Richard E. Waldhorn, MDClinical Professor of MedicineDivision of Pulmonary, Critical Care and Sleep MedicineGeorgetown University School of Medicine

Sleep Disorders

The Nightmare- Henry Fuseli, 1781

Sleep DisordersWhat is sleep and how is it

structured?What are the normal rhythms of

sleep and wakefulness?How does sleep change as we age?What are the presenting symptoms

of the most common sleep disorders?

Sleep - Definition

Sleep is a physiologic, recurrent, reversible behavioral state of perceptual disengagement from and unresponsiveness to the environment.

Influenced by a homeostatic and a circadian drive

Sleep is not the absence of wakefulness:• Active• Highly Regulated• Involves different areas in the brain • Purpose is not understood• Essential to life

Sleep RegulationHomeostatic process: determined by sleep

and wakingThe pressure for sleep increases proportionately

to the time since last sleepCircadian process: Approximately 24 hr

cycle of sleep and wakefulness periods with high and low sleep propensityindependent of sleep and wakingSuprachiasmatic nucleus- regulated by

zeitgebers: sunlight and eating timeUltradian process: occurring within sleep-

the alternation of Non REM and REM sleep

Sleep StagesTwo separate sleep states have been defined on

the basis of a constellation of physiological parameters:

Non-rapid eye movement (NREM) sleep: A relatively inactive (yet actively regulating) brain in a

movable body Fast wave sleep (Stages 1 & 2) Slow wave sleep (Stages 3 & 4; delta)

Rapid eye movement (REM) sleep: A highly activated brain in a paralyzed body

Rapid eye movements Low amplitude, mixed frequency EEG Lowest muscular tone

Sleep Stages - Adult

REM Sleep- bilateral synchronous eye movements, muscle atonia

Normal sleepSleep latency

Normal: 10 minutesStage N1-N2 sleep

Initial period: 20-40 minutesStage N3 sleep

Onset at 30-40 minutes after lights outStage REM sleep

Onset at 90 minutes after lights out

Sleep cycle: normal hypnogram

Normal SleepN1-N2 sleep—light sleep

50-60% of sleep timeSleep onset and in latter part of the night

N3 “deep”—slow wave sleep“restorative” part of the nightEarly in the sleep cycle20-25% of sleep time

REM “dream” sleepBrain active/muscles paralyzed4 REM periods thru the nightLongest is just prior to awakening20-25% of the night

Key Polysomnographic TermsSleep latency- lights out until sleep onsetREM latency- sleep onset to the first epoch of

REMSleep efficiency- Total sleep time/total

recording timeWake after sleep onset (WASO)Percent REM sleepPercent slow-wave sleep (SWS)Percent stage 1-2 sleep

What causes sleep ?Activation of neural structures in the

brainstemCortex is variably active—most in REM sleepComplex interplay

Brain: light and darkHormones: cortisolTemperatureCircadian rhythm

Circadian Rhythms

Suprachiasmatic Nuclei (SCN)

Light Output Rhythms Physiology Behavior

Normal Circadian Sleep Rhythm

Circadian Rhythms

Sleep Changes with Age

Breathing during sleepCentral nervous system controlStretch receptorsChemoreceptors

Blood carbon dioxide levelSlightly higher trigger to breathe than when

awakeVery sensitiveCan be affected by drugs, chronic diseasesAltitude

Sleep and Psychiatry- Historical note 1900-Freud: The Interpretation of Dreams 1953 -Kleitman and Aserinsky at the University of

Chicago describe the rapid eye movement (REM) stage of sleep and propose a correlation with dreaming

1957- Dement and Kleitman describe the repeating stages of the human sleep cycle.

1968-Rechtschaffen and Kales publish a scoring manual that allows for the universal, objective comparison of human sleep stage data.

1980- Sullivan, Rapoport, Sanders: nasal CPAP for OSA2000-Mignot and colleagues at Stanford discover that

human narcolepsy also is associated with hypocretin deficiency.

Sleep DisordersDOES—disorders of excessive somnolence

Quantity of sleepQuality of sleep

DIMS—disorders of initiation and maintenance of sleepSleep onset insomniaSleep maintenance insomnia

Sleep DisordersCircadian rhythm disorders

Delayed sleep phase syndrome “night owl”Advanced sleep phase syndrome “lark”Jet lagNight shift worker

ParasomniasExcessive motor activity during sleepSleep walking/talking/eatingSleep terrorsREM behavior disorder

Question 1What is the most common cause of DOES?

1. sleep disordered breathing2. narcolepsy3. inadequate sleep hours4. sleep walking

DOESInadequate sleep hours

Adult sleep requirement: 7-9 hoursAdequate sleep architecture

50-60% light sleep (N1-N2) 20-25% deep sleep (N3) 20-25% REM sleep

Good sleep behaviorsProper sleep conditions

Case 162 year old male with history of diabetes, hypertensionChief complaint: “ I am tired all the time”Has been feeling “down “ for the past few weeks every

dayHas been having trouble with memory and concentrationHas gained 20 lbs in past 2 yearsSH:20 pack year smoking; drinks beer on weekendsPhysical exam: obese, neck circumference 19 inchesStarted on Paroxetine 20 mg

Case 1- 3 months laterStill troubled by daytime sleepinessNow reports he fell asleep at red light driving

to workWife accompanied him to appointment,

reports she has sought refuge on another floor of house due to loud snoring disturbing her sleep

Wife also reports he is gasping and choking during sleep

DOESSleep disordered breathing: Obstructive sleep apnea

6-12% of the populationMales and femalesObesityAnatomic abnormalitiesIncreases with ageSymptoms

snoring, observed apneas, daytime sleepiness

Airway disorder

PATENT vs COLLAPSED AIRWAY

2006 American Academy of Sleep medicine

Sleep Disordered Breathing

Central and Obstructive Apnea

Obstructive Hypopnea

Consequences of recurrent obstructive sleep apnea/hypopneaExcessive daytime somnolenceSnoringMorning headachesSleep maintenance insomniaImpaired cognitive performanceSocial/sexual/psychologic problemsPoor quality of lifeIncreased risk of MVAAdverse cardiovascular outcomes

Systemic hypertensionPulmonary hypertension (?DM/metabolic syndrome)?Stroke

Burwell et al: Extreme Obesity associated with alveolar hypoventilation: A pickwickian syndrome. Am J Med 1956;21: 811- 818

•An obese patient came to the emergency room of the Peter Bent Brigham Hospital•CC: Fell asleep at Poker with a full house and a large pot•PE: Obese, hypersomnolence, hypoventilation, cor pulmonale

This reminded Burwell of Joe, the fat boyFrom the Dickens novel, “The posthumous papers of the Pickwick Club.”

The term was initially coined by Osler (1918)

Psychologic, cognitive, behavioral sequelae of sleep apneaDaytime sleepiness- different from “fatigue or low

energy” as in depressionExcessive sleepInvoluntary napsFighting sleepiness while sedentaryCapacity to nap voluntarily

Hyperactivity in childrenImpaired memory, attention, vigilanceDepression extremely common in OSADepressive symptoms reduced with CPAPConfusional states and psychotic disorders

Depression and Sleep ApneaWheaton, CDC study; (Sleep, 2012)

Survey on sleep disordered breathing and

PHQ-9 depression screen 9714 adultsFrequent snorting/stopping breathing, but not snoring,

associated with higher prevalence of probable major depression

Possible mechanisms underlying association between depression and OSASleep fragmentation and hypoxemiaNeurobiology of depression and upper airway control:

serotonin mediated, SSRIs in treatment of OSA?Shared risk factors- Depression in patients with obesity,

hypertension, diabetes should raise suspicion of coexisting OSA

Positive Airway Pressure

2006 American Academy of Sleep Medicine

Nasal CPAP

Nasal CPAP/BIPAPBroad acceptance as treatment of choice in

moderate to severe OSA with improvement in:Symptoms of sleepiness( Epworth)Objective measures of sleepiness( MSLT)Cognitive function scoresQOL scoresBlood pressure, Pulmonary artery pressureReduction in MVAs

White et al. Cochrane database 2000,Kaneko et al. NEJM 2003;348:1233-1241

Dental orthotic or mandibular repositioning devices

Surgical Management:Uvulopalatopharyngoplasty (UPPP)

2006 American Academy of Sleep Medicine

Mandibular advancement surgery

Midface, palate, and mandible advanced anteriorly

Increases posterior airway space

Follow up orthodontic procedures, wiring of jaw

For severe disease

Upper-Airway Stimulation for Obstructive Sleep Apnea N Engl J Med

Volume 370(2):139-149January 9, 2014

“The fat boy for once had not been fast asleep. He was awake—wide awake to what had been going forward.”

DOES Narcolepsy

Relatively rare but under-recognizedOnset in adolescenceFour cardinal symptoms

Excessive daytime sleepiness Sleep paralysis Vivid dreams/hallucinations Cataplexy

CNS disorder

Sleep initiation problemsPrimary sleep disorderMedical problem/ medication

Restless legs syndrome Pain, “creepy/crawly” sensation

Pain: arthritis/fibromyalgia, etcMedications: stimulants including

caffeine/decongestantsPoor bedroom conditions“Psychophysiologic” insomniaDepression/anxiety

Sleep maintenance disordersPrimary sleep disorder

Sleep disordered breathingPeriodic limb movements of sleep

Medical problems/medicationsAsthma/GERD/arthritis/urinary frequency

Poor bedroom conditions“Psychophysiologic insomniaDepression/anxiety

Co-morbidity between sleep disorders and psychiatric disordersComplex bi-directional relationshipSleep disturbance is a common feature of a wide

range of psychiatric disordersDepressionAnxiety DisordersSchizophreniaCognitive disordersSubstance abuse

Psychotropic medications can affect sleep and wakefulness

Sleep disorders may be independent risk factors for the development of psychiatric disorders and adverse outcomes

Treatment emergent side effects of antidepressants (2008- PDR)

Antidepressant Insomnia, % Anxiety, % Somnolence,%

Trazodone 6 6 41

Mirtazapine 6 …. 54

Fluoxetine 16-33 12-14 13-17

Sertraline 16-28 6 13-15

Paroxetine 13 5 23

Venlafzine 18 6-13 23

Bupropion 11-16 5-6 2-3

Nefazodone >300mg

11 … 25

Nefazodone <300mg

9 … 16

Sleep in DepressionDisturbed sleep is a defining symptom of

depressionMore than 90% of patients with major

depression have insomniaSleep onset and sleep maintenance

insomniaEarly morning awakeningsFatigue, not usually excessive

somnonlence, when awake20 % of patients with insomnia have major

depression

Sleep Disturbance in Depression: more than a symptom?Insomnia seems to predict greater risk of

development of depression( Chang: Am J Epidemiol 1997, Salo: Sleep Med 2012)

Chronic insomnia may contribute to the persistence of depression (Pigeon: Sleep, Vol 31, No 4 2008)

Addition of hypnotic agent to antidepressant leads to greater improvement of sleep and faster, more complete antidepressant response (Fava: Biol Psyhciatry 2006)

CBT of insomnia alone improved symptoms of depression in patients with mild depression ( Taylor, Behavior Therapy 2007)

Sleep disturbance in anxiety disordersGeneralized Anxiety Disorder

Sleep disorders found in over 50% of patientsSleep onset insomnia

PTSDInsomniaNightmaresAt higher risk of sleep related movement and

breathing disordersPanic disorder:

sleep onset and sleep maintenance insomnia; Nocturnal panic attacks- can be confused with

choking of sleep apnea or night terrors

Case 222 year old recent college graduate with chief

complaint of inability to fall asleep at night and daytime fatigue

Recently moved to DC to work on Capitol Hill; first jobTries to get to bed at 11pm, and uses 2 alarms to get

up to try to get up at 7:00amCannot fall asleep before 2 amSleeps until 10 am on weekends and feels better

during the dayStarted on paroxetine for depression and trazodone

for sleep by primary care physicianAlso takes Zolpidem 1-2 times per week after several

nights of inability to get to sleep

Sleep diary

Delayed Sleep Phase SyndromeMost common of circadian rhythm

disturbancesOccurs at all ages, but especially adolescentsBiological clock is reset; physiologically

impossible to go to sleep earlierSleeping late when able to maintains sleep

delayDiagnostic issues: adolescent behavior,

depression, complicated by substance abuseTreatment: chronotherapy, bright light,

melatonin

Advanced sleep phase syndrome“early to bed/early to rise”More common in older peopleUsually not problematic Usually does not require intervention

Jet lagTime zone changes

East to westWest to east

“Natural” solutions bestSynchronizing with day/night in new time

zonesAvoidance of alcohol/sedatives

No effective drug remedies

Shift workersNight shift work

Associated with medical problemsShortened sleep timeRotating shifts worse than consistent nights? Employment of choice for delayed sleep

phaseNatural remedies best

Control of light and darkAlerting medication approved for this

indication

Case 366 year old man with history of snoring and

frequent awakenings from sleepAwakenings occur in the latter third of the

nightHe wakes up “acting out dreams” according

to his wifeDreams relate to someone trying to “hurt his

children” and an old burn injuryHe has knocked over bedside table on more

than one occasion

Polysomnogram- Sleep Stage? Diagnosis?

Parasomnias“things that go bump in the night”

Deep sleep parasomnias Walking, talking, screaming, terrors, eating Rocking, repetitive behaviors Usually do not require medications Environmental safety measures

REM sleep parasomnias REM behavior disorder Older males Treatable with medication

Parasomnias in AdultsIn the past, believed to be associated with

significant psychopathology; usually not present inpersistent adult parasomnias

Violence or aggressive behavior can occurwith arousal disorders such as confusionalarousals and sleepwalking

Triggering factors– Sleep deprivation– Alcohol– Stress/anxiety– Loud noise– Drugs (sedatives, neuroleptics, stimulants, antihistamines)– Fever (in children)

Parasomnias in the AdultArousal (NREM) disorders

• Confusional arousals• Sleepwalking

REM parasomnias

• Nightmares• Sleep paralysis• REM behavior disorder

REM behavior disorderVivid dreams often with a violent themeVigorous behaviors accompanying these

dreams which may result in injury to patient or partner

Excessive chin or extremity EMG tone duringREM sleep on PSG (REM without atonia)

Excessive limb or body jerking, complex movements, vigorous or violent movements during REM sleepUsually treated successfully with clonazepamMust rule out Obstructive sleep apnea

REM Behavior DisorderAcute form:

– Withdrawal from drugs or alcohol– Adverse reaction to antidepressant drugs,

especially SSRIsChronic form:

– Males, > 60– Lengthy prodrome of subtle abnormalities of sleep– Associated with alpha-synucleinopathies with dementia, including Parkinson’s disease, dementia with Lewy bodies and multi-system atrophy, about 10 years after the diagnosis of RBD.

REM Behavior disorderhttp://www.youtube.com/watc

h?v=rFXYRQ9xPUA

Differential diagnosis and management of sleep disorders in psychiatric practice

Because of similarity in clinical manifestations, sleep disorders may be mistaken for primary psychiatric conditions

Sleep disorders that are secondary to physical disorders may also be mistakenly viewed as psychiatric in origin

Three major types of sleep complaints:DIMS – disorder of initiation or maintenance of

sleepDOES- Disorders of Excessive SleepinessParasomnias-episodes of disturbed behavior or

experiences related to sleep

Summary: Sleep disorders at risk of misdiagnosis as primary psychiatric disorders

Circadian Rhythm DisordersObstructive Sleep Apnea syndromeNarcolepsyREM Behavior Disorder Other Parasomnias

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