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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