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INSOMNIA AND RESULTING DAYTIME SLEEPINESS

Asking the right questions to investigate the type of insomnia (i.e.,

trouble falling asleep, staying asleep, or early morning awakening),

possible causes (lifestyle issues, drugs), resulting impairment, and

concomitant conditions are essential to determine proper management.

Case 84-1 (Questions 1, 2)

Table 84-1, 84-4,

Figure 84-2

Nonpharmacologic treatments such cognitive-behavioral interventions

are recommended first-line therapy for managing insomnia in a variety

of patients owing to high efficacy and avoidance of medication side

effects.

Case 84-1 (Questions 3, 4)

Table 84-2

Pharmacologic treatments for insomnia are selected based on their

efficacy, tolerability, onset and duration of effect, potential for next-day

hangover, and abuse potential.

Case 84-1 (Questions 5–10)

Table 84-3

Insomnia concurrent with medical illness is frequently chronic (>1

month) and, if left untreated, may affect recovery from the medical

condition. Treating both conditions at the same time is recommended.

Case 84-2 (Questions 1–4)

Table 84-5,

Figure 84-2

Insomnia concurrent with psychiatric illness requires optimization of

psychiatric maintenance medications and the judicious use of hypnotic

medications based on type of sleep complaint and substance abuse

history.

Case 84-3 (Questions 1–4)

Figure 84-2

Managing insomnia in an elderly individual involves consideration of agerelated pharmacodynamic and pharmacokinetic changes and counseling

regarding realistic treatment expectations. Medication doses lower than

those used in younger individuals should be prescribed.

Case 84-4 (Questions 1–5)

Table 84-3

If nonpharmacologic treatment is ineffective, diphenhydramine is

considered safe for short-term use (<1 week) in pregnancy. Risks

outweigh benefits for benzodiazepines and nonbenzodiazepine receptor

agonists in pregnancy.

Case 84-5 (Question 1)

SLEEP APNEA

Sleep apnea leads to excessive daytime sleepiness, fatigue, and

increased risk of cardiovascular and cerebrovascular disease. Effective

Case 84-6 (Questions 1, 2)

treatment with continuous positive airway pressure or surgical

interventions can decrease cardiovascular disease and improve overall

functioning and quality of life.

It is essential to avoid sedating medications in patients with sleep apnea

because these agents interfere with mini-arousals that keep the patient

alive.

Case 84-6 (Question 3)

NARCOLEPSY

Narcolepsy is an incurable neurologic disease characterized by sleep

attacks and cataplexy. Stimulants modafinil or armodafinil help decrease

sleep attacks and promote daytime alertness but do not help with

cataplexy or nocturnal insomnia.

Case 84-7 (Questions 1, 2)

Sodium oxybate is effective for cataplexy and improves nocturnalsleep,

but it has high abuse potential and has been associated with psychiatric

side effects.

Case 84-7 (Questions 3, 4)

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OVERVIEW

Approximately one-third of the adult life is expended on sleep. The innate necessity

of sleep is present in almost all mammals, though all the functions of sleep are not

fully understood.

1,2 Naturally with human physiology devoted to sleep and the

numerous factors that can disrupt this process, sleep disorders are remarkably

common. Sleep deficiency, including insufficient sleep duration, irregular timing of

sleep, poor sleep quality, and sleep or circadian rhythm disorders, is highly

prevalent and threaten public safety.

3,4 Decades of scientific findings associate sleep

deficiency with increased disease risk, including cardiovascular and metabolic

disease, psychiatric illness, substance abuse, pregnancy complications, and impaired

neurobehavioral and cognitive impairment.

4,5 At least 10% of the American

population is reported to suffer from a sleep disorder that is clinically significant and

of public health concern.

3 Major sleep disorders in the United States include

insomnia ranging from 15% to 35%,

6,7 sleep apnea at 6% to 24%8,9 periodic limb

movements in sleep (PLMS, previously known as nocturnal myoclonus), and restless

leg syndrome (RLS) ranging from 3% to 15%,

10,11 and narcolepsy at 0.025% to

0.05%.

12 Untreated sleep disorders, including chronic insomnia, sleep apnea, PLMS,

and narcolepsy, are all associated with diminished mental and physical functioning

and poor quality of life.

3,4,7

Nightmares, nocturnal leg cramps, and snoring are more benign sleep disorders.

Nightmares occur in 5% to 30% of children 3 to 6 years of age, and approximately

2% to 6% of adults have weekly nightmares.

13 Sleepwalking occurs in 1% to 2% of

the population. Complex sleep behavior disorders, such as driving or eating while

still half asleep, are uncommon to rare. These behaviors are more common in people

taking hypnotics, and medication counseling should be provided for patients

prescribed any sleep medication.

13,14

CIRCADIAN RHYTHM AND SLEEP CYCLES

Sleep is a dynamic process with a cyclical recurrence and varying stages. The

endogenous sleep–wake pattern of humans is based on the solar day–night cycle

called the circadian rhythm. Circadian rhythm is controlled both by internal and

external factors and sets the sleep–wake cycle at 24.2 hours. Sensory input (visual

and acoustic) or other external factors modify the “internal clock” to a 24 hour day

through working with the internal network and signaling brain centers to either wake

or sleep. Thus, darkness is a visual cue that prepares the brain for sleep. Similarly,

bright light serves to prepare the brain for wakefulness.

1,2

Once sleep is initiated, it alternates between the two phases of rapid eye

movement (REM) and nonrapid eye movement (NREM) sleep. These phases vary in

length throughout the sleep cycles. During a normal night of sleep, a person generally

has four to six cycles of sleep which last an average of 90 minutes (vary 70–120

minutes).

15 See Figure 84-1 for normal sleep cycles by age.

Polysomnography

Each sleep stage serves a physiologic function and can be monitored in sleep

laboratories by polysomnography (PSG). PSG is the term used to describe three

electrophysiologic measures: the electroencephalogram (EEG), the electromyogram,

and the electrooculogram of each eye. It may also include an electrocardiogram, air

thermistors, abdominal and thoracic strain belts, and oxygen saturation monitoring.

The pattern of brain waves, muscle tone, and eye movements measured can be used

to categorize the various sleep stages.

15,16

Figure 84-1 Normalsleep cycles.

Nonrapid Eye Movement Sleep

NREM sleep is divided into four stages, with different quantities of time and

functions in each stage. Stage 1 is a transition between sleep and wakefulness known

as relaxed wakefulness, which generally makes up approximately 2% to 5% of sleep.

The function of stage 1 is to initiate sleep. Approximately 50% of total sleep time is

spent in stage 2, which is rapid-wave (theta) or lighter sleep. Stage 2 provides rest

for the muscles and brain through muscle atonia and low-voltage brain wave activity.

Arousability from sleep is highest during stages 1 and 2. Stages 3 and 4 are slowwave (delta) or deep sleep. Stage 3 occupies an average of 5% of sleep time,

whereas stage 4 constitutes 10% to 15% of sleep time in young, healthy adults. In

contrast to stages 1 and 2, it is difficult to awaken someone during stages 3 and 4, or

delta sleep.

15 Delta sleep, also known as restorative sleep, is enhanced by serotonin,

adenosine, cholecystokinin, and IL-1. The ability of IL-1 to promote slow-wave

sleep supports a widely held theory linking deep sleep to the augmentation of immune

function. Some hormones (e.g., somatostatin, growth hormone) are released mainly

during slow-wave sleep. Deep sleep is most abundant in infants and children and

tends to level off at approximately 4 hours a night during adolescence. At age 65,

deep sleep accounts for only 10% of sleep, and at age 75, it is often nonexistent.

1,15–17

Rapid Eye Movement Sleep

Whereas NREM sleep is necessary for rest and rejuvenation, the purpose of REM

sleep remains a mystery. REM sleep is greatest in infants, accounting for about 50%

of total sleep time. As aging occurs before 2 years and throughout adulthood, REM

sleep is usually 20% to 25% of sleep. This percentage of total REM sleep

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is maintained into healthy old age, but can decline markedly in the presence of

organic brain dysfunctions of the elderly. REM sleep is also called paradoxical sleep

because it has aspects of both deep sleep and light sleep. Body and brainstem

functions appear to be in a deep sleep state as muscle and sympathetic tone drop

dramatically. In contrast, neurochemical processes and higher cortical brain function

appear active. Dreaming is associated closely with REM sleep, and when a person is

awakened from REM, alertness returns relatively quickly.

15