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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

Financial Disclosure: Nothing to declare

Today we will cover: Basic sleep physiology Narcolepsy – a disorder of the REM control system Periodic Limb Movement Disorder Obstructive Sleep Apnea Insomnia – diagnosis & treatment

DSM-IV-TR

Great clinical

textbook:

(Mayo Clinic, 2004)

Sleep waveform schematic

Sleep Stage % by Age

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

The “10 – 20” system of EEG electrode placement (C3 / C4 in yellow – where sleep is scored).

10 – 20 electrodes

10-20

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

Narcolepsy: MSLT, SOREMs

mid-saggital section.

Netter / CIBA

Whole Brain

Neurotransmitters in Sleep

REM: only time of day when monoamines not firing !

REM Control Nuclei

“Biological Clock”

REM induces muscle

paralysis

OREXIN

SCNclock

DA (+)

Histamine (+)

NA (+)

5HT (+)

Orexin / Hypocretin

Monoamines controlled by Orexin

~

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REM Control

REM Trigger: nucleus reticularis pontis oralis

Orexin-Hypocretin projections

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Narcolepsy -- Cataplexy

Narcolepsy: night sleep

Narcolepsy “Tetrad” (4 symptoms)

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 here too.

Narcolepsy: age of onset

Silber 2004, p.97.

Narcolepsy Biology

HUMAN DOG

Orexin / Hypo-cretin cells

Destroyed by immune system

Normal

Orexin receptors

Normal Genetic abnormality,

inactive

REM intrusion: (SP, Cataplexy) + +

Narcolepsy Treatments:

SLEEPINESS: Stimulants (noradrenalin receptor

agonists): amphetamine, methylphenidate, modafinil.

CATPLEXY:Antidepressants that increase serotonin

and or noradrenaline and block ACh, i.e. clomipramine, venlafaxine.

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Narcolepsy versus Schizophrenia

Narcolepsy

Actually Daytime

REM sleep intrusion

Apparent “Schizophreni

c” Hallucinations

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.

Worm in lateral hypothalamus causing narcolepsy.

(neurocysticercosis)

J. Clin. Sleep Med. 1(1) 2005, p. 41.

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Obstructive Sleep Apnea

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 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)

Periodic Limb Movement Disorder

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RLS – PLMD: neurochemistry

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 SYMPTOMS Late evening / night Legs cramp, squirm,

move by themselves Multiple awakenings “Charley Horses” Can’t tolerate legs

being immobilized Worse in 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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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

Sleep Latency (SL) – sleep onset defined as first 3 contiguous 30-sec. pages of Stage 1 sleep

REM Latency (RL) – time from sleep onset to first epoch of REM sleep

REM Latency Minus Awake (RLMA) – subtract any interposed pages of waking from the RL

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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REM Latency (RL & RLMA) 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 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.) 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

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

Crushing fatigue

Extreme appetite

“Atypical Depression”

Actually Depressed Phase

of Bipolar Disorder

DDx: Narcolepsy, Idiopathic Hypersomnolence

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Bipolar Disorder with Narcolepsy

Apparent Schizophreni

c Hallucination

s

Narcolepsy

Bipolar Disorder

+ Actually Hypnagogic

Hallucinations

These 2 illnesses when found together give a misdiagnosis: “psychotic bipolar,” “schizo-

affective”

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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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Management of 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.

Causes of acute insomnia

. . . acute insomnia #2

Note: all of these conditions are likely to be self-limited, 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

These conditions also illustrate that a state of stress / hyper-arousal is intrinsic in acute insomnia. This has been confirmed by measured elevations of the following in such patients:

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:

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:

Anxiety Disorders: Obsessive compulsive disorder Panic disorder & PTSD Generalized anxiety disorder Hypochondriasis

Substance Abuse (especially alcohol & cocaine)

. . . Chronic insomnia #2 Mood Disorders:

Bipolar disorder, especially mania or hypomania Major depression Dysthymic disorder

Psychoses: 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).

. . . 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:

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 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.”

DSM-IV-TR lumps all of these under “Primary Insomnia” & places the threshold for diagnosis at one month of symptoms or more.

Certain patterns of insomnia have diagnostic specificity, I.e., early morning awakening in Major Depression, and initial insomnia in anxiety disorders.

Assessment of Insomnia

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 it ACUTE? Y

N

Does reassurance & support

help?

Y

N

end

Rx benzos short-term

Identify & treat medical, surgical, or environmental

causesNo

better? Go to

next page

Is the insomnia acute?

Ask psychiatric questions: substance

abuse, depression,

anxiety

+Treat

psychiatric illness or refer

to psychiatrist.

-

Ask: sleep hygiene, naps,

caffeine, shifts

Counsel pt. yourself

Refer to sleep psychologist, esp. if “primary insomnia”

-

+

Physical sleep disorders? Refer to sleep lab if (+).

+

When to refer to sleep clinic Symptoms of sleep apnea (obese, snores, HTN, weight

gain, awakens choking, morning headache).

Symptoms of RLS / PLMD – legs squirm, cramp, tingle after supper and especially at night

If nocturnal injuries – could be sleepwalking, REM Behaviour Disorder, or nocturnal epilepsy.

Any chronic insomnia that does not have an obvious cause after reasonable investigations are negative.

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Questions ?