Sleep Disorders Medicine In Psychiatry

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Sleep Disorders MedicineIn 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

• 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

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DSM-IV-TR
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Great clinical textbook (Mayo Clinic, 2004)
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Sleep waveform schematic
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Sleep Stage by Age
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Stg
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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
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10-20
The 10 20 system of EEG electrode placement
(C3 / C4 in yellow where sleep is scored).
10 20 electrodes
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Wake gt Sleep Transition
Wake gt Sleep Transition
R K 1968
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Stage 2 Sleep
R K 1968
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Stage 4 Sleep
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REM sleep onset
Onset of REM
R K 1968
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Sleep Histogram
RL
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24-hr Sleepiness Profile
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Multiple Sleep Latency Test (MSLT)
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Sleep Restriction
MSLT
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Narcolepsy MSLT, SOREMs
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Whole Brain
mid-saggital section. Netter / CIBA
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Neurotransmitters in Sleep
REM only time of day when monoamines not firing
!
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REM Control Nuclei
Biological Clock
OREXIN
REM induces muscle paralysis
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Monoamines controlled by Orexin
SCNclock
DA ()

Orexin / Hypocretin
Histamine ()
5HT ()
NA ()
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REM Control
REM Trigger nucleus reticularis pontis
oralis
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Orexin-Hypocretin projections
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Narcolepsy -- Cataplexy
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Narcolepsy night sleep
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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. Cant
  breathe voluntarily or talk. HH often occur here
  too.

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Narcolepsy age of onset
Silber 2004, p.97.
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Narcolepsy Biology
HUMAN DOG
Orexin / Hypo-cretin cells Destroyed by immune system Normal
Orexin receptors Normal Genetic abnormality, inactive
REM intrusion (SP, Cataplexy)
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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
Apparent Schizophrenic Hallucinations

Actually Daytime REM sleep intrusion
Narcolepsy

• 90 aassociation of narcolepsy with an HLA
  antigen DNA fragment (DQB10602) 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.
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Obstructive Sleep Apnea
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(No Transcript)
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Normal
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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)
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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, Parkinsons, 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
• Cant 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 nights 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
Actually Depressed Phase of Bipolar Disorder
Atypical Depression
DDx Narcolepsy, Idiopathic Hypersomnolence
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Bipolar Disorder with Narcolepsy
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

Hallucination visual, gustatory, tactile
dream-like imagery
Actually REM sleep without physiological
paralysis
Withdrawal after chronic alcohol intoxication
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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.

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. . . 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.

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. . . 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.

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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)

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. . . 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).

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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
• Erratic sleep-wake schedules
• Poor sleep hygiene
• Unreasonable expectations about their sleep (I
  have to get 9 hours of sleep each night or Ill
  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).

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. . . 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.

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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 1900h?
• Is there caffeine consumption after 1400h?
• Is there stimulant drug use or abuse?
• If indicated, do a full psychiatric diagnostic
  screening.
• Consider pain and physical illnesses that could
  cause it.

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Treatment Plan for Insomnia
Does reassurance support help?
Y
Is the insomnia acute?
Y
Is it ACUTE?
end
N
N

Rx benzos short-term
Identify treat medical, surgical, or
environmental causes
No better? Go to next page
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Ask psychiatric questions substance abuse,
depression, anxiety
Treat psychiatric illness or refer to
psychiatrist.

-
Physical sleep disorders? Refer to sleep lab if
().
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Ask sleep hygiene, naps, caffeine, shifts

Counsel pt. yourself
Refer to sleep psychologist, esp. if primary
insomnia

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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 ?