1. Sleep Disorders Richard E. Waldhorn, MD Clinical Professor of Medicine
The Nightmare is a 1781 oil painting by Anglo-Swiss artist Henry Fuseli (1741–1825). Since its creation, it has remained Fuseli's best-known work. With its first exhibition in 1782 at the Royal Academy of London, the image became famous; an engraved version was widely distributed and the painting was parodied in political satire. Due to its fame, Fuseli painted at least three other versions of the painting.
Interpretation of The Nightmare have varied widely. The canvas seems to portray simultaneously a dreaming woman and the content of her nightmare. The incubus and the horse's head refer to contemporary belief and folklore about nightmares, but have been ascribed more specific meanings by some theorists.[1] Contemporary critics were taken aback by the overt sexuality of the painting, which has since been interpreted by some scholars as anticipating Freudian ideas about the unconscious.
The Nightmare- Henry Fuseli, 1781
Richard E. Waldhorn, MD
Clinical Professor of Medicine
Division of Pulmonary, Critical Care
and Sleep Medicine
Georgetown University School of Medicine

2. Sleep Disorders What 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?
As our aging population increases, so do their concerns and experiences with sleep problems and disorders. Along with the body and brain changes that occur as we age, sleep also changes as part of the normal aging process. Many older people want to know how much sleep they need, how to sleep better and the signs and symptoms of sleep disorders. This program will address these questions as well as some of the common myths about sleep and aging. It will cover basic sleep physiology, sleep patterns, habits and quality of sleep along with the sleep changes that occur in the normal aging process. In addition, it discusses the association of sleep with health and disease, the importance of sleep to the lives of aging persons and provides an overview of the sleep disorders that become more prevalent as we age. Lastly, it provides some practical tips that help address sleep problems, when to seek help and how to get a good night’s sleep.

3. 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
Greek god hypnos

4. Sleep Regulation Homeostatic process: determined by sleep and waking
The pressure for sleep increases proportionately to the time since last sleep
Circadian process: Approximately 24 hr cycle of sleep and wakefulness
periods with high and low sleep propensity
independent of sleep and waking
Suprachiasmatic nucleus- regulated by zeitgebers: sunlight and eating time
Ultradian process: occurring within sleep- the alternation of Non REM and REM sleep
The pressure, or drive, for sleep
increases proportionately to the time
since last sleep
• Sleep deprivation increases desire for
sleep
• Sleep deprivation causes decline in
cognitive functioning
Approximately 24-hour cycle of sleep
and wakefulness
• Biological clock regulating sleep and
wake is located in the suprachiasmatic
nucleus (SCN)
• SCN is regulated by zeitgebers: sunlight
and eating time

5. Sleep Stages
Two 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

6. Sleep Stages - Adult

7. REM Sleep- bilateral synchronous eye movements, muscle atonia

8. Normal sleep Sleep latency Stage N1-N2 sleep Stage N3 sleep
Normal: 10 minutes
Stage N1-N2 sleep
Initial period: minutes
Stage N3 sleep
Onset at minutes after lights out
Stage REM sleep
Onset at 90 minutes after lights out

9. Sleep cycle: normal hypnogram

10. Normal Sleep N1-N2 sleep—light sleep N3 “deep”—slow wave sleep
50-60% of sleep time
Sleep onset and in latter part of the night
N3 “deep”—slow wave sleep
“restorative” part of the night
Early in the sleep cycle
20-25% of sleep time
REM “dream” sleep
Brain active/muscles paralyzed
4 REM periods thru the night
Longest is just prior to awakening
20-25% of the night

11. Key Polysomnographic Terms
Sleep latency- lights out until sleep onset
REM latency- sleep onset to the first epoch of REM
Sleep efficiency- Total sleep time/total recording time
Wake after sleep onset (WASO)
Percent REM sleep
Percent slow-wave sleep (SWS)
Percent stage 1-2 sleep

12. What causes sleep ? Activation of neural structures in the brainstem
Cortex is variably active—most in REM sleep
Complex interplay
Brain: light and dark
Hormones: cortisol
Temperature
Circadian rhythm

13. Circadian Rhythms Light Output Rhythms Physiology Behavior
Suprachiasmatic Nuclei (SCN)

14. Normal Circadian Sleep Rhythm

15. Circadian Rhythms

16. Sleep Changes with Age

17. Breathing during sleep
Central nervous system control
Stretch receptors
Chemoreceptors
Blood carbon dioxide level
Slightly higher trigger to breathe than when awake
Very sensitive
Can be affected by drugs, chronic diseases
Altitude

18. 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 OSA
2000-Mignot and colleagues at Stanford discover that human narcolepsy also is associated with hypocretin deficiency.

19. Sleep Disorders DOES—disorders of excessive somnolence
Quantity of sleep
Quality of sleep
DIMS—disorders of initiation and maintenance of sleep
Sleep onset insomnia
Sleep maintenance insomnia

20. Sleep Disorders Circadian rhythm disorders Parasomnias
Delayed sleep phase syndrome “night owl”
Advanced sleep phase syndrome “lark”
Jet lag
Night shift worker
Parasomnias
Excessive motor activity during sleep
Sleep walking/talking/eating
Sleep terrors
REM behavior disorder

21. Question 1 What is the most common cause of DOES?
1. sleep disordered breathing
2. narcolepsy
3. inadequate sleep hours
4. sleep walking

22. DOES Inadequate sleep hours Adult sleep requirement: 7-9 hours
Adequate sleep architecture
50-60% light sleep (N1-N2)
20-25% deep sleep (N3)
20-25% REM sleep
Good sleep behaviors
Proper sleep conditions

23. Case 1 62 year old male with history of diabetes, hypertension
Chief complaint: “ I am tired all the time”
Has been feeling “down “ for the past few weeks every day
Has been having trouble with memory and concentration
Has gained 20 lbs in past 2 years
SH:20 pack year smoking; drinks beer on weekends
Physical exam: obese, neck circumference 19 inches
Started on Paroxetine 20 mg

24. Case 1- 3 months later Still troubled by daytime sleepiness
Now reports he fell asleep at red light driving to work
Wife 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

25. DOES Sleep disordered breathing: Obstructive sleep apnea
6-12% of the population
Males and females
Obesity
Anatomic abnormalities
Increases with age
Symptoms snoring, observed apneas, daytime sleepiness
Airway disorder

26. PATENT vs COLLAPSED AIRWAY
2006 American Academy of Sleep medicine

27. Sleep Disordered Breathing

28. Central and Obstructive Apnea

29. Obstructive Hypopnea

30. Consequences of recurrent obstructive sleep apnea/hypopnea
Excessive daytime somnolence
Snoring
Morning headaches
Sleep maintenance insomnia
Impaired cognitive performance
Social/sexual/psychologic problems
Poor quality of life
Increased risk of MVA
Adverse cardiovascular outcomes
Systemic hypertension
Pulmonary hypertension
(?DM/metabolic syndrome)
?Stroke

31. Burwell et al: Extreme Obesity associated with alveolar hypoventilation: A pickwickian syndrome. Am J Med 1956;21:
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 boy
From the Dickens novel, “The posthumous papers of the Pickwick Club.”
The term was initially coined by Osler (1918)

33. Psychologic, cognitive, behavioral sequelae of sleep apnea
Daytime sleepiness- different from “fatigue or low energy” as in depression
Excessive sleep
Involuntary naps
Fighting sleepiness while sedentary
Capacity to nap voluntarily
Hyperactivity in children
Impaired memory, attention, vigilance
Depression extremely common in OSA
Depressive symptoms reduced with CPAP
Confusional states and psychotic disorders

34. Depression and Sleep Apnea
Wheaton, CDC study; (Sleep, 2012)
Survey on sleep disordered breathing and
PHQ-9 depression screen 9714 adults
Frequent snorting/stopping breathing, but not snoring, associated with higher prevalence of probable major depression
Possible mechanisms underlying association between depression and OSA
Sleep fragmentation and hypoxemia
Neurobiology 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

35. Positive Airway Pressure
This slide depicts the therapeutic effect of continuous positive airway pressure (CPAP). In the panel on the left, you can see upper airway closure in an untreated sleep apnea patient. Note that the airway closure is diffuse, involving both the palate and the base of the tongue. In the second panel, CPAP is applied and the airway is splinted open by the positive pressure.
2006 American Academy of Sleep Medicine
69. Sullivan CE, Issa FG, Berthon-Jones M, Eves L. Reversal of obstructive sleep apnoea by continuous positive airway pressure applied through the nares. Lancet 1981;1(8225):

36. Nasal CPAP

37. Nasal CPAP/BIPAP
Broad acceptance as treatment of choice in moderate to severe OSA with improvement in:
Symptoms of sleepiness( Epworth)
Objective measures of sleepiness( MSLT)
Cognitive function scores
QOL scores
Blood pressure, Pulmonary artery pressure
Reduction in MVAs
White et al. Cochrane database 2000,Kaneko et al. NEJM 2003;348:

38. Dental orthotic or mandibular repositioning devices
Mandibular advancing dental devices increasingly used in OSA
Attach to one or both dental arches and advance mandible
Less effective but better tolerated than CPAP

39. Surgical Management: Uvulopalatopharyngoplasty (UPPP)
This slide depicts the uvulopalatopharyngoplasty (UPPP) surgical technique.
The panel on the left depicts the preoperative upper airway, demonstrating a long soft palate and the presence of palatine tonsils. The incision site is marked with the dotted line.
The panel on the right depicts the postoperative oropharynx, with amputation of the uvula, bilateral palatine tonsillectomy, and trimming and suturing together of the anterior and posterior tonsillar pillars.
2006 American Academy of Sleep Medicine
89. Fujita S, Conway W, Zorick F, Roth T. Surgical correction of anatomic abnormalities in obstructive sleep apnea syndrome: uvulopalatopharyngoplasty. Otolaryngol Head Neck Surg 1981;89(6):

40. Mandibular advancement surgery
Midface, palate, and mandible advanced anteriorly
Increases posterior airway space
Follow up orthodontic procedures, wiring of jaw
For severe disease

41. Upper-Airway Stimulation for Obstructive Sleep Apnea
N Engl J Med
Volume 370(2):
January 9, 2014

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

43. DOES Narcolepsy Relatively rare but under-recognized
Onset in adolescence
Four cardinal symptoms
Excessive daytime sleepiness
Sleep paralysis
Vivid dreams/hallucinations
Cataplexy
CNS disorder

44. Sleep initiation problems
Primary sleep disorder
Medical problem/ medication
Restless legs syndrome
Pain, “creepy/crawly” sensation
Pain: arthritis/fibromyalgia, etc
Medications: stimulants including caffeine/decongestants
Poor bedroom conditions
“Psychophysiologic” insomnia
Depression/anxiety

45. Sleep maintenance disorders
Primary sleep disorder
Sleep disordered breathing
Periodic limb movements of sleep
Medical problems/medications
Asthma/GERD/arthritis/urinary frequency
Poor bedroom conditions
“Psychophysiologic insomnia
Depression/anxiety

46. Co-morbidity between sleep disorders and psychiatric disorders
Complex bi-directional relationship
Sleep disturbance is a common feature of a wide range of psychiatric disorders
Depression
Anxiety Disorders
Schizophrenia
Cognitive disorders
Substance abuse
Psychotropic medications can affect sleep and wakefulness
Sleep disorders may be independent risk factors for the development of psychiatric disorders and adverse outcomes
Patients with sleep complaints are frequently seen in psychiatric practice- differential dignosis- ?primary sleep disorder vs. primary psychiatric disorder

47. Treatment emergent side effects of antidepressants (2008- PDR)
Insomnia, %
Anxiety, %
Somnolence,%
Trazodone 6 41
Mirtazapine …. 54
Fluoxetine
16-33
12-14
13-17
Sertraline
16-28
13-15
Paroxetine 13 5 23
Venlafzine 18
6-13
Bupropion
11-16
5-6
2-3
Nefazodone >300mg 11 … 25
Nefazodone <300mg 9 16
Trazodone
Mirtazapine-Remeron- alpha 2 adrenergic and serotonin antagonist
Fluoxetine-Prozac
Sertraline-Zoloft
Paroxetine- Paxil
Venlafzine-effexor
Bupropion-Aplenzin
Nefazodone >300mg-Serzone- norepi and serotonin reuptake inhibitor

48. Sleep in Depression
Disturbed sleep is a defining symptom of depression
More than 90% of patients with major depression have insomnia
Sleep onset and sleep maintenance insomnia
Early morning awakenings
Fatigue, not usually excessive somnonlence, when awake
20 % of patients with insomnia have major depression

49. 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 )
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)

51. Sleep disturbance in anxiety disorders
Generalized Anxiety Disorder
Sleep disorders found in over 50% of patients
Sleep onset insomnia
PTSD
Insomnia
Nightmares
At higher risk of sleep related movement and breathing disorders
Panic disorder:
sleep onset and sleep maintenance insomnia;
Nocturnal panic attacks- can be confused with choking of sleep apnea or night terrors

52. Case 2
22 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 job
Tries to get to bed at 11pm, and uses 2 alarms to get up to try to get up at 7:00am
Cannot fall asleep before 2 am
Sleeps until 10 am on weekends and feels better during the day
Started on paroxetine for depression and trazodone for sleep by primary care physician
Also takes Zolpidem 1-2 times per week after several nights of inability to get to sleep

53. Sleep diary

54. Delayed Sleep Phase Syndrome
Most common of circadian rhythm disturbances
Occurs at all ages, but especially adolescents
Biological clock is reset; physiologically impossible to go to sleep earlier
Sleeping late when able to maintains sleep delay
Diagnostic issues: adolescent behavior, depression, complicated by substance abuse
Treatment: chronotherapy, bright light, melatonin

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

57. Jet lag Time zone changes “Natural” solutions best
East to west
West to east
“Natural” solutions best
Synchronizing with day/night in new time zones
Avoidance of alcohol/sedatives
No effective drug remedies

58. Shift workers Night shift work Associated with medical problems
Shortened sleep time
Rotating shifts worse than consistent nights
? Employment of choice for delayed sleep phase
Natural remedies best
Control of light and dark
Alerting medication approved for this indication

59. Case 3
66 year old man with history of snoring and frequent awakenings from sleep
Awakenings occur in the latter third of the night
He wakes up “acting out dreams” according to his wife
Dreams relate to someone trying to “hurt his children” and an old burn injury
He has knocked over bedside table on more than one occasion
This is a 55 year old man with a history of snoring and frequent awakenings from sleep. The awakenings occur in the latter third of the night where he wakes up acting out dreams related to someone trying to ‘hurt his children’ and of an old burn injury. Questions: What is the sleep stage? What is the diagnosis

60. Polysomnogram- Sleep Stage? Diagnosis?

61. 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

62. Parasomnias in Adults
In the past, believed to be associated with significant psychopathology; usually not present in
persistent adult parasomnias
Violence or aggressive behavior can occur
with arousal disorders such as confusional
arousals and sleepwalking
Triggering factors
– Sleep deprivation
– Alcohol
– Stress/anxiety
– Loud noise
– Drugs (sedatives, neuroleptics, stimulants, antihistamines)
– Fever (in children)

63. Parasomnias in the Adult
Arousal (NREM) disorders
• Confusional arousals
• Sleepwalking
REM parasomnias
• Nightmares
• Sleep paralysis
• REM behavior disorder

64. REM behavior disorder Vivid dreams often with a violent theme
Vigorous behaviors accompanying these
dreams which may result in injury to patient or partner
Excessive chin or extremity EMG tone during
REM sleep on PSG (REM without atonia)
Excessive limb or body jerking, complex
movements, vigorous or violent movements
during REM sleep
Usually treated successfully with clonazepam
Must rule out Obstructive sleep apnea

65. REM Behavior Disorder Acute form: – Withdrawal from drugs or alcohol
– Adverse reaction to antidepressant drugs,
especially SSRIs
Chronic 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.

66. REM Behavior disorder

67. 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 sleep
DOES- Disorders of Excessive Sleepiness
Parasomnias-episodes of disturbed behavior or experiences related to sleep

68. Summary: Sleep disorders at risk of misdiagnosis as primary psychiatric disorders
Circadian Rhythm Disorders
Obstructive Sleep Apnea syndrome
Narcolepsy
REM Behavior Disorder
Other Parasomnias

69. END