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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
END