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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 ?
