VITAL, JADE ANGELA M.

Sleep is a complex biological process. While you are sleeping, you are unconscious,
but your brain and body functions are still active. They are doing a number of
important jobs that help you stay healthy and function at your best. So when you
don't get enough quality sleep, it does more than just make you feel tired. It can
affect your physical and mental health, thinking, and daily functioning.

Sleep disorders are conditions that result in changes in the way that you sleep.

Some of the signs and symptoms of sleep disorders include excessive daytime
sleepiness, irregular breathing or increased movement during sleep. Other signs and
symptoms include an irregular sleep and wake cycle and difficulty falling asleep.

Anatomy of Sleep

Several structures within the brain are involved with sleep.

The hypothalamus, a peanut-sized structure deep inside the brain, contains groups
of nerve cells that act as control centers affecting sleep and arousal. Within the
hypothalamus is the suprachiasmatic nucleus (SCN) – clusters of thousands of cells
that receive information about light exposure directly from the eyes and control your
behavioral rhythm.

The brain stem, at the base of the brain, communicates with the hypothalamus to
control the transitions between wake and sleep. Sleep-promoting cells within the
hypothalamus and the brain stem produce a brain chemical called GABA, which acts
to reduce the activity of arousal centers in the hypothalamus and the brain stem.
The brain stem (especially the pons and medulla) also plays a special role in REM
sleep; it sends signals to relax muscles essential for body posture and limb
movements, so that we don’t act out our dreams.

The thalamus During most stages of sleep, the thalamus becomes quiet, letting you
tune out the external world. But during REM sleep, the thalamus is active, sending
the cortex images, sounds, and other sensations that fill our dreams.

The pineal gland, located within the brain’s two hemispheres, receives signals from
the SCN and increases production of the hormone melatonin, which helps put you to
sleep once the lights go down. Scientists believe that peaks and valleys of melatonin
over time are important for matching the body’s circadian rhythm to the external
cycle of light and darkness.
The basal forebrain, near the front and bottom of the brain, also promotes sleep and
wakefulness, while part of the midbrain acts as an arousal system. Release of
adenosine (a chemical by-product of cellular energy consumption) from cells in the
basal forebrain and probably other regions supports your sleep drive. Caffeine
counteracts sleepiness by blocking the actions of adenosine.

The amygdala, an almond-shaped structure involved in processing emotions,

becomes increasingly active during REM sleep.

Sleep Stages

There are two basic types of sleep: rapid eye movement (REM) sleep and non-REM
sleep (which has three different stages). Each is linked to specific brain waves and
neuronal activity.You cycle through all stages of non-REM and REM sleep several
times during a typical night, with increasingly longer, deeper REM periods occurring
toward morning.

Stage 1 non-REM sleep is the changeover from wakefulness to sleep. During this
short period (lasting several minutes) of relatively light sleep, your heartbeat,
breathing, and eye movements slow, and your muscles relax with occasional
twitches.

Stage 2 non-REM sleep is a period of light sleep before you enter deeper sleep. Your
heartbeat and breathing slow, and muscles relax even further. Your body
temperature drops and eye movements stop. Brain wave activity slows but is
marked by brief bursts of electrical activity. You spend more of your repeated sleep
cycles in stage 2 sleep than in other sleep stages.

Stage 3 non-REM sleep is the period of deep sleep that you need to feel refreshed in
the morning. It occurs in longer periods during the first half of the night. Your
heartbeat and breathing slow to their lowest levels during sleep. Your muscles are
relaxed and it may be difficult to awaken you. Brain waves become even slower.

REM sleep first occurs about 90 minutes after falling asleep. Your eyes move rapidly
from side to side behind closed eyelids. Mixed frequency brain wave activity
becomes closer to that seen in wakefulness. Your breathing becomes faster and
irregular, and your heart rate and blood pressure increase to near waking levels.
Most of your dreaming occurs during REM sleep, although some can also occur in
non-REM sleep. Your arm and leg muscles become temporarily paralyzed, which
prevents you from acting out your dreams. As you age, you sleep less of your time in
REM sleep. Memory consolidation most likely requires both non-REM and REM
sleep.
Sleep mechanisms

Two internal biological mechanisms–circadian rhythm and homeostasis–work

together to regulate when you are awake and sleep.

Circadian rhythms direct a wide variety of functions from daily fluctuations in

wakefulness to body temperature, metabolism, and the release of hormones. They
control your timing of sleep and cause you to be sleepy at night and your tendency
to wake in the morning without an alarm. Your body’s biological clock, which is
based on a roughly 24-hour day, controls most circadian rhythms. Circadian rhythms
synchronize with environmental cues (light, temperature) about the actual time of
day, but they continue even in the absence of cues.

Sleep-wake homeostasis keeps track of your need for sleep. The homeostatic sleep
drive reminds the body to sleep after a certain time and regulates sleep intensity.
This sleep drive gets stronger every hour you are awake and causes you to sleep
longer and more deeply after a period of sleep deprivation.

Factors that influence your sleep-wake needs include medical conditions,

medications, stress, sleep environment, and what you eat and drink. Perhaps the
greatest influence is the exposure to light. Specialized cells in the retinas of your
eyes process light and tell the brain whether it is day or night and can advance or
delay our sleep-wake cycle. Exposure to light can make it difficult to fall asleep and
return to sleep when awakened.

Night shift workers often have trouble falling asleep when they go to bed, and also
have trouble staying awake at work because their natural circadian rhythm and
sleep-wake cycle is disrupted. In the case of jet lag, circadian rhythms become out of
sync with the time of day when people fly to a different time zone, creating a
mismatch between their internal clock and the actual clock.

The Role of Neurotransmitters

Chemical signals to sleep

Clusters of sleep-promoting neurons in many parts of the brain become more active
as we get ready for bed. Nerve-signaling chemicals called neurotransmitters can
“switch off” or dampen the activity of cells that signal arousal or relaxation. GABA is
associated with sleep, muscle relaxation, and sedation. Norepinephrine and orexin
(also called hypocretin) keep some parts of the brain active while we are awake.
Other neurotransmitters that shape sleep and wakefulness include acetylcholine,
histamine, adrenaline, cortisol, and serotonin.
Sleep studies

Your health care provider may recommend a polysomnogram or other test to

diagnose a sleep disorder. A polysomnogram typically involves spending the night at
a sleep lab or sleep center. It records your breathing, oxygen levels, eye and limb
movements, heart rate, and brain waves throughout the night. Your sleep is also
video and audio recorded. The data can help a sleep specialist determine if you are
reaching and proceeding properly through the various sleep stages. Results may be
used to develop a treatment plan or determine if further tests are needed.

INSOMNIA

Insomnia is a common sleep disorder. If you have it, you may have trouble falling
asleep, staying asleep, or both. As a result, you may get too little sleep or have poor-
quality sleep. You may not feel refreshed when you wake up.

What are the types of insomnia?

Insomnia can be acute (short-term) or chronic (ongoing). Acute insomnia is common

and often is brought on by situations such as stress at work, family pressures, or a
traumatic event. Acute insomnia lasts for days or weeks.

Chronic insomnia lasts for a month or longer. Most cases of chronic insomnia are
secondary, which means they are the symptom or side effect of some other
problem. Certain medical conditions, medicines, sleep disorders, and substances can
cause secondary insomnia.

In contrast, primary insomnia isn't due to medical problems, medicines, or other

substances. It is its own distinct disorder, and its cause isn’t well understood. Many
life changes can trigger primary insomnia, including long-lasting stress and emotional
upset.

SLEEP APNEA

Sleep apnea is a common disorder that causes your breathing to stop or get very
shallow. Breathing pauses can last from a few seconds to minutes. They may occur
30 times or more an hour.

The most common type is obstructive sleep apnea. It causes your airway to collapse
or become blocked during sleep. Normal breathing starts again with a snort or
choking sound. People with sleep apnea often snore loudly. However, not everyone
who snores has sleep apnea.
You are more at risk for sleep apnea if you are overweight, male, or have a family
history or small airways. Children with enlarged tonsils or adenoids may also get it.

When your sleep is interrupted throughout the night, you can be drowsy during the
day. People with sleep apnea are at higher risk for car crashes, work-related
accidents, and other medical problems. If you have it, it is important to get
treatment. Lifestyle changes, mouthpieces, surgery, and breathing devices can treat
sleep apnea in many people.

RESTLESS LEG SYNDROME

Restless legs syndrome (RLS) causes a powerful urge to move your legs. Your legs
become uncomfortable when you are lying down or sitting. Some people describe it
as a creeping, crawling, tingling, or burning sensation. Moving makes your legs feel
better, but not for long. RLS can make it hard to fall asleep and stay asleep.

In most cases, there is no known cause for RLS. In other cases, RLS is caused by a
disease or condition, such as anemia or pregnancy. Some medicines can also cause
temporary RLS. Caffeine, tobacco, and alcohol may make symptoms worse.

Lifestyle changes, such as regular sleep habits, relaxation techniques, and moderate
exercise during the day can help. If those don't work, medicines may reduce the
symptoms of RLS.

Most people with RLS also have a condition called periodic limb movement disorder
(PLMD). PLMD is a condition in which a person's legs twitch or jerk uncontrollably,
usually during sleep. PLMD and RLS can also affect the arms.

HYPERSOMNIA

Hypersomnia is characterized by recurrent episodes of excessive daytime sleepiness

or prolonged nighttime sleep. Different from feeling tired due to lack of or
interrupted sleep at night, persons with hypersomnia are compelled to nap
repeatedly during the day, often at inappropriate times such as at work, during a
meal, or in conversation. These daytime naps usually provide no relief from
symptoms. Patients often have difficulty waking from a long sleep, and may feel
disoriented. Certain medications, or medicine withdrawal, may also cause
hypersomnia. Medical conditions including multiple sclerosis, depression,
encephalitis, epilepsy, or obesity may contribute to the disorder. Some people
appear to have a genetic predisposition to hypersomnia; in others, there is no known
cause. Typically, hypersomnia is first recognized in adolescence or young adulthood.
CICARDIAN SLEEP DISORDERS

Circadian rhythm sleep disorders all involve a problem in the timing of when a
person sleeps and is awake. The human body has a master circadian clock in a
control center of the brain known as the suprachiasmatic nucleus (SCN). This internal
clock regulates the timing of such body rhythms as temperature and hormone levels.
The primary circadian rhythm that this body clock controls is the sleep-wake cycle.
The circadian clock functions in a cycle that lasts a little longer than 24 hours.

The circadian clock is “set” primarily by visual cues of light and darkness that are

communicated along a pathway from the eyes to the SCN. This keeps the clock

synchronized to the 24-hour day. Other time cues, know as zeitgebers, also can
influence the clock’s timing. These cues include meal and exercise schedules.
Circadian rhythms

and their sensitivity to time cues may change as a person ages.

Each circadian rhythm sleep disorder involves one of these two problems:

• You have a hard time initiating sleep.

• You struggle to maintain sleep, waking up frequently during the night.
• You tend to wake up too early and are unable to go back to sleep.
• You sleep is nonrestorative or of poor quality.

Types of Circadian Rhythm Sleep Disorders

• Delayed sleep phase disorder (DSP):

• Advanced sleep phase disorder (ASP)
• Jet lag disorder
• Shift work disorder

Parasomnias

are a group of sleep disorders that involve unwanted events or experiences that
occur while you are falling asleep, sleeping or waking up. Parasomnias may include
abnormal movements, behaviors, emotions, perceptions or dreams. Although the
behaviors may be complex and appear purposeful to others, you remain asleep
during the event and often have no memory that it occurred. If you have a
parasomnia, you may find it hard to sleep through the night.
Confusional Arousals REM Sleep Behavior Sleep Hallucinations
Disorder
Sleepwalking Exploding Head
Sleep Paralysis Syndrome
Sleep Terrors
Nightmares Sleep Talking
Sleep Eating Disorder
Bedwetting

Treatments

• Lifestyle changes:

People may cope better with certain circadian rhythm sleep disorders by doing
such things as adjusting their exposure to daylight, making changes in the timing
of their daily routines, and strategically scheduling naps
• Sleep hygiene:

These instructions help patients develop healthy sleep habits and teach them to
avoid making the problem worse by attempting to self-medicate with drugs or
alcohol.
• Bright light therapy:
This therapy synchronizes the body clock by exposing the eyes to safe levels of
intense, bright light for brief durations at strategic times of day.
• Medications:
A hypnotic may be prescribed to promote sleep or a stimulant may be used to
promote wakefulness
• Melatonin:
This hormone is produced by the brain at night and seems to play a role in
maintaining the sleep-wake cycle. Taking melatonin at precise times and doses
may alleviate the symptoms of some circadian rhythm sleep disorders.

5 Drug Classes for Sleep Disorders

1. The “Z” Sedative-Hypnotics

Zolpidem, zaleplon, and eszopiclon work as facilitators/agonists of GABA receptors in

the body’s central nervous system to inhibit brain activity. In clinical studies, these
drugs have been shown to improve onset and duration of sleep. They are widely
considered as part of first-line drug therapy for insomnia.

These drugs do have their issues, though. For instance, there is related risk for abuse
and dependence, so the drugs are listed as controlled substances.
The most common side effects involve the next-day hangover effect of residual
somnolence/drowsiness, dizziness, and ataxia. Zolpidem, zaleplon, and eszopiclone
also have some weird side effects like parasomnias and vivid dreams.

2. Benzodiazepines

There a lot of benzodiazepines on the market for various mental health conditions,
but for insomnia, a shorter-acting agent in this class is generally better tolerated.

The acronym LOT (lorazepam, oxazepam, temazepam) will be help you remember
the less harmful benzodiazepines. Of note, however, oxazepam is not approved for
sleep disorders, but the others are.

Because benzodiazepines have shorter durations of action, the next-day hangover

effect is not as prominent for benzodiazepines as it is for the “Z” sedative-hypnotics.
However, the abuse potential of benzodiazepines is stronger because they have less-
selective binding to the GABAA receptors.

3. Dual Orexin Receptor Antagonists

Suvorexant (Belsomra), the newest drug to enter the dual orexin receptor
antagonists party, was introduced to the market in the summer of 2014.

Belsomra works to inhibit/antagonize the orexin receptor, which normally promotes

wakefulness. Unfortunately, there haven’t been any updated treatment guidelines
for sleep disorders since Belsomra was made available, and there also haven’t been
head-to-head studies with established therapies, so it is hard to tell its place in
therapy.

4. Melatonin Receptor Agonists

With more than 30 million users, melatonin has become a crowd favorite for not
only insomnia, but also jet lag.

Melatonin is naturally found in the body as a hormone created by the pineal gland.

Ramelteon (Rozerem) is a melatonin receptor agonist that has been approved for
use in the United States since 2005. It has shown benefit in sleep-onset insomnia but
not maintenance insomnia, due to its short duration of action.
Another melatonin receptor agonist, tasimelteon (Hetlioz), is not approved for
insomnia, but it is approved for Non-24-Hour Sleep-Wake Disorder, a neurological
sleep disorder that affects primarily blind patients.

5. Antidepressants

Antidepressants generally work on either histamine or serotonin receptors to cause

sedation in those with sleep disorders.

Silenor is a brand-name form of doxepin that is approved for insomnia. Silenor isn’t
great for sleep-onset insomnia, but it does show benefit for sleep maintenance.

Trazodone is frequently used off-label at lower doses for depressed patients.

Mirtazapine is used off-label in a similar manner as trazodone.

Tricyclic antidepressants like amitriptyline and imipramine have also been used for
insomnia. Their side effect profiles are stronger than the other antidepressants’ and
should thus be used with extreme caution, especially in the elderly.

Other Available Options

Herbals

A 2015 meta-analysis took a look at 4 different herbals and compared each of them
with placebo. The researchers primarily examined valerian, but they also reviewed
kava, chamomile, and wuling (Xylaria nigripes).

The researchers considered various insomnia endpoints and found poor evidence of
the herbals providing benefit. The aforemented 2008 clinical guidelines do not
recommend the use of herbals for chronic insomnia.

Antihistamines

Antihistamines like diphenhydramine and doxylamine are main ingredients in OTC

sleep products, but they are not recommended for sleep disorders. Antihistamines
may be effective for a night or 2, but tolerance quickly occurs, which reduces their
effects. These drugs are also associated with a large number of anticholinergic side
effects, even at normal doses.

Barbiturates

Phenobarbital and some other barbiturates are actually approved for insomnia, but
they are generally used for other indications like seizures and preoperative sedation.
Quetiapine (Seroquel) is indicated for schizophrenia, bipolar, and major depressive
disorder, but off-label use at a low dose (25 mg initially) has been beneficial for
insomnia patients.