This document provides an overview of physiology of sleep and sleep disorders. It discusses brain waves during different sleep stages, the cycles of non-REM and REM sleep, theories of what causes sleep, the effects of sleep on physiological functions, comparative aspects of sleep across species, and consequences of sleep deprivation. Key topics covered include the different sleep stages, roles of neurotransmitters like serotonin in regulating sleep, and restoration of brain and body during sleep.

1. Physiology of Sleep & its
Disorders
- Dr. Chintan Parmar
- 2nd Year Resident
- Dept. of Physiology
- Govt. Medi. College,
Bhavnagar.
- Dt. : 05/07/11

2. Outline
• Introduction
• Brain Waves
• Sleep stages : NREM,
REM
• Basic Theories of Sleep
• Physiological Effects of
Sleep
• Comparative Aspect
• Sleep Deprivation
• Sleep Disorders & Rx

3. SLEEP
• Sleep is a naturally recurring state
characterized by reduced or absent
consciousness, relatively suspended sensory
activity, and inactivity of nearly all voluntary
muscles.
• It is distinguished from wakefulness by a
decreased ability to react to stimuli.It is to be
distinguished from coma, which is unconsciousness
from which the person cannot be aroused.
• Sleep is observed in all mammals, all birds and
many reptiles, amphibians and fish.

4. SLEEP
• The purposes and mechanisms of sleep are
only partially clear and are the subject of
intense research. Sleep is often thought to help
conserve energy, but actually decreases
metabolism only about 5 – 10 %.
• Hibernating animals need to sleep despite the
hypometabolism seen in hibernation, and in
fact they must return from hypothermia to
euthermia in order to sleep, making sleeping
"energetically expensive."

5. SLEEP
• Sleep stages and other characteristics of sleep
are commonly assessed by polysomnography
in a specialized sleep laboratory.
• Measurements taken include
electroencephalogram (EEG) of brain waves,
electrooculography (EOG) of eye movements
and electromyography (EMG) of skeletal
muscle activity.
• In humans, each sleep cycle lasts from 90 to
110 minutes on average.

7. Brain Waves
• Alpha waves are rhythmical waves that occur at
frequencies between 8 and 13 cycles per second and
are found in the EEGs of almost all normal adult
people when they are awake and in a quiet, resting
state.
• These waves occur most intensely in the occipital
region but can also be recorded from the parietal and
frontal regions of the scalp. Their voltage usually is
about 50 μv.
• During deep sleep, the alpha waves disappear.

8. Brain Waves
• Beta waves occur at frequencies greater than
14 cycles per second and as high as 80 cycles
per second.
• They are recorded mainly from the parietal
and frontal regions during specific activation
of these parts of the brain.
• When the awake person's attention is directed
to some specific type of mental activity, the
alpha waves are replaced by asynchronous,
higher-frequency but lower-voltage beta
waves.

9. Brain Waves
• Theta waves have frequencies between 4 and 7
cycles per second.
• They occur normally in the parietal and
temporal regions in children, but they also
occur during emotional stress in some adults,
particularly during disappointment and
frustration.
• Theta waves also occur in many brain
disorders, often in degenerative brain states.

10. Brain Waves
• Delta waves include all the waves of the EEG
with frequencies less than 3.5 cycles per
second, and they often have voltages two to
four times greater than most other types of
brain waves.
• They occur in very deep sleep, in infancy and
in serious organic brain disease.

11. Brain Waves

12. Sleep stages
• In mammals and birds, sleep is divided
into two broad types : Rapid Eye
Movement (REM) and Non-Rapid Eye
Movement (NREM or non-REM) sleep –
slow wave sleep.
• Each type has a distinct set of associated
physiological, neurological and
psychological features.

13. Sleep stages
• The American Academy of Sleep Medicine
(AASM) further divides NREM into three
stages : N1, N2 and N3, the last of which is
also called delta sleep or slow-wave sleep
(SWS).
• There is a greater amount of deep sleep (stage
N3) earlier in the sleep cycle, while the
proportion of REM sleep increases later in the
sleep cycle and just before natural awakening.

14. NREM sleep – N1
• According to the 2007 AASM standards,
NREM consists of three stages. There is
relatively little dreaming in NREM.
• Stage N1 refers to the transition of the brain
from alpha waves having a frequency of
8–13 Hz (common in the awake state) to theta
waves having a frequency of 4–7 Hz.
• This stage is sometimes referred to as
somnolence or drowsy sleep.

15. NREM sleep – N1
• Sudden twitches and jerks, also known as
positive myoclonus, may be associated
with the onset of sleep during N1.
• Some people may also experience
hypnagogic hallucinations during this
stage.
• During N1, the subject loses some muscle
tone and most conscious awareness of the
external environment.

16. NREM sleep – N2
• Stage N2 is characterized by sleep
spindles ranging from 11–16 Hz and
K-complexes.
• During this stage, muscular activity as
measured by EMG decreases, and
conscious awareness of the external
environment disappears.
• This stage occupies 45–55% of total sleep
in adults.

17. NREM sleep – N3
• Stage N3 (deep or slow-wave sleep) is characterized
by the presence of a minimum of 20% delta waves
ranging from 0.5–2 Hz.
• This is the stage in which parasomnias such as night
terrors, nocturnal enuresis, somnabulism and
somniloquy occur.
• Many illustrations and descriptions still show a
stage N3 with 20–50% delta waves and a stage N4
with greater than 50% delta waves; these have been
combined as stage N3.

18. NREM sleep
• Most sleep during each night is of the NREM
variety ; this is the deep, restful sleep that the
person experiences during the 1st hour of sleep
after having been awake for many hours.
• This sleep is exceedingly restful and is
associated with decrease in both peripheral
vascular tone and many other vegetative
functions of the body.
• There are 10 to 30 per cent decreases in blood
pressure, respiratory rate and basal
metabolic rate.

19. NREM sleep
• Although slow-wave sleep is frequently called
"dreamless sleep“, dreams and sometimes
even nightmares occur during slow-wave
sleep.
• The difference between the dreams that occur
in slow-wave sleep and those that occur in
REM sleep is that those of REM sleep are
associated with more bodily muscle activity.
• The dreams of slow-wave sleep usually are not
remembered.

20. REM Sleep (Paradoxical
Sleep, Desynchronized Sleep)
• Rapid eye movement sleep, or REM sleep, accounts
for 20–25% of total sleep time in most human
adults.
• The criteria for REM sleep include rapid eye
movements as well as a rapid low-voltage EEG.
• Most memorable dreaming occurs in this stage.
• At least in mammals, a descending muscular atonia
is seen. Such paralysis may be necessary to protect
organisms from self-damage through physically
acting out scenes that occur during this stage.

21. REM Sleep
• The person is even more difficult to arouse
by sensory stimuli than during deep slow-wave
sleep, and yet people usually awaken
spontaneously in the morning during an
episode of REM sleep.
• Muscle tone throughout the body is
exceedingly depressed, indicating strong
inhibition of the spinal muscle control areas.
• Heart rate and respiratory rate usually
become irregular, which is characteristic of
the dream state.

22. REM Sleep
• Despite the extreme inhibition of the
peripheral muscles, irregular muscle
movements do occur.
• The brain is highly active in REM sleep, and
overall brain metabolism may be increased as
much as 20 per cent.
• The electroencephalogram (EEG) shows a
pattern of brain waves similar to those that
occur during wakefulness.

23. REM Sleep
• This type of sleep is also called paradoxical
sleep because it is a paradox that a person can
still be asleep despite marked activity in the
brain.
• In summary, REM sleep is a type of sleep in
which the brain is quite active.
• However, the brain activity is not channeled in
the proper direction for the person to be fully
aware of his or her surroundings, and
therefore the person is truly asleep.

26. Hours by age
• Children need more sleep per day in order
to develop and function properly.
• Up to 18 hours for newborn babies, with a
declining rate as a child ages.
• A newborn baby spends almost 9 hours a
day in REM sleep.
• By the age of five or so, only slightly
over two hours is spent in REM.

27. Hours by age
Age Average amount of sleep
per day
Newborn up to 18 hours
1–12 months 14–18 hours
1–3 years 12–15 hours
3–5 years 11–13 hours
5–12 years 9–11 hours
Adolescents 9–10 hours
Adults, including elderly 7–8 hours
Pregnant women 8(+) hours

28. Basic Theories of Sleep
• Sleep Is Believed to Be Caused by an Active
Inhibitory Process.
• An earlier theory of sleep was that the excitatory
areas of the upper brain stem, the reticular
activating system, simply fatigued during the
waking day and became inactive as a result. This
was called the passive theory of sleep.
• An important experiment changed this view to the
current belief that sleep is caused by an active
inhibitory process : it was discovered that
transecting the brain stem at the level of the
midpons creates a brain whose cortex never goes to
sleep.

29. Basic Theories of Sleep
• Neuronal Centers, Neurohumoral Substances and
Mechanisms That Can Cause Sleep - A Possible Specific
Role for Serotonin.
• Stimulation of several specific areas of the brain can
produce sleep with characteristics near those of natural
sleep.
• The most conspicuous stimulation area for causing almost
natural sleep is the raphe nuclei in the lower half of the pons
and in the medulla.
• Nerve fibers - brain stem reticular formation - upward into
the thalamus, hypothalamus, limbic system, neocortex of
the cerebrum.
• Nerve fibers – downward - spinal cord - posterior horns.

30. Basic Theories of Sleep
• Many nerve endings of fibers from these raphe
neurons secrete serotonin. When a drug that blocks
the formation of serotonin is administered to an
animal, the animal often cannot sleep for the next
several days.
• Stimulation of some areas in the NTS can also cause
sleep.
• Stimulation of several regions in the diencephalon
can also promote sleep, including (1) the rostral part
of the hypothalamus, suprachiasmal area and (2) an
area in the diffuse nuclei of the thalamus.

31. Basic Theories of Sleep
• Lesions in Sleep-Promoting Centers Can Cause Intense
Wakefulness.
• Discrete lesions in the raphe nuclei lead to a high state of
wakefulness. This is also true of bilateral lesions in the
medial rostral suprachiasmal area in the anterior
hypothalamus.
• In both instances, the excitatory reticular nuclei of the
mesencephalon and upper pons seem to become released
from inhibition, thus causing the intense wakefulness.
• Sometimes lesions of the anterior hypothalamus can cause
such intense wakefulness that the animal actually dies of
exhaustion.

32. Basic Theories of Sleep
• Other Possible Transmitter Substances Related to
Sleep.
• Experiments have shown that the CSF as well as the
blood or urine of animals that have been kept awake for
several days contains a substance muramyl peptide that
will cause sleep when injected only in micrograms into
the brain ventricular system of another animal.
• Another substance that has similar effects in causing
sleep is a nonapeptide isolated from the blood of
sleeping animals.
• And still a third sleep factor, not yet identified
molecularly, has been isolated from the neuronal tissues
of the brain stem of animals kept awake for days.

33. Basic Theories of Sleep
• Possible Cause of REM Sleep.
• Why slow-wave sleep is broken periodically by
REM sleep is not understood.
• However, drugs that mimic the action of Ach
increase the occurrence of REM sleep.
• So, it has been postulated that the large
Ach-secreting neurons in the upper brain stem
reticular formation might activate many portions of
the brain.
• This theoretically could cause the excess activity
that occurs in certain brain regions in REM sleep.

34. Basic Theories of Sleep
• Cycle Between Sleep and Wakefulness.
• When the sleep centers are not activated, the
mesencephalic and upper pontile reticular activating
nuclei are released from inhibition, which allows the
reticular activating nuclei to become spontaneously
active.
• This in turn excites both the cerebral cortex and the
peripheral nervous system, both of which send
numerous positive feedback signals back to the same
reticular activating nuclei to activate them still further.
• So, once wakefulness begins, it has a natural tendency
to sustain itself because of all this positive feedback
activity.

35. Basic Theories of Sleep
• Then, after the brain remains activated for
many hours, even the neurons themselves in
the activating system presumably become
fatigued.
• Consequently, the positive feedback cycle
between the mesencephalic reticular nuclei
and the cerebral cortex fades.
• Then the sleep - promoting effects of the sleep
centers take over, leading to rapid transition
from wakefulness back to sleep.

36. Basic Theories of Sleep
• Slow waves in the EEG and slow-wave sleep,
can be produced by stimulation of at least
three subcortical regions.
• The diencephalic sleep zone is in the
posterior hypothalamus and the nearby
intralaminar and anterior thalamic nuclei. The
stimulus frequency must be about 8 Hz ; faster
stimuli produce arousal.

37. Basic Theories of Sleep
• The second zone is the medullary synchronizing
zone in the reticular formation of the medulla
oblongata at the level of the NTS. Stimulation of
this zone, like stimulation of the diencephalic sleep
zone, produces sleep if the frequency is low but
arousal if the frequency is high.
• The third synchronizing region is the basal
forebrain sleep zone. This zone includes the
preoptic area and the diagonal band of Broca.

38. Physiologic Effects of Sleep
• Sleep causes two major types of physiologic effects:
first, effects on the nervous system itself, and
second, effects on other functional systems of the
body.
• Lack of sleep certainly affect the functions of the
CNS.
• Prolonged wakefulness is often associated with
progressive malfunction of the thought processes
and sometimes even causes abnormal behavioral
activities.

39. Physiologic Effects of Sleep
• Increased sluggishness of thought that occurs
toward the end of a prolonged wakeful period,
but in addition, a person can become irritable
or even psychotic after forced wakefulness.
• So, we can assume that sleep in multiple ways
restores both normal levels of brain activity
and normal "balance" among the different
functions of the CNS.
• The specific physiologic functions of sleep
remain a mystery.

40. Physiologic Effects of
Sleep
•Wound healing
• Immune system
• Development of the brain
• Memory processing
• Preservation

41. Comparative Aspect
• Neurological sleep states can be difficult to
detect in some animals. In these cases, sleep may
be defined using behavioral characteristics such
as minimal movement, postures typical for the
species, and reduced responsiveness to external
stimulation.
• Herbivores, who require a long waking period to
gather and consume their diet, typically sleep less
each day than similarly sized carnivores, who
might well consume several days' supply of meat
in a sitting.

42. Comparative Aspect
• Horses and other herbivorous ungulates
can sleep while standing, but must
necessarily lie down for REM sleep
(which causes muscular atony) for short
periods.
• Giraffes only need to lie down for REM
sleep for a few minutes at a time.

43. Comparative Aspect
• Bats sleep while hanging upside down.
• Some aquatic mammals and some birds can sleep
with one half of the brain while the other half is
awake, so-called unihemispheric slow-wave sleep.
• Birds' cycles are much shorter and they do not lose
muscle tone to the extent that most mammals do.
• Many mammals sleep for a large proportion of each
24-hour period when they are very young. However,
killer whales and some dolphins do not sleep during
the first month of life.

44. Sleep deprivation
• Aching muscles
• Confusion, memory lapses or loss
• Depression
• Hallucinations
• Hand tremors
• Headaches
• Periorbital puffiness
• Increased blood pressure

45. Sleep deprivation
• Increased stress hormone levels
• Increased risk of diabetes
• Irritability
• Nystagmus
• Obesity
• Temper tantrums in children
• Yawning
• Symptoms similar to ADHD & Psychosis

46. Sleep deprivation

47. Sleep deprivation
• Randy Gardner holds the scientifically documented
record for the longest period of time a human being
has intentionally gone without sleep not using
stimulants of any kind. Gardner stayed awake for
264 hours (11 days), breaking the previous record of
260 hours held by Tom Rounds of Honolulu.
• Other sources claim that the Guinness World
Records record stands at 449 hours (18 days, 17
hours), held by Maureen Weston, of Peterborough,
Cambridgeshire in April, 1977, in a rocking-chair
marathon.

48. Sleep disorders
(somnipathy) • Primary insomnia : Chronic difficulty in falling
asleep and/or maintaining sleep when no other cause
is found for these symptoms.
• Bruxism : Involuntarily grinding or clenching of the
teeth while sleeping.
• Delayed sleep phase syndrome (DSPS) : inability to
awaken and fall asleep at socially acceptable times
but no problem with sleep maintenance, a disorder
of circadian rhythms - jet lag and shift work sleep
disorder
• Hypopnea syndrome : Abnormally shallow
breathing or slow respiratory rate while sleeping.

49. Sleep disorders
• Narcolepsy : Excessive daytime sleepiness often
culminating in falling asleep spontaneously but
unwillingly at inappropriate times.
• Cataplexy : a sudden weakness in the motor muscles
that can result in collapse to the floor.
• Night terror : Pavor nocturnus, sleep terror
disorder : abrupt awakening from sleep with
behavior consistent with terror.
• Parasomnias : Disruptive sleep-related events
involving inappropriate actions during sleep ; sleep
walking ( Somnabulism ) and talking (Somniloquy).

50. Sleep disorders
• Periodic limb movement disorder : Sudden involuntary
movement of arms and/or legs during sleep, for
example kicking the legs. Also known as nocturnal
myoclonus.
• Restless legs syndrome : An irresistible urge to move
legs.
• Sleep Apnea, and mostly Obstructive sleep apnea :
Obstruction of the airway during sleep, causing lack of
sufficient deep sleep ; often accompanied by snoring.
• Rapid eye movement behavior disorder : Acting out
violent or dramatic dreams while in REM sleep (REM
sleep disorder or RSD).

51. Sleep disorders
• Sleep paralysis : is characterized by temporary
paralysis of the body shortly before or after sleep.
Sleep paralysis may be accompanied by visual,
auditory or tactile hallucinations. Not a disorder
unless severe. Often seen as part of narcolepsy.
• Nocturia : A frequent need to get up and go to the
bathroom to urinate at night. It differs from
Enuresis, or bed-wetting, in which the person does
not arouse from sleep, but the bladder nevertheless
empties.

52. Symptoms
Do you . . .
• feel irritable or sleepy during the day?
• have difficulty staying awake when sitting still, watching
television or reading?
• fall asleep or feel very tired while driving?
• have difficulty concentrating?
• often get told by others that you look tired?
• react slowly?
• have trouble controlling your emotions?
• feel like you have to take a nap almost every day?
• require caffeinated beverages to keep yourself going?
If you answered “yes” to any of the previous questions, you
may have a sleep disorder.

53. Insomnia
• Insomnia, the inability to get to sleep or sleep
well at night — the most common sleep
complaint.
• Insomnia can be caused by a wide variety of
things including stress, jet lag, a health
condition, the medications , or the amount of
coffee .
• Insomnia can also be caused by other sleep
disorders or mental health conditions such as
anxiety and depression.

54. Insomnia
- Common signs and symptoms of insomnia
include:
• Difficulty falling asleep at night or getting back to
sleep after waking during the night.
• Waking up frequently during the night.
• Sleep is light, fragmented or unrefreshing.
• There is need to take sleeping pills in order to get to
sleep.
• Sleepiness and low energy during the day.

55. Sleep apnea
• Sleep apnea is a common sleep disorder
in which breathing temporarily stops
during sleep due to blockage of the upper
airways. These pauses in breathing
interrupt sleep, leading to many
awakenings each hour.
• While most people with sleep apnea don’t
remember these awakenings, they feel the
effects in other ways, such as exhaustion
during the day, irritability and depression,
and decreased productivity.

56. Sleep apnea
• Sleep apnea is a serious, and potentially life-threatening,
sleep disorder.
• Sleep apnea can be successfully treated with
Continuous Positive Airway Pressure (CPAP), a
mask-like device that delivers a stream of air while
sleeping.
• Losing weight, elevating the head of the bed, and
sleeping on one side can also help in cases of mild
to moderate sleep apnea.

57. Sleep apnea
- Symptoms of sleep apnea include :
• Loud, chronic snoring
• Frequent pauses in breathing during sleep
• Gasping or choking during sleep
• Feeling unrefreshed after waking and sleepy
during the day
• Waking up with shortness of breath, chest
pains, headaches, nasal congestion, or a dry
throat.

58. Restless legs syndrome
• Restless legs syndrome (RLS) is a sleep disorder that causes
an almost irresistible urge to move legs (or arms). The urge
to move occurs while resting or lying down and is usually
due to uncomfortable, tingly, aching or creeping sensations.
- Common signs and symptoms of restless legs syndrome
include :
• Uncomfortable sensations deep within the legs,
accompanied by a strong urge to move them.
• The leg sensations are triggered by rest and get worse at
night.
• The uncomfortable sensations temporarily get better when
you move, stretch or massage your legs.
• Repetitive cramping or jerking of the legs during sleep.

59. Narcolepsy
• Narcolepsy is a sleep disorder that
involves excessive, uncontrollable
daytime sleepiness. It is caused by a
dysfunction of the brain mechanism that
controls sleeping and waking.
• The person may have “sleep attacks”
while in the middle of talking, working,
or even driving.

60. Narcolepsy
- Common signs and symptoms of narcolepsy
include :
• Seeing or hearing things when the person is drowsy
or starting to dream before he is fully asleep.
• Suddenly feeling weak or losing control of muscles
while laughing, angry or experiencing other strong
emotions.
• Dreaming right away after going to sleep or having
intense dreams.
• Feeling paralyzed and unable to move while waking
up or dozing off.

61. Circadian rhythm sleep
disorders
• We all have an internal biological clock that
regulates our 24-hour sleep-wake cycle, also
known as our circadian rhythms.
• Light influences circadian rhythms. When the
sun comes up in the morning, the brain tells
the body that it’s time to wake up. At night,
when there is less light, brain triggers the
release of melatonin, a hormone that triggers
sleep.

62. Circadian rhythm sleep
disorders
• When circadian rhythms are disrupted , there
is disorientation & sleep at inconvenient times.
• Circadian rhythms have been linked to a
variety of sleeping problems and sleep
disorders, including insomnia, jet lag and shift
work sleep difficulties.
• Abnormal circadian rhythms have also been
implicated in depression, bipolar disorder and
seasonal affective disorder.

63. Jet lag
• Jet lag is a temporary disruption in circadian
rhythms that occurs when traveling across
time zones.
• Symptoms include daytime sleepiness, fatigue,
headache, stomach problems and insomnia.
• The symptoms typically appear within a day
or two after flying across two or more time
zones.

64. Jet lag
• The longer the flight, the more
pronounced the symptoms.
- Jet lag can be worse if the person :
• lost sleep during travel
• are under a lot of stress
• drink too much alcohol or caffeine

65. Shift work
• Shift work sleep disorder is a circadian rhythm
sleep disorder that occurs when work schedule
and biological clock are out of sync.
• In our 24-hour society, many workers have to
work night shifts, early morning shifts, or
rotating shifts.
• These schedules force them to work when
their body is telling them to go to sleep, and
sleep when their body is signaling them to
wake.

66. Shift work
• While some people adjust better than others to
the demands of shift work, most shift workers
get less quality sleep than their daytime
counterparts.
• As a result of sleep deprivation, many shift
workers struggle with sleepiness and mental
lethargy on the job. This cuts into their
productivity and puts them at risk of injury.

67. Shift work
There are a numbers of things that reduce
the impact of shift work on sleep :
• Minimize the frequency of shift changes
• Use bright lights at work and take regular
breaks
• Create a dark bedroom environment

68. Delayed sleep phase disorder
• Delayed sleep phase disorder is a sleep
disorder in which 24-hour cycle of sleep and
wakefulness is significantly delayed. As a
result, the person goes to sleep and wakes up
much later than other people.
• Delayed sleep phase disorder makes it difficult
to keep normal hours — to make it to morning
classes, get the kids to school on time, or keep
a 9-to-5 job.

69. Delayed sleep phase
disorder
• People with delayed sleep phase disorder are
unable to get to sleep earlier than 2 to 6 a.m. no
matter how hard they try. They struggle to go to
sleep and get up at socially acceptable times.
• But when allowed to keep their own hours (such
as during a school break or holiday), they fall
into a regular sleep schedule.
• Delayed sleep phase disorder is most common in
teenagers, and many teens will eventually grow
out of it.

70. Treatment of Sleep
Disorders
1. Keep a sleep diary
2. Improve sleep hygiene and daytime habits
- Keep a regular sleep schedule
- Set aside enough time for sleep
- Make sure that the bedroom is dark, cool and
quiet
- Turn off TV, smartphone and computer

71. Treatment of Sleep
Disorders
3. Eat right and get regular exercise
- Stay away from big meals at night.
- Avoid alcohol before bed
- Cut down on caffeine
- Avoid drinking too many liquids in the evening
- Quit smoking
4. Get anxiety and stress in check
• A relaxing bedtime routine
• Abdominal breathing
• Progressive muscle relaxation

72. Treatment of Sleep
Disorders
5. Sleeping Pills
• Only take a sleeping pill when there is enough
time to get a full 7 to 8 hours of sleep.
• Pay careful attention to the potential side
effects, dosage instructions.
• Never mix alcohol and sleeping pills.
• Never drive a car or operate machinery after
taking a sleeping pill

75. Sleeping Pills
1. OTC – Antihistaminics : Diphenhydramine
2. Benzodiazepine : Estazolam, Flurazepam,
Quazepam, Temazepam, Triazolam
3. Non-benzodiazepine : Eszopiclone, Zalepon,
Zolpidem
4. Melatonin receptor agonist : Ramelteon
5. Antidepressants : Imipramine, Amitryptiline,
Fluoxetine , Fluvoxamine, Sertraline, Citalopram,
Bupropion, Venlafaxine, Duloxetine

76. THANK YOU