This document provides a summary of Dr. A V Srinivasan's presentation on the management of insomnia in the modern era. It begins with background on the Greek and Roman personifications of sleep. It then discusses normal sleep architecture and stages, factors that can affect sleep, and common sleep disorders like insomnia, hypersomnias, circadian rhythm disorders and parasomnias. It also summarizes the effects of neurological/psychiatric conditions and medications on sleep architecture and how diagnosis of sleep disorders is conducted. The overall document provides a comprehensive overview of sleep and sleep disorders.

1. MANAGEMENT OF INSOMNIA IN THIS
MILLENNIUM
Dr A V Srinivasan M.D, D.M., PhD (Neuro),FAAN,FIAN
Emeritus Professor
The TamilNadu Dr M.G.R Medical University
Former Head- Institute of Neurology
Madras Medical College, Chennai
In Greek mythology,
Hypnos was the
personification of sleep; the
Roman equivalent was
known as Somnus. His twin
was Thanatos ("death");
their mother was the
goddess Nyx ("night"). His
palace was a dark cave
where the sun never shines.
At the entrance were a
number of poppies and
other hypnogogic plants.

2. Sleep architecture revisited
What is it & How is it relevant in
Psychiatry and Neurology?
Science is below the mind; Spirituality is beyond the
mind

3. What is sleep?
Sleep is a physiological state of reduced sensory
awareness and an absence of voluntary movements.
Sleep is necessary for life.
Sleep is also an essential component of good health
(body development and restitution as well as mental
health and well-being). It is also important for optimal
cognitive functioning.
A woman’s desire for revenge outlasts all her
other emotions

4. Total Sleep Requirement
Percentage of
All People
50
40
30
20
10
0
0 2 4 5 6 7 8 9 10
Length of Sleep in Hours
In order to be at your peak performance you need at
least 8 hours of sleep.

5. Function of Sleep
1. Restoration and recovery
– Sleep serves to reverse and/or restore biochemical
and / or physiological processes degraded during
prior wakefulness
2. Energy conservation
– 10% reduction of metabolic rate below basal level
3. Memory consolidation
4. Thermoregulation
The world shall perish not
5. Homeostasis for lack of wonders but lack
of wonder

6. Memory Consolidation at Sleep Onset
Impairment of Memory Consolidation
during Sleep
80
60
40
20
0
10 9 8 7 6 5 4 3 2 1
Subjects awakened 30 seconds after sleep onset
Subjects awakened 10 minutes after sleep onset
Word Presentation Minutes BeforeMinnesota, Sleep Onset
Assessment of Sleepiness / Sleep Deprivation, M. Mahowald, University of
Sleep Academic Award

7. Sleep and Hormones
Hormones Tightly Coupled with
Sleep
Determinants of Sleepiness / Circadian Rhythms, M. Mahowald, University of Minnesota, Sleep Academic Award

8. Illustration of Normal vs. Insomnia
Sleep Pattern
Normal Sleep Pattern
Onset
Insomnia Sleep Pattern
Onset
Awakenings

9. Normal sleep architecture
NATURE, TIME AND PATIENCE
are the 3 great physicians

10. Normal Sleep Architecture
Stages of sleep
__________________________
1. NREM Sleep
A. Stage 1
B. Stage 2
C. Stage 3
D. Stage 4
2. REM Sleep
Truth comes out of error
sooner than that of confusion
10

11. Thought is the labour of
Sleep Stages the intellect
Reverie is its pleasure
___________________________
Wake
2/3 of life
NREM Sleep REM Sleep
~80% of night ~20% of night
11

12. Normal Sleep Histogram
Sequences of States and Stages
of Sleep on a Typical Night
Identification and Staging of Adult Human Sleep, L. Shigley, Sleep Academic Award

13. Normal Sleep Stages
Stage 1 Stage 2 Stage 3&4 REM
Body starts to relax Brain slows Body and tissue restored Learning and memory
‘Falling asleep’ ‘Stable, light sleep’ ‘Deep, consolidation
restorative sleep’ ‘Dreaming sleep’
3-8% 45-55% 15-20% 20%
NREM 75-80% REM 20-25%
1 cycle = 80-100 minutes
Adapted from Damien R.Stevens MD.Sleep medicine secrets.2004

15. Wakefulness, NREM, and REM
Wake NREM REM
Arousability High Lowest Low
EEG amplitude Low High Low
EEG frequency Fast Slow Mixed fast
Muscle tone Variable Low Absent
Eye movements Voluntary Infrequent Rapid
Heart Rate, Blood Variable Slow/ low, Variable
Pressure, regular
Respiratory Rate
O2, CO2 response Full Lower Lowest
Thermoregulation Behavioral/ Physiological Reduced
Physiological physiological
Mental activity Full None/ limited Story-like
dreams

16. Importance of sleep architecture
• Sleep architecture provides a useful means for
quantitatively analyzing sleep.
• It includes both macroarchitectural features
(those derived from sleep staging) and
microarchitectural features (those derived from
waveform analysis). Architectural features can
characterize:
– sleep integrity and continuity
– global sleep-stage structure
– presumed underlying physiologic mechanisms

17. Neurochemical control of sleep-
wake states
Neurotransmitter Location Action
Acetylcholine LDT, PPT (pons) REM, wake
Histamine TMN (posterior Wake
hypothalamus)
GABA, galanin VLPO NREM sleep
Serotonin Raphe nuclei Wake, NREM
Norepinephrine Locus coeruleus Wake
Hypocretin Later hypothal Wake

18. Neurochemical control of sleep-
wake states
• Dopamine
• Adenosine
• Nitrous oxide
• Cytokines (IL-1, IL-6, TNF-α)
• Prostaglandins
• Hormones: melatonin, growth hormone,
VIP NPY
• Delta sleep-inducing peptide

19. Aminergic Cholinergic
Wake
Fig. 2.1 aldrich
Sleep
REM
Basal Forebrain Cholinergic
Reticular Formation Thalamus Serotonergic
Post. Hypothalamus Monoaminergic
Histaminergic

20. Social Isolation
Factors that affect sleep is in itself a
pathogenic
Factor for
disease
production
• Age
– Increased wakefulness during sleep period
– Decreased Stage 3/4 NREM
– Earlier timing
– Greater daytime sleepiness
• Sex (women have longer sleep, more
Stage 3/4 NREM)
• Timing: Sleep is best at night!
• Illnesses, medications

21. Sleep in healthy young and
older adults
20 year old woman 71 year old woman
Motivation is the Spark that lights
the Fire of Knowledge and
fuels the engine of Accomplishment

22. Sleep stages across the life
span
Ohayon et al., SLEEP 2004; 27: 1255-73
Minutes
Age (years)

23. Is there any difference
between sleep and sedation?
Mind is the great level of all things;
human thought is the process by
which human ends are ultimately
answered - Daniel Webster

24. Traits to define sleep and sedation
NREM/REM sleep SEDATION
• Hypotonia/atonia • Analgesia
• Slow/fast eye • Amnesia
movements • Obtundation of
• Regular/irregular waking
breathing, heart • Anxiolysis
rate, BP
Social Isolation is in itself a
pathogenic
Factor for disease production

25. Knowledge without
action is useless;
Sleep v/s sedation Action without
knowledge is
foolish
• Sleep is reversible with sensory stimulation;
sedation depresses sensory processing
in the face of noxious physical &/or aversive
psychological stimulation
• Sleep disrupts mammalian temperature
regulation during REM phase; Sedation can alter
the relationship between body temp and energy
expenditure
• Nausea and vomiting are not associated with
sleep; but can be positively correlated with
sedation level.

26. Sleep architecture in
neurological and psychiatric
conditions
A bad teacher
complains;
A good teacher
explains;
The best teacher
inspires;

27. Effect of Sleep Stage in
Epileptic patients on Interictal
and Ictal Discharges
Pure love ever gives. Never
seeks

28. Seizure effect on sleep architecture
• Seizures acutely alter the sleep-wake state.
• The most prominent clinical features of this
seizure effect are postictal somnolence and
insomnia.
• Patients with nocturnal seizures are subjectively
and objectively sleepy on the day following a
seizure.
• Seizures or the postictal state produce
pathophysiological changes in the CNS that
result in sleep fragmentation and suppression of
REM sleep. Individuals with partial or
generalized seizures have less REM sleep on
nights with seizures.
“Anger Begins In Folly And Ends In
Repentance”

29. Sleep in Patients With Depression
• Primary sleep complaints1,3
– Difficulty falling asleep
– Frequent nocturnal awakenings
– Waking too early in the morning
– Daytime fatigue
• Effects on sleep architecture in depression1-3
– Prolonged sleep latency
– Increased wake time after sleep onset (WASO)
– Decreased slow wave sleep (stages 3 and 4)
– Reduced REM sleep latency; prolonged first REM
period
1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed, text rev (DSM-IV-TR®). 2000:645-650.
2. Perlis M, et al. Biol Psychiatry 1997;42:904-913.
3. Benca RM. In: Principles and Practice of Sleep Medicine. 4th ed. 2005:1311-1326.

30. Sleep pattern in Alzheimer’s Disease
• Sleep pattern in early stage :
– Disruption in sleep-wake patterns, rhythmicity,
– Increased amounts and frequency of nighttime
wakefulness,
– Reduction of slow-wave sleep - worsen with disease
progression.
• Sleep pattern in late stage:
– Reduction of REM sleep,
– Increased REM latency,
– Alteration of the circadian rhythm resulting in daytime
sleepiness.
– Daytime napping and somnolence increase with
disease progression.

31. Effect of drugs on sleep
architecture
“The Wise Man Before He Speaks ,
Will Consider Well What He Speaks

32. Effect of antidepressants on sleep
architecture
• Tricyclic antidepressants
– Mostly produce sedation
– Variation in the reported effects on sleep from
TCAs.
– Amitriptyline, trimipramine, nortriptyline,
dothiepin and doxepin have all been
associated with sedation,
– Imipramine and desipramine are less likely to
be linked with sedation, but have been
associated with insomnia;
– The evidenceMayersless al. Hum Psychopharmacol Clin Exp 2005; 20: 533-559.
is AG et clear with clomipramine.

33. Effect of antidepressants on sleep
architecture
• SSRIs
– SSRIs immediately suppress REM sleep,
and continue to do so throughout treatment.
– REM parameters return to normal once the
SSRI is discontinued.
– SSRIs block serotonin reuptake, but some
also block noradrenaline reuptake. Both
actions have been associated with REM
suppression and sleep disruption.
Mayers AG et al. Hum Psychopharmacol Clin Exp 2005; 20: 533-559.

34. Effect of antidepressants on sleep Discipline
Weighs
architecture ounces:
Regret
• Fluoxetine weighs Tons
– Sleep was significantly less efficient, and
nocturnal awakenings were significantly greater,
with fluoxetine (20-40 mg) - Rush et al. (1998)
– Fluoxetine significantly suppressed REM sleep
– Fluoxetine (20 mg) was associated with less
efficient, shorter and more disrupted sleep -
Wolf et al. (2001)
– Improvements in sleep latency and total sleep
time were not marked for fluoxetine
Mayers AG et al. Hum Psychopharmacol Clin Exp 2005; 20: 533-559.

35. Effect of hypnotics drugs on sleep
architecture
• Benzodiazepines
– Being anticonvulsants, they tend to suppress
synchronized EEG activity (such as slow waves) and
confer some risk of seizure if abruptly withdrawn.
• Barbiturates
– Decrease REM and slow-wave sleep.
• Non-BZD hypnotics.
– Do not alter sleep architecture when taken at
therapeutically recommended doses.
Some people feel the rain;
Others just get wet

36. Stilnoct®
Preservation of Sleep Stages
Placebo Stilnoct
Stage 0 Stage 0
REM REM 6.64% Stage 1
10.50% Stage 1 7.27%
19.02% 16.39%
6.26%
Stage 4 11.22% Stage 4 15.81%
44.48%
8.51% 46.23%
7.65%
Stage 3
Stage 2 Stage 3
Stage 2
Opinion is ultimately determined by the
N=36 feelings
Data on file. Sanofi-aventis. and not by the intellect

37. Sleep Disorders
• International Classification of Sleep Disorders (ICSD-2)
(1) insomnias
(2) sleep-related breathing disorders
(3) hypersomnias not due to a breathing disorder
(4) circadian rhythm sleep disorders
(5) parasomnias
(6) sleep-related movement disorders
(7) other sleep disorders, and
(8) isolated symptoms, apparently normal variants, and
unresolved issues.
It is the province of the knowledge to speak
and it is the privilege of the wisdom to listen -

38. Insomnia
• Difficulty in initiating sleep and staying
asleep
• Waking up earlier
• Poor quality sleep, non restorative.
• Subjective
• Day time impairment (RDC-AASN)
The meek shall inherit the earth
- but not its mineral rights

39. Etiology
• Primary
• Secondary
Medications
Psychiatric
Medical
Sleep Disorders
A Man Of Words And Not Of Deeds Is
Like
A Garden Full Of Weeds

40. Drugs
• SSRI’s & SNRI’s
• Alpha and beta blockers
• Diuretics
• Decongestants
• Stimulants
• Steroids, thyroid harmones
What is mind no matter
What is matter never mind

41. Psychiatric and Sleep disorders
• Mood & anxiety disorders
• Circadian rhythm disorders
• Parasomnias
• Apneas
• Movement disorders
''When Beauty Fires The Blood; Love Exalts
The Mind"

42. Hypersomnias
• Excessive day time sleepiness
• Interfering with day time activities,
productivity, enjoyment
• Reflects insufficient sleep, disrupted
sleep, primar sleep disorder
Experience : “Yesterday’s Answer To Today’s Problems”

43. Diagnosis
• Detailed medical and sleep history
• Snoring or apnoea
• Restlessness, jerking
• Hypnogogic or hypnopompic
hallucinations
• Sleep paralysis, cataplexy
• Automatic behavior which, through the process of
Teachers are reservoirs from
education,
the students draw the water of life

44. Narcolepsy
• Excessive day time sleepiness (EDS)
Sedentary and active pursuit's
Short and refreshing
Followed by recurrent somnolence
Ranging from mild to disabling
Name and form are destroyed in the
sands of time

45. Cataplexy
• Unique
• Paroxysmal episodes of weakness
• Triggered by emotions
• Secs to Min
• Can be localized
• Consciousness and respiration not
affected.
Time and tide wait for no man;
And sins and sorrows are also swallowed in
time

46. • Develops years after EDS
• Frequency varies
• Adolescence, young adulthood
• Narcolepsy with and without
cataplexy
• Loss of hypocretin – 1 secreting
cells Every man is a volume if you know how
to read him

47. Being ignorant
• Narcolepsy – non obligate is not so much
a shame as
manifestations being unwilling
to learn
Sleep paralysis – muscle atonia at
interface between sleep and
wakefulness; for few minutes.
Hypnogogic hallucinations
brief, Sec to Mins, dream-like vivid and
distressing
Automatic behavior
Purposeful/inappropriate with impaired
recollection of the activities.

48. Other Hypersomnias
• Recurrent hypersomnias
Recurrent hypersomnias
Kleine – Levin syndrome
Menstrual associated
• Idiopathic hypersomnias
With long sleep time
Without long sleep time
Beauty lies in the eyes of the
beholder

49. The secret of walking on water is knowing
where the stones are
Parasomnias
• Include abnormal movements,
behaviors, emotions and
automatic activities.
• Intrusion of sleep and wakeful
state into one another with CNS
activation.
• Not a unitary phenomenon.

50. Parasomniasis
• Disorders of arousal –
NREM sleep – confusional arousal
sleep walking
sleep terrors
REM sleep – RBD
Isolated sleep paralysis
Nightmares
Others – enuresis
eating disorders
Future Medicine – Scientific
etc determinism or humanism

51. RBD – REM Sleep Behavior
Disorders
• Prevalence of 0.5%; 90% Men
• Above 50 years
• 25% with PD, OPCA, DCBD
• Complex motor activity during REM
• Augmentation of EMG tone during REM
sleep
• Toxic/metabolic disorders

52. RBD
• During second half
• Abnormal brain stem control of medullary
inhibitory regions
• Cat models- locus ceruleous adjacent lesions
• SPECT – decrease striatal dopa innervations
decrease dopa transportation
• Withdrawal of alcohol, sedatives
• Hypnotics
• TCA, SSRI, MAOI, cholinergics
The sign wasn’t placed there
By the Big Printer in the sky

53. Sleep-Related Movement
Disorders- Restless Legs
Syndrome
• 5-15% - healthy people
• 15-20% - uremia
• 30% - R.A
• High prevalence in West
• Low in South & S.E Asia
A open foe may prove a curse ; but
a pretended friend is worse

54. Diagnostic criteria – NIH –IRLSSG
(2003)
1. Disagreeable leg sensations before
sleep onset
2. Irresistible urge to move the limbs
3. Partial or complete relief on leg
movement
4. Return of symptoms on cessation of
movement
When they tell you to grow up, they mean
stop growing

55. Restless Leg Syndrome
• Bilateral, though asymmetrical
• Ankle & knees. Can involve thigh or
feet & arm
• Minutes to hours
• Dopamine dysfunction, Iron storage
deficiency
• Anti emetics, antihistamines, TCA,
SSRI, neuroleptics

56. Rest less Leg
Syndr ome wit h
Per iodic Limb
Movement s
Speak obligingly even
if you cannot oblige

57. Periodic Limb Movement
Disorder
• Common as age advances
• Nocturnal myoclonus captured on
Polysomnography
• Extension of the big toe with flexion of
ankle, knee & hip
• Sleep may or may not be affected
• Centrally mediated event
“The True Art of Memory is The Art of Attention” -
S.Johnson

58. • Can accompany OSA & Narcolepsy
• Uremia, metabolic disorders
• TCA, MAOI
• Withdrawal of AED, benzodiazepines,
hypnotics
• Hypnic jerks & nocturnal seizures to
be differentiated
Through Action You Create your Own Education - D.B.
ELLIS

59. PLMS –Secondary (previous
Myelopathy)
“ We Sometimes think we have forgotten something when
in fact we never really learned it in the first place”
Imp.Your Memory Skills

60. Sleep Related Leg Cramps
• Not uncommon with increasing age
• “Charley horse” muscular tightness
involving the calf & foot during sleep
• Results in arousal and can lead to
insomnia or EDS
• Pregnancy, DM, fluid & electrolytes,
arthritis, vigorous exercise

61. Sleep related Bruxism
• Children and adults, MR
• Stereotyped grinding or clenching
• Diurnal & nocturnal
• Situational or psychological stress
• SSRI, dopa, alcohol exacerbate
Thought is the labour of the intellect
Reverie is its pleasure

62. Sleep-Related Rhythmic Movement
Disorder
• Head Banging – back & forth down
into the pillow
• Head Rolling – side to side
• Body Rocking – forward & backward
• Humming or chanting
• Persistence with autism, MR
Whatever the Mind can conceive and Believe,
the mind can Achieve
Napoleon Hill

63. Nocturnal Paroxysmal Dystonia
(NPD)
• Repeated, stereotyped, dystonia or
dyskinetic episodes in NREM sleep
• Sleep related epilepsy
• Short episodes < 1 min. every night and
many times
• Long episodes – up to 60 min
• Can have sleep disruption
Imagination is more Important than Knowledge

64. Sleep-Disordered Breathing
(SDB)
• Primary snoring
• Upper airway resistance syndrome (UARS) –
lab support, day time dysfunction
• Obstructive sleep apnea-hypopnea syndrome
(OSAHS)
• Central sleep apnea
• Asthma
• Chronic obstructive pulmonary disease
(COPD).

65. Obstructive Sleep Apnea-
Hypopnea Syndrome
• Asphyxia with decreased O2 & increased
CO2
• Associated with snoring and obstruction of
the pharynx
• Day time – sleepiness, decreased
concentration, fatigue
• Nocturnal – chocking, dyspnoea,
diaphoresis, nocturia
A open foe may prove a curse ; but a pretended
friend is worse

66. • Apnoea – 70% reduction in airflow
• Hypopnea – 30% reduction in airflow
for minimum 10 sec
• Apnea-hypopnea index (AHI) of at
least five apneas plus hypopneas per
hour of sleep together with complaints
of persistent daytime sleepiness.
It is a great misfortune not to possess sufficient wit to speak
well
nor sufficient judgment to keep silent
La Broyers character

67. Risk Factors
• Obesity ( BMI > 30 kg/m2)
• Male gender
• Family history of obstructive sleep apnea-hypopnea
syndrome
• Consumption of alcohol before bedtime
• Smoking
• Drugs (growth hormone, β-blockers, testosterone,
flurazepam)
• Use of sedatives
• Sleeping in a supine position
• Anatomic upper airway obstruction
• Comorbid medical conditions

68. Central Sleep Apnea
• 10 sec of no airflow
• Reduced ventilatory drive
• Ventilatory responses to hypoxia,
hypercapnia are reduced
• Day time sleepiness, mild snoring
• PSG – no airflow or ventilatory effort
You are what you think and not what you think you are

69. Circadian rhythm Sleep
Disorders (CRSD)
• Master Clock – SCN in anterior hypothalamus
Sleep wake cycle/temperature control and
melatonin levels.
• Zeitgebers (time given) are light and
melatonin
• Input into SCN from ganglion cells-
melanopsin
• Melatonin > pineal > SCN, shifts circadian
rhythm Discipline Weighs ounces; Regret
weighs Tons

70. • DD for insomnia & hypersomnia
Delayed sleep phase
Advanced sleep phase
Free running
Irregular sleep-wake
Shift work sleep disorder
Jet lag
A great many people think they are thinking when they are merely re
arranging their prejudices
W. James

71. When they tell you to
Criteria for CRSD grow up, they mean
stop growing -Piccaso
• Persistent or recurrent pattern of sleep
disturbance due to
- Alteration in circadian timing or misalignment
of endogenous & external factors
- Leading to insomnia, EDS or both
- Associated with impairment of function
• CRSDs are important in practice but
parameters for treatment have not been
established.

72. Thank you
Many Ideas grow better when transplanted into another mind
than in the one where they sprang UP
O.W. Holmos