (ICSD)
Resembles DSM-IV-TR, but more specific diagnostic criteria
DSM-IV-TR
Sleep waveform schematic
Sleep Stage % by Age
Table of Stg. %
Stg%
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
EEG Frequencies
Table of Stg. %
Wake => Sleep TransitionR & K 1968
Wake => Sleep Transition
R & K 1968
Stage 2 Sleep
Stage 4 Sleep
Onset of REMR & K 1968
REM sleep onset
Sleep Histogram
RL
24-hr Sleepiness Profile
Multiple Sleep
Latency Test (MSLT)
MSLT
Sleep Restriction
REM Control Nuclei
SCNclock
DA (+)
Histamine (+)
NA (+)
5HT (+)
Orexin / Hypocretin
Monoamines controlled by Orexin
~
REM Paralysis Control (from LDT / PPT)
Neurotransmitters in Sleep
Normal
Sleep Apnea
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OSA Clinical Symptoms
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Clinical Applicability – Apnea
Sleep apnea and depression share clinical features; apnea can produce secondary depression
Serious sleep apnea can cause sufficient sleep impairment to suggest dementia
Serious snoring in demented patient could suggest treatable illness
Apnea or PLMD can cause sleep deprivation, then relapse of mania or depression
Periodic Limb Movement Disorder
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RLS – PLMD: Sx and Tx SYMPTOMS Late evening / night Legs cramp, squirm,
move by themselves Multiple awakenings “Charley Horses” Can’t tolerate legs
being immobilized Majority elderly
TREATMENT Check Fe, ferritin,
B12, folate Dopamine agonists
(L-DOPA, ropinirole, pramipexole)
Benzodiazepines or opiates now 2nd line
Quinine obsolete
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RLS – PLMD: neurochemistry
Likely due to iron deficiency in basal ganglia (Fe is co-factor in enzymes that synthesize DA).
May predict onset of “syn-nuclein-opathies” (REM behaviour disorder, PSP, Parkinson’s, Lewy Body dementia).
Narcolepsy: age of onset
Silber 2004, p.97.
Narcolepsy: night sleep
Narcolepsy: MSLT, SOREMs
Narcolepsy “Tetrad”
True sleep attacks Falls asleep without warning, unusual situations
Cataplexy Flaccid muscle paralysis; eyes and diaphragm OK;
pt. remains awake but paralyzed. Hypnagogic / Hypnopompic
hallucinations “Multimodal” – visual, tactile, auditory, smell.
Often highly emotional, sexual, frightening Sleep Paralysis
Awakes unable to move anything but eyes. Can’t breathe voluntarily or talk. HH often occur.
Narcolepsy Biology
HUMAN DOG
Orexin / Hypo-cretin cells
Destroyed by immune system
Normal
Orexin receptors
Normal Genetic abnormality,
inactive
REM intrusion: (SP, Cataplexy) + +
Narcolepsy Treatment
SLEEPINESS: Stimulants (noradrenaline receptor
agonists): d-amphetamine (Dexedrine), methylphenidate (Ritalin), modafinil (Alertec).
CATPLEXY: Antidepressants that increase
serotonin and / or noradrenaline and block Ach.
Worm in lateral hypothalamus causing narcolepsy.
(neurocysticercosis)
J. Clin. Sleep Med. 1(1) 2005, p. 41.
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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
Most polysomnographic measurements are the same as for a clinical study (“epoch”= 30 sec.): Sleep Latency (SL) – sleep onset measured as first
three contiguous epochs of Stage 1 sleep REM Latency (RL) – time from sleep onset to first
epoch of REM sleep REM Latency Minus Awake (RLMA) –
RL subtracting any interposed epochs of wake Eye Movement Density in REM Sleep (REM
Density, RD) – the actual number of eye movements divided by minutes spent in REM
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RL and RLMA REM Latency is shortened by the
cholinergic agonists arecoline, pilocarpine, physostigmine
Prolonged by anti-cholinergics (benztropine, trihexyphenidyl, diphenhydramine
RL correlates inversely with age RLMA – superior statistical properties;
smaller variance, more normal distribution
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MDD Long initial insomnia, early morning
wakening Shallow sleep, easily awakened Non-refreshing sleep Antidepressants are REM suppressants
Increase neurotransmission in serotonergic and adrenergic monoamine pathways
REM is under tonic inhibition by monoamines Monoamine nuclei are under control of
OREXIN from lateral hypothalamus
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MDD (cont) Some powerful sleep mechanism
underlies the expression of depression Total sleep deprivation or selective
REM deprivation dramatically improves mood of severely depressed patients Benefit lost after one night’s sleep or nap
Amount of Non-REM sleep in nap predicts worsening of mood
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Alcoholism
Acute administration of alcohol produces REM suppression, then:
Withdrawal after
chronic alcohol
intoxication
Actually REM sleep
without physiological paralysis
Hallucination – visual,
gustatory, tactile dream-like imagery
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Narcolepsy versus Schizophrenia
Narcolepsy
Actually Daytime
REM sleep intrusion
Apparent “Schizophreni
c” Hallucinations
90% aassociation of narcolepsy with a 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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Bipolar Disorder vs. Depression
Excessive sleeping
Crushing fatigue
Extreme appetite
“Atypical Depression”
Actually Depressed Phase
of Bipolar Disorder
DDX: Narcolepsy, Idiopathic Hypersomnolence
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Bipolar Disorder (cont) “Switch process” from depression to
mania often occurs at night Significantly reduced sleep on that
night is often seen REM deprivation may be the key
factor in the switch May also explain seasonal cyclicity
of some bipolars (shorter sleep in Spring)
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Bipolar Disorder + Narcolepsy
Apparent Schizophreni
c Hallucination
s
Narcolepsy
Bipolar Disorder
+ Actually Hypnagogic
Hallucinations
Narcolepsy gives mis-Dx: psychotic bipolar, schizo-affective
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REM Latency (RL) Short RL not specific for depression Seen also in schizophrenia, bipolar disorder,
schizoaffective disorder, alcoholism, and borderline personality disorder
Puzzle: RL abnormalities not correlated with any shared clinical feature of these illnesses
Psychotic bipolar depression has the shortest RL values observed (10 – 40 min.)
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REM Latency (cont)MDD - Short RL, usually < 65 minutes (normal
controls > 80 minutes) Short RL predicts eventual successful
antidepressant response in MDD Psychotic MDD patients have shorter mean RL than
non-psychotic MDD
Depression, schizophrenia – RL inversely correlated to symptom severity
Bipolar – RL short in depressive phase RL abnormalities exist in relatives of bipolar
patients
Sleep abnormalities are state rather than trait markers – normalize with treatment
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Sleep Efficiency (SE)
SE in MDD less than normals, but equal to insomniacs 75-150 mg doxepin qHS improves SE;
mirtazepine also very effective SE also poor in schizophrenia
Normalizes after adequate antipsychotic drug treatment
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Clinical Applicability Bipolar Mania - Initial insomnia is the
most persistent symptom in treated bipolar patients, even when euthymic.
Higher levels of mood stabilizer eliminate insomnia without need for sleep lab referral
Alcohol Withdrawal DTs - REM rebounds strongly after cessation of drinking
Absence of customary REM paralysis allows patient to act out dreams (similar to REM behavior disorder patients)
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Clinical Applicability
Depressed Bipolar patient with hypersomnia (“atypical depression”) can be mistaken for Idiopathic Hypersomnolence, or even narcolepsy.
Cataplexy is the key differential symptom – only present in narcolepsy
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Bipolar Disorder MDD patients typically have reduced
night sleep but normal day alertness In depressed phase, Bipolars often
have excess of sleep (18 hours/day), with crushing fatigue when awake
Accompanied by ravenous appetite Termed “atypical depression” In the extreme, blends into catatonia
