FitSugar

Fight Jet Lag: Don't Eat?

FitSugar — Tue, 27 May 2008 08:00:00 -0700

If you're getting ready to cross time zones, new research suggests that fasting may help you deal with jet lag. While it's true that light regulates the circadian rhythm, an internal clock that determines when you sleep, wake, and eat, there may be a second internal clock that takes over when your body thinks food is scarce. It takes 16 hours of fasting to kick this clock into gear, and manipulating this clock by denying yourself food may help to adjust to a new time zone. Scientists experimented with this concept by offering food to mice only during times when they were supposed to be sleeping. Eventually, the mice that adjusted to this new eating schedule remained awake at nighttime in order to eat. Since we are mammals too, scientists think this strategy may work on humans as well.

It may be worth a try if you're traveling across the globe, but personally, I think not eating is a bad idea. Not only will it screw up your metabolism, but it'll make you cranky, dizzy, and give you a headache, which will only worsen your symptoms of jet lag.

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Daylight Savings Time (It May Take Weeks to Adjust)

FitSugar — Fri, 02 Nov 2007 12:30:00 -0700

It is time to change our clocks again this Sunday. That means that at 2 a.m. on November 4, you've got to set your clock back one hour. The saying, "Spring forward and fall back," always helps me remember which way the clocks go.

It's great that we gain an hour, but a new study shows that our bodies don't adjust well to the time shift. Although it's just a one hour difference, our natural clock (known as circadian rhythm), may take up to four weeks to adjust in the Spring and another six weeks to adjust in the Fall.

There have only been a few studies on the connection between Daylight Savings Time and human circadian rhythms, so it's not yet known if the constant changing has any significant long-term effects on our health. Hopefully this subject will be studied soon.

Since gaining an hour will definitely mess with your internal clock, be sure to listen to your body's needs. Eat and sleep when your body wants to, and gradually shift your old schedule back an hour. It may take a few days, or even a few weeks for things to feel normal again.

Fit's Tip: When you change your clocks back, don't forget to change the batteries in your smoke detectors.

People seem split on this time change and I am curious to know how you feel about gaining an hour? Tell me how you feel in the comment section below.

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Feel the Circadian Rhythm

FitSugar — Thu, 21 Jun 2007 11:00:00 -0700

We all have a biological clock, and I am not talking about the biological clock some women refer to when discussing the sudden need to have a baby. I am talking about the daily clock of the circadian rhythm, the energy ups and downs we all experience through out the day.

Scientist have located the clock that controls the circadian rhythm. It is actually a pair of pinhead-sized structures that together contain about 20,000 neurons, that is housed deep on our brains, near the optical nerve. Animals, plants and microbes display circadian rhythms; it's part of deep biology. While circadian rhythm, the pattern of sleep and awake cycles, is affected by light, but people living in complete darkness will adjust to a 25 hour clock with normal sleep / wake patterns. Personally, I would not like to be a subject in a study that determined this.

Want to know how the circadian rhythm works throughout your day? then read more

According to Women's Health the daily rhythm goes something like this:

6:30 a.m. to 7:00 a.m. - Sleep Inertia
During the first 30 minutes you're awake, thinking and reaction times are substantially impaired.
7:00 a.m. to 12:00 p.m. - Morning Hustle
Between breakfast and lunch, your sense of alertness peaks. This is the time to get things done.
12:00 p.m. to 5:00 p.m. - Nap Time
At some point in the afternoon, we experience an energy drag that usually lasts about 2 hours. The Spanish siesta might have some science behind it.
5:00 p.m. to 8:00 p.m. - Sunset Spike
A rise in energy occurs making this a very difficult time to nap.
8:00 p.m. to 6:30 a.m. - Back to Bed
The chemical melatonin, which helps you to sleep, floods your body as you snooze.

Fit's Tip: According to the circadian rhythm it is best to do all your heady work in the morning and save all those menial tasks for the afternoon.

Ease Your Body Into Daylight Savings Time

FitSugar — Fri, 09 Mar 2007 12:00:00 -0800

This Sunday is Daylight Savings Time. That means that at 2 am on March 11, the clocks skip ahead 1 hour. Remember the saying - "Spring forward and Fall back."

Losing one hour of sleep can really screw up your circadian rhythm (your body's inner clock), so you might want to think about easing into it.

On the day before, try going to sleep earlier and waking up earlier. You can also adjust your mealtime schedule and eat an hour earlier.

Before you go to sleep on Saturday night, set all the clocks in your house ahead 1 hour. That way, when you wake up on Sunday morning, it won't be so obvious that you lost an hour.

On that Sunday, avoid taking a nap to make up for the hour you lost. It'll only make it harder to get to sleep on Sunday night.

On that Monday, try to keep your schedule light. You might be feeling tired and cranky, so if you have less to do, it'll give your body time to relax and adjust.

Fit's Tips: Don't forget to change the batteries in your smoke detectors too.

Insomnia

FitSugar — Wed, 08 Oct 2008 17:35:00 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Sedative Hypnotic Drug Warnings

In March 2007, the FDA ordered stronger warning labels on sedative hypnotic drugs. These medications include benzodiazepine and non-benzodiazepine drugs, such as zolpidem (Ambien), eszopiclone (Lunesta), ramelteon (Rozerem), and triazolam (Halcion). The FDA warned that these drugs may be associated with:

Severe allergic reactions (anaphylaxis) and severe facial swelling (angioedema), which can occur even the first time a drug is taken
Complex sleep-related behaviors, such as sleep driving, making phone calls, and preparing and eating food while asleep

Patients who take sleeping pills should be sure to follow the directions. These include not combining sleeping pills with alcohol or other drugs and not taking more than the prescribed dose. All patients prescribed sedative hypnotic drugs should receive a patient medication guide that describes the potential risks, and precautions to reduce these risks.

Behavioral and Psychological Therapies

Behavioral and psychological treatments, such as cognitive behavioral therapy and relaxation techniques, are effective approaches for insomnia and can produce long-lasting benefits, according to a 2006 study in Sleep.
Behavioral interventions help over 80% of children who try them, indicates another 2006 Sleep study.

Complementary and Alternative Medicine

More than 1.6 million adults use complementary and alternative medicine to treat their insomnia, according to results of a national survey published in the Archives of Internal Medicine. About half of patients who tried herbal medicine or relaxation techniques found that these approaches helped improve their sleep.
In 2006, the American Academy of Sleep Medicine issued a position statement advising that there is only limited scientific evidence that herbal remedies are effective sleep aids.

Insomnia and Mood Disorders

Chronic insomnia can increase the risk of developing depression and anxiety, according to a 2007 study in Sleep. Research also indicates that insomnia and daytime sleepiness can cause and worsen depression and anxiety in children as well as adults.

Introduction

Insomnia comes from the Latin words for “no sleep.” Insomnia is characterized by:

Difficulty falling asleep
Difficulty staying asleep
Waking up too early in the morning

Some experts believe that poor quality (“non-restorative”) sleep is also related to insomnia. Insomnia can cause daytime fatigue, irritability, and impaired performance. About 60 million Americans each year suffer from insomnia.

Insomnia may be primary or secondary:

Primary insomnia means that the inability to sleep is not caused by other health problems.
Secondary insomnia is due to other health conditions that interfere with sleep. Some experts prefer the term “co-morbid insomnia.”

Insomnia, usually temporary, is often categorized by how long it lasts:

Transient insomnia lasts for a few days.
Short-term insomnia lasts for no more than 3 weeks.
Chronic insomnia occurs at least 3 nights per week for 1 month or longer.

Insomnia may also be defined in terms of inability to sleep at conventional times. The following examples are referred to as circadian rhythm disorders:

Delayed Sleep-Phase Syndrome. Delayed sleep-phase syndrome is the term for a circadian clock that runs late but reliably. People who have this condition (usually adolescents) fall asleep very late at night or in early morning hours, but then sleep normally.
Advanced Sleep-Phase Syndrome. This syndrome tends to develop in older people. It produces excessive sleepiness in the morning and undesired awakening early (3 - 5 a.m.) in the morning.

In sleep studies, subjects spend about one-third of their time asleep, suggesting that most people need about 8 hours of sleep each day. Individual adults differ in the amount of sleep they need to feel well rested, however. (Infants may sleep as many as 16 hours a day.)

The daily cycle of life, which includes sleeping and waking, is called a circadian (meaning "about a day") rhythm, commonly referred to as the biologic clock. Hundreds of bodily functions follow biologic clocks, but sleeping and waking comprise the most prominent circadian rhythm. The sleeping and waking cycle is approximately 24 hours. (If confined to windowless apartments, with no clocks or other time cues, sleeping and waking as their bodies dictate, humans typically live on slightly longer than 24-hour cycles.) It usually takes the following daily patterns:

Humans are designed for daytime activity and nighttime rest.
Additionally, there is a natural peak in sleepiness at mid-day, the traditional siesta time.

In addition, daily rhythms intermesh with other factors that may interfere or change individual patterns:

The fraction-of-a-second-firing of nerve cells in the brain may be faster or slower in different individuals.
The monthly menstrual cycle in women can shift the pattern.
Light signals coming through the eyes reset the circadian cycles each day, so changes in season or various exposures to light and dark can unsettle the pattern. The importance of sunlight as a cue for circadian rhythms is dramatized by the problems experienced by people who are totally blind. They commonly suffer trouble sleeping and other rhythm disruptions.

The response to light signals in the brain is an important key factor in sleep:

Light signals travel to a tiny cluster of nerves in the hypothalamus in the center of the brain, the body's master clock, which is called the supra chiasmatic nucleus (SCN).
This nerve cluster takes its name from its location, which is just above (supra) the optic chiasm, which is a major junction for nerves transmitting information about light from the eyes.
The approach of dusk each day prompts the SCN to signal the nearby pineal gland (named so because it resembles a pine-cone) to produce the hormone melatonin.
Melatonin is thought to act as the body's time-setting hormone. The longer a person is in darkness the longer the duration of melatonin secretion. Secretion can be diminished by staying in bright light. Melatonin also appears to trigger the need to sleep.

Sleep consists of two distinct states that alternate in cycles and reflect differing levels of brain nerve cell activity:

Non-Rapid Eye Movement Sleep (NonREM). NonREM sleep is also termed quiet sleep. NonREM is further subdivided into three stages of progression:

Stage 1 (light sleep)
Stage 2 (so-called true sleep)
Stage 3 to 4 (deep "slow-wave" or delta sleep)

With each descending stage, awakening becomes more difficult. It is not known what governs NonREM sleep in the brain. A balance between certain hormones, particularly growth and stress hormones, may be important for deep sleep.

Rapid Eye-Movement Sleep (REM). REM sleep is termed active sleep. Most vivid dreams occur in REM sleep. REM-sleep brain activity is comparable to that in waking, but the muscles are virtually paralyzed, possibly preventing people from acting out their dreams. In fact, except for vital organs like lungs and heart, the only muscles not paralyzed during REM are the eye muscles. REM sleep may be critical for learning and for day-to-day mood regulation. When people are sleep-deprived, their brains must work harder than when they are well rested.

The REM/NREM Cycle. The cycle between quiet (nonREM) and active (REM) sleep generally follows this pattern:

After about 90 minutes of nonREM sleep, eyes move rapidly behind closed lids, giving rise to REM sleep.
As sleep progresses the nonREM/REM cycle repeats.
With each cycle, nonREM sleep becomes progressively lighter, and REM sleep becomes progressively longer, lasting from a few minutes early in sleep to perhaps an hour at the end of the sleep episode.

Causes of Short-Term or Transient Insomnia

A reaction to change or stress is one of the most common causes of short-term and transient insomnia. This condition is sometimes referred to as adjustment sleep disorder.

The trigger could be a major or traumatic event such as:

An acute illness
Injury or surgery
The loss of a loved one
Job loss

Temporary insomnia could also develop after a relatively minor event, including:

Extremes in weather
An exam
Traveling
Trouble at work

In most cases, normal sleep almost always returns when the condition resolves, the individual recovers from the event, or the person becomes used to the new situation. Treatment is needed if sleepiness interferes with functioning or if it continues for more than a few weeks. Individual responses to stress vary and some people may not experience insomnia at all, even during very stressful situations while others may suffer from insomnia in response to very mild stressors.

Fluctuations in female hormones play a major role in insomnia in women over their lifetimes. This insomnia is usually temporary.

During Menstruation. Progesterone promotes sleep, and levels of this hormone plunge during menstruation, causing insomnia. (When they rise during ovulation, women may become sleepier than usual.)
During Pregnancy. The effects of changes in progesterone levels in the first and last trimester can disrupt normal sleep patterns.
Menopause. Insomnia can be a major problem in the first phases of menopause, when hormones are fluctuating intensely. Insomnia during this period may be due to different factors that occur. In some women, hot flashes, sweating, and a sense of anxiety can awaken women suddenly and frequently at night. Insomnia may also be caused by psychologic distress provoked by this life passage. In many cases, insomnia is temporary. However, a 2006 study found that hot flashes in perimenopausal and postmenopausal women are strongly associated with chronic insomnia (sleep problems lasting more than 1 month). Treating hot flashes may help resolve chronic insomnia.

Air travel across time zones often causes insomnia. After long plane trips, 1 day of adjustment is usually needed for each time zone crossed. Traveling west to earlier times seems to be less traumatic than going east to a later time because it is easier to lengthen a circadian phase than to shorten it.

In one study, 20% of adults reported that light, noise, and uncomfortable temperatures caused their sleeplessness. Depending on the time of day, too much or too little light can disrupt sleep.

Excessive Light at Night. A person's biologic circadian clock is triggered by sunlight, and very bright artificial light maintains wakefulness. One study indicated that even dim artificial light might disrupt sleep.
Insufficient Light During the Day. Insufficient exposure to light during the day, as occurs in some disabled elderly patients who rarely venture outside, may also be linked with sleep disturbances. One study suggested that when a person is exposed to bright daylight, melatonin levels increase in response to darkness at night, which aids sleep.

Caffeine. Caffeine is a stimulant, which can interfere with falling asleep.

Nicotine. Nicotine is also a stimulant, but quitting smoking itself can lead to transient insomnia. In fact, it has been suggested that if sleeping could be improved during withdrawal from smoking, perhaps it would be easier to quit smoking.

Partner's Sleep Habits. In one survey, 17% of women and 5% of men reported that their partner's sleep habits impaired their own sleep. Snoring can certainly be a factor in a partner's insomnia.

Medications. Insomnia is a side effect of many common medications, including over-the-counter preparations that contain caffeine. People who suspect their medications are causing them to lose sleep should check with their doctors or pharmacists.

Causes of Chronic Insomnia

Sleep problems seem to run in families. About 35% of people with insomnia have a family history of insomnia, with the mother being the most commonly affected family member. Still, because so many factors are involved in insomnia, a genetic component is difficult to define.

Abnormal levels of certain brain chemicals have been observed in some people with chronic insomnia.

Melatonin. Low levels of melatonin, the hormone secreted by the pineal gland, have sometimes been observed in chronic insomnia.
Stress Hormones. Some studies have reported persistently high levels of stress hormones, particularly cortisol, in people with chronic insomnia, particularly insomnia related to aging and psychiatric disorders. High levels of cortisol reduce REM sleep. However, a 2003 study of people with chronic insomnia reported that cortisol levels were high only when their sleep was of poor quality. When they slept well, levels were lower. This study and other research suggests that high levels of stress hormones are caused by poor sleep, rather than being the cause.
Growth Hormone. Normal aging is associated with a blunting of regular, cyclical surges of growth hormone, which may affect sleep as one gets older. This hormone, which is normally secreted in the late night, is associated not only with growth but with deep, slow-wave sleep. (Older people generally have less slow-wave sleep.)

Chronic insomnia occurs in people who have persistently high levels of stress hormones and a shift in the levels of certain immune factors. Studies indicate that people with chronic insomnia have higher levels of interleukin-6 and tumor necrosis factor during the day, but lower levels at night. These immune factors, called cytokines, cause symptoms of fatigue. Levels are usually higher at night in people with healthy sleep. The implications of these immune changes in people with insomnia are not known.

Many cases of chronic insomnia cases have a psychologic or psychiatric basis. The disorders that most often cause insomnia are:

Anxiety.
Depression. Sleep abnormalities are an integral part of depressive disorders, with more than 90% of depressed patients experiencing insomnia.
Bipolar disorder.

Insomnia may also cause emotional problems. It is often unclear which condition has triggered the other, or if the two conditions, in fact, have a common source.

In many cases, it is unclear if chronic insomnia is a symptom of some physical or psychological condition or if it is a primary disorder of its own. In most instances, a mix of psychological and physical conditions causes the insomnia.

Psychophysiologic insomnia occurs when:

An episode of transient insomnia disrupts the person's circadian rhythm.
The patient begins to associate the bed not with rest and relaxation but with a struggle to sleep. A pattern of sleep failure emerges.
Over time, this event repeats, and bedtime becomes a source of anxiety. Once in bed, the patient broods over the inability to sleep, the consequences of sleep loss, and the lack of mental control. All attempts to sleep fail.
Eventually excessive worry about sleep loss becomes persistent and provides an automatic nightly trigger for anxiety and arousal. Unsuccessful attempts to control thoughts, images, and emotions only worsen the situation. After such a cycle is established, insomnia becomes a self-fulfilling prophecy that can persist indefinitely.

Sometimes anxiety and the inability to sleep dates back to childhood when parents used various threats to force their children into sleep for which they may not have been ready.

In one survey, 22% of adults reported that health conditions, pain, or discomfort impaired their sleep. These conditions can include:

Nightly Leg Problems. Leg disorders that occur at night, such as restless legs syndrome or leg cramps, are of special note. They are very common and an important cause of insomnia, particularly in older people.

Medical Problems. Among the many medical problems that can cause chronic insomnia are allergies, arthritis, cancer, fibromyalgia, heart disease, gastroesophageal reflux disease (GERD), hypertension, asthma, emphysema, rheumatologic conditions, Alzheimer's disease, Parkinson's disease, hyperthyroidism, and attention deficit hyperactivity disorder.

Medications. Among the many medications that can cause insomnia are antidepressants (fluoxetine, bupropion), theophylline, lamotrigine, felbamate, beta-blockers, and beta-agonists.

An estimated 10 -15% of chronic insomnia cases result from substance abuse, especially alcohol, cocaine, and sedatives. One or two alcoholic drinks at dinner, for most people, pose little danger of alcoholism and may help reduce stress and initiate sleep. Excess alcohol or alcohol used to promote sleep, however, tends to fragment sleep and cause wakefulness a few hours later. It also increases the risk for other sleep disorders, including sleep apnea and restless legs. Alcoholics often suffer insomnia during withdrawal and, in some cases, for several years during recovery.

Shift work throws off the body's circadian rhythm and may lead to chronic insomnia.

Risk Factors

Studies estimate that between 25 - 33% of adults experience some insomnia each year. In spite of this widespread problem, however, studies suggest that only about 30% of American adults who visit their doctor ever discuss sleep problems. And, doctors seem rarely to ask patients about their sleep habits or problems.

A 2003 study suggested that there were seven significant factors that predicted high risk for insomnia:

Being older
Having conflicts with relatives
Being overworked on the job
Being overworked at home
Having a sick relative
Having low social status
Having a psychiatric or psychologic problem

Stressful events do not cause insomnia in everyone. However, negative thoughts and attitudes toward events can be significant factors in insomnia. In one study, for example, the number of stressful events did not differ between good and poor sleepers. Those with insomnia, however, tended to experience these stressful events more intensively than the healthy sleepers.

In another study, patients with insomnia and good sleepers were asked to record their pre-sleep images using a handheld counter. People with insomnia not only reported fewer images, but their images also tended to be more unpleasant than those of good sleepers. More of the images in people with insomnia were related to intimate relationships and to sleep itself. The images of sleepers were more likely to be random and disconnected.

Studies report that the strongest risk factors for insomnia are psychiatric problems (particularly depression) and physical complaints (such as headaches and chronic pain) that have no identifiable cause (called somatic symptoms). About 90% of people with depression have insomnia. A study presented at the 2005 Associated Professional Sleep Societies meeting indicated that insomnia may contribute to, and prolong, depression. Researchers analyzed data from over 1,800 adults age 65 years and older. Compared with depressed patients who did not have sleep problems, depressed patients with insomnia were 11 times more likely to remain depressed after 6 months and 17 times more likely to still be depressed after a year. The researchers suggested that treating insomnia may help patients recover from depression more quickly.

Overall, insomnia is more common in women than men, although men are not immune from insomnia. Sleep efficiency deteriorates equally in men and women as they get older.

Men. One major study suggested that as men age from 16 - 50, they lose about 80% of their deep sleep. During that period, light sleep increases and REM sleep remains unchanged. (The study did not use women as subjects, and there is some evidence to suggest they are not as affected.) After age 44, REM and total sleep diminish and awakenings increase.

Women. It is not clear why women suffer more from insomnia than men. Some theories include:

In women, a number of hormonal events can disturb sleep, including premenstrual syndrome, menstruation, pregnancy, and menopause. All these conditions are short-term, however, and in most cases the wakefulness associated with them is temporary and can be eliminated with sleep hygiene and time.
After childbirth, most women develop a high sensitivity to the sounds of their children, which causes them to wake easily. Women who have had children sleep less efficiently than women who have not had children. It is possible that many women never unlearn this sensitivity and continue to wake easily long after the children have grown.
Women are at higher risk than men are for depression and anxiety, which are known risk factors for insomnia. In fact, some researchers believe that this is a main reason for the gender differences in insomnia.

After menopause, women are susceptible to the same environmental and biologic causes of insomnia as men. In fact, older women who are not bothered by sleeplessness tend to have longer and better sleep than noninsomniac men their own age.

As people grow older, sleep patterns change. In a major 2003 survey, a third of older adults reported that they woke up frequently during the night. About a quarter of participants reported waking up too early and being unable to go back to sleep. In the same study, 33% of adults age 55 - 64 reported waking up feeling unrefreshed.

Although age itself does not appear to be a risk factor for insomnia, a number of factors may interfere with sleep as one gets older:

Elderly people are more likely to be sedentary than younger adults.
Medical conditions that cause pain or nighttime distress are common in the elderly and pose a high risk for insomnia. They include arthritis, gastrointestinal distress, frequent urination, lung disease, and heart conditions.
Neurologic diseases in the elderly, such as restless legs syndrome, Parkinson's, Alzheimer's, and other forms of dementia can cause nighttime disorientation, confused wandering, and delirium.
Older people often take a number of prescription drugs whose side effects include insomnia.
The elderly are prone to grief, depression, and anxiety, emotional factors that can cause sleeplessness. One study of healthy older adults found that psychologic factors, such as anxiety and depression, were more likely to cause insomnia than illness, medications, or living conditions.
Melatonin levels are generally lower in older people. Some research suggests, however, that elderly people have lower levels simply because they stay mostly indoors and do not receive adequate sunlight.

Lack of sleep at night can lead to excessive sleepiness during the day. A 2006 study reported the following risk factors for excessive daytime sleepiness among the elderly:

Male gender
Sleep apnea or other sleep breathing disorders
Nighttime chest wheezing
Poor sleep quality
Longer time spent in REM sleep
More than 3 episodes of nighttime pain within a week
Medications that cause sleepiness

Sleep loss among the elderly is not inevitable. While older people are more susceptible to many conditions that can cause insomnia, treatments and a healthy lifestyle, particularly regular exercises, are as useful in providing relief to the elderly as to the young. And, a number of studies have found no significant increase in insomnia in older healthy adults.

Shift workers are at considerable risk for insomnia. In a major survey, 65% of shift workers reported one or more symptoms of insomnia at least a few nights a week. Workers over age 50 and those whose shifts are always changing are particularly susceptible to insomnia, although night-shift workers also have a high rate of sleeplessness. One study found that 53% of night-shift workers fall asleep on the job at least once a week, implying that their internal clocks do not adjust to unusual work times. (They are also at much higher risk than other workers for automobile accidents due to their drowsiness and may also have a higher risk for health problems in general.) A Japanese study reporting on different aspects of insomnia found that excessive computer work was associated with all forms of insomnia. People who were over-involved with their work tended to have trouble falling asleep, and they tended to awaken earlier than average.

Among the many conditions that pose a high risk for insomnia are:

Frequent travel, particularly crossing time lines
Post-traumatic stress syndrome
Brain injuries
Many chronic medical conditions ranging from seemingly minor ones, such as tinnitus (ringing in the ears) to major conditions, such as respiratory problems, heart disease, or being on dialysis

Prognosis

A 2002 study of sleeping habits in over 1 million people reported that people who slept 7 hours a night lived the longest. People who slept more than 8 hours or less than 6 hours, or who took sleeping pills, had lower survival rates.

Insomnia is not life-threatening, except in very rare cases, such as in those who have the genetic disorder called fatal familial insomnia. This rare degenerative brain disease develops in late adulthood.

Sleepiness causes as many as 200,000 automobile accidents in the U.S. and 1,500 deaths from such accidents. Studies indicate that drowsy driving is as risky as drunk driving. In a major 2003 survey, 60% of young adults reported driving while drowsy, and 20% dosed off while driving. In the study, 1% of adults who dozed off reported having an accident because of it. (One study strongly suggested that it is habitual sleepiness, however, and not just being sleepy at the time of an accident that places people at higher risk.)

Surveys show that people with severe insomnia have a quality of life that is almost as poor as those who have chronic conditions, such as heart failure. In addition to more daytime sleepiness, people with insomnia complain of more attention and memory problems compared to good sleepers.

Insomnia can also lead to irritability, mistakes at work, and poorer relationships.

Effect on Thinking and Performance. Studies suggest that insomnia makes it harder to concentrate and perform tasks.

Reduced concentration. Deep sleep deprivation impairs the brain's ability to process information.
Impaired task performance. One study reported that missing only 2 - 3 hours of sleep every night for a week significantly impaired performance and mood. An Australian study reported that 17 hours of sleep deprivation causes impaired performance levels comparable to those found in people who have blood alcohol levels indicating intoxication.
Memory problems. Whether insomnia significantly impairs learning is unclear. Some studies have reported problems in memorization, although others have found no differences in test scores between people with temporary sleep loss and those with full sleep.

Insomnia and Depression. Although stress and depression are major causes of insomnia, insomnia may also increase the activity of the hormones and pathways in the brain that can produce emotional problems. Research indicates that chronic insomnia can increase the risk of developing depression and anxiety. Some investigators are exploring the possibility of preventing psychiatric disorders by early recognition and treatment of insomnia.

Even modest alterations in waking and sleeping patterns can have significant effects on a person's mood. In both children and adults, the combination of insomnia and daytime sleepiness can produce more severe depression than either condition alone.

Effects on the Heart. Although there has been some concern that insomnia may increase the risk for heart problems, little evidence has supported any significant dangers. One study reported signs of heart and nervous system activity in people with chronic insomnia that might place such individuals at risk for coronary heart disease. If it exists, however, this increased danger is very modest compared with other risk factors for heart disease. Yet another report suggested that sleep complaints in elderly people without coronary artery disease predicted a first heart attack. Sleep disorders in such cases may have been a marker for depression, however, which is a risk factor for heart attacks in elderly people.

Effects on Weight. Lack of sleep can cause weight gain and obesity. In a 16-year study of over 68,000 women, those who slept no more than 5 hours a night were 32% more likely to gain at least 33 pounds, and those who slept 6 hours had a 12% increased risk of weight gain compared to women who slept at least 7 hours a night.

Effects on the Immune System. A 2003 study reported significant differences in immune factors among sleepers, with higher levels of certain infection-fighters observed in good sleepers than in people with chronic insomnia. The significance of these findings is still unknown, however.

Diagnosis

Diagnosing sleep disturbance and its cause is the most important step in restoring healthy sleep. However, there is little agreement, even among experts, on the best methods for effectively assessing a patient's insomnia.

A major difficulty in diagnosing this problem is its subjective nature. One study showed that there was no difference in sleep behaviors between people who said they were insomniacs and people who said they weren't. People who believe they have insomnia may have actually had frequent brief awakenings during sleep that they perceive as being continuously awake.

A number of questionnaires are available for determining whether a patient has insomnia or other sleep disorders. For example, the doctor may ask:

How would you describe your sleep problem?
How long have you had the sleep problem?
How long does it take to fall asleep?
How many times a week does it occur?
How restful is sleep?
Do you have trouble falling asleep or do you wake up too early?
What is the sleep environment like (Noisy? Not dark enough?)?
How does insomnia affect daytime functioning?
What medications do you take? (Include herbs, alcohol, and over-the-counter or prescription drugs.)
Are you taking or withdrawing from stimulants, such as coffee or tobacco?
How much alcohol is consumed per day?
What stresses or emotional factors may be present?
Have you experienced any significant life changes?
Do you snore or gasp during sleep (an indication of sleep apnea)?
Do you have leg problems (cramps, twitching, crawling feelings)?
If there is a bed partner? Is this person's behavior distressing or disturbing?
Are you a shift worker?

Sleep Diary. If the patient cannot answer these questions, keeping a sleep diary is a helpful diagnostic tool. Every day for 2 weeks, the patient should record all sleep-related information, including responses to questions listed above described on a daily basis. A bed partner can help by adding their observations of the patient's sleep behavior.

The Epworth Sleepiness Scale. The Epworth Sleepiness Scale (ESS) uses a simple questionnaire to measure excessive sleepiness during eight situations.


Situation	Chance of Dozing 0 = no chance of dozing 1 = slight chance of dozing 2 = moderate chance of dozing 3 = high chance of dozing
Sitting and reading.	(Indicate a score of 0 to 3)
Watching TV.	(Indicate a score of 0 to 3)
Sitting inactive in a public place (e.g., a theater or a meeting).	(Indicate a score of 0 to 3)
As a passenger in a car for an hour without a break.	(Indicate a score of 0 to 3)
Lying down to rest in the afternoon when circumstances permit.	(Indicate a score of 0 to 3)
Sitting and talking to someone.	(Indicate a score of 0 to 3)
Sitting quietly after a lunch without alcohol.	(Indicate a score of 0 to 3)
In a car, while stopped for a few minutes in traffic.	(Indicate a score of 0 to 3)
Score Results	1-6: Getting enough sleep 4-8: Tends to be sleepy but is average. 9-15: Very sleepy and should seek medical advice. Over 16: Dangerously sleepy

Multiple Sleep Latency Test. The multiple sleep latency test (MSLT) uses a machine to measure the time it takes to fall asleep while lying in a quiet room during the day:

The patient takes four or five scheduled naps 2 hours apart.
People with healthy sleep habits fall asleep in about 10 - 20 minutes.
The test can detect changes in sleepiness associated with sleep deprivation in patients with insomnia.

It has limitations, however, and does not take into consideration any situations that may affect the patients' mental state and the actual home situation. The test is used mainly after other sleep disorders have been ruled out and the doctor is uncertain whether or not insomnia is a correct diagnosis.

If unexplained insomnia persists after treatment or there is evidence of a primary sleep disorder, such as sleep apnea or narcolepsy, the doctor may recommend a sleep specialist or a sleep disorders center. Centers are accredited by the American Academy of Sleep Medicine. Patients should investigate centers carefully, to be sure that they offer full sleep studies.

Among the signs that may indicate a need for a sleep disorders center are:

Insomnia due to psychologic disorders
Sleeping problems due to substance abuse
Snoring and sudden awakening with gasping for breath (possible sleep apnea)
Severe restless legs syndrome
Persistent daytime sleepiness
Sudden episodes of falling asleep during the day (possible narcolepsy)

At most sleep disorders centers, patients undergo an in-depth analysis, usually supervised by a multidisciplinary team of consultants who can provide both physical and psychiatric evaluations.

Treatment

The American Academy of Sleep Medicine (AASM) recommends cognitive behavioral therapy (CBT) and prescription medications as the main treatments for insomnia. According to the AASM, these treatment options can improve both quality and quantity of sleep for people with insomnia.

Experts agree that behavioral therapies should be the first-line treatment for insomnia. For children in particular, medications should rarely be used as initial treatment. A 2006 study reported that behavioral interventions can provide sustained improvement in over 80% of children with insomnia.

Prevention of sleeplessness depends upon the patient's ability to learn how to relax and sleep well. A number of behavioral methods are aimed at achieving these goals. Behavioral techniques can actually cure chronic insomnia in many cases and studies report that they help nearly all patients with primary chronic insomnia. The benefits of psychological and behavioral therapy in managing insomnia are long-lasting.

Although medications are equally effective for helping people with insomnia to sleep, they cannot cure the condition. In addition, behavioral methods act faster. Behavioral methods work in all age groups, including children and elderly patients.

Behavioral methods include:

Stimulus control
Cognitive behavioral therapy
Progressive muscle relaxation
Paradoxical intention
Biofeedback
Sleep restriction
Imagery tasks

Studies have reported that between 70 - 80% of patients who are treated with non-drug methods experience improved sleep with an average treatment duration of only 5 hours over a 4-week period. Furthermore, studies report that 75% of those who have been taking drugs are able to stop or reduce their use.

Proper sleep hygiene is the first step and should accompany any behavioral method. A number of behavioral approaches are available, but all have the same basic goals:

To reduce the time it takes to go to sleep to below 30 minutes
Reduce wake-up periods during the night

Stimulus Control. Stimulus control is now considered the standard treatment for primary chronic insomnia and may be helpful for some patients with secondary insomnia as well. The primary goal of stimulus control is to regain the idea that the bed is for sleeping. It involves the following:

Go to bed only when ready to sleep or for sex.
If unable to sleep within 15 - 20 minutes, get up and go into another room. (People who find it physically difficult to get out of bed should sit up and do something relatively arousing, like reading a book.)
Maintain a regular wake-up time no matter how few hours you actually sleep.
Avoid naps.

Cognitive-Behavioral Therapy. Cognitive behavioral therapy (CBT) is a form of therapy that emphasizes observing and changing negative thoughts about sleep such as, "I'll never fall asleep." It uses actions intended to change behavior. A 2004 study of young and middle-aged adults suggested that CBT is more effective than medication in treating chronic insomnia, and should be considered as a first-line intervention. Adding medication to CBT did not provide additional benefit. In a 2006 study of older adults, CBT worked better than zopiclone (Imovane) in managing chronic insomnia. [Zopiclone is a European sleep medication that is similar to the American drug eszopiclone (Lunesta).] Compared to zopiclone or placebo, CBT helped patients spend less time awake at night. The benefits of 6 weeks of weekly CBT sessions lasted for 6 months.

Progressive Muscle Relaxation. Progressive muscle relaxation is another technique for inducing sleep that works well for many people. It takes about 10 minutes to perform:

Focus on one specific muscle group at a time. Most people start with the muscles in one foot. Inhale and tense the foot muscles for about 8 seconds. (Do this gently. It is not intended to cause severe pain or muscle contractions.)
Relax the foot, and let it become loose and limp. Stay relaxed for 15 seconds, then repeat with the other foot.
Move up to the next muscle group and repeat the sequence, doing one side of the body at a time. Move progressively from each foot and leg up through the abdomen and chest, to each hand and arm, then to the neck, shoulders, and face.

Paradoxical Intention. Paradoxical intention is a psychological approach that is based on doing the opposite of what one wants or fears and takes it to the extreme. The first step is to make a plan to take such a paradoxical approach to insomnia.

Instead of going through activities leading to sleep, the patient prepares for staying awake and doing something energetic.
In some cases, people may take specific psychological barriers to sleep to an extreme limit. For example, if worry is a factor in insomnia, the patient intensifies the worries.

Biofeedback. Biofeedback is also effective, but requires being monitored with an electroencephalogram (EEG), a device that measures brain waves. Patients are given feedback to recognize certain states of tension or sleep stages so that they can either avoid or repeat them voluntarily.

Sleep Restriction Therapy. Sleep restriction therapy may be effective, although evidence is inconclusive. In a 2001 study, patients practiced sleep hygiene and sleep restriction. Sleep hygiene was very helpful during the first 2 months while sleep restriction led to sustained benefits and deeper sleep. The approach is a systematic method for achieving sleep and restricting the time spent in bed.

The first step is to calculate a person's sleep efficiency number:

Keep a sleep diary for 14 days. Calculate the average hours of actual sleep and hours in bed. Then divide the average hours slept by the hours spent in bed. The result, given as a percentage, is the sleep efficiency number. (For example, if a patient sleeps an average of 5 hours out of 7 hours spent in bed then the result is .714, and the sleep efficiency percentage is 71%.)
The patient's goal is to achieve sleep efficiencies of between 85 - 90%, which means only 10 - 15% of the time is spent staying awake in bed. (Sleep efficiency in older people normally falls between 75 - 85%.)

To achieve this goal, the patient takes the following actions:

Begin by going to bed 15 minutes later than usual the first week.
If 85% sleep efficiency isn't reached by the end of the week, add another 15 minutes before going to bed. Refrain from going to bed even if tired, although bedtime should not be reduced below 5 hours.
Once efficiency reaches 90% or more, begin to go to bed 15 minutes earlier each week.

Other parts of the program include stopping any sleep medications and following good sleep hygiene. People using this treatment have reported lasting improvements after just 8 weeks, and studies suggest that it is significantly more successful than relaxation techniques.

Imagery Tasks. A 2002 study enrolled people whose chronic insomnia was associated with unwanted thoughts and worries. They were given specific positive mental tasks that gave them a sense of positive control (as opposed to their real life concerns, which felt out of their control). These images distracted them and allowed them to fall asleep faster. In support of this approach, another study evaluated patients with insomnia who were given a problem before sleep. One group was asked to think of the problem in images and the other in words. The group who used imagery fell asleep more quickly and woke up with less anxiety.

Sleep Hygiene. The term sleep hygiene is used to describe simple behaviors that may help everyone improve their sleep.

Establish a regular time for going to bed and getting up in the morning. Stick to this schedule even on weekends and during vacations.
Use the bed for sleep and sexual relations only, not for reading, watching television, or working. Excessive time in bed disrupts sleep.
Avoid naps, especially in the evening.
Exercise before dinner. A low point in energy occurs a few hours after exercise; sleep will then come more easily. Exercising close to bedtime, however, may increase alertness.
Take a hot bath about 1.5 - 2 hours before bedtime. This alters the body's core temperature rhythm and helps people fall asleep more easily and more continuously. (Taking a bath shortly before bed increases alertness.)
Do something relaxing in the 30 minutes before bedtime. Reading, meditation, and a leisurely walk are all appropriate activities.
Keep the bedroom relatively cool and well ventilated.
Do not look at the clock. Obsessing over time will just make it more difficult to sleep.
Eat light meals, and schedule dinner 4 - 5 hours before bedtime. A light snack before bedtime can help sleep, but a large meal may have the opposite effect.
Spend a half hour in the sun each day. The best time is early in the day. (Take precautions against overexposure to sunlight by wearing protective clothing and sunscreen.)
Avoid fluids just before bedtime so that sleep is not disturbed by the need to urinate.
Avoid caffeine in the hours before sleep.
If one is still awake after 15 - 20 minutes, go into another room, read or do a quiet activity using dim lighting until feeling very sleepy. (Don't watch television or use bright lights.)
If distracted by a sleeping bed partner, moving to the couch or a spare bed for a couple of nights might be helpful.
If a specific worry is keeping one awake, thinking of the problem in terms of images rather than in words may allow a person to fall asleep more quickly and to wake up with less anxiety.

Exercise may be one of the best ways to promote healthy sleep. One study found that exercise is as good for inducing sleep as the use of benzodiazepines, a prescription sleep aid. Some research has found that yoga practice may have specific benefits on sleep health. Yoga uses meditation, deep breathing techniques, and movements that emphasize stretching and balance.

The circadian rhythm is more a function of darkness and light rather than actual time of day. Bright light can discourage drowsiness, and darkness can cause sleepiness, day or night. The use of a special box that gives off very bright fluorescent light (over 4,000 lux) for about 30 minutes each day may be helpful.

The following people might benefit from light therapy:

Shift workers. Light therapy should be maximized during hours they are at work and minimized when they need to sleep.
Frequent travelers. Light therapy may be useful for adjusting to new time zones and reducing jet lag.
Nursing home patients.
People with delayed sleep-phase syndrome. These people have a natural tendency to fall asleep very late at night or in early morning hours, but then sleep normally.

Patients should check with their doctors before using light therapy. The following people should avoid light therapy or use it only under a doctor's direction:

Anyone with eyes or skin that are highly sensitive to light
Anyone taking medications that increase the risk for photosensitivity
People with bipolar disorder

Timing of the therapy depends on the type of insomnia or sleep schedule of the individual. For example, in people who cannot get to sleep at night, light therapy in the morning and restricting bright light at night may be helpful. People who wake up early in the morning may benefit from light therapy performed in the evening, although a 2002 study reported that it had no effect in this group. Some light boxes have dawn/dusk simulators that help determine the correct brightness.

Medications

According to a major 2003 survey, about 20% of American older adults use some form of sleep aid, including prescription or over-the-counter drugs or alcohol. Furthermore, 15% use such aids every night.

However, while behavioral or psychologic techniques can actually cure insomnia, prolonged use of sleeping pills can only result in dependency.

In general, the following precautions are important:

Start with non-prescription medication.
Drugs used specifically for improving sleeping are called sedative hypnotics. These drugs include benzodiazepines and non-benzodiazepines. Until recently benzodiazepines were most commonly prescribed, but newer non-benzodiazepines may be better tolerated and have less risk of dependency. These medicines, however, may be associated with potentially severe allergic reactions, such as anaphylaxis and facial swelling (angioedema). These medicines may also cause hazardous behaviors, such as driving, making phone calls, or eating while asleep. If you need to take one of these prescription drugs, start with as low a dose as possible.
For adults over age 60 years, studies suggest that the risks of sedative hypnotics may far outweigh their benefits.
As a general rule, do not take either prescription nor non-prescription sleeping pills on consecutive days or for more than 2 - 4 days a week.
If insomnia is still a problem after stopping the drug and continuing with good sleep hygiene, this pattern can be repeated again, but for only up to 4 weeks.
Medication should be withdrawn gradually, and the patient should be aware of the possibility of rebound insomnia after stopping medication.
Alcohol intensifies the side effects of all sleeping medication and should be avoided.
If chronic insomnia is a companion to depression or anxiety, treating these problems first may be the best approach.

Brands with Antihistamines. Many over-the-counter sleeping medications use antihistamines, which cause drowsiness. Diphenhydramine is the most common antihistamine used non-prescription sleep aids. Some drugs contain diphenhydramine alone (Nytol, Sleep-Eez, Sominex), while others contain combinations of diphenhydramine with pain relievers (Anacin P.M., Excedrin P.M., Tylenol P.M.). Doxylamine (Unison) is another antihistamine used in sleep medications. Certain antihistamines indicated only for allergies, such as chlorpheniramine (Chlor-Trimeton), diphenhydramine (Benadryl), or hydroxyzine (Atarax or Vistaril) may also be used as mild sleep-inducers.

Unfortunately, most of these drugs leave patients feeling drowsy the next day and may not be very effective in providing restful sleep. Side effects include:

Daytime sleepiness
Dizziness
Drunken movements
Blurred vision
Dry mouth and throat

In general, these drugs should be avoided by people with angina, heart arrhythmias, glaucoma, or problems urinating. They should not be used at the same time as medications that prevent nausea or motion sickness. Some non-prescription sleeping aids, such as those containing doxylamine, should also be avoided by patients with chronic lung disease.

Common Pain Relievers. When sleeplessness is caused by minor pain, simply taking acetaminophen (Tylenol) or a non-steroidal anti-inflammatory drug (NSAID) such as ibuprofen (Advil, Motrin), can be very helpful without causing any daytime sleepiness. The extra "P.M." antihistamine found in combination products is simply an extra, needless chemical in these situations.

Benzodiazepines, also referred to as benzodiazepine receptor agonists (BzRAs), were once the most commonly prescribed sedative hypnotics. Originally developed in the 1960s to treat anxiety, these drugs nonselectively target receptor sites in the brain that modulate the effects of the neurotransmitter gamma-aminobutyric acid (GABA).

Brands. Commonly prescribed benzodiazepines:

Long-acting benzodiazepines include flurazepam (Dalmane) and clonazepam (Klonopin), quazepam (Doral).
Medium- to short-acting benzodiazepines include triazolam (Halcion), lorazepam (Ativan), alprazolam (Xanax), temazepam (Restoril), oxazepam (Serax), prazepam (Centrax), estazolam (ProSom), and flunitrazepam (Rohypnol). Short-acting benzodiazepines may be useful for air travelers who want to reduce the effects of jet lag.

Side Effects. Elderly people are more susceptible to side effects and should usually start at half the dose prescribed for younger people. They should not take long-acting forms.

Side effects may differ depending on whether the benzodiazepine is long- or shorting acting. They include:

Severe allergic reactions, including facial swelling, can occur even with the first use of a benzodiazepine drug.
Respiratory problems may occur with overuse or in people with pre-existing respiratory illness
The drugs may increase depression, a common co-condition in many people with insomnia.
Respiratory depression may occur with overuse or with people with pre-existing respiratory illness.
Long-acting drugs have a very high rate of residual daytime drowsiness compared to other types of sleeping pills. They have been associated with a significantly increased risk for automobile accidents and falls in the elderly, particularly in the first week after taking them. Shorter-acting benzodiazepines do not appear to pose as high a risk.
Memory loss (so-called traveler's amnesia), sleepwalking, sleep driving, eating while asleep and other odd mood states may occur. These effects are enhanced by alcohol.
Incontinence. In one study, 33% of patients experienced incontinence at least twice a week. The risk is highest in the elderly and with older, long-acting drugs.
Because these drugs cross the placenta and enter breast milk, pregnant women or nursing mothers should not use them. Benzodiazepine use in the first trimester of pregnancy may be associated with the development of cleft lip in newborns.
In rare cases, overdoses have been fatal.

Interactions. Benzodiazepines are potentially dangerous when combined with alcohol. Some medications, like the ulcer medication cimetidine, can slow the metabolism of the benzodiazepine.

Withdrawal Symptoms. Withdrawal symptoms usually occur after prolonged use and indicate dependence. They can last 1 - 3 weeks after stopping the drug and may include:

Gastrointestinal distress
Sweating
Disturbed heart rhythm
In severe cases, patients might hallucinate or experience seizures, even a week or more after the drug has been stopped.

Rebound Insomnia. Rebound insomnia, which often occurs after withdrawal, typically includes 1 - 2 nights of sleep disturbance, daytime sleepiness, and anxiety. In some cases, patients may experience the return of the original severe insomnia. The chances for rebound are higher with the short-acting benzodiazepines than with the longer-acting ones.

Newer short-acting non-benzodiazepines can induce sleep with fewer side effects than the benzodiazepines. Both benzodiazepine and non-benzodiazepine sedative hypnotics act on GABA-A receptor sites in the brain, but non-benzodiazepines are more specific in the subunits they target. Developed in the late 1980s, these drugs are increasingly prescribed and are becoming the hypnotics of choice for many doctors.

Brands and Benefits. Non-benzodiazepine hypnotics currently approved in the United States are zolpidem (Ambien, Ambien CR), zaleplon (Sonata), eszopiclone (Lunesta), and ramelteon (Rozerem).

Zolpidem (Ambien, generic) is one of the most commonly prescribed drugs for insomnia. It lasts longer than zaleplon. Patients should not take it unless they plan on getting at least 7 - 8 hours of sleep. The recommended dose is 10 mg/day for adults, although elderly patients may be prescribed half that dose. A 2002 study suggested that the drug might be used on an as-needed basis, with up to 5 tablets taken a week. After 3 weeks, two-thirds of the patients taking zolpidem this way were able to reduce their tablet intake by more than 25% without losing improvements in sleep. Ambien CR, an extended-release form, received approval from the Food and Drug Administration (FDA) in late 2005. It is the first extended-release prescription medicine for insomnia. The medicine is delivered in two steps. The first layer dissolves quickly, allowing the patient to fall asleep. The second layer helps the patient stay asleep.
Zaleplon (Sonata) is the shortest-acting hypnotic available. Because it is rapidly eliminated from the body it may be best for people who have difficulty falling asleep, not those who wake up often throughout the night. The drug takes effect within 30 minutes and may be taken at bedtime or later as long as the patient can sleep for at least 4 hours. The recommended dose is 5 - 10 mg/day. The drug is usually taken for 7 - 10 days.
Eszopiclone (Lunesta) is a newer, non-benzodiazepine hypnotic approved by the FDA in 2004. It may help improve both sleep maintenance and daytime alertness. Eszopiclone is related to zopiclone (Imovane), which has been used for many years in Europe. Unlike other sleep medications, eszopiclone can be taken on a long-term basis. In clinical trials, patients used eszopiclone for up to 6 months. Recommended doses are 2 - 3 mg/day for adults and 2 mg/day for elderly patients. Patients whose main problem is falling asleep may need only 1 mg/day.
Ramelteon (Rozerem) was approved by the FDA in 2005. Ramelteon is a novel non-benzodiazepine hypnotic. Unlike most sleep drugs, which target the gamma-aminobutyric acid (GABA) receptors, ramelteon targets the MT1 and MT2 receptors. Ramelteon does not cause dependence and is the first sleep drug not designated as a controlled substance.

These drugs can be particularly helpful for preventing jet lag (but zolpidem should not be used on flights less than 7 - 8 hours). They also may be helpful for people who also have accompanying mood disorders, such as depression or post-traumatic stress disorder. Because they are short-acting, zaleplon and zolpidem may pose fewer risks for falls and memory loss in elderly patients. In general, these drugs are recommended for short-term use (7 - 10 days) and treatment should not exceed 4 weeks. No studies have yet confirmed safety for longer-term use.

Side Effects. All of these drugs have fewer morning side effects than the benzodiazepines, including morning sedation and memory loss (although they can occur to some degree). Zolpidem’s (Ambien) record of adverse effects is similar to that of triazolam (Halcion), the short-acting benzodiazepine. Zaleplon (Sonata) and Ramelteon (Rozerem) appear to have less severe morning side effects. When patients first start taking any of these drugs, they should use caution during morning activities until they are sure how the drug affects them.

General side effects are mild but may include:

Drowsiness
Dizziness
Fatigue
Headache
Unpleasant taste
Diarrhea

Rarer side effects may include sleepwalking and hallucinations. In 2006, reports emerged of zolpidem (Ambien) causing sleepwalking and, even more bizarrely, sleep-driving. Most of these cases likely were due to patients using zolpidem along with alcohol or other drugs or taking more than the recommended dose. However, in March 2007, the FDA ordered stronger warning labels for zolpidem and all other non-benzodiazepine drugs. The new labels warn that that these drugs can cause sleep-related behavior, including sleep-driving, making phone calls, and preparing and eating food while asleep. In addition, severe allergic reactions (anaphylaxis) and facial swelling (angioedema) can occur even the first time one of these drugs is taken.

Anyone who receives a prescription for these medicines will also get a patient medication guide explaining the risks of the drugs and the precautions to take. Talk to your doctor if you have any questions concerning these drugs or their potential side effects.

Patients should carefully read the information labels for all drugs and follow the directions. Some sleeping pills take 30 - 60 minutes to take effect, while others (such as zolpidem) are fast-acting. For zolpidem, patients should:

Take zolpidem immediately before going to sleep
Take zolpidem only when able to get a full night’s sleep (7 – 8 hours)
Not drink alcohol the same evening
Not take more than the prescribed dose
Use caution in the morning when getting out of bed, driving, or operating heavy machinery

Interactions. As with any hypnotics, alcohol increases the sedative effects of these drugs. These hypnotics also interact with other drugs, including rifampin, ketoconazole, erythromycin, and cimetidine. They may also interfere or be interfered by other drugs. Patients should report all medications to their doctors.

Dependency, Withdrawal Symptoms, and Rebound Insomnia. The risk for rebound insomnia, dependence, and tolerance is lower with non-benzodiazepine hypnotics than with benzodiazepine drugs. These drugs are still subject to abuse. In any case, no hypnotic should be taken for more than 7 - 10 days or at higher than the recommended dose without a doctor's approval.

Antidepressants are sometimes used to treat insomnia that may be caused by depression (secondary insomnia). In addition, some antidepressants with sedating properties are prescribed for the treatment of primary insomnia. For example, trazodone has been frequently prescribed in low doses as a hypnotic to help induce sleep. However, there are few studies that address its safety and efficacy as a drug for treating insomnia in non-depressed patients. Several studies have warned against trazodone's use in elderly patients, due to its risk for side effects (daytime sleepiness, dizziness, priapism) and drug interactions. In fact, all hypnotics can have serious side effects in the elderly, and all must be used with caution.

Chloral Hydrate. Chloral hydrate has been in use since 1832. It has significant adverse effects, however, and most experts believe it no longer has a role in the treatment of insomnia. In any case, it does not appear to be effective in the elderly. Chloral hydrate poses a risk for addiction, and it can be fatal in overdose. It also has cancer-causing properties. Side effects include irritation of the skin, mucous membranes, and stomach. People with stomach, heart, kidney, or liver disorders should not take this drug at all. If a child is given it (usually for minor surgery), that child should never be given chloral hydrate again in their lifetime.

Barbiturates. Barbiturates (Seconal, Nembutal) were the standard sleeping medications before the introduction of benzodiazepines. Overdose is dangerous and frequent; addiction and abuse are common. These drugs should rarely or never be prescribed for insomnia.

Indiplon. The FDA is reviewing indiplon, a new non-benzodiazepine hypnotic.

According to results from a national survey published in 2006 in the Archives of Internal Medicine, more than 1.6 million Americans use complementary and alternative therapies to treat insomnia. Many people choose herbal and dietary supplement remedies. Some, such as chamomile tea or lemon balm, are generally harmless for most people. Others have more serious side effects and interactions. [See Box.] According to a 2007 study, valerian and melatonin are among the most popular alternative remedies for insomnia.

Although about half of people who use herbal medicine report that these products help their sleep, experts are not sure whether these remedies really work or whether a placebo effect is the main reason for the improvement. The American Academy of Sleep Medicine (AASM) states that there is only limited scientific evidence to show that herbal and dietary supplements are effective sleep aids. The AASM recommends that these products should be taken only if approved by a doctor. Be sure to talk to your doctor if you are considering taking any herbal or dietary supplement. Some of these products can interact with prescription medications.

Melatonin is the most studied natural remedy for insomnia. A 2005 analysis of 17 melatonin studies found that melatonin significantly reduced the time to fall asleep (sleep onset) and the time spent asleep (sleep duration). However, there are no consistent standards on melatonin doses. Some research suggests that 0.3 mg may be the most effective dosage in many people with insomnia. However, higher doses may keep some people awake.

Although melatonin may not have many benefits for most people with chronic insomnia, studies suggest that it may help the following individuals:

Elderly people. It may help certain older people with insomnia, such as those with evidence of low melatonin levels and those dependent on prescription sleeping medications. It is not clear, however, how significant the benefits are.
People without sight. A 2000 study reported that melatonin can help people without sight retrain their circadian cycle so that they can sleep at regular hours. The best dosages and timing, however, need to be clarified.
Travelers suffering jet lag. Some studies have reported that melatonin may help prevent jet lag in some travelers.
Those in withdrawal from prescription sleep medication. Melatonin may help people who are dependent on sleeping medications withdraw from these drugs and maintain good quality sleep.
People with delayed sleep syndrome. It might be somewhat helpful for people who fall asleep very late at night or in early morning hours but then sleep normally.
Children. Melatonin may help some children with chronic insomnia. In one small study, or example, melatonin was specifically helpful for children with Asperger syndrome, who are at risk for sleep disturbances. More research is warranted, however. At this time, no one should give their child melatonin without a doctor's recommendation.

Melatonin is a powerful hormone that can have major effects on all parts of the body. Doses of melatonin over 0.3 mg can disrupt the circadian system in the brain. Long-term consequences are unknown. High doses have been associated with the following adverse events:

Mental impairment
Severe headaches
Nightmares

Interactions with other drugs are not completely known. Melatonin is classified as a dietary supplement and not as a drug, so its quality is not regulated in the U.S.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Patients should always check with their doctors before using any herbal remedies or dietary supplements.

The following are special concerns for people taking natural remedies for insomnia:

Chamomile. Many people drink chamomile tea for its sedative properties. Although it is generally safe, it may cause allergic reactions in people who have plant or pollen allergies.

Valerian root. Valerian is an herb that has sedative qualities and has been helpful in people with insomnia. One study reported that it was also useful for helping patients withdraw from benzodiazepines -- the standard prescription sleeping pills. In another study, 83% of patients rated the effects of valerian on sleep as being very good. In the same study, valerian was as effective as oxazepam, a standard prescription sleeping medication. Valerian's side effects may include vivid dreams. High doses of valerian can cause blurred vision, excitability, and changes in heart rhythm. Valerian's effects can be dangerously increased if it is used with standard sedatives.

Chinese Herbal Remedies. Studies suggest that up to 30% of herbal patent remedies imported from China are laced with potent pharmaceuticals such as phenacetin and steroids. They may also contain toxic metals. The herbal remedy Sleeping Buddha was recalled in 1998 because it contained a benzodiazepine, the major ingredient in many prescription sleeping pills, and also appeared to increase the risk for birth defects in pregnant women. Reports of a few cases of acute hepatitis have occurred from Jin Bu Huan, a Chinese herbal remedy sold as treatment for pain and insomnia.

Kava. Kava has been used to relieve anxiety and improve sleep. It is not considered safe. There have been reports of liver failure and death from this herb, with highest risk in those with liver disease. Other side effects include itchy, scaly skin, muscle weakness, and problems with coordination. It also interacts dangerously with certain medications, including alprazolam, an anti-anxiety drug. Kava also increases the strength of certain other drugs, including other sleep medications, alcohol, and antidepressants.

Tryptophan and 5-L-5-hydroxytryptophan (HTP). Tryptophan is an amino acid used in the formation of the neurotransmitter serotonin, which is known to promote well-being and has been associated with healthy sleep. L-tryptophan was marked for insomnia and other disorders but was withdrawn from the market after contaminated batches caused a rare and even fatal disorder called eosinophilia myalgia syndrome. 5-HTP, a byproduct of tryptophan, is still available as a supplement. There have been reports that some brands contain a substance called Peak X, which may be harmful. There is little evidence that 5-HTP relieves insomnia.

Resources

www.aasmnet.org -- American Academy of Sleep Medicine
www.nhlbi.nih.gov/about/ncsdr -- National Center for Sleep Disorders Research
www.sleepfoundation.org -- National Sleep Foundation
www.sleepeducation.com -- Sleep Education from the American Academy of Sleep Medicine
www.wfsrs.org -- World Federation of Sleep Research Societies
www.clinicaltrials.gov -- Find clinical trials

References

Bliwise DL, Ansari FP. Insomnia associated with valerian and melatonin usage in the 2002 National Health Interview Survey. Sleep. 2007 July 1;30(7):881-884.

Liu X, Buysse DJ, Gentzler AL, Kiss E, Mayer L, Kapornai K, et al. Insomnia and hypersomnia associated with depressive phenomenology and comorbidity in childhood depression. Sleep. 2007 Jan 1;30(1):83-90.

Mindell JA, Emslie G, Blumer J, Genel M, Glaze D, Ivanenko A, et al. Pharmacologic management of insomnia in children and adolescents: consensus statement. Pediatrics. 2006 Jun;117(6):e1223-32.

Mindell JA, Kuhn B, Lewin DS, Meltzer LJ, Sadeh A; American Academy of Sleep Medicine. Behavioral treatment of bedtime problems and night wakings in infants and young children. Sleep. 2006 Oct 1;29(10):1263-76.

Morin CM, Bootzin RR, Buysse DJ, Edinger JD, Espie CA, Lichstein KL. Psychological and behavioral treatment of insomnia: update of the recent evidence (1998-2004). Sleep. 2006 Nov 1;29(11):1398-414.

Neckelmann D, Mykletun A, Dahl AA. Chronic insomnia as a risk factor for developing anxiety and depression. Sleep. 2007 July 1;30(7):873-880.

Pearson NJ, Johnson LL, Nahin RL. Insomnia, trouble sleeping, and complementary and alternative medicine: Analysis of the 2002 National Health Interview Survey data. Arch Intern Med. 2006 Sep 18;166(16):1775-82.

Review Date:
7/18/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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Melatonin

FitSugar — Wed, 08 Oct 2008 17:35:26 -0700

Overview

Overview
Uses
Available Forms
How to Take It
Precautions
Possible Interactions
Supporting Research

HEALTH GUIDE REFERENCE FROM A.D.A.M

Overview

Melatonin is a hormone secreted by the pineal gland in the brain that helps regulate other hormones and maintains the body's circadian rhythm. The circadian rhythm is an internal 24-hour time-keeping system that plays a critical role in determining when we fall asleep and when we wake up. Darkness stimulates the production of melatonin while light suppresses its activity. Exposure to excessive light in the evening or too little light during the day can disrupt the body’s normal melatonin cycles. For example, jet lag, shift work, and poor vision can disrupt melatonin cycles. In addition, some experts claim that exposure to low-frequency electromagnetic fields (common in household appliances) may disrupt normal cycles and production of melatonin.

Melatonin also helps control the timing and release of female reproductive hormones. It helps determine when menstruation begins, the frequency and duration of menstrual cycles, and when menstruation ends (menopause).

Many researchers also believe that melatonin levels are related to the aging process. For example, young children have the highest levels of nighttime melatonin. Researchers believe these levels diminish as we age. In fact, the decline in melatonin may explain why many older adults have disrupted sleep patterns and tend to go to bed and wake up earlier than when they were younger. However, emerging research calls this theory into question.

In addition to its hormonal actions, melatonin has strong antioxidant effects. Preliminary evidence suggests that it may help strengthen the immune system.

If you are considering using melatonin supplements, talk to your doctor.

Uses

Insomnia

Studies suggest that melatonin supplements may help induce sleep in people with disrupted circadian rhythms (such as those suffering from jet lag or poor vision or those who work the night shift) and those with low melatonin levels (such as some elderly and individuals with schizophrenia). A review of clinical studies suggests that melatonin supplements may help prevent jet lag, particularly in people who cross five or more time zones.

A few clinical studies suggest that when taken for short periods of time (days to weeks) melatonin is significantly more effective than a placebo, or “dummy pill,” in decreasing the amount of time required to fall asleep, increasing the number of sleeping hours, and boosting daytime alertness.

Multiple human studies have measured the effects of melatonin supplements on sleep in healthy individuals. A wide range of doses has been used, often taken by mouth 30 - 60 minutes prior to sleep time. A study of 334 people aged 55 and older found that prolonged-release melatonin produced significant and clinically meaningful improvements in sleep quality, morning alertness, sleep onset latency, and quality of life in primary insomnia patients aged 55 years and over.

Osteoporosis

Melatonin has been shown to stimulate cells called osteoblasts that promote bone growth. Since melatonin levels may be lower in some older individuals such as postmenopausal women, current studies are investigating whether decreased melatonin levels contribute to the development of osteoporosis, and whether treatment with melatonin can help prevent this condition.

Menopause

Melatonin supplements may benefit menopausal women by promoting and sustaining sleep. Peri- or postmenopausal women who use melatonin supplements to regulate sleep patterns should do so only for a short period of time since long term effects are not known.

Depression

Clinical studies have found that melatonin may be useful in depression, especially associated with postmenopausal depression and anxiety. Other clinical studies show that people who suffer from major depression or panic disorder have low levels of melatonin. Healthy individuals with mild episodic depression and patients who have Seasonal Affective Disorder, (SAD -- a mild depression that correlates with fall and winter -- periods of light-phase shortening) also have lower than normal melatonin levels. Laboratory studies show that melatonin causes a surge in the chemical serotonin, which helps alleviate symptoms of depressive illness, including major and mild depression and SAD. Melatonin should be used with caution in people with depression and should be appropriately timed with light therapy and sleep-phase changes. Disruption of normal circadian rhythm by poorly timed melatonin administration may worsen depression.

Melatonin use along with certain anti-depressant medications can pose potential health risks and should only be used under direct supervision of a qualified doctor.

Benzodiazepine Withdrawal

Some clinical research has found that melatonin may assist with tapering or cessation of benzodiazepines such as diazepam (Valium), alprazolam (Xanax), or lorazepam (Ativan). Sleep quality was improved in those stopping benzodiazepine use. Although preliminary results are promising, further study is needed.

High Blood Pressure

Several controlled studies in patients with high blood pressure report small reductions blood pressure when taking melatonin by mouth (orally) or inhaled through the nose (intranasally). Better-designed research is necessary before a firm conclusion can be reached.

Breast Cancer

Several studies indicate that melatonin levels may be linked with breast cancer risk. For example, women with breast cancer tend to have lower levels of melatonin than those without the disease. In addition, laboratory experiments have found that low levels of melatonin stimulate the growth of certain types of breast cancer cells, while adding melatonin to these cells inhibits their growth. Preliminary laboratory and clinical evidence also suggests that melatonin may enhance the effects of some chemotherapy drugs used to treat breast cancer. In a study that included a small number of women with breast cancer, melatonin (administered 7 days before beginning chemotherapy) prevented the lowering of platelets in the blood. This is a common complication of chemotherapy, known as thrombocytopenia that can lead to bleeding.

In another study of a small group of women whose breast cancer was not improving with tamoxifen (a commonly used chemotherapy medication), adding melatonin caused tumors to modestly shrink in over 28% of the women. People with breast cancer who are considering taking melatonin supplements should consult their doctors before beginning supplementation.

Prostate Cancer

Like breast cancer, studies show that people with prostate cancer have lower melatonin levels than men without the disease. Melatonin blocks the growth of prostate cancer cells in test tube studies. In one small-scale study, melatonin (when used in combination with conventional medical treatment) improved survival rates in 9 out of 14 patients with metastatic prostate cancer. Interestingly, since meditation may cause melatonin levels to rise it appears to be a valuable addition to the treatment of prostate cancer. More research is needed before doctors can make recommendations in this area.

Cancer-related Weight Loss

Weight loss and malnutrition are concerns for people with cancer. In one study of 100 people with advanced cancer, those who received melatonin supplements were less likely to lose weight than those who did not receive the supplements.

Rheumatoid Arthritis

Melatonin levels are lower in patients with rheumatoid arthritis than in healthy individuals without arthritis. However, when arthritis patients were treated with the anti-inflammatory medication indomethacin, melatonin levels returned to normal. The chemical structure of melatonin resembles indomethacin, so researchers suspect that melatonin supplements may work similarly to this medication for people with rheumatoid arthritis. However, this theory has not been tested.

Attention Deficit Hyperactivity Disorder (ADHD)

Although melatonin supplementation does not appear to improve the key behavioral symptoms of ADHD, it may be effective in managing sleep disturbances in children with this condition.

Heart Disease

Low blood levels of melatonin are associated with heart disease, but it is not clear whether melatonin levels are low in response to having heart disease or if low levels of melatonin cause people to develop this condition. In addition, several animal studies suggest that melatonin may protect the heart from the damaging effects of ischemia (decreased blood flow and oxygen that often leads to a heart attack). However, researchers are unclear whether melatonin supplements may help prevent or treat heart disease in people. More studies are needed before scientists can draw any conclusions.

Others Uses

Sunburn -- A few small clinical studies suggest that gels, lotions, or ointments containing melatonin may protect against redness (erythema) and other skin damage when used alone or in combination with topical vitamin E prior to exposure to UV radiation from the sun.
Epilepsy -- Preliminary clinical research suggests that melatonin reduces the number of seizures in certain animals and may reduce seizures in people with epilepsy. However, some researchers are concerned that melatonin (1 - 5 mg per day) may actually induce seizures, particularly in children with neurologic disorders. Since this research is in the early stages, some experts suggest that doctors should administer melatonin only to a select group of people who suffer from seizures that cannot be controlled by any other type of therapy.
Sarcoidosis -- Some doctors use melatonin to help treat sarcoidosis (a condition where fibrous tissue develops in the lungs and other tissues). A few clinical studies suggest that melatonin may be helpful for those who do not improve from conventional steroid treatment.
Schizophrenia -- Melatonin may be a useful short-term hypnotic for schizophrenic patients with insomnia. A clinical study found that melatonin significantly improved the quality and depth of nighttime sleep, reduced the number of nighttime awakenings, and increased the duration of sleep without producing a morning hangover. Melatonin also significantly reduced sleep-onset latency, heightened freshness on awakening, improved mood, and improved daytime functioning Melatonin may be a useful short-term hypnotic for schizophrenic patients with insomnia. Melatonin could be considered for patients in whom conventional hypnotic drug therapy or higher sedative antipsychotic drug doses may be problematic.

Available Forms

Melatonin is available as tablets, capsules, cream, and lozenges that dissolve under the tongue.

How to Take It

There is currently no recommended dose for melatonin supplements. Different people will have different responses to its effects. Lower doses appear to work better in people who are especially sensitive. Higher doses may cause anxiety and irritability.

The best approach for any condition is to begin with very low doses of melatonin. Keep the dose close to the amount that our bodies normally produce (< 0.3 mg per day). You should only use the lowest amount possible to achieve the desired effect. Your doctor can help you determine the most appropriate dose for your situation, including how to increase the amount, if needed.

Pediatric

Less than 0.3 mg/day. Although studies in children suggest that doses of 1 - 10 mg melatonin have little to no side effects, there is not enough information to clearly say that doses greater than 0.3 mg per day are safe in children under age 15. In fact, doses between 1 - 5 mg may cause seizures in this age group.

Adult

Insomnia: 3 mg 1 hour before bedtime is usually effective, although doses as low as 0.1 -0.3 mg may improve sleep for some people. If 3 mg per night is not effective after 3 days, try 5 - 6 mg 1 hour before bedtime. An effective dose should produce restful sleep with no daytime irritability or fatigue.
Jet lag: 0.5 - 5 mg of melatonin 1 hour prior to bedtime at final destination has been successful in several studies. Another approach that has been used clinically is 1 - 5 mg 1 hour before bedtime for 2 days prior to departure and for 2 - 3 days upon arrival at final destination.
Sarcoidosis: 20 mg per day for 4 - 12 months. Take melatonin to treat this specific health condition only under medical supervision. Do not take melatonin supplements long-term without consulting your doctor.
Depression: 0.125 mg twice in the late afternoon, each dose 4 hours apart (for example, 4 p.m. and 8 p.m.). People with depression tend to be particularly sensitive to the effects of melatonin -- meaning that a very low dose is generally enough to achieve the desired outcomes.

Precautions

Because of the potential for side effects and interactions with medications, people should take dietary supplements only under the supervision of a knowledgeable health care provider.

Some people may experience vivid dreams or nightmares when they take melatonin. Overuse or incorrect use of melatonin may disrupt circadian rhythms. Melatonin can cause drowsiness if taken during the day. If you experience morning drowsiness after taking melatonin at night take a lower dose. Additional side effects include stomach cramps, dizziness, headache, irritability, decreased libido, breast enlargement in men (called gynecomastia), and decreased sperm count.

Pregnant or nursing women should not take melatonin as it could interfere with fertility.

Some studies show that melatonin supplements actually worsened symptoms of depression. For this reason, individuals with depression should consult their doctor before using melatonin supplements.

Although many researchers believe that melatonin levels diminish with age, emerging evidence has brought this theory into question. Since findings are inconsistent, people older than 65 years of age should consult their doctor before taking melatonin supplements, so blood levels of this hormone can be monitored appropriately.

Possible Interactions

If you are being treated with any of the following medications, you should not use melatonin without first discussing it with your health care provider.

Antidepressant medications -- In an animal study, melatonin supplements reduced the antidepressant effects of desipramine and fluoxetine. More research is needed to determine whether these effects would occur in people. In addition, fluoxetine (a member of a class of drugs called selective serotonin reuptake inhibitors, or SSRIs) has led to measurable depletion of melatonin in people.

Antipsychotic medications -- A common side effect of antipsychotic medications used to treat schizophrenia is a condition called tardive dyskinesia, a movement disorder of the mouth characterized by a constant chewing motion and darting action of the tongue. In a study of 22 people with schizophrenia and tardive dyskinesia caused by antipsychotic medications, those who took melatonin supplements had significantly reduced mouth movements compared to those who did not take the supplements.

Benzodiazepines -- The combination of melatonin and triazolam (a benzodiazepine medication used to treat anxiety and sleep disorders) improved sleep quality in one study. In addition, a few reports have suggested that melatonin supplements may help individuals stop using long-term benzodiazepine therapy. (Benzodiazepines are highly addictive.)

Blood pressure medications -- Melatonin may reduce the effectiveness of blood pressure medications like methoxamine and clonidine. In addition, medications in a class called calcium channel blockers (such as nifedipine, verapamil, diltiazem, amlodipine, nimodipine, felodipine, nisoldipine, and bepridil) may decrease melatonin levels.

Use of beta-blockers (another class of high blood pressure medications that includes propranolol, acebutolol, atenolol, labetolol, metoprolol, pindolol, nadolol, sotalol, and timolol) may reduce melatonin production in the body.

Blood-thinning medications, anticoagulants -- Melatonin may increase the risk of bleeding from anticoagulant medications such as warfarin.

Interleukin-2 -- In one study of 80 cancer patients, use of melatonin in conjunction with interleukin-2 led to more tumor regression and better survival rates than treatment with interleukin-2 alone.

Nonsteroidal anti-inflammatory drugs (NSAIDs) -- NSAIDs such as ibuprofen may reduce the levels of melatonin in the blood.

Steroids and immunosuppressant medications -- People should not take melatonin with corticosteroids or other medications used to suppress the immune system because the supplement may cause them to be ineffective.

Tamoxifen -- Preliminary research suggests that the combination of tamoxifen (a chemotherapy drug) and melatonin may benefit certain patients with breast and other cancers. More research is needed to confirm these results.

Other Substances -- Caffeine, tobacco, and alcohol can all diminish levels of melatonin in the body while cocaine and amphetamines may increase melatonin production.

Supporting Research

Acuna-Castroviejo D, Escames G, Rodriguez MI, Lopez LC. Melatonin role in the mitochondrial function. Front Biosci. 2007;12:947-63.

Altun A, Ugur-Altun B. Melatonin: therapeutic and clinical utilization. Int J Clin Pract. 2007;61(5):835-45.

Arendt J. Melatonin, circadian rhythms and sleep. New Engl J Med; 2000;343(15):1114-1116.

Attele AS, Xie JT, Yuan CS. Treatment of insomnia: an alternative approach.Altern Med Rev. 2000;5(3):249-259.

Barcelo E. Melatonin -- estrogen interactions in breast cancer. J of Pineal Res. 2005;38:217-222.

Barcelo E. melatonin and mammary cancer: a short review. Endocrine-Related Cancer. 2003;10:153-159.

Bazil CW, Short D, Crispin D, Zheng W. Patients with intractable epilepsy have low melatonin, which increases following seizures. Neurology. 2000;55(11):1746-1748.

Bylesjo I, Forsgren L, Wetterberg L. Melatonin and epileptic seizures in patients with acute intermittent porphyria. Epileptic Disord. 2000;2(4):203-208.

Cornelissen G, Halberg F, Burioka N, Perfetto F, Tarquini R, Bakken EE. Do plasma melatonin concentrations decline with age? Am J Med. 2000;109(4):343-345.

Cos S, Sanchez-Barcelo EJ. Melatonin and mamary pathological growth. Frontiers Neuroendo. 2000;21:133-170.

Cos S, Sanchez-Barcelo EJ. Melatonin, experimental basis for a possible application in breast cancer prevention and treatment. Histo Histopath. 2000;15:637-647.

Eck-Enriquez K, Kiefer TL, Spriggs LL, Hill SM. Pathways through which a regimen of melatonin and retinoic acid induces apoptosis in MCF-7 human breast cancer cells. Breast Cancer Res Treat. 2000;61(3):229-239.

Gordon N. The therapeutics of melatonin: a paediatric perspective. Brain Dev. 2000;22(4):213-217.

Herxheimer A, Petrie KJ. Melatonin for preventing and treating jet lag. Cocharane Database Syst Rev. 2001;(1):CD001520.

Jacobson JS, Workman SB, Kronenberg F. Research on complementary/alternative medicine for patients with breast cancer: a review of the biomedical literature. J Clin Onc. 2000;18(3):668-683.

Kaneko S, Okumura K, Numaguchi Y, Matsui H, Murase K, Mokuno S, et al. Melatonin scavenges hydroxyl radical and protects isolated rat hearts from ischemic reperfusion injury. Life Sciences. 2000;67(2):101-112.

Lagneux C, Joyeux M, Demenge P, Ribuot C, Godin-Ribuot D. Protective effects of melatonin against ischemia-reperfusion injury in the isolated rat heart. Life Sciences. 2000;66(6):503-509.

Lewy AJ, Emens J, Jackman A, Yuhas K. Circadian uses of melatonin in humans. Chronobiol Int. 2006;23(1-2):403-12.

Low Dog T, Riley D, Carter T. Traditional and alternative therapies for breast cancer. Alt Ther. 2001;7(3):36-47.

Lusardi P, Piazza E, Fogari R. Cardiovascular effects of melatonin in hypertensive patients well controlled by nifedipine: a 24-hour study. Br J Clin Pharmacol. 2000;49(5):423-7.

Malhotra S, Sawhney G, Pandhi P. The therapeutic potential of melatonin: a review of the science. Medscape General Medicine 2004;6(2).

Moretti RM, Marelli MM, Maggi R, Dondi D, Motta M, Limonta P. Antiproliferative action of melatonin on human prostate cancer LNCaP cells. Oncol Rep. 2000;7(2):347-351.

Nagtagaal JE, Laurant MW, Kerkhof GA, Smits MG, van der Meer YG, Coenen AM. Effects of melatonin on the quality of life in patients with delayed sleep phase syndrome. J Psychosom Res. 2000;48(1):45-50.

Peled N, Shorer Z, Peled E. Pillar G. Melatonin effect on seizures in children with severe neurologic deficit disorders. Epilepsia. 2001;42(9):1208-1210.

Piccirillo JF. Melatonin. Prog Brain Res. 2007;166:331-3.

Pillar G, Shahar E, Peled N, Ravid S, Lavie P, Etzioni A. Melatonin improves sleep-wake patterns in psychomotor retarded children. Pediatr Neurol. 2000;23(3):225-228.

Ram PT, Yuan L, Dai J, Kiefer T, Klotz DM, Spriggs LL, et al. Differential responsiveness of MCF-7 human breast cancer cell line stocks to the pineal hormone, melatonin. J Pineal Res. 2000;28(4):210-218.

Reiter RJ. Melatonin: clinical relevance. Best Pract Res Clin Endocrinol Metab. 2003;17(2):273-85.

Sack RL, Brandes RW, Kendall AR, Lewy AJ. Entrainment of free-running circadian rhythms by melatonin in blind people. N Engl J Med. 2000;343(15):1070-1077.

Schernhammer E, Hankinson S. Urinary melatonin levels and breast cancer risk. J Nat Canc Instit 2005;97(14):1084-1087.

Shamir E, Barak Y, Shalman I, Laudon M, Zisapel N, Tarrasch R, et al. Melatonin treatment for tardive dyskinesia: a double-blind, placebo-controlled, crossover study. Arch Gen Psych. 2001;58(11):1049-1052.

Shamir E, Laudon M, Barak Y, Anis Y, Rotenberg V, Elizur A, et al. Melatonin improves sleep quality of patients with chronic schizophrenia. J Clin Psychiatry. 2000;61(5):373-377.

Smits MG, Nagtegaal EE, van der Heijden J, Coenen AM, Kerkhof GA. Melatonin for chronic sleep onset insomnia in children: a randomized placebo-controlled trial. J Child Neurol. 2001;16(2):86-92.

Stewart LS. Endogenous melatonin and epileptogenesis: facts and hypothesis. Int J Neurosci. 2001;107(1-2):77-85.

van Wijingaarden E, Savitz DA, Kleckner RC, Cai J, Loomis D. Exposure to electromagnetic fields and suicide among electric utility workers: a nested case-control study. West J Med. 2000;173;94-100.

Review Date:
11/30/2007
Reviewed By:
Ernest B. Hawkins, MS, BSPharm, RPh, Health Education Resources; and Steven D. Ehrlich, NMD, private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

adam.com

Insomnia

FitSugar — Wed, 08 Oct 2008 17:34:55 -0700

Overview

Signs and Symptoms
Causes
Risk Factors
Diagnosis
Preventive Care
Treatment
Other Considerations
Supporting Research

HEALTH GUIDE REFERENCE FROM A.D.A.M

Insomnia is the inability to sleep when sleep should normally occur. Sufficient and restful sleep is a human necessity. The average adult needs slightly more than 8 hours of sleep a day, but only 35% of American adults consistently get this amount of rest.

People with insomnia tend to experience one or more of the following sleep disturbances:

Difficulty falling asleep at night
Waking too early in the morning
Waking frequently throughout the night

Insomnia may stem from a disruption of the body's circadian rhythm, an internal clock that governs the timing of hormone production, sleep, body temperature, and other functions. While occasional restless nights are normal, prolonged insomnia can interfere with daytime function, concentration, and memory. Insomnia increases the risk of substance abuse, motor vehicle accidents, headaches, and depression. Recent surveys indicate that 50% of people suffer from sleep difficulties, and 20 - 36% of them struggle with such difficulties for at least 1 year. Other studies show that one person out of three in the United States has insomnia, but only 20% tell their health care providers about it.

Signs and Symptoms

Not feeling refreshed after sleep
Inability to sleep despite being tired
Daytime drowsiness, fatigue, irritability, difficulty concentrating, and impaired ability to perform normal activities
Anxiety as bedtime approaches

Causes

No known physical or mental condition causes primary insomnia. Everyday anxiety and stress, coffee, and alcohol are the most common culprits.

An underlying medical or psychological condition, such as depression,, often causes secondary insomnia.

About 50% of insomnia cases have no identifiable cause.

Some conditions or situations that commonly lead to insomnia include:

Substance abuse -- consuming excessive amounts of caffeine, alcohol, recreational drugs, or certain prescription medications such as stimulants. Smoking can cause restlessness and quitting smoking may also cause temporary insomnia.
Disruption of circadian rhythms -- shift work, travel across time zones, or vision loss. Circadian rhythms are regulated, in part, by release of a hormone called melatonin from the brain. As individuals age, less melatonin is available for use by the body.
Menopause -- between 30 - 40% of menopausal women experience insomnia. This may be due to hot flashes, night sweats, anxiety, or fluctuations in hormone levels.
Hormonal changes during menstrual cycle -- insomnia may occur during menstruation. Sleep improves mid-cycle with ovulation.
Advanced age -- biological changes associated with aging, underlying medical conditions, and side effects from medications all contribute to insomnia.
Medical conditions -- gastroesophageal reflux (return of stomach contents into the esophagus), fibromyalgia, other chronic pain syndromes, heart disease, arthritis, attention deficit hyperactivity disorder, and obstructive sleep apnea (difficulty breathing during sleep).
Psychiatric and neurologic conditions -- anxiety, depression, manic-depressive disorder, dementia, Parkinson's disease, restless legs syndrome, post-traumatic stress disorder.
Certain medications -- decongestants (such as pseudoephedrine or Sudafed), bronchodilators (such as albuterol or Proventil inhaler), and beta-blockers (such as metoprolol or Lopressor).
Excessive computer work.
Partners who snore.

Risk Factors

The following factors may increase an individual's risk for insomnia:

Age -- the elderly are more prone to insomnia
Stressful or traumatic event
Night shift or changing work schedule
Travel across time zones
Substance abuse
Asthma -- bronchodilators occasionally cause insomnia
Excessive computer work

Diagnosis

Clinical history (including all current medication and recreational drug use) and physical exam are usually sufficient to make the diagnosis. Polysomnography, an overnight sleep study, can be helpful to rule out other types of sleep disorders (such as breathing-related sleeping disorder).

Preventive Care

The following lifestyle changes can help prevent insomnia:

Exercising regularly -- best when done before dinner. Exercise should not be done too close to bedtime because it can cause restlessness.
Avoiding caffeine (especially after noon) and nicotine.
Getting regular exposure to late afternoon sun. This helps to stimulate release of melatonin to regulate circadian rhythm.
Practicing stress reduction techniques, such as yoga, meditation, or deep relaxation.
Early treatment of insomnia may also help prevent psychiatric disorders, such as depression.

Treatment

The preferred treatments for people with chronic insomnia are lifestyle changes and behavioral approaches that establish healthy sleeping habits. This is called improving sleep hygiene.

Mind-body therapies -- such as stimulus control therapy, bright-light therapy, and cognitive-behavioral therapy -- are particularly helpful.

Acupuncture and acupressure have a long tradition of treating insomnia successfully, particularly in the elderly. Vitamins, along with homeopathic and herbal remedies, may also improve symptoms in some individuals.

Lifestyle

Healthy sleep habits are essential for treating insomnia. The following strategies (in addition to the steps mentioned in the "Preventive Care" section) may help treat the condition:

Maintain a consistent sleeping and waking time.
Establish the bedroom as a place for sleep and sexual activity only, not for reading, watching television, or working.
Avoid naps, especially in the evening.
Take a hot bath about 2 hours before bedtime.
Keep the bedroom cool, well-ventilated, quiet, and dark.
Avoid looking at the clock -- this promotes anxiety and obsession about time.
Avoid fluids just before bedtime.
Avoid exercising before bedtime.
Avoid television just before bedtime.
Eat a carbohydrate snack, such as cereal or crackers, just before bedtime.
Move to another room with dim lighting if sleep does not occur within 15 - 20 minutes in bed.

Medications

If changes in sleep hygiene do not help, prescription medications (including benzodiazepines) may be appropriate. Benzodiazepines include temazepam (Restoril), flurazepam (Dalmane), estazolam (ProSom), and triazolam (Halcion). Benzodiazepines may cause psychological and physical dependence. Physical withdrawal symptoms may occur if the drug is not carefully tapered following long-term use. Most common side effects of benzodiazepines include drowsiness, impaired coordination, fatigue, confusion and disorientation, dizziness, decreased concentration, short-term memory problems, dry mouth, blurred vision, and irregular heart beat.

Another class of sedative hypnotic medications includes the non-benzodiazepine, benzodiazepine receptor agonists. These newer medications appear to have better safety profiles and fewer adverse effects than the benzodiazepines. They are also associated with a lower risk of abuse and dependence than the benzodiazepines, although abuse and dependence do occur. Examples of medications in this class include zolpidem (Ambien), zaleplon (Sonata), and eszopiclone (Lunesta).

Ramelteon (Rozerem) belongs to a new class of drugs called melatonin agonists. Ramelteon promotes the onset of sleep by increasing levels of the natural hormone melatonin, which helps normalize normal circadian rhythm and sleep/wake cycles. Side-effects may include daytime sleepiness, dizziness, and fatigue.

Over-the-counter (OTC) antihistamines may be used short-term for insomnia. Diphenhydramine (Benadryl) is the most commonly used OTC antihistamine sleep aid, and can be purchased alone (Benadryl, Nytol, Sominex) or in combination with other OTC items, such as acetaminophen (Tylenol PM). Diphenhydramine can cause sedation, dry mouth, and constipation. In the elderly, diphenhydramine can cause confusion and oversedation.

Generally, OTC and prescription medications help promote sleep, but they are not recommended for insomnia that last for more than 4 weeks. Long-term use of some medications may cause addiction, particularly if the patient has a history of substance abuse.

Nutrition and Dietary Supplements

Following these nutritional tips may help reduce symptoms:

Eliminate all potential food allergens, including dairy, wheat (gluten), soy, corn, preservatives, and food additives. Your health care provider may want to test for food sensitivities.
Eat more antioxidant rich foods (such as green leafy vegetables) and fruits (such as blueberries, pomegranates, and cherries).
Avoid refined foods, such as white breads, pastas, and sugar.
Eat fewer red meats and more lean meats, cold-water fish, or beans for protein.
Use healthy cooking oils, such as olive oil or vegetable oil.
Reduce or eliminate trans-fatty acids, found in commercially baked goods such as cookies, crackers, cakes, French fries, onion rings, donuts, processed foods, and margarine.
Avoid coffee and other stimulants, alcohol, and tobacco.
Drink 6 - 8 glasses of filtered water daily.
Exercise 30 minutes daily, 5 days a week. Exercising in the evening after dinner may lead to insomnia.
Foods rich in carbohydrates and low in protein and fat may boost the production of serotonin and melatonin, brain chemicals that are associated with sleep. A carbohydrate snack of granola, non-sweetened cereals, or crackers with milk before bed may help.

The following dietary supplements may also be helpful in promoting sleep:

A multivitamin daily, containing the antioxidant vitamins A, C, E, the B-complex vitamins, and trace minerals such as magnesium, calcium, zinc, and selenium.
Omega-3 fatty acids, such as fish oil, 1 - 2 capsules or 1 tbsp. oil one to three times daily, to help decrease inflammation and help with mental balance.
Coenzyme Q10, 100 - 200 mg at bedtime, for antioxidant, immune, and muscular support.
5-hydroxytryptophan (5-HTP), 50 mg two to three times daily, for mood stabilization and sleep improvement.
L-theanine, 200 mg one to three times daily, for nervous system support.
Melatonin, 1 - 6 mg one hour before bedtime, for sleep and immune protection. Ask your health care provider about potential prescription interactions.

L-tryptophan and 5-hydroxytryptophan (5-HTP)

Medical research indicates that taking 1 g L-tryptophan before bedtime can induce sleepiness and delay wake times. Researchers think L-tryptophan brings on sleep by raising levels of serotonin, a body chemical that promotes relaxation. However, consumers should take this supplement with caution as it may adversely interact with certain antidepressants [including selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs)] and cause serious negative side effects. Reports of eosinophilia myalgia syndrome (EMS: an autoimmune disorder characterized by fatigue, fever, muscle pain and tenderness, cramps, weakness, hardened skin, and burning, tingling sensations in the extremities) from contaminated L-tryptophan supplements surfaced in 1989, and isolated incidents of EMS continue to be reported.

Studies also suggest that 5-hydroxytryptophan (5-HTP), made from tryptophan in the body or available in supplement form, may be useful in treating insomnia associated with depression. Like tryptophan, reports of EMS have been associated with use of 5-hydroxytryptophan. Talk to a health care professional before taking 5-HTP supplements if you are on antidepressant medications. Drug interactions may occur.

Melatonin

Melatonin supplements help induce sleep, particularly in people who have disrupted circadian rhythms (such as from jet lag or shift work), or those with low levels of melatonin (such as some people with schizophrenia). In fact, a recent review of scientific studies found that melatonin supplements help prevent jet lag, particularly in people who cross five or more time zones. A few clinical studies suggest that melatonin is significantly more effective than placebo, or dummy pill, in decreasing the amount of time required to fall asleep, increasing the number of sleeping hours, and boosting daytime alertness. Although research suggests that melatonin may be modestly effective for treating certain types of insomnia, few studies have investigated whether melatonin supplements are safe and effective for long term use. More research is needed in this area.

Herbs

Herbs are generally a safe way to strengthen and tone the body's systems. As with any therapy, you should work with your health care provider to get your problem diagnosed before starting any treatment. You may use herbs as dried extracts (capsules, powders, teas), glycerites (glycerine extracts), or tinctures (alcohol extracts). Unless otherwise indicated, you should make teas with 1 tsp. herb per cup of hot water. Steep covered 5 - 10 minutes for leaf or flowers, and 10 - 20 minutes for roots. Drink two to four cups per day. You may use tinctures alone or in combination as noted:

Kava kava (Piper methysticum) standardized extract, 100 - 250 mg one to three times daily, as needed for relaxation. Kava should not be used in those with liver problems or those drinking alcohol in excessive quantities.
Rhodiola (Rhodiola rosea ) standardized extract, 100 - 600 mg daily, for antioxidant and antistress activity.
Valerian (Valeriana sp.) standardized extract, 200 - 400 mg at bedtime, for sleep.
Chamomile (Anthemis nobilis), standardized extract, 400 - 1,600 mg daily, for relaxation. A tea may be prepared from chamomile flowers. Chamomile is not recommended for individuals allergic to flowers in the daisy family.

Homeopathy

A few studies have examined the effectiveness of specific homeopathic remedies. However, a professional homeopath may recommend one or more of the following treatments for insomnia, based on their knowledge and clinical experience. Before prescribing a remedy, homeopaths take into account a person's constitutional type -- your physical, emotional, and intellectual makeup. An experienced homeopath assesses all of these factors when determining the most appropriate remedy for a particular individual.

Aconitum -- for insomnia that occurs as a result of illness, fever, or vivid, frightening dreams; commonly used for children.
Argentum nitricum -- for impulsive children who are restless and agitated before bedtime and cannot fall asleep if the room is too warm.
Arsenicum album -- for insomnia that occurs after midnight due to anxiety or fear. This remedy is most appropriate for demanding individuals who are often restless, thirsty, and chilly.
Chamomilla -- for insomnia caused by irritability or physical pains; sleep may be disturbed by twitching and moaning. This remedy is appropriate for infants who have difficulty sleeping because they are teething or colicky, and older children may demand things, then refuse them when they are offered.
Coffea -- for insomnia due to excitable news or sudden emotions. This remedy is most appropriate for individuals who generally have difficulty falling asleep and tend to be light sleepers. Often used to counteract the effects of caffeine, including in infants exposed to caffeine through breast-feeding.
Ignatia -- for insomnia caused by grief or recent loss. This remedy is most appropriate for individuals who yawn frequently or sigh while awake.
Kali phosphoricum -- for night terrors associated with insomnia. This remedy is most appropriate for individuals who are easily startled and restless, often with fidgety feet. Anxiety is often caused by both nightmares and events in the individual's life.
Nux vomica -- for insomnia caused by anxiety, anger, irritability, or use of caffeine, alcohol, or drugs. This remedy is most appropriate for individuals who wake up early in the morning, or for children who often have dreams of school or fights and may be awakened by slight disturbances. Nux vomica may also be used to treat insomnia that occurs as a side effect of medications.
Passiflora -- for the elderly and young children with often overactive minds.
Pulsatilla -- for women and children who are particularly emotional and do not like sleeping alone. Also used when sleeping in a warm room tends to worsen insomnia or when the individual may cry due to the inability to fall asleep.
Rhus toxicodendron -- for restlessness and insomnia caused by pains that occur when the individual is lying down.

Acupuncture

Some reports suggest that certain acupuncture procedures have a nearly 90% success rate for the treatment of insomnia. Through a complex series of signals to the brain, acupuncture increases the amount of certain substances in the brain, such as serotonin, which promote relaxation and sleep.

Several clinical studies have found that auricular acupuncture is effective in reducing symptoms of insomnia, such as difficultly in falling asleep and remaining asleep. Auricular acupuncture uses needles placed at various points in the ear. Further studies should be performed.

Clinical studies of elderly people with sleep disturbances suggest that acupressure enhances sleep quality and decreases awakenings during the night. An acupressure practitioner works with the same points used in acupuncture, but stimulates these healing sites with finger pressure, rather than inserting fine needles. Clinical studies support the use of auricular (ear) acupressure for improving sleep quality in elderly patients and possibly in healthy adults of all ages. A small clinical study also found that acupressure may help with sleep apnea.

Chiropractic

No well-designed studies have evaluated the effect of chiropractic care on individuals with insomnia, but chiropractors report that spinal manipulation may improve symptoms of the condition in some individuals. In these cases, spinal manipulation may have a relaxing effect on the nervous system.

Massage and Aromatherapy

Massage has long been known to enhance relaxation and improve sleep patterns. While massage alone is an effective method for relaxation, studies suggest that massage with essential oils (called aromatherapy), particularly lavender (Lavandula angustifolia), may result in improved sleep quality, more stable mood, increased mental capacity, and reduced anxiety. Clinical studies have found participants who received massage with lavender felt less anxious and more positive than participants who received massage alone.

Mind-Body Medicine

A variety of behavioral techniques have proved helpful in treating insomnia. These methods, with the guidance of a sleep specialist or a sleep specialty team, are singly used to treat insomnia, but they may also be combined with other treatment methods including:

Sleep Diary. Keeping a daily/nightly record of sleep habits (including the amount of sleep, how long it takes to fall asleep, the quality of sleep, the number of awakenings throughout the night, any disruption of daytime behaviors, attempted treatments and how well they worked, mood, and stress level) can help a person understand and, consequently overcome their insomnia.
Stimulus Control Techniques. This technique involves learning to use the bedroom only for sleep and sexual activity. Individuals using this technique learn to go to bed only when tired and leave the bedroom when they’re not sleeping. They wake up at the same time every day, including weekends and vacations, regardless of the amount of sleep they had.
Sleep Restriction. This method improves sleep "efficiency" by attempting to sleep at least 85% of time spent in bed asleep. The time spent in bed is decreased each week by 15 - 20 minutes until the 85% goal is achieved. Once accomplished, the amount of time in bed is increased again on a weekly basis.
Relaxation Training Techniques. Progressive relaxation, meditation, yoga, guided imagery, hypnosis, or biofeedback can break the vicious cycle of sleeplessness by decreasing feelings of anxiety about not being asleep. Studies indicate that these therapies significantly reduce the amount of time it takes to fall asleep, increase total sleep time, and decrease the number of nightly awakenings.
Cognitive-Behavioral Therapy. This therapy is intended to re-establish healthy sleep patterns by helping an individual cope with their sleep problem. One cognitive-behavioral approach, called paradoxical intention, helps to retrain an individual's fears of sleep by doing the opposite of the behavior that causes anxiety. For example, a person with insomnia worries long before going to bed about not being able to sleep and the difficulty they will have at bedtime. Rather than preparing to go to sleep, the person prepares to stay awake. Another cognitive-behavioral technique, called thought stopping, allows a person with insomnia a certain period of time to repeatedly and continuously think about going to bed. This technique helps "wear out" the anxiety associated with going to bed, and decreases the likelihood that he they will obsess about falling asleep at other times.

Traditional Chinese Medicine

Many methods have been used historically in Traditional Chinese Medicine to treat insomnia, including herbal remedies, acupuncture, acupressure, Chinese massage (tui na), and qi gong.

Other Considerations

Pregnancy

Insomnia usually occurs in the later months of pregnancy when the mother's size and need to urinate disrupt sleep.
Women who are pregnant and nursing mothers should avoid benzodiazepines.

Warnings and Precautions

People who are taking prescription medications or over-the-counter sleeping pills should avoid alcohol.
Discontinuing prescription medications or over-the-counter sleeping pills can lead to rebound insomnia.

Prognosis and Complications

Most people who have insomnia with no underlying medical conditions recover within a few weeks. For those who develop insomnia from a traumatic event (such as those with posttraumatic stress disorder), sleep disruptions can continue indefinitely. People who become dependent on sleeping pills and prescription medication for sleep often have the most difficulty overcoming insomnia.

Supporting Research

Altun A, Ugur-Altun B. Melatonin: therapeutic and clinical utilization. Int J Clin Pract. 2007;61(5):835-45.

Atkinson G, Davenne D. Relationships between sleep, physical activity and human health. Physiol Behav. 2007;90(2-3):229-35.

Attele AS, Xie JT, Yuan CS. Treatment of insomnia: an alternative approach. Altern Med Rev. 2000;5(3):249-259.

Barion A, Zee PC. A clinical approach to circadian rhythm sleep disorders. Sleep Med. 2007;8(6):566-77.

Beghe C. Review: behaviour therapy is effective for insomnia. Evid Based Med. 2006;11(5):147.

Chasens ER. Understanding sleep in persons with diabetes. Diabetes Educ. 2007;33(3):435-6, 438, 441.

Chen HY, Shi Y, Ng CS, Chan SM, Yung KK, Zhang QL. Auricular acupuncture treatment for insomnia: a systematic review. J Altern Complement Med. 2007;13(6):669-76.

Dolder C, Nelson M, McKinsey J. Use of non-benzodiazepine hypnotics in the elderly: are all agents the same? CNS Drugs. 2007;21(5):389-405.

Epstein DR, Dirksen SR. Randomized trial of a cognitive-behavioral intervention for insomnia in breast cancer survivors. Oncol Nurs Forum. 2007;34(5):E51-9.

Harrington JJ, Avidan AY. Treatment of sleep disorders in elderly patients. Curr Treat Options Neurol. 2005;7(5):339-52.

Herxheimer A, Petrie KJ. Melatonin for preventing and treating jet lag. Cocharane Database Syst Rev. 2001;(1):CD001520.

Krystal AD. Treating the health, quality of life, and functional impairments in insomnia. J Clin Sleep Med. 2007;3(1):63-72.

Krystal A. The changing perspective of chronic insomnia management. J Clin Psychiatry. 2004;65 Suppl 8:20-5.

McCurry SM, Logsdon RG, Teri L, Vitiello MV. Evidence-based psychological treatments for insomnia in older adults. Psychol Aging. 2007;22(1):18-27.

Ramakrishnan K, Scheid DC. Treatment options for insomnia. Am Fam Physician. 2007;76(4):517-26.

Ringdahl E, Pereira S, Delzell J. Treatment of primary insomnia. J Am Board Fam Pract. 2004;17:212-219.

Shamir E, Laudon M, Barak Y, Anis Y, Rotenberg V, Elizur A, Zisapel N. Melatonin improves sleep quality of patients with chronic schizophrenia. J Clin Psychiatry. 2000;61(5):373-377.

Vandermeer BW, Buscemi N, Liang Y, Witmans M. Comparison of meta-analytic results of indirect, direct, and combined comparisons of drugs for chronic insomnia in adults: a case study. Med Care. 2007;45(10 Supl 2):S166-72.

Wade AG, Ford I, Crawford G, et al. Efficacy of prolonged release melatonin in insomnia patients aged 55-80 years: quality of sleep and next-day alertness outcomes. Curr Med Res Opin. 2007;23(10):2597-605.

Walsh JK, Krystal AD, Amato DA, et al. Nightly treatment of primary insomnia with eszopiclone for six months: effect on sleep, quality of life, and work limitations. Sleep. 2007;30(:959-68.

Wolkove N, Elkholy O, Baltzan M, Palayew M. Sleep and aging: 2. Management of sleep disorders in older people. CMAJ. 2007;176(10):1449-54.

Zammit G, Erman M, Wang-Weigand S, Sainati S, Zhang J, Roth T. Evaluation of the efficacy and safety of ramelteon in subjects with chronic insomnia. J Clin Sleep Med. 2007;3(5):495-504.

Review Date:
12/7/2007
Reviewed By:
Ernest B. Hawkins, MS, BSPharm, RPh, Health Education Resources; and Steven D. Ehrlich, NMD, private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

adam.com

Sleep apnea

FitSugar — Wed, 08 Oct 2008 17:35:30 -0700

In This Report

Highlights
Introduction
Symptoms
Causes
Risk Factors
Prognosis
Diagnosis
Lifestyle Changes
Treatment
Dental Devices
Surgery
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Sleep Apnea and Heart Attack

Obstructive sleep apnea can increase the risk of heart attack by as much as 30% over the course of 5 years, suggests a study presented at the 2007 American Thoracic Society International Conference. Researchers noted that the risk of developing or dying from heart disease rises with increasing sleep apnea severity.

Sleep Apnea and Diabetes

Obstructive sleep apnea may increase the risk of developing type 2 diabetes, indicates research presented at the American Thoracic Society conference. Patients who had severe obstructive sleep apnea had more than 2.5 times the risk of developing diabetes as those who did not suffer from nighttime breathing problems.
Sleep apnea may also increase the risk for women developing diabetes during pregnancy (gestational diabetes). Pregnancy-associated high blood pressure is also linked with sleep apnea.

Sleep Apnea and Depression

As sleep apnea worsens, the odds for developing depression increase, indicates a 2006 study in the Archives of Internal Medicine.

Continuous Positive Airway Pressure (CPAP)

CPAP is the best treatment for severe sleep apnea. However, according to a 2007 study in Sleep, most patients need to use it for a full night’s duration to achieve optimal benefits. The researchers noted that many patients experience some improvement in daytime sleepiness after 4 - 6 nightly hours of CPAP use, but that the best improvements in quality of life occur mostly after 7.5 hours of CPAP use each night.

Risk Factors for Sleep Apnea Surgery

According to a 2006 study in the Archives of Otolaryngology - Head & Neck Surgery, the risks for complications following uvulopalatopharyngoplasty (UPPP) increase with:

Severity of sleep apnea
Being overweight (higher body mass index)
Having other medical conditions in addition to sleep apnea
Undergoing other surgical procedures at the same time as UPPP

Introduction

Sleep apnea is a disorder in which a person stops breathing during the night, perhaps hundreds of times, usually for periods of 10 seconds or longer and sometimes for as long as a minute. These gaps in breathing are called apneas. The word apnea means absence of breath.

Sleep apnea is usually accompanied by snoring. People might not even know they have the condition. It inevitably causes daytime sleepiness.

Sleep apnea is grouped into three categories:

Obstructive
Central
Mixed

There is also another, less severe form of obstructed breathing, called upper airway resistance syndrome (UARS).

Obstructive sleep apnea (OSA) is the most common form of apnea. It occurs when tissues in the upper throat collapse at different times during sleep, thereby blocking the passage of air. In general, OSA occurs as follows:

On its way to the lungs, air passes through the nose, mouth, and throat (the upper airway).
Under normal conditions, the back of the throat is soft and tends to collapse inward as a person breathes.
Dilator (widening) muscles work against this collapse to keep the airway open. Interference or abnormalities in this process cause air turbulence.
If the tissues at the back of the throat collapse and become momentarily blocked, apnea occurs. Breath is temporarily stopped. In most cases the person is unaware of it, although sometimes they awaken and gasp for breath.
In some cases, the interference is incomplete (called obstructive hypopnea) and causes continuous but slow and shallow breathing. In response, the throat vibrates and makes the sound of snoring. Snoring can occur whether a person breathes through the mouth or the nose. (Snoring also occurs without sleep apnea.)
Apnea decreases the amount of oxygen in the blood, and eventually this lack of oxygen triggers the lungs to suck in air.
At this point, the patient may make a gasping or snorting sound but does not usually fully wake up.

Obstructive sleep apnea is defined as five or more episodes of apnea or hypopnea per hour of sleep in individuals who have excessive daytime sleepiness.

Central sleep apnea is much less common. It is caused by some problem in the central nervous system, most likely a failure of the brain to signal the airway muscles to breathe. In such cases, oxygen levels drop abruptly and usually the sleeper wakes with a start. Often people with central sleep apnea recall waking up. They generally experience less sleepiness during the day than people with obstructive sleep apnea. Heart disease, and in particular heart failure, is the most common cause of central sleep apnea.

Mixed apnea is the term used when the two apneas occur together.

Upper airway resistance syndrome (UARS) is a condition in which patients snore, wake frequently during the night, and have excessive daytime sleepiness. However, UARS patients do not have the breathing abnormalities that characterize sleep apnea and they do not show a reduction in blood oxygen levels. Unlike apnea, UARS is more likely to occur in women than in men. Treatments are similar to those of sleep apnea. It is not known if UARS has any serious health complications.

The daily cycle of sleeping and waking is called the circadian rhythm. It's commonly referred to as the biologic clock. Circadian means "about a day." Hundreds of bodily functions follow biologic clocks, but sleeping and waking comprise the most prominent circadian rhythm. The sleeping and waking cycle is approximately 24 hours. (People who are confined to windowless homes, with no clocks or other time cues, sleep and wake on a slightly longer cycle.) The 24-hour circadian rhythm typically adheres to the following factors:

Humans are designed for daytime activity and nighttime rest.
There is a natural peak in sleepiness at mid-day, the traditional siesta time.

In addition, daily rhythms mix with other factors that may interfere or change individual patterns:

The firing of nerve cells in the brain may be faster or slower in different individuals.
The monthly menstrual cycle in women can shift the pattern.
Light signals coming through the eyes reset the circadian cycles each day, so changes in season or various exposures to light and dark can unsettle the pattern. The importance of sunlight as a cue for circadian rhythms is dramatized by the problems experienced by people who are totally blind. They commonly suffer trouble sleeping and other rhythm disruptions.

The Response in the Brain to Light Signals

The response to light signals in the brain is an important key factor in sleep:

Light signals travel to a tiny cluster of nerves in the hypothalamus in the center of the brain, the body's master clock, which is called the supra chiasmatic nucleus or SCN.
This nerve cluster takes its name from its location. It sits just above (supra) the optic chiasm, a major junction for nerves transmitting information about light from the eyes.
The approach of dusk each day prompts the SCN to signal the nearby pineal gland to produce the hormone melatonin.
Melatonin is thought to act as the body's time-setting hormone. The longer a person is in darkness the longer the duration of melatonin secretion. Secretion can be diminished by staying in bright light. Melatonin also appears to trigger the need to sleep.

Sleep Cycles

Sleep consists of two distinct states that alternate in cycles and reflect differing levels of brain nerve cell activity:

Non-Rapid Eye Movement Sleep (NonREM). NonREM sleep is also termed quiet sleep. NonREM is further subdivided into three stages of progression:

Stage 1 (light sleep)
Stage 2 (so-called true sleep)
Stage 3 to 4 (deep "slow-wave" or delta sleep)

The REM/NREM Cycle. The cycle between quiet (NonREM) and active (REM) sleep generally follows this pattern:

After about 90 minutes of NonREM sleep, eyes move rapidly behind closed lids, giving rise to REM sleep.
As sleep progresses the NonREM/REM cycle repeats.
With each cycle, NonREM sleep becomes progressively lighter, and REM sleep becomes progressively longer, lasting from a few minutes early in sleep to perhaps an hour at the end of the sleep episode.

Symptoms

People with sleep apnea usually do not remember waking during the night.

Symptoms may include:

Excessive daytime sleepiness
Morning headaches
Irritability and impaired mental or emotional functioning
Snoring (bed partners may report very loud and interrupted snoring)
Heartburn (acid back-up that causes heartburn may be responsible for some cases of sleep apnea)

Sleep apnea occurs in about 2% of children. They may have symptoms that differ from adults, including:

Longer total sleep time than normal in some children, especially obese children or those with severe apnea.
Snoring. (An estimated 3 - 12% of all children snore. However, not all of them have sleep apnea.)
More effort in breathing (flaring nostrils, heaving chests, sweating). The chest may have an inward motion during sleep.
Behavioral difficulties without any obvious cause, such as hyperactivity and inattention. (Some patients may even be misdiagnosed with attention-deficit hyperactivity disorder.)
Irritability
Bed-wetting
Morning headaches
Failure to grow and gain weight

Causes

Any structural abnormality in the face, skull, or airways that causes some obstruction or collapse in the upper airways and reduces air pressure can produce sleep apnea syndrome. Abnormalities in tissues that lie between the back of the mouth and the esophagus (food pipe) are one of the most common structural causes of sleep apnea. Enlarged soft palates (the base of the tongue and surrounding throat walls) are also associated with many cases of sleep apnea.

Researchers have identified several physiologic abnormalities that may play a role in causing sleep apnea or in making it worse. These include an inability to regulate levels of carbon dioxide, impaired brain and nervous system responsiveness to various chemical messengers, and poor reflexes or muscle tone in the upper airways. The underlying reasons for these disturbances and their connection to apnea require further study.

Obesity is strongly associated with sleep apnea and is a cause of it in some cases. Imaging scans have shown fatty cells clogging the throat tissue, which indicates that they narrow the airways. In one study, the more obese a person with sleep apnea was, the higher the pressure on the airway and therefore the greater the obstruction of the airway. (Obstructive sleep apnea may also contribute to obesity itself, however, since a sleepy person tends to be sedentary.)

Snoring. Chronic snoring itself may actually be a cause of sleep apnea. Over time, the vibrations and the increased pressure against the upper airways as snoring people inhale may cause the soft palate to lengthen. This stretched palate is more prone to collapse and obstruction.

It should be stressed that snoring is very common. Snoring occurs in about a third of the population, while apnea, according to one study, occurs in only 6%. Snoring, then, does not always cause apnea, nor is it always a sign of the respiratory disorder. Furthermore, while snoring is also associated with daytime sleepiness regardless of whether apneas are present, snoring alone does not appear to pose any major health risks.

Mouth Breathing. Some evidence suggests that a tendency to breathe through the mouth (rather than the nose) during childhood can actually produce structural changes in the face (longer face, narrow jaw, receding chin). Such facial characteristics may eventually put people at risk for sleep apnea.

Sleep apnea occurs in about 2% of children and can occur even in very young children. The most likely causes are the following:

Facial or skull abnormalities in infants.
Overgrown tonsils, adenoids, or both in small children. (Removal of tonsils or adenoids can free the airways and solve the problem.)
Premature infants also commonly have a form of apnea that may be related to lung or nervous system problems.

Risk Factors

Gender. More men than women appear to have sleep apnea. In the U.S., about 4% of men and 2% of women age 30 - 60 meet the criteria for obstructive sleep apnea. Such people have at lease five episodes of apnea or hypopnea (shallow nighttime breathing) for each hour of sleep plus excessive daytime sleepiness. A much higher percentage has just one of these two conditions.

Sleep apnea actually may be underdiagnosed in women, particularly older women. In general, older women have the same incidence of sleep apnea as men their own age. It is not clear why apnea occurs more often in men than women before menopause and why prevalence equalizes after menopause. Men tend to have larger necks and to weigh more than women and women tend to gain weight and develop larger necks after menopause. However, studies have not found that these physical factors fully explain the differences in risk by gender in young adults or the increase in sleep apnea in postmenopausal women.

Age. Sleep apnea is most common and its symptoms are worse in middle-aged adults age 40 - 60 years old. Nevertheless, it affects people of all ages.

Ethnicity. African-Americans face a higher risk for sleep apnea than any other ethnic group in the United States. Other groups at increased risk include Pacific Islanders and Mexicans.

Obesity, especially having fat around the abdomen (the so-called apple shape), is a particular risk factor for sleep apnea, even in adolescents and children. However, many people with sleep-related breathing disorders, particularly women and small children, are not obese. Also, not all people who are obese have sleep apnea. Specific anatomical and physiological properties in the airways are more likely to be present in obese individuals with apnea.

Having a Larger Neck. Having a large neck is a risk factor for sleep apnea. In fact, larger necks in men may be the primary reason for their higher risk for sleep apnea compared to women. A neck measurement of 17 inches or greater in men or at least 16 inches in women is one indicator that may suggest the condition. Postmenopausal women are more likely than younger women to have sleep apnea, in part because they tend to be heavier and have larger necks.

Specific Facial and Skull Characteristics. Structural abnormalities in the face and skull may be responsible for many cases of sleep apnea. These are likely to be the cause in many non-obese people with early-onset sleep apnea, particularly if they also have a family history of the problem.

Specific physical characteristics that may increase the risk for sleep apnea in both adults and children include:

A long lower part of the face
Brachycephaly, a birth defect in which the head tends to be shorter and wider than average
A narrow upper jaw
A receding chin
An overbite
A larger tongue

Characteristics in the Soft Palate. Some people have specific abnormalities in the soft area (palate) at the back of the mouth and throat that may lead to sleep apnea. These abnormalities include:

The soft palate is stiffer, larger than normal, or both. An enlarged soft palate may be a significant risk factor for sleep apnea.
The soft palate and the walls of the throat around it collapse easily.

Smoking. Smokers are at higher risk for apnea. Those who smoke more than two packs a day have a risk 40 times greater than nonsmokers.

Alcohol. Alcohol use has been associated with apnea, although studies are mixed. A major survey reported that 53% of people who use alcohol to help fall sleep experience symptoms of sleep apnea. Another study found no relationship.

Diabetes. Diabetes is associated with sleep apnea and snoring. It is not clear if there is an independent relationship between the two conditions or whether obesity is the only common factor.

Gastroesophageal Reflux Disease (GERD). GERD is a condition caused by acid backing up into the esophagus. It is a common cause of heartburn. GERD and sleep apnea often coincide. In one study, almost half of apnea patients had symptoms of GERD. Some experts suggest that the backup of stomach acid in GERD may produce spasms in the vocal cords (larynx), thereby blocking the flow of air to the lungs and causing apnea. Or, apnea itself may cause pressure changes that trigger GERD. Some evidence suggests that treating sleep apnea with continuous positive airway pressure (CPAP) may reduce GERD symptoms by nearly 50%. However, obesity is common in both conditions. More research is needed to clarify the association.

Polycystic Ovary Syndrome (PCOS). In a 2000 study, women with PCOS were 30 times more likely than other premenopausal women to have obstructive sleep apnea and excessive daytime sleepiness. Women with PCOS produce high amounts of male hormones, particularly testosterone, which can cause obesity, facial hair, and acne. About half of PCOS patients also have diabetes. Obesity and diabetes are both associated with sleep apnea and may be the common factors.

Chronic Problems in the Upper Airways. A 2001 Swedish study found that people with respiratory tract disorders, including asthma, chronic bronchitis, or seasonal allergies, reported symptoms of sleep apnea more often than those without any of these ailments.

Hypothyroidism. In rare cases, hypothyroidism (low thyroid) has been reported as a possible cause of sleep apnea. In such cases, treating the thyroid condition improves the sleep apnea.

Prognosis

Sleep apnea has a strong association with several diseases, particularly those related to the heart and circulation.

Researchers are intensively investigating why a problem in the upper airways is associated with serious conditions of the heart and circulatory system. Here are some of their findings:

Major known risk factors for hypertension and heart disease (obesity, smoking, and alcohol abuse) are associated with sleep apnea. These factors, however, do not explain all cases of higher heart-related risks in people with sleep apnea. For example, among overweight people, those who have sleep apneas have a greater risk of heart problems than those without them.
When breathing stops during episodes of apnea, carbon dioxide levels in the blood increase and oxygen levels drop. This effect may trigger a cascade of physical and chemical events that can then increase risk for heart problems.
Apnea also causes decreased levels of the gas nitric oxide (NO), a potent substance that causes blood vessels to be elastic and expand. NO plays a crucial role in blood pressure control and heart health.
Apnea may also increase levels of a substance called angiotensin-converting enzyme (ACE), which is known to play a role in high blood pressure and congestive heart failure.
Researchers have reported high levels of certain immune factors called tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) in people with sleep apnea, particularly those who are obese. High levels of TNF-alpha and IL-6 produce a damaging inflammatory response, which can harm cells in the body, including those in the arteries. Elevated TNF-alpha may be associated with fatigue, shortness of breath, and a diminished heart-pumping action.

At this time, however, evidence of a clear causal relationship with any of these health problems is still weak. Some studies have found no significant independent risk for heart disease from obstructive sleep apnea. The following are some discussions on the possible effects of apnea on specific health problems.

High Blood Pressure. A number of studies have found a strong association between sleep apnea and high blood pressure (hypertension). (In the past, the link between sleep apnea and hypertension was thought to be due to obesity, a risk factor for both conditions, but more recent studies contradict that theory.) A 2000 study followed patients for 4 years; the more nightly apnea episodes they had in the first year, the more likely they were to develop hypertension by the fourth year. A weak, but still higher-than-normal, association with high blood pressure has also been observed in those who snore, wake frequently during the night, or have mild sleep apnea.

A 2004 data analysis of over 200,000 patient records revealed that people who took both antidepressants and antihypertensives were 18 times more likely to be diagnosed with obstructive sleep apnea than those who did not take the medications. The probability was highest among adults age 20 - 39 years. These drugs do not cause sleep apnea, but antidepressants may be prescribed to treat hypertensive patients’ complaints of fatigue even if sleep apnea is the real cause. The researchers recommended that patients being treated for high blood pressure, depression, and fatigue should also be evaluated for sleep apnea.

One way that apnea may directly affect blood pressure, regardless of other risk factors:

Blood pressure fluctuates widely and suddenly in response to episodes of apnea and hypopnea (shallow nighttime breathing).
Such fluctuations are possibly due to a sudden surge in the sympathetic nervous system, which controls involuntary muscle responses, importantly those in the blood vessels and heart, and may also play a role in sleep apnea.
These fluctuations lead to transient constriction of blood vessels that, over time, could possibly lead to sustained hypertension and heart damage.
Effective treatment of sleep apnea with continuous positive airway pressure (CPAP) may reduce blood pressure. Sleep apneas must be significantly reduced, however, to have any effect on blood pressure. Even a 50% reduction in apneas has no effect.

Coronary Artery Disease and Heart Attack. Sleep apnea has been associated with heart disease regardless of the presence of high blood pressure or other heart risk factors. In a 2001 study, researchers observed that the more episodes of apnea and hypopnea a patient had, the higher the risk for a heart attack.

Many of the factors associated with stroke and sleep apnea (a risk for blood clots and narrowing of the arteries) may also increase the risk for heart attacks. Research presented at the 2007 American Thoracic Society conference suggested that severe obstructive sleep apnea can increase the risk of dying from a heart attack by as much as 30% over a 4 - 5 year period. Obstructive sleep apnea, however, may have other effects that increase the risk for heart problems:

Some evidence suggests that obstructive apneas cause an increase in stiffness and inflammation in the arteries, which is now proving to be an important aspect of heart disease, particularly in older adults.
A 2002 study reported that the white blood cells of patients with apnea have an increased number of proteins called adhesion molecules on their surface that may bind to the lining of blood vessels and cause inflammation. Increasingly, scientists believe that inflammation plays an important role in the development of coronary artery disease, heart attacks, and many other major ailments.

Stroke. Sleep apnea doubles the risk for stroke. The worse the sleep apnea, the greater the risk; moderate-to-severe obstructive sleep apnea can triple the risk of stroke. Sleep apnea is also associated with high blood pressure, a known risk factor for stroke. However, people who have sleep apnea, but not high blood pressure, are also still at increased risk for stroke. Sleep apnea in stroke patients is also associated with a higher risk for worse symptoms after a stroke, including delirium, depression, poor response to speech, and difficulty conducting daily chores.

A 2000 study observed that blood becomes more viscous (stickier) in the morning in people with obstructive sleep apnea compared to people without the sleep disorder. Such "sticky" blood is more apt to form clots that can lead to strokes. To support this, another 2000 study reported that stroke victims with sleep apnea tended to have higher levels of the blood protein fibrinogen than stroke victims without sleep apnea. Fibrinogen is a factor in blood that causes it to clot. Higher levels of fibrinogen have been linked to both strokes and heart attacks.
A 1998 study reported that the carotid artery, the major artery to the brain, is in far greater danger of becoming sclerotic (hardened and narrower) in people with obstructive sleep apnea than in the average person. People with both diabetes and sleep apnea are at particularly high risk for this effect.

Heart Failure. Studies suggest that 11 - 37% of patients with heart failure also have sleep apnea. Both central and obstructive sleep apnea are linked with heart failure. The evidence for the association between heart failure and sleep apnea includes:

High blood pressure, which is associated with sleep apnea, is a major cause of later heart failure.
Sleep apnea reduces oxygen levels and causes abnormal changes in blood pressure and heart rate that add to the burden of the failing heart.
Obstructive sleep apnea can affect breathing functions that are particularly harmful for patients with existing congestive heart failure.
Sleep apnea is associated with poorer survival in patients with heart failure. Some studies have suggested that treating sleep apnea with CPAP may improve heart function in these patients. However, a 2005 New England Journal of Medicine study found that CPAP did not improve survival in patients with heart failure and central sleep apnea

Atrial Fibrillation. Sleep apnea is more common in people with atrial fibrillation (irregular heartbeat) than in patients with other heart conditions. In a 2005 study published in Circulation, 49% of patients with atrial fibrillation were at risk for developing apnea, compared with 32% of general cardiology patients. An earlier study indicated that patients with untreated obstructive sleep apnea may be at increased risk for recurrence of atrial fibrillation. Patients with atrial fibrillation who received CPAP treatment had a lower risk for recurrence.

Metabolic Syndrome. The metabolic syndrome (also called Syndrome X) is a cluster of abnormalities that cause insulin resistance. Some of these factors, including hypertension and obesity, are also associated with sleep apnea. A 2004 study found that metabolic syndrome was nine times more common among patients with obstructive sleep apnea, independent of obesity.

Diabetes. Severe obstructive sleep apnea may more than double the risk of developing type 2 diabetes. Sleep apnea also increases the risk for diabetes during pregnancy (gestational diabetes).

When it comes to sleep apnea and obesity, it is not always clear which condition is responsible for the other. For example, obesity is often a risk factor and possibly a cause of sleep apnea, but it is also likely that sleep apnea increases the risk for weight gain. Some studies indicate that sleep apnea disrupts rapid eye movement (REM) sleep, which, in turn, increases the risk for obesity. Research indicates that animals deprived of REM sleep tend to eat more. People with apnea may also become too tired to exercise and so put on weight.

Sleep apnea is associated with a higher incidence of many medical conditions, other than heart and circulation. The links between apneas and the conditions are unclear.

Pulmonary hypertension.
Asthma. Sleep apnea may worsen asthma symptoms and interfere with the effectiveness of asthma medications. Treating the apnea may help asthma control.
Kidney failure.
Peripheral nerve damage (tingling, pain, or numbness in the hands and feet).
Liver damage in obese individuals with sleep apnea. Recent research suggests that severe apnea may increase the risk of liver disease regardless of weight.
Seizures, epilepsy, and other nerve disorders. Sleep apnea appears to pose a particularly risk for nocturnal epilepsy, a condition in which seizures occur during sleep.
Headaches. Sleep disorders, including apnea, may be the underlying causes of some chronic headaches. In some patients with both chronic headaches and apnea, treating the sleep disorder has cured the headache, even the very severe and disabling form known as a cluster headache.
High-risk pregnancies. Sleep apnea causes higher rates of pregnancy complications, including gestational diabetes and high blood pressure.
Eye disorders, including glaucoma, conjunctivitis, dry eye, and various other infections and irritations. Findings presented at the 2003 annual meeting of the American Academy of Ophthalmology suggested that patients with sleep apnea may be at increased risk for glaucoma and should be tested for this eye disease. A vision-damaging condition called intracranial hypertension has also been observed in some patients with sleep apnea.

Studies report an association between severe apnea and psychological problems. In one study, 32% of patients had symptoms of depression. According to a 2006 study, the risk for depression rises with increasing severity of sleep apnea. Sleep-related breathing disorders can also worsen nightmares and post-traumatic stress disorder. Certainly, daytime sleepiness interferes with mental alertness and quality of life.

Because sleep apnea so often includes noisy snoring, the condition can also adversely affect the sleep quality of a patient's bed partner. Spouses or partners may also suffer from sleeplessness and fatigue. In some cases, the snoring can disrupt relationships. Diagnosis and treatment of sleep apnea in the patient can help eliminate these problems.

Failure to Thrive. Small children with undiagnosed sleep apnea may "fail to thrive," that is, they do not gain weight or grow at a normal rate and they have low levels of growth hormone. In severe cases, this may affect the heart and central nervous system. Most often, sleep apnea in children is caused by overgrown tonsils or adenoid. Their removal often completely solves all of these problems, including resolution of sleep apnea and restoring weight gain and normal growth hormone levels.

Attention Deficits and Hyperactivity. Problems in attention and hyperactivity are common in children with sleep apnea. There is some evidence that such children may be misdiagnosed with attention-deficit hyperactivity disorder. Snoring, rather than sleepiness, is a stronger risk factor for hyperactivity in many of these children, especially boys under 8 years old. (Even children who snore and do not have sleep apnea may be at higher risk for poor concentration.)

Some researchers believe that sleepiness associated with sleep apnea is the greatest risk factor for car accidents. As many as 200,000 automobile accidents in the U.S. and 1,500 deaths from such accidents are caused by sleepiness. Studies continue to report that drowsy driving is as risky as drunk driving. Several studies have suggested that people with sleep apnea have two to three times as many car accidents, and five to seven times the risk for multiple accidents.

Diagnosis

Not all people with suspected sleep apnea require medical tests. Expensive diagnostic efforts are probably not required for individuals who have no other health risk factors and whose suspected apnea does not affect their quality of life or safety on the road.

Doctors, however, should order diagnostic sleep studies if:

The patient has a serious medical condition that might be worsened or caused by sleep apnea. Such conditions include heart disease, high blood pressure, heart failure, diabetes, chronic headaches, epilepsy, obstructive lung disease, or severe acid reflux (GERD).
A child who shows signs of sleep apnea also has attention deficit problems or fails to thrive.
The sleep apnea is severe enough to impair quality of life, increase the risk for accidents, or both.

In some cases of an uncertain diagnosis, high-risk patients may need to consult a sleep specialist or go to a sleep disorders center. At most centers, patients undergo an in-depth analysis, usually supervised by a multi-disciplinary team of consultants who can provide both physical and psychiatric evaluations. Centers should be accredited by the American Academy of Sleep Medicine.

To help determine the presence of sleep apnea, the doctor will ask the following questions:

Is the patient taking any medications?
How many periods of sleepiness are there each day and when do they occur? (Patients with apnea often do not describe this symptom as feeling "sleepy." They are more apt to describe this feeling as "lack of energy" or "feeling tired all day.")
How restful is sleep?
Do headaches occur regularly in the morning?
Is the patient taking or withdrawing from stimulants, such as coffee or tobacco?
How much alcohol is consumed per day?
Does the patient have any problems with mental or emotional functioning?
Does the patient suffer from heartburn?
What is the normal sleeping position (back, side, or stomach)?
If there is a sleeping partner, does he or she complain about the patient's snoring or gasping for breath? (Many times it is useful to interview the bed partner.)

Keeping a Record of Sleep. To help answer these questions, the patient may need to keep a sleep diary. Every day for 2 weeks, the patient should record all sleep-related information, including responses to questions listed above described on a daily basis. Recording sleep behavior using an extended-play audio or videotape can be very helpful in diagnosing sleep apnea.

To diagnose sleep apnea, the doctor will check for physical indications of sleep apnea, including:

Abnormalities in the soft palate or upper airways, including enlarged tonsils
Upper body obesity
A wide neck measurement

Some evidence suggests that doctors may accurately identify nearly all cases of suspected sleep apnea using physical criteria, including taking measurements of body mass (the indication of obesity), neck circumference, and four areas inside the mouth.

If sleep apnea is not obvious after a physical examination and history, the doctor will need to rule out any other problems. These include sleep disorders, (such as narcolepsy, insomnia, or restless legs disorder), or any medical or psychologic conditions (chronic fatigue syndrome, depression) that may be causing daytime sleepiness.

Polysomnography is the technical term for an overnight sleep study that involves recording brain waves and other sleep-related activity. Polysomnography involves many measurements and is typically performed at a sleep center.

The patient arrives about 2 hours before bedtime without having made any changes in daily habits. Polysomnography electronically monitors the patient as he or she passes, or fails to pass, through the various sleep stages. Polysomnography tracks:

Brain waves
Body movements
Breathing
Heart rate
Eye movements

Changes in breathing and blood oxygen levels are also recorded. In patients with suspected sleep apnea, the sleep expert will track instances of apnea and hypopnea that last longer than 10 seconds. In general, if there are more than five episodes per hour, apnea is significant and if there are more than 15, the condition is serious.

Overnight polysomnography has been the gold standard for diagnosing obstructive sleep apnea in both adults and children. It is very labor-intensive and expensive, however, and also misses snoring-induced arousals. It is not always covered by health insurance, and some centers have waiting lists that are months long.

A number of portable devices are available, or are being developed, so that patients have the convenience of being monitored at home. Experts hope that such monitors eventually will replace the need for overnight sleep clinics or the need for attended monitoring at home. Limited evidence exists, however, on the accuracy of many portable monitors. Patients with serious medical conditions, including heart failure or a history of stroke or respiratory failure, should not use home tests.

The following are descriptions of some home monitoring techniques.

Home Oximetry. Pulse oximetry is a procedure that determines if oxygen levels in the blood are low. This is called hypoxia. Normal levels during the night would generally rule out sleep apnea. With this procedure, a device called a pulse oximeter is attached to the patient's finger. The oximeter transmits red and infrared light through the capillaries in the finger. Hemoglobin, a molecule in the blood that carries oxygen, absorbs part of these light waves. The ratio of the two light beams provides the measurement of oxygen. The test is not always accurate, however. A combination with polysomnography, especially heart rate measurements, may be best for diagnosing sleep apnea.

Home oximetry monitors are available to rule out sleep apnea, but their accuracy is unclear. A 2003 study indicated that home oximetry alone was not very helpful in discriminating between patients with or without sleep apnea. Home oximetry however, may be helpful in identifying patients with unsuspected and seriously low oxygen levels.

Unattended Monitoring with Auto-CPAP. This method is a recent and simple method for detecting impaired breathing. It uses an auto-CPAP machine, which is programmed to apply pressure through the airways via a tube that attaches to a mask that fits the nose. A monitor is attached that digitizes and records on a computer all the information on any apnea episodes during sleep.

Nasal Pressure Recording. One promising technique uses a very simple prong device that attaches to the nostrils. A monitor records the airflow through the mouth and nose.

Peripheral Arterial Tonometry. An investigative technique called peripheral arterial tonometry measures changes in blood flow in the arteries of the fingertips during sleep. Such measurements are proving to be accurate in detecting sleep apnea in 80% of cases.

The Epworth Sleepiness Scale uses a simple questionnaire to measure excessive sleepiness during eight situations.


Situation	Chance of Dozing 0 = no chance of dozing 1 = slight chance of dozing 2 = moderate chance of dozing 3 = high chance of dozing
Sitting and reading.	(Indicate a score of 0 to 3)
Watching TV.	(Indicate a score of 0 to 3)
Sitting inactive in a public place (a theater or a meeting).	(Indicate a score of 0 to 3)
As a passenger in a car for an hour without a break.	(Indicate a score of 0 to 3)
Lying down to rest in the afternoon when circumstances permit.	(Indicate a score of 0 to 3)
Sitting and talking to someone.	(Indicate a score of 0 to 3)
Sitting quietly after a lunch without alcohol.	(Indicate a score of 0 to 3)
In a car, while stopped for a few minutes in traffic.	(Indicate a score of 0 to 3)
Score Results	1-6: Getting enough sleep 4-8: Tends to be sleepy but is average. 9-15: Very sleepy and should seek medical advice. Over 16: Dangerously sleepy

Lifestyle Changes

Sleeping on the back causes sleep apnea in about half of all people with mild sleep apnea. Body position greatly affects the number and severity of episodes of obstructive sleep apnea, with at least twice as many apneas occurring in people who lay on their back as in those who sleep on their side. This may be due to the effects of gravity, which cause the throat to narrow when a person lies on the back. (Indeed, astronauts show a marked reduction in apneas and snoring in the weightlessness of space.) Positional sleep apnea affects people of all ages, including young children.

As a first step in dealing with sleep apnea, the patient should simply try rolling over onto the side. Patients who sleep on their backs and have 50 - 80 apneas per hour can sometimes nearly eliminate them when they shift to one side or the other. (Changing positions is less effective the more overweight a person is, but it still helps.)

Here are some suggestions that might help a person maintain a low-risk sleeping position:

Sew a small pocket to the back of the pajamas and place a tennis ball or other small ball into it.
A special pillow that helps to stretch the neck may reduce snoring and improve sleep for people with mild sleep apnea.
Sleeping in an upright position may improve oxygen levels in overweight people with sleep apnea. Elevating the head of the bed may help.

Over-the-counter nasal strips, such as the Breathe Right strip or other devices that open the nostrils, are inexpensive and useful to prevent snoring. They may significantly improve early-stage sleep in people with sleep disorders associated with nasal obstruction and help reduce morning tiredness. They are not intended as treatments for sleep apnea, however.

All patients with obstructive sleep apnea who are overweight should attempt a weight-reducing program. Weight loss certainly reduces snoring in many people, sometimes stopping it completely. It also improves sleep and significantly reduces daytime sleepiness. A 2000 study suggested that people who lost 10% of body weight experienced an average 26% reduction in risk for developing sleep apnea in the first place. (Gaining 10% of their body weight, on the other hand, increased the odds of sleep apnea 6-fold.)

Smokers should quit, since smoking worsens apnea
Alcohol should be avoided within 4 hours of sleep

Treatment

Treatment for sleep apnea depends on the severity of the problem. Given the data on the long-term complications of sleep apnea, it is important for patients to treat the problem as they would any chronic disease. Simply trying to treat snoring will not treat sleep apnea. Because of its association with heart problems and stroke, sleep apnea that does not respond to lifestyle measures should be treated by a doctor, ideally a sleep disorders specialist.

At this time, the most effective treatments for sleep apnea are devices that deliver slightly pressurized air to keep the throat open during the night. There are a number of such devices available.

The best treatment for severe obstructive and mixed sleep apnea is a system known as continuous positive airflow pressure (CPAP), sometimes referred to as nasal continuous positive airflow pressure (nCPAP). It is safe and effective in sleep apnea patients of all ages, including children. CPAP is not recommended for patients with mild apnea. Patients with apnea but no daytime sleepiness report little or no benefit from this treatment.

CPAP works in the following way:

The device itself is a machine weighing about 5 pounds that fits on a bedside table.
A mask containing a tube connects to the device and fits over just the nose.
The machine supplies a steady stream of air through a tube and applies sufficient air pressure to prevent the tissues from collapsing during sleep.

Effects on Sleep and Wakefulness. A major 2003 analysis confirmed the benefits of CPAP on both objective and subjective measures of sleep. After using CPAP regularly many patients report the following benefits:

Restoration of normal sleep patterns.
Greater alertness and less daytime sleepiness.
Less anxiety and depression and better mood.
Improvements in work productivity.
Better concentration and memory. Some adults with symptoms of attention deficit hyperactivity disorder have improved after CPAP treatments for apnea. In two studies, however, equal improvements were also observed in people on sham CPAP, suggesting that the actual cognitive benefits from CPAP may be modest.
Patients' bed partners also report improvement in their own sleep when their mates use CPAP, even though objective sleep tests showed no real difference in the partners' sleep quality.

If patients do not experience less sleepiness after a period of time and are still complying with the regimen, then the airflow pressure may not be high enough. Patients may require retesting. Many patients report feeling more alert after CPAP treatments even if objective laboratory tests fail to show significant differences in the number of apneas and wake-up periods.

Protection from Accidents. Studies suggest that treatment with CPAP can reduce the risk for accidents. In a 2001 study, untreated patients had a risk for automobile accidents that was three times the risk in the general population. When these patients were treated, their risk fell to normal.

Effects on the Heart and Circulation. Evidence is mixed on whether CPAP treatment may reduce serious heart conditions. Early studies suggested that CPAP could improve heart function, lower blood pressure, and prevent new cardiac events (such as heart attacks) in patients with congestive heart failure and coronary artery disease. However, a 2005 study in the New England Journal of Medicine found that, while CPAP helped improve some heart disease symptoms, it did not affect overall survival in patients with heart failure and central sleep apnea. (Patients with heart failure often have central sleep apnea.)

It is also unclear whether CPAP improves blood pressure. A 2006 study of patients with high blood pressure and sleep apnea indicated that short-term (4 weeks) CPAP treatment has no significant effect on lowering blood pressure. (It is possible that longer-term treatment may be helpful.) Other studies have found blood pressure benefits from short-term CPAP treatment. Treatment for sleep apneas must be very effective, however, to have any benefits on blood pressure. Even a 50% reduction in apneas has no effect.

Effects on Other Medical Conditions. Some studies suggest other benefits with the use of CPAP:

Fewer morning headaches
Reduction in abdominal fat (abdominal fat has been related to a higher risk for diabetes and heart disease)
Lower blood sugar levels in patients with type 2 diabetes
Improved thinking and concentration in people with impaired mental function from sleep apnea
Modest lung improvement in patients with both apnea and chronic obstructive lung disease (such as emphysema)

CPAP works well for both adults and children, but many patients have problems getting used to the device. Unfortunately, CPAP devices are often cumbersome, which can lead to patients becoming discouraged and stopping treatment. All patients should be warned that the first few nights of CPAP therapy are unnerving. The device often produces anxiety, primarily because of the mask. Starting out with low pressure to get used to the mask may help. Patients may actually experience less sleep or sleep of a different quality in the beginning of treatment.

Nearly all patients complain about at least one side effect. Nearly half of complaints are related to the mask. Many of these problems can be reduced with a well-chosen mask that is comfortable and reduces leakage as much as possible. Common complaints include:

Irritation in the nose and throat. The most common complaints are nasal congestion and sore or dry mouth, which are caused by leakage that dries the airway. (This may be severe in elderly people or patients who have had uvulopalatopharyngoplasty, a surgical treatment for sleep apnea. Such patients are more likely to stop using CPAP.) Chin straps, nasal salt water sprays, or humidifiers may prevent these side effects. Heated humidification devices are also now available for CPAP users.
Excessive application of pressure making exhalation difficult.
A feeling of claustrophobia is a major factor in noncompliance. This can be improved by a lightweight and transparent mask or with masks known as nasal pillows, which are used only around the nostrils.
Up to 30% of patients experience irritation and sores over the bridge of the nose. Getting a properly fitted and cushioned mask can help reduce this effect.
Eye irritation or conjunctivitis.
Upper respiratory infections. It is very important to keep the unit clean.
Patients may also experience temporary chest muscle discomfort, which is caused by an increase in lung volume.
Severe side effects are very rare but may include heart rhythm disorders (arrhythmias), severe nose bleeding, and air pockets in the skull.
In addition to initial difficulties with its use, the fixed CPAP needs to be periodically readjusted. Patients can be trained to adjust the CPAP at home, thereby avoiding trips to the sleep professional for machine adjustments and making the process more convenient.

Although studies have reported that long-term compliance with CPAP systems is low, with about one-third of patients giving up the treatment, recent information suggests that it is improving, probably due to better technologies and better education. Patient education and support groups, a dedicated nurse to ensure close follow-up of patients (particularly in the first 2 weeks of therapy), and ready access to doctors to make adjustments as needed have all been shown to greatly improve compliance. (However, sleeping pills do not appear to help patients adapt to the device.) Not surprisingly, patients whose symptoms are noticeably relieved by the procedure early on are more likely to continue the therapy.

Because many patients find CPAP uncomfortable and difficult, they tend not to use it for the duration of the entire night. A 2007 study indicated that while some patients’ daytime sleepiness may improve after 4 - 6 hours of CPAP use each night, maximum benefits in quality of life require at least 7.5 hours of nightly CPAP use. It appears that longer nightly duration of CPAP use is best for achieving normal daytime functioning.

Bilevel Positive Airway Pressure. Bilevel positive airway pressure (BPAP) systems may be particularly helpful for patients with coexisting lung disease and those with excessive levels of carbon dioxide. These devices have a sensing feature that helps determine and vary the appropriate pressure depending on whether a person is breathing in or out. Greater pressure is needed on inhalation and less on exhalation. These machines are more expensive than the CPAP and may not be covered by insurance.

Automatic Titrating (Auto)-CPAP Pressure Devices. Even more sophisticated systems, called auto-CPAP devices, are available. These devices automatically customize air pressure for the individual patient. They usually use one of three methods:

Overall pressure is kept low until a specific problem is detected. At that time the pressure is automatically increased rapidly.
Pressure is low when there are no problems but is raised gradually when they are detected.
Pressure is gradually raised and lowered in response to problems or their absence. In addition, the device can change depending on problems within single breaths.

Brands include AutoAdjust, Virtuoso, and AutoSet. These devices are more expensive than those that provide continuous airflow. A 2003 study indicated that they may improve compliance, particularly in patients who require high CPAP use. They may be especially helpful for patients who require varying levels of pressure due to other conditions, such as seasonal allergies. They may also be useful as home diagnostic tools for sleep apnea. Auto-CPAP devices are not recommended for all patients, particularly those with heart failure or serious lung disease.

In general, drugs have not been very beneficial except for specific situations. Medications that treat accompanying disorders associated with sleep apnea may be helpful. The following may be helpful for certain patients:

Modafinil (Provigil), which is also used to treat narcolepsy, was approved by the FDA in 2004 as the first drug to treat the sleepiness associated with obstructive sleep apnea. However, Provigil is meant to be used in combination with -- not as a substitute for -- standard apnea treatments such as CPAP. Sleep experts stress that patients who take Provigil should adhere to CPAP treatment as the drug treats only the symptom of sleepiness, not the underlying health risks associated with sleep apnea.
Thyroid hormone may help sleep apnea in those with low thyroid (hypothyroidism).
Theophylline, a drug commonly used for asthma management, has shown promise in treating central sleep apnea in patients with heart failure.
Omeprazole (Prilosec), a drug used for patients with severe heartburn, may help patients with both sleep apnea and gastroesophageal reflux disorder (GERD).

Note on Sedatives. Sedatives, narcotics, and anti-anxiety drugs can actually worsen the breathing disturbances and arousal conditions that occur with sleep apnea. These substances cause the soft tissues in the throat to sag and diminish the body's ability to inhale. Apnea sufferers should never use sleeping pills or tranquilizers. Apnea patients undergoing surgery should be sure that their surgeons, anesthesiologists, and other doctors are aware of their sleeping disorder in considering sedatives, anesthetics, and medications taken to relieve pain due to surgery.

Dental Devices

Oral appliances, also called dental appliances or devices, may be an option for patients who cannot tolerate CPAP. The American Academy of Sleep Medicine recommends dental devices for patients with mild-to-moderate obstructive sleep apnea who are not appropriate candidates for CPAP or who have not been helped by it. (CPAP should be used for patients with severe sleep apnea whenever possible.)

Several different dental devices are available. A trained dental professional such as a dentist or orthodontist should fit these devices. Devices include:

Mandibular advancement device (MAD). This is the most widely used dental device for sleep apnea. It is similar in appearance to a sports mouth guard. MAD forces the lower jaw forward and down slightly, which keeps the airway open.
Tongue retraining device (TRD). This is a splint that holds the tongue in place to keep the airway as open as possible.

Patients fitted with one of these devices should have a check-up early on to see if it is working; short-term success usually predicts long-term benefits. It may need to be adjusted or replaced periodically.

MAD and similar devices seem to offer the following benefits:

Significant reduction in apneas for those with mild-to-moderate apnea, particularly if patients sleep either on their backs or stomachs. They do not work as well if patients lie on their side. The devices may also improve airflow for some patients with severe apnea.
Improvement in sleep in many patients.
Improvement and reduction in the frequency of snoring and loudness of snoring in most (but not all) patients.
Higher compliance rates than with CPAP.

According to a 2006 review, dental devices help control sleep apnea in 52% of treated patients. A 2002 report indicated that long-term use of a dental device achieved an 81% success rate in apnea improvement, which was significantly higher than the 53% success rate noted for uvulopalatopharyngoplasty (UPPP), the standard surgical treatment. There were also few complications with the dental device.

Dental devices, including MAD, are not as effective as CPAP therapy. The cost of these devices tends to be high. Side effects associated with dental devices include:

Nighttime pain, dry lips, tooth discomfort, and excessive salivation. In general, these side effects are mild, although over the long term they cause nearly half of patients stop using dental devices. Devices made of softer materials may produce fewer side effects.
Permanent changes in the position of the teeth or jaw have occurred in some cases of long-term use. Patients should have regular visits with a health professional to check the devices and make adjustments.
In a small percentage of patients, the treatment may worsen apnea. Patients should be monitored with polysomnography (sleep lab evaluation) before and after therapy and when apnea symptoms worsen or recur.

An orthodontic treatment called rapid maxillary expansion, in which a screw device is temporarily applied to the upper teeth and tightened regularly, may help patients with sleep apnea and a narrow upper jaw. This nonsurgical procedure helps to reduce nasal pressure and improve breathing.

Surgery

Surgery is sometimes recommended, usually by throat specialists, for severe obstructive sleep apnea. A patient should be sure to seek a second opinion from a specialist in sleep disorders. Few randomized clinical trials, the gold standard of medical research, have been conducted to verify the long-term efficacy of sleep apnea surgery.

The Procedure. Surgery known as uvulopalatopharyngoplasty (UPPP) removes soft tissue on the back of the throat. Such tissue includes all or part of the uvula (the soft flap of tissue that hangs down at the back of the mouth) and parts of the soft palate and the throat tissue behind it. If tonsils and adenoids are present, they are removed. The surgery typically requires a stay in the hospital.

The Goal of Surgery. The goal of UPPP is threefold:

Increase the width of the airway at the throat's opening
Block some of the muscle action in order to improve the ability of the airway to remain open
Improve the movement and closure of the soft palate

Success Rates. Success rates for sleep apnea surgery are rarely higher than 65% and often deteriorate with time, averaging about 50% or less over the long term. Few studies have been conducted on which patients make the best candidates. Some studies suggest that surgery is best suited for patients with abnormalities in the soft palate, which may or may not involve the tonsils. Results are poor if the problems involve other areas or the full palate. In such cases, CPAP is superior. In one study, sleeping on the side (rather than the back) after surgery significantly boosted success rates.

Complications. Uvulopalatopharyngoplasty is among the most painful treatments for sleep apnea, and recovery takes several weeks. It is recommended only for select patients with severe obstructive sleep apnea. The procedure also has a number of potentially serious complications. In fact, in one study, 42% of patients had complaints about the procedure. Some complications include:

Infection. In one study, this complication was so common that 40% of patients needed another operation because of it. Preventive antibiotics administered an hour before surgery can help reduce this risk.
Impaired function in the soft palate and muscles of the throat.
Mucus in the throat.
Changes in voice frequency.
Swallowing problems.
Regurgitation of fluids through the nose or mouth.
Impaired sense of smell.
Failure and recurrence of apnea. In such cases, CPAP is often less effective afterward, although one study found that oral appliances (plastic mouth retainer-like devices) may still help.

Experts estimate that in general about 1.6% of patients experience serious complications. Many of these complications can be avoided with proper technique and experienced surgeons. However, a patient’s health status may also affect outcomes. According to a 2006 study, patients are more likely to experience complications if they have severe sleep apnea, are overweight, have other medical problems, or undergo other surgical procedures at the same time as UPPP.

A variation on UPPP called laser-assisted uvulopalatoplasty (LAUP) is being increasingly performed to reduce snoring. It removes less tissue at the back of the throat than UPPP and can be done in a doctor's office. At this time, however, long-term success rates from LAUP are very modest, particularly for reducing apneas. Some doctors, in fact, are concerned that if LAUP eliminates snoring, they may miss a diagnosis of apnea in patients who have the more serious condition.

More than 50% of patients complain of throat dryness after surgery. Throat narrowing and scarring have also been reported. In a minority of patients, snoring becomes worse afterward.

The pillar palatal implant is a noninvasive surgical treatment for mild-to-moderate sleep apnea and snoring. It helps reduce the vibration and movement of the soft palate. In this procedure, a doctor inserts 3 short pieces of polyester string into the soft palate. The procedure can be performed in a doctor’s office and takes about 10 minutes. Unlike uvulopalatopharyngoplasty (UPPP), the pillar procedure requires only local anesthesia. Studies indicate it works as well as UPPP, with less pain and quicker recovery time.

Tracheostomy used to be the only treatment for sleep apnea. It is quite straightforward:

The surgeon makes an opening through the neck into the windpipe and inserts a tube.
It is almost 100% successful, but it requires a quarter-size opening in the throat. This produces a number of medical and psychological problems associated with recovery.

Today, this operation is performed rarely, usually only if sleep apnea is life-threatening.

A technique called radiofrequency ablation uses radiofrequency energy to shrink tissues in the upper airways:

The radio waves heat, stiffen, and shrink a small amount of tissue at the base of the tongue.
The therapy takes about 20 minutes and can be done in a doctor's office.
It typically requires 10 treatments within five or six sessions. (A newer form requires fewer treatment sessions, and it appears to be effective.)
It is far less invasive than standard surgery and results in far less pain and fewer complications. Discomfort can be controlled with simple pain relievers.

Studies reporting significant improvement in reduced snoring and less daytime sleepiness for some patients although, as with other surgeries, the benefits may be short term in the majority of patients. It may be helpful for mild obstructive sleep apnea.

Other surgical procedures may be appropriate to correct facial abnormalities or obstructions that cause sleep apnea. They may be used alone or combined with each other or with UPPP. They include:

Tongue advancement, in which an opening is cut where the tongue joins the jawbone and the area is pulled forward.
Genioplasty, which is plastic surgery on the chin.
Hyoid surgery, in which the movable bone underneath the chin is moved forward, pulling the tongue muscle along with it.
Maxillary or maxillomandibular advancement (MMA), which moves the upper (maxilla) or lower (mandible) jawbone forward. A survey of patients who had MMA found that the surgery changed their facial appearance, but most people thought it was a change for the better.
Surgery for nasal obstructions (such as a deviated septum) that contribute to snoring and other symptoms.

Adenotonsillectomy, or surgical removal of the tonsils and adenoids, is a first-line treatment for children and adolescents with sleep apnea. It cures the condition in 75 - 100% of cases. Two studies, published in 2005, suggested that adenotonsillectomy can significantly improve quality of life for children with obstructive sleep apnea.

Complications include respiratory illness, which occurs in about 25% of children after the surgery. The highest risk for respiratory complications is associated with:

Age under 3 years old
Severe sleep apnea
Heart complications
Failure to thrive
Obesity
Prematurity
Recent lung infections
Certain facial structures
Neuromuscular disease

The procedure may fail to improve apnea in some patients, such as those with very severe disease. Such children are candidates for continuous positive airway pressure (CPAP) therapy.

Removal of the tonsils and adenoids alone is not an effective treatment for adults with sleep apnea, although the procedure may be effective when combined with UPPP surgery.

Resources

www.sleepapnea.org -- American Sleep Apnea Association
www.nhlbi.nih.gov -- National Heart, Lung, and Blood Institute
www.aasmnet.org -- American Academy of Sleep Medicine
www.sleepfoundation.org -- National Sleep Foundation
www.nhlbi.nih.gov/about/ncsdr -- National Center on Sleep Disorders Research
www.sleepeducation.com -- Sleep Education from the American Academy of Sleep Medicine
www.wfsrs.org -- World Federation of Sleep Research Societies

References

Bradshaw DA, Ruff GA, Murphy DP. An oral hypnotic medication does not improve continuous positive airway pressure compliance in men with obstructive sleep apnea. Chest. 2006 Nov;130(5):1369-76.

Kezirian EJ, Weaver EM, Yueh B, Khuri SF, Daley J, Henderson WG. Risk factors for serious complication after uvulopalatopharyngoplasty. Arch Otolaryngol Head Neck Surg. 2006 Oct;132(10):1091-8.

Peppard PE, Szklo-Coxe M, Hla KM, Young T. Longitudinal association of sleep-related breathing disorder and depression. Arch Intern Med. 2006 Sep 18;166(16):1709-15.

Weaver TE, Maislin G, Dinges DF, Bloxham T, George CF, Greenberg H, et al. Relationship between hours of CPAP use and achieving normal levels of sleepiness and daily functioning. Sleep. 2007 Jun 1;30(6):711-9.

Review Date:
7/18/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Restless legs syndrome and related disorders

FitSugar — Wed, 08 Oct 2008 17:35:14 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Complications
Diagnosis
Treatment
Medications
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Treatment

The American Academy of Sleep Medicine recommends medications for restless legs syndrome (RLS) or periodic limb movement disorder (PLMD) only for persons who fulfill strict diagnostic criteria and experience too much daytime sleepiness as a result of these conditions. (Excessive daytime sleepiness results from nighttime sleeplessness due to RLS or PLMD symptoms).
The U.S. Food and Drug Administration (FDA) announced in March 2007 that the dopamine agonist drug pergolide (Permax) has been voluntarily withdrawn from the market. This drug can cause serious damage to the heart valves of patients who take it.
The FDA approved pramipexole (Mirapex) for use in moderate-to-severe restless legs syndrome (RLS) in November 2006.
Bupropion (Wellbutrin), a newer antidepressant, may also be helpful for RLS. Bupropion, a weak dopamine reuptake inhibitor, causes a slight increase in the availability of dopamine in the brain. It is not addictive and does not have the severe side effects of other RLS drugs, but more research is needed to determine its usefulness. It is not FDA approved for RLS.

Research

Results from a large study show that RLS is more common in children and teens than epilepsy and diabetes. The study also found that more than 70% of affected children had at least one biological parent with RLS.
Two recently-published studies found an abnormal gene on chromosome 6 makes some people susceptible to RLS and PLMD.
People with type 2 diabetes have higher rates of secondary RLS. Nerve pain (neuropathy) related to their diabetes cannot fully explain this increased rate in RLS.

Introduction

Restless legs syndrome (RLS) is an unsettling and poorly understood movement disorder affecting 3 - 15% of the general population. RLS can affect both children and adults. Although effective treatments are available, the condition often remains undiagnosed.

Symptoms of RLS. The core symptom of RLS is an irresistible urge to move the legs (medically known as akathisia). Some people describe this symptom as a sense of unease and weariness in the lower leg, which is aggravated by rest and relieved by movement. Specific characteristics of RLS include:

"Pulling, searing, drawing, tingling, bubbling, or crawling" beneath the skin, usually in the calf area, causing an irresistible urge to move the legs. These sensations can occur not only in the lower legs, but they can also affect the thighs, feet, and even the upper body. RLS-type symptoms may also occur in the arms. This may be the first symptom of RLS in some people.
About 80% of patients with RLS also experience semi-rhythmic movements called periodic limb movement disorder (PLMD).
Itching and pain, particularly aching pain, may be present.
Patients experience symptoms when they feel most relaxed and their legs are at rest. (Movement, however, brings relief.) Symptoms usually occur at night when lying down, or sometimes during the day while sitting.
Episodes of RLS usually develop between 10 p.m. and 4 a.m. Symptoms are often most severe shortly after midnight. They typically occur for 30 - 60 seconds, and they usually resolve by morning. If the condition becomes more severe, people may begin to have symptoms during the day. These symptoms are always worse at night, however.
At night, the unpleasant sensations and the resulting uncontrollable urge to move the legs can often disturb sleep. Ignoring the need to move the legs usually only builds up tension until they jerk uncontrollably. If patients experience symptoms during the day, they usually feel compelled to move their legs in order to relieve the symptoms, making it difficult to sit during air or car travel or through classes or meetings.

Late-onset and Early-onset Forms. There appear to be two forms of RLS, early-onset and late-onset. Each form may have different characteristics:

People with early-onset RLS (occurring in the teenage years or earlier) tend to have a family history of the disorder. They also usually have RLS without accompanying pain.
Those with late-onset RLS usually do not have a family history of RLS. Their condition is more likely the result of a problem with the nervous system, and symptoms may include pain in the lower legs.

The medical term for periodic limb movement disorder (PLMD) is nocturnal myoclonus. PLMD symptoms include:

Episodes that usually occur during the night, peaking near midnight, as they do in restless legs syndrome (RLS).
Leg muscles contract and jerk every 20 - 40 seconds during sleep. Such movements may last less than 1 second, or as long as 10 seconds.
Unlike RLS, contractions in PLMD usually do not wake patients. PLMD is distinct from the brief and sudden movements that occur just as people are falling asleep, jolting them awake.

Although 80% of RLS sufferers have PLMD, only about 30% of people with PLMD also have RLS. While treatments for the two conditions are similar, PLMD is a separate syndrome. PLMD is also very common in narcolepsy, a sleep disorder that causes people to fall asleep suddenly and uncontrollably.

Cramps that awaken people during sleep are very common, and they are not part of restless legs syndrome or periodic limb movement disorder. They can be very painful and may cause a person jump out of bed in the middle of the night. They typically affect a specific area of the calf or the sole of the foot.

Circadian Rhythm. In sleep studies, subjects spend about one-third of their time asleep, suggesting that most people need about 8 hours of sleep each day. However, individual adults differ in the amount of sleep they need to feel well rested. Infants may sleep as many as 16 hours a day.

The daily cycle of life, which includes sleeping and waking, is called a circadian rhythm (circadian means "about a day"), or the biological clock. Hundreds of bodily functions follow biologic clocks, but sleeping and waking comprise the most prominent circadian rhythm. The sleeping and waking cycle is about 24 hours long. If confined to windowless apartments, with no clocks or other time cues, sleeping and waking only as their bodies dictate, humans typically live on slightly longer than 24-hour cycles.

The circadian rhythm usually takes the following daily patterns:

Humans prefer daytime activity and nighttime rest.
A natural peak in sleepiness occurs at mid-day, the traditional siesta time.
Daily rhythms interact with other factors that may interfere or change individual patterns:
- The fraction-of-a-second-firing of nerve cells in the brain may be faster or slower in different individuals.
- The monthly menstrual cycle in women can shift the pattern.

Light signals coming through the eyes reset the circadian cycles each day, so changes in season, or changes in exposures to light and dark, can unsettle the pattern.

The Response in the Brain to Light Signals. The brain's response to light signals is an important key factor in sleep:

Light signals travel to a tiny cluster of nerves in the hypothalamus (in the center of the brain). This cluster is the body's master clock, which is called the supra chiasmatic nucleus (SCN). The SCN is named for its location, which is just above (supra) the optic chiasm, a major junction where nerves transmit information about light from the eyes.
The approach of dusk each day prompts the SCN to signal the nearby pineal gland (named so because it resembles a pinecone) to produce the hormone melatonin.
Researchers think that melatonin acts as the body's time-setting hormone. It also appears to trigger the need to sleep. The longer a person is in darkness, the longer the duration of melatonin secretion. Staying in bright light can decrease the secretion of melatonin.

Sleep consists of two distinct states that alternate in cycles, and reflect differing levels of brain nerve cell activity:

Non-Rapid Eye Movement Sleep. Non-rapid eye movement (NREM) sleep is also called quiet sleep. NREM is further subdivided into three stages of progression:

Stage 1: Light sleep
Stage 2: "True" sleep
Stage 3 to 4: Deep "slow-wave" or delta sleep

With each ascending stage, awakening becomes more difficult. It is not clear what governs NREM sleep in the brain. A balance between certain hormones, particularly growth and stress hormones, may be important for deep sleep.

Rapid Eye-Movement Sleep. Rapid eye-movement (REM) sleep is also called active sleep. Most vivid dreams occur in REM sleep. Brain activity in REM sleep is comparable to that in waking, but the muscles are virtually paralyzed, possibly preventing people from acting out their dreams. Except for vital organs like the lungs and heart, the only muscles not paralyzed during REM sleep are the eye muscles. REM sleep may be critical for learning and for day-to-day mood regulation. When people are sleep-deprived, their brains must work harder than when they are well rested.

The REM/NREM Cycle. The cycle between quiet and active sleep generally follows this pattern:

After about 90 minutes of NREM sleep, eyes move rapidly behind closed lids, giving rise to REM sleep.
As sleep progresses the NREM/REM cycle repeats.
With each cycle, NREM sleep becomes progressively lighter, and REM sleep becomes progressively longer, lasting from a few minutes early in sleep to perhaps an hour at the end of the sleep cycle.

The hypothalamus is a highly complex structure in the brain that regulates many important brain chemicals. Malfunction of this area of the brain may give rise to cluster headaches.

Causes

The main cause of restless legs syndrome (RLS) is unknown. Researchers are investigating neurologic (nervous system) problems that may arise either in the spinal cord or the brain. One current theory suggests that a deficiency in a brain chemical called dopamine causes restless legs syndrome.

RLS may often have a genetic basis, particularly in those who develop it before age 40. When the condition occurs in older adults, it is most likely due to a neurological problem.

The central nervous system is comprised of the brain and spinal cord. The peripheral nervous system includes all peripheral nerves.

People with restless legs syndrome (RLS) often have a family history of the disorder. Researchers have detected specific genetic locations or factors that might be responsible for this condition. Much of the research comes from studies of families with a strong history of RLS-related conditions. In 2005, researchers linked a location on chromosome 12 to RLS. They named this genetic marker RLS1. Locations on chromosomes 14 and 9 may also be associated with hereditary forms of RLS.

Dopamine and Neurologic Abnormalities in the Brain. Some research suggests that neurologic abnormalities involved with restless legs syndrome (RLS) and periodic limb movement disorder (PLMD) start in the brain. A variety of studies support the theory that an imbalance in neurotransmitters (chemical messengers in the brain), notably dopamine and serotonin, may play a part in RLS. Dopamine and serotonin cause numerous nerve impulses that affect muscle movement. The effect is similar to what happens in Parkinson's disease. Moreover, drugs that increase dopamine levels treat both disorders. However, Parkinson's disease itself does not seem to increase the risk for RLS. Nor does RLS early in life predispose to Parkinson's later on.

Neurologic Abnormalities in the Spine. Other research suggests that restless legs syndrome may be due to nerve impairment in the spinal cord. Researchers considered that such abnormalities were likely to start in nerve pathways in the lower spine. However, some patients with RLS have symptoms in the arms, indicating that the upper spine may also be involved.

Neuropathy. Some experts suggest that RLS, particularly if it occurs in older adults, may be a form of neuropathy, which is an abnormality in the nervous system outside the spine and brain. Nevertheless, there is no evidence of a causal relationship.

Iron deficiency, even at a level too mild to cause anemia, has been linked to restless legs syndrome (RLS) in some people. Studies suggest, in fact, that RLS in some people may be due to a problem with getting iron into cells that regulate dopamine in the brain. Some studies have reported RLS in 25 - 30% of people with low iron levels. The common connection between RLS and Parkinson's disease, in turn, may be not having enough iron in these patients.

The cause or causes of periodic limb movement disorder (PLMD) are not clear. Some research suggests that it may be due to abnormalities in the autonomic nervous system, which regulates the involuntary actions of the smooth muscles, heart, and glands.

Risk Factors

Restless legs syndrome (RLS) may affect 2.5 - 15% of the general population. It is more common in women than in men, and its frequency increases with age. The disorder affects an estimated 10 - 28% of adults older than age 65. In about 40% of patients, RLS begins in adolescence.

RLS may be more common than epilepsy and diabetes in children and teens. More than 70% of affected children in one study had at least one biological parent with RLS.

As many as two-thirds of people with restless legs syndrome (RLS) have a family history of the disorder. If so, RLS is more likely to occur before they turn 40. (A family history of RLS is less likely in people who develop it as older adults.) RLS is also more common in people from northern and western Europe, giving added support for a genetic basis for some cases.

Restless legs syndrome (RLS) and periodic leg movement disorder (PLMD) in children are strongly associated with inattention and hyperactivity. One study suggested that a quarter of children diagnosed with attention-deficit hyperactivity disorder (ADHD) also have RLS or PLMD, and this may actually contribute to inattentiveness and hyperactivity. The disorders have much in common, including poor sleep habits, twitching, and the need to get up suddenly and walk about frequently. Some evidence suggests that the link between the diseases may be a deficiency in the brain chemical dopamine.

About 20% of pregnant women report having restless legs syndrome (RLS). The condition usually goes away about a month after delivery. RLS in this population has been strongly associated with deficiencies in iron and the B vitamin folate.

Between 20 - 62% of people undergoing dialysis report restless legs syndrome. Symptoms often disappear after a kidney transplant.

Anxiety can cause restlessness and agitation at night. These symptoms can cause (or strongly resemble) restless legs syndrome.

The following medical conditions are also associated with restless legs syndrome (RLS), although the relationships are not clear. In some cases, these conditions may contribute to RLS, or they may have a common cause. In some cases, they may coexist due to other risk factors:

Osteoarthritis (degenerative joint disease). About 72% of patients with RLS also have osteoarthritis, a common type of arthritis affecting mostly older adults.
Varicose veins. Varicose veins occur in 14% of patients with RLS. Sclerotherapy treatments, in which doctors inject medications into affected veins, may relieve symptoms in such cases.
Obesity
Diabetes -- people with type 2 diabetes may have higher rates of secondary RLS. Nerve pain (neuropathy) related to their diabetes cannot fully explain this increased rate in RLS.
Hypertension
Hypothyroidism (a condition in which the thyroid gland does not make enough hormones)
Fibromyalgia (chronic pain of unknown cause)
Rheumatoid arthritis
Emphysema (a lung disease usually caused by smoking)
Chronic alcoholism
Sleep apnea (pauses in breathing during sleep) and snoring
Chronic headaches
Brain or spinal injuries

Many muscle and nerve disorders. Hereditary ataxia, a group of genetic diseases that affects the central nervous system and causes loss of motor control, is of particular interest. Researchers believe that hereditary ataxia may supply clues to the genetic causes of RLS.

Osteoarthritis is a chronic disease of the joint cartilage and bone, often thought to result from "wear and tear" on a joint, although there are other causes such as congenital defects, trauma, and metabolic disorders. Joints appear larger, are stiff and painful, and usually feel worse the more they are used throughout the day.

Click the icon to see an image of hypothyroidism.

Click the icon to see an image of fibromyalgia.

Click the icon to see an image of rheumatoid arthritis.

Click the icon to see an image of emphysema.

Several environmental and dietary factors can worsen or provoke restless legs syndrome (RLS):

Iron deficiencies. People who are deficient in iron are at risk for restless legs syndrome, even if they do not have anemia
Folic acid or magnesium deficiencies
Smoking
Alcohol abuse
Caffeine (coffee drinking is specifically associated with PLMD)
Stress
Fatigue
Prolonged exposure to cold

Drugs that worsen or provoke the condition include:

Antidepressants
Antipsychotic drugs
Anti-nausea drugs
Beta-blockers (a type of heart medication)
Antihistamines
Oral decongestants
Diuretics
Asthma drugs
Spinal anesthesia (anesthesia-induced restless legs syndrome typically disappears on its own within several months)

About 6% of the general population has periodic limb movement disorder (PLMD). Among the elderly, the prevalence increases to 25 - 58%. Studies suggest that PLMD may be especially common in elderly women. As with RLS, numerous conditions are associated with PLMD. They include sleep apnea, spinal cord injuries, stroke, narcolepsy, and diseases that destroy nerves or the brain over time. Certain medications, including some antidepressants and anti-seizure medications, may also contribute to PLMD.

Complications

Restless legs syndrome rarely results in any serious consequences. But in some cases, severe and persistent symptoms can cause considerable mental distress, chronic insomnia, and daytime sleepiness.

Sleep deprivation, and the daytime sleepiness that follows, is increasingly recognized as a cause of mood disruption and a contributor to industrial errors and motor vehicle crashes.

Effect on Daily Performance and Activities. Studies suggest that sleeplessness worsens many waking behaviors. These include:

Reduced concentration. Deep sleep deprivation appears to impair the brain's ability to process information.
Impaired task performance. Missing several hours of nightly sleep over the course of a week can negatively affect performance levels and mood. In fact, sleep deprivation can cause impaired performance levels comparable to those of intoxicated people.
Effect on learning. Whether sleeplessness significantly impairs learning is unclear. Some studies have reported problems in memorization, although others have found no differences in test scores between people with temporary sleep loss and those with full sleep.

In addition, since restless legs syndrome (RLS) is worse when resting, people with severe RLS may avoid daily activities that involve long periods of sitting, such as going to movies or traveling long distances.

Studies in Swedish working-aged men and women reported that those with restless legs syndrome (RLS) were more apt to be socially isolated, to have frequent daytime headaches or depression, and to complain of reduced libido or problems related to sleepiness.

RLS can contribute to insomnia. Insomnia itself can increase the activity of hormones and pathways in the brain that produce emotional problems. Even modest alterations in waking and sleeping patterns can have significant effects on a person's mood. Persistent insomnia may even predict the future development of mood disorders in some cases.

It is not clear if RLS is responsible for negative mood states or if anxiety or depression contributes to RLS. Anxiety can cause agitation and leg restlessness that resemble RLS, and depression and RLS symptoms also overlap. In addition, certain types of antidepressant drugs -- such as serotonin reuptake inhibitors -- can increase periodic limb movements during sleep.

Diagnosis

A diagnosis of restless legs syndrome or nocturnal leg cramps often relies solely on the patient's description of symptoms. In general, the recommended approach is first to take a sleep and personal history. The doctor may conduct an interview that includes the following questions:

How would you describe your sleep problem?
How long have you had this sleep problem?
How long does it take you to fall asleep?
How many times a week does the problem occur?
How restful is your sleep?
What are the leg problems like (cramps, twitching, crawling feelings)?
What is your sleep environment like? Noisy? Not dark enough?
What medications are you taking (including the use of antidepressants and self-medications -- such as herbs, alcohol, and over-the-counter or prescription drugs)?
Are you taking or withdrawing from stimulants, such as coffee or tobacco?
How much alcohol do you drink per day?
What stresses or emotional factors may be present in your life?
Have you experienced any significant life changes?
Do you snore or gasp during sleep? (This may be an indication of sleep apnea. Sleep apnea is a condition in which breathing stops for short periods many times during the night. It may worsen symptoms of restless legs syndrome or insomnia.)
If you have a bed partner, does he or she notice that you have jerking legs, interrupted breathing, or thrashing while you sleep?
Are you a shift worker?

A bed partner can help by adding their observations of the patient's sleep behavior.

Some high-risk patients may need to consult a sleep specialist or go to a sleep disorders center before their sleep problem can be diagnosed. At most centers, patients undergo an in-depth analysis, usually supervised by a team of consultants from various specialties, who can provide both physical and psychiatric evaluations. Centers should be accredited by the American Academy of Sleep Medicine.

Among the signs that may indicate a need for a sleep disorders center are:

Insomnia due to psychological disorders
Sleeping problems due to substance abuse
Snoring and sudden awakening with gasping for breath (possible sleep apnea)
Severe restless legs syndrome
Persistent daytime sleepiness
Sudden episodes of falling asleep during the day (possible narcolepsy)

Overnight polysomnography involves several tests to measure different functions during sleep. It is typically performed in a sleep center and may help rule out sleep apnea or confirm the effectiveness of restless legs syndrome (RLS) treatments.

Brain waves
Body movements
Breathing
Heart rate
Eye movements
Changes in breathing and blood levels of oxygen

Actigraphy uses a small wristwatch-like device (such as Actiwatch) to monitor sleep quality in people with suspected restless legs syndrome (RLS), periodic leg movement disorder (PLMD), insomnia, sleep apnea, and other sleep-related conditions. Patients can wear the device on their wrists or ankles. It measures and records muscle movements during sleep. For example, with PLMD, actigraphy can provide information on the total duration of movements, the number of occurrences, whether PLMD occurs simultaneously in both legs, and its effects on sleep.

Actigraphy is not as accurate as polygraphy because it cannot measure all the biological effects of sleep. It is more accurate than a sleep log, however, and very helpful for recording long periods of sleep.

The Epworth sleepiness scale uses a simple questionnaire to measure excessive sleepiness during eight situations.


Situation	Chance of Dosing
Sitting and reading	(Indicate a score of 0 to 3) 0 = no chance of dozing 1 = slight chance of dozing 2 = moderate chance of dozing 3 = high chance of dozing
Watching TV	(Indicate a score of 0 to 3) 0 = no chance of dozing 1 = slight chance of dozing 2 = moderate chance of dozing 3 = high chance of dozing
Sitting inactive in a public place	(Indicate a score of 0 to 3) 0 = no chance of dozing 1 = slight chance of dozing 2 = moderate chance of dozing 3 = high chance of dozing
Riding as a passenger in a car for an hour without a break	(Indicate a score of 0 to 3) 0 = no chance of dozing 1 = slight chance of dozing 2 = moderate chance of dozing 3 = high chance of dozing
Lying down to rest in the afternoon when circumstances permit	(Indicate a score of 0 to 3) 0 = no chance of dozing 1 = slight chance of dozing 2 = moderate chance of dozing 3 = high chance of dozing
Sitting and talking to someone	(Indicate a score of 0 to 3) 0 = no chance of dozing 1 = slight chance of dozing 2 = moderate chance of dozing 3 = high chance of dozing
Sitting quietly after a lunch without alcohol	(Indicate a score of 0 to 3) 0 = no chance of dozing 1 = slight chance of dozing 2 = moderate chance of dozing 3 = high chance of dozing
Sitting in a car while stopped for a few minutes in traffic	(Indicate a score of 0 to 3) 0 = no chance of dozing 1 = slight chance of dozing 2 = moderate chance of dozing 3 = high chance of dozing
Score Results 1-6: Getting enough sleep. 4-8: Tends to be sleepy but is average. 9 and over: Very sleepy and suggestive of sleep-disordered breathing. Patient should seek medical advice.

Because of the high association between restless legs syndrome and iron deficiency, a test for low iron stores should be part of the diagnostic workup in restless legs syndrome (RLS). There are two steps in making this diagnosis:

The first step is to determine if a person is actually deficient in iron.
If iron stores are low, the second step is to diagnose the cause of the iron deficiencies, which will help determine treatment.

Determining if Iron Stores are Low: The following findings are important in determining that a person is iron deficient:

Blood cells viewed under the microscope are pale (hypochromic) and abnormally small (microcytic). They are also mostly uneven in shape. These findings suggest iron deficiency, but they can also appear in anemia resulting from chronic disease and in thalassemia.
Hemoglobin and iron levels are low. These findings further suggest iron deficiency, but they can also occur in cases of anemia due to chronic disease.
Ferritin levels are low. Ferritin is a protein that binds to iron, and low levels typically mean the patient does not have enough iron in their body. However, high levels of ferritin in the blood do not always mean a patient has enough iron. For example, pregnant women may have high ferritin levels even in their third trimester, yet still be iron deficient. Ferritin levels may also be normal, or even elevated, in patients with inflammation resulting from anemia due to chronic disease, even if these patients also so not have enough iron in their body.
A test that measures a factor called serum transferrin receptor (TfR) is proving to be very sensitive in identifying iron deficiency in some patients, including the elderly with chronic diseases and possibly pregnant women.

Determining Causes of Iron Deficiency. When iron deficiency anemia is diagnosed, the next step is to determine what causes the iron deficiency itself.

Dietary iron deficiency is most common in children and infants. It is rare in adults.
Heavy menstrual or abnormal uterine bleeding is usually the cause of iron deficiencies in young women. Increased need for iron during pregnancy is also a common cause of iron deficiency in pregnant women.
If doctors suspect internal bleeding as the cause of iron deficiency, they look first to the digestive tract as the possible source. A diagnosis in such cases can often be made if the patient has noticed blood in their stools, (the stool would be black and tarry or red-streaked). Often, however, bleeding may be present but not visible. In such cases, stool tests for this hidden (occult) blood are required. The patient may need additional tests to diagnose the cause of bleeding. One common test is endoscopy, in which a fiberoptic tube is used to look into the gastrointestinal tract. Doctors recommend it particularly when the source of bleeding is unclear.

If the patient's diet suggests low iron intake and doctors cannot find other causes of iron deficiency, they may recommend a month-long trial of iron supplements. If the patient fails to respond, they will need further evaluation.

Certain laboratory tests may be helpful in determining causes of restless legs syndrome (RLS) or conditions that rule it out. They include:

Blood glucose tests for diabetes
Tests for kidney problems
In certain cases, tests for thyroid hormone, magnesium, and folate levels

In addition to other sleep-related leg disorders, a number of other medical conditions may have features that resemble restless legs syndrome (RLS). The doctor will need to consider these disorders in making a diagnosis.

Peripheral Neuropathies. Peripheral neuropathies are nerve disorders in the hands or feet. Several conditions can cause these disorders, and they can produce pain, burning, tingling, or shooting sensations in the arms and legs. Diabetes is a very common cause of painful peripheral neuropathies. Other causes include alcoholism, rheumatoid arthritis, systemic lupus erythematosus, amyloidosis, HIV infection, kidney failure, and certain vitamin deficiencies. Symptoms of peripheral neuropathies may mimic RLS. However, unlike RLS, they are not usually associated with restlessness, movement does not relieve the discomfort, and they do not worsen at bedtime.

Deep Vein Thrombosis. Deep vein thrombosis (DVT) is a blood clot in a deep vein in the body, usually in the leg. It may cause pain, swelling, and aching in the leg where the clot has developed. It can occur in people with heart disease, with varicose veins, during pregnancy, in women from hormonal treatments, from injury to the leg, or from inactivity (such as after surgery or during long flights). In women, it can also result from hormonal treatments. Left untreated, DVT can be a very serious and even life-threatening condition.

This picture shows a red and swollen thigh and leg caused by a blood clot (thrombus) in the deep veins in the groin (iliofemoral veins), which prevents normal return of blood from the leg to the heart.

Intermittent Claudication and Peripheral Artery Disease. Peripheral artery disease (PAD) occurs when atherosclerosis (commonly called hardening of the arteries) affects the feet and legs. In such cases, blocked arteries reduce the flow of oxygen-rich blood to the legs or feet. Intermittent claudication is an important symptom of PAD and occurs in between one-third and one-half of these patients. The word claudication describes the pain that occurs in PAD patients when they exercise, particularly when they walk. In intermittent claudication, blood flows only enough to meet the needs of the person at rest. The result is leg pain during exercise, which disappears during rest.

Click the icon to see an image of peripheral artery disease.

Akathisia. Akathisia is a state of restlessness or agitation, and feelings of muscle quivering. A condition called hypotensive akathisia is caused by failure in the autonomic nervous system. Unlike RLS, it occurs at any time of the day and usually only when the patient is sitting -- not lying down. Drugs used to treat schizophrenia and other psychoses can cause akathisia, as can anti-nausea drugs. The condition also occurs when drugs to treat Parkinson's disease are withdrawn.

Painful Legs and Moving Toes Syndrome. A rare disorder affecting one or both legs, painful legs and moving toes syndrome is marked by a constant, deep, throbbing ache in the limbs and involuntary toe movements. The discomfort may be mild or severe. It gets worse with activity and usually stops during sleep. Usually, the cause is unknown, though it may arise from spinal injuries or herpes zoster infection. The condition is difficult to treat, although the drug baclofen, combined with either clonazepam or carbamazepine, has shown some success. Other treatments that may help include orthotics for the shoes and transcutaneous electrical nerve stimulation (TENS).

Meralgia Paresthetica. An uncommon nerve condition, meralgia paresthetica causes numbness, pain, tingling, or burning on the front and side of the thigh. It usually occurs on one side of the body, and the cause may be compression of the thigh nerve as it passes through the pelvis. It typically occurs in people aged 30 - 60 years, but it can affect people of all ages. It often goes away on its own.

Treatment

The first step in treating a patient who complains of sleeplessness and restless legs syndrome is to try to improve sleep and eliminate possible causes of restless legs syndrome (RLS). Doctors normally try to achieve these goals without the use of drugs, initially. A non-drug approach is a particularly important first step for elderly patients.

The doctor should first try to treat any underlying medical conditions that may be causing restless legs.
If medications may be causing RLS, the doctor should try to prescribe alternatives, if possible.

If the cause cannot be determined, it is best to first try better sleep habits and relaxation methods. These approaches may help, even if the patient needs drug therapy later on.

Some people report help or relief from restless legs syndrome (RLS) with the following behaviors or devices:

Hot baths or cold compresses help some patients.
Ergonomic measures -- for example, patients might find it useful to work at a high stool, where they can dangle their legs. In meetings or during air travel, it is helpful to have an aisle seat.
Changing sleep patterns -- some patients report that symptoms do not occur if they sleep late in the morning. Therefore, if feasible, patients can try changing sleep patterns.
Avoiding caffeine, alcohol, and nicotine also improves some cases of RLS.

Some patients recommend alternative treatments for RLS, such as acupuncture and massage. To date, however, there is not enough data on the effectiveness of these treatments.

Some people have reported benefits from:

Vitamin E (800 - 1,200 IU per day)
Calcium, magnesium, or potassium supplements
Folic acid supplements for people with folate deficiencies

Folate (folic acid) is necessary for the production of red blood cells and for the synthesis of DNA (which controls heredity and is used to guide the cell in its daily activities). Folic acid also helps with tissue growth and cell function. In addition, it helps to increase appetite when needed and stimulates the formation of digestive acids.

Because restless legs syndrome (RLS) is associated with iron insufficiency, people with the condition should get enough iron from their diet. [See In-Depth Report #57: Anemia.] Iron is found in foods either in the form of heme or non-heme iron:

Foods containing heme iron are the best for increasing or maintaining healthy iron levels. Such foods include (in decreasing order of iron-richness) clams, oysters, organ meats, beef, pork, poultry, and fish.
Non-heme iron is less well absorbed. About 60% of the iron in meat is non-heme (although meat itself helps absorb non-heme iron). Eggs, dairy products, and iron-containing vegetables (including dried beans and peas) have only the non-heme form. Other sources of non-heme iron include iron-fortified cereals, bread, and pasta products, dark green leafy vegetables (chard, spinach, mustard greens, kale), dried fruits, nuts, and seeds.

The Effects of Food on Iron Absorption. The absorption of non-heme iron often depends on the food balances in meals. The following are foods that enhance absorption of non-heme iron.

Meat and fish not only contain heme iron, the best form for maintaining stores, but they also help absorb non-heme iron.
Eating more vitamin C-rich foods can enhance absorption of non-heme iron during a single meal. In any case, vitamin C-rich foods are healthy. They include broccoli, cabbage, citrus fruits, melon, tomatoes, and strawberries. One orange or 6 ounces of orange juice can double the amount of iron your body absorbs from plant foods. (Taking vitamin C supplements does not appear to have any significant effect on how much iron your body stores.)
Foods containing riboflavin (vitamin B2) may help enhance the formation of hemoglobin from iron. Sources include liver, dried fortified cereals, and yogurt.

Certain nutrients impede the body's absorption of dietary iron. They include:

Polyphenols (found in tea, coffee, red wine, berries, and apples)
Phytates (found in foods such as seeds, dried beans, soy, and bran). Such foods are typically high in fiber. It is often believed that fiber itself impedes iron absorption, but researchers report that it has little or no effect.
Calcium. Calcium impairs the absorption of heme and non-heme iron. However, calcium intake must be quite high to cause any significant problems.

The Effects of Cooking Methods on Iron. Cooking methods can enhance the amount of iron in your body. Cooking in cast iron pans and skillets is a well-known way to increase the iron content of food. According to one study, boiling, steaming, or stir-frying in utensils composed of any material significantly increased the release of non-heme iron stored in vegetables.

Iron supplements can significantly reduce symptoms in people with restless legs syndrome (RLS) who are also iron deficient. Patients should use them only when dietary measures have failed. Iron supplements do not appear to be useful for RLS patients with normal or above normal iron levels.

Supplement Forms. To replace iron, the preferred forms of iron tablets are ferrous salts, usually ferrous sulfate (Feosol, Fer-In-Sol, Mol-Iron). Other forms include ferrous fumarate (Femiron, FerroSequels, Feostat, Fumerin, Hemocyte, Ircon), ferrous gluconate (Fergon, Ferralet, Simron), polysaccharide-iron complex (Niferex, Nu-Iron), and carbonyl iron (Elemental Iron, Feosol Caplet, Ferra-Cap). Specific brands and forms may have certain advantages. The following are some examples:

Prolonged-release ferrous sulfate (Slow Fe) may enhance iron absorption with fewer side effects than standard ferrous sulfate pills.
FerroSequels contains a stool softener, which helps prevent constipation.
Polysaccharide-iron complex has fewer side effects and equal absorption rates compared to ferrous salts. It is very expensive, however.
Carbonyl iron is composed of very fine tiny uniform spheres of iron powder and may prove to be less toxic than ferrous iron.
Coated or combination pills do not appear to offer any additional advantages and may hinder absorption of the iron.

Regimen. A reasonable approach for patients with RLS is to take 65 mg of iron (or 325 mg of ferrous sulfate) along with 100 mg of vitamin C on an empty stomach, 3 times a day.

IMPORTANT: As few as 3 adult iron tablets can poison, and even kill, children. This includes any form of iron pill. No one, not even adults, should take a double dose of iron if they miss one dose.

Tips for taking iron are:

For best absorption, take iron between meals. (Iron may cause stomach and intestinal disturbances, however. Some experts believe that you can take low doses of ferrous sulfate with food and avoid the side effects.)
Always drink a full 8 ounces of fluid with an iron pill.
Keep tablets in a cool place. Bathroom medicine cabinets may be too warm and humid, which may cause the pills to disintegrate.

Side Effects. Common side effects of iron supplements include the following:

Constipation and diarrhea -- these are rarely severe, although iron tablets can aggravate existing digestive problems such as ulcers and ulcerative colitis.
Nausea and vomiting may occur with high doses, but you can control this by taking smaller amounts. Switching to ferrous gluconate may help some people with severe digestive problems.
Black stools are normal when taking iron tablets. In fact, if they do not turn black, the tablets may not be working effectively. This tends to be a more common problem with coated or long-acting iron tablets.
If the stools are tarry looking as well as black, if they have red streaks, or if cramps, sharp pains, or soreness in the stomach occurs, bleeding in the digestive tract may be causing the iron deficiency, and the patient should call the doctor immediately.
Acute iron poisoning is rare in adults, but can be fatal in children who take adult-strength tablets.

Interactions With Other Drugs. Certain medications, including antacids, can reduce iron absorption.

Iron tablets may also reduce the effectiveness of other drugs, including:

Antibiotics: tetracycline, penicillamine, and ciprofloxacin
Anti-Parkinson's disease drugs: methyldopa, levodopa, and carbidopa

At least 2 hours should elapse between doses of these drugs and doses of iron supplements.

Supplementary Treatments. The following supplements may improve iron absorption:

Adding either ascorbic acid (vitamin C) or succinic acid to ferrous sulfate treatment will improve absorption of iron stores. Ascorbic acid added to iron treatment, however, may worsen some of the side effects. Succinic acid added to ferrous sulfate does not appear to increase side effects.
Some studies have found that the addition of zinc to iron supplements increases hemoglobin levels more than iron alone. Some evidence suggests that zinc affects a hormone called insulin-like growth factor-I (IGF-I), which plays a role in the regulation of red blood cell production.

Exercise earlier in the day may be one of the best ways to achieve healthy sleep. However, vigorous exercise and stimulation (including sexual activity) within 1 - 2 hours of bed time may worsen restless legs syndrome (RLS). A study found that people who walked briskly for 30 minutes, four times a week, improved minor sleep disturbances after 4 months. Regular, moderate exercise, healthful in any case, may help prevent RLS. Patients report that either bursts of excessive energy or long sedentary periods worsen symptoms.

Benign nocturnal leg cramps, sometimes known as a charley horse, are muscle spasms in the calf that can occur one or many times during the night. Cramping may also occur in the soles of the feet. They typically last from a few seconds to a few minutes. Some people experience them regularly, others only on isolated occurrences.

Causes of Nocturnal Leg Cramps. In most cases, the cause of nocturnal leg cramps remains unknown. Among the conditions that might cause leg cramps are:

Calcium and phosphorus imbalances, particularly during pregnancy
Low potassium or sodium (salt) levels
Overexertion, standing on concrete for long periods, or prolonged sitting (especially with the legs contorted)
Having structural disorders in the legs or feet (such as flat feet)
Medical causes of muscle cramping include hypothyroidism, Addison's disease, uremia, hypoglycemia, anemia, and certain medications. Various diseases that affect nerves and muscles, such as Parkinson's, cause leg cramps. Peripheral neuropathy, a complication of diabetes, can cause cramp-like pain, numbness, or tingling in the legs. Patients with kidney disease undergoing dialysis are also prone to leg cramps.

Individuals at Higher Risk for Nocturnal Leg Cramps. Nocturnal leg cramps occur at all ages but peak at different times. They are particularly common in adolescence, during pregnancy, and in older age, affecting up to 70% of adults over age 50 at some point.

Pregnant women and those taking diuretics are also at risk for leg cramps because of low calcium levels and an imbalance in calcium and phosphorus.

Consequences of Nocturnal Leg Cramps. Nocturnal leg cramps, like restless legs syndrome, rarely have any serious consequences. However, they can be extremely painful and long lasting. In some cases, severe and persistent symptoms can cause chronic insomnia and considerable mental distress.

Managing Nocturnal Leg Cramps. Once a cramp begins, straighten the leg, flex the foot upward toward the knee, or grab the toes and pull them toward the knee.

Walking or shaking the affected leg, then elevating it, may also help.

If soreness persists, a warm bath or shower or an ice pack may bring relief.

Lifestyle Tips for Preventing Nocturnal Leg Cramps. Nighttime leg cramps are generally treated with lifestyle changes.

Everyone with leg cramps should drink plenty of water (at least 6 - 8 glasses daily) to maintain adequate fluid levels.
Pregnant women and others who get legs cramps due to low calcium levels should reduce milk intake, because drinking milk does not correct the underlying imbalances in calcium and phosphorus. Instead, they should boost calcium levels by taking nonphosphate calcium supplements.
To prevent cramps from occurring, nightly stretching exercises may be the best preventive measure. Patients should stand about 30 inches from a wall and, keeping the heels flat on the floor, lean forward and slowly move the hands up the wall to achieve a comfortable stretch. A few minutes on a stationary bicycle at bedtime may also help.
While in bed, loose covers should be used to prevent the toes and feet from pointing, which causes calf muscles to contract and cramp. Propping the feet up higher than the torso may also help.
During the week, swimming and water exercises are a good way to keep muscles stretched, and wearing supportive footwear is also important.

Quinine. Quinine had been widely used to prevent leg cramping. The U.S. Food and Drug Administration (FDA) banned its sale over the counter because it reportedly caused some serious, although rare, side effects. These side effects include bleeding problems and heart irregularities. Other, less serious side effects include headaches, vision problems, and rash.

The FDA has since banned the marketing of most quinine drugs, cautioning against the off-label (non-approved) use of the drug to treat RLS. Only one form of the drug, Qualaquin, is approved for sale, for the treatment of some types of malaria. Pregnant women and those with liver problems should avoid quinine in any form.

Supplements. Some small studies indicate that the mineral magnesium, taken as magnesium citrate or magnesium lactate, may provide some benefit to people with leg cramps, including pregnant women.

In one small study, taking vitamin B complex was helpful. Other supplements tried for leg cramps include vitamin E, calcium, and potassium or sodium chloride, but these do not appear to be very effective. Sodium chloride (salt) may be helpful, but Western diets already contain too much sodium.

Medications

The American Academy of Sleep Medicine recommends medications for restless legs syndrome (RLS) or periodic limb movement disorder (PLMD) only for persons who fit strict diagnostic criteria, and who experience excessive daytime sleepiness as a result of these conditions. (Excessive daytime sleepiness results from nighttime sleeplessness due to RLS or PLMD symptoms). Little is known about the best way to treat RLS, but some experts suggest the following:

Over-the-counter pain relievers and possibly mineral and vitamin supplements (particularly folic acid in people who might be deficient) should be the first form of treatment.
People with RLS should have a test for iron deficiency. If they are iron deficient, they should start treatment with iron supplements.
Dopaminergic drugs (drugs that increase levels of dopamine) are the standard medicines for treating severe RLS, PLMD, or both.
Other drugs may be helpful if dopaminergic drugs fail, or for patients who have frequent -- but not nightly -- symptoms. These include opiates (pain relievers), benzodiazepines (sedative hypnotic drugs), or anticonvulsants. However, benzodiazepines and opiates can become habit forming and addictive.

Before taking stronger medications, people should try over-the-counter pain relievers, such as acetaminophen (Tylenol) or non-steroidal anti-inflammatory drugs (NSAIDs), which include ibuprofen (Advil, Motrin, Rufen), naproxen (Anaprox, Naprosyn, Aleve), and ketoprofen (Orudis KT, Aktron).

Although NSAIDs work well, long-term use can cause stomach problems, such as ulcers and bleeding, and possible heart problems. In April 2005, the Food and Drug Administration asked drug manufacturers of NSAIDs to include a warning label on their product that alerts users of an increased risk for heart-related problems and digestive tract bleeding.

Dopaminergic drugs increase the availability of the chemical messenger dopamine in the brain, and are the first-line treatment for severe restless legs syndrome (RLS) and periodic leg movement disorder (PLMD). These drugs significantly reduce the number of limb movements per hour, and improve the subjective quality of sleep. Patients with either condition who take these drugs have experienced up to 100% reduction in symptoms.

Dopaminergic drugs, however, can have severe side effects (they are ordinarily used for Parkinson's disease). They do not appear to be as helpful for RLS related to dialysis as they do for RLS from other causes.

Dopaminergic drugs include dopamine precursors and dopamine receptor agonists.

Dopamine Precursors. The dopamine precursor levodopa (L-dopa) was once a popular drug for severe RLS. The standard preparations (Sinemet, Atamet) combine levodopa with carbidopa, which improves the action of levodopa and reduces some of its side effects, particularly nausea. Levodopa can also be combined with benserazide (Madopar) with similar results, but Sinemet is almost always used in America. (Levodopa combinations are well tolerated and safe.)

Patients typically start with a very low dose taken 1 hour before bedtime. The dosage is increased until the patient finds relief. Patients sometimes need to take an extended form or to take it again during the night.

Levodopa acts fast, and the treatment is usually effective within the first few days of therapy. One study reported that a combination therapy of regular-release L-dopa plus sustained release L-dopa was effective in improving sleep.

Serious common side effects of L-dopa treatment (and, to lesser extent, of dopamine receptor agonists) are augmentation and rebound. Many studies report that augmentation (worsening of symptoms that occur earlier in the day) occurs in up to 70% of patients who take L-dopa. The risk is highest for patients who take daily doses, especially doses at high levels (greater than 200 mg/day). For this reason, patients should use L-dopa only intermittently (fewer than 3 times per week). The drug should be immediately discontinued if augmentation does occur. Following withdrawal from L-dopa, patients can switch to a dopamine receptor agonist.

The rebound effect causes increased leg movements at night or in the morning as the dose wears off, or as tolerance to the drug builds up.

Dopamine Receptor Agonists. Dopamine receptor agonists (also called dopamine agonists) mimic the effects of dopamine by acting on dopamine receptors in the brain. They are now generally preferred to L-dopa. Because they have fewer side effects than L-dopa, including rebound effect and augmentation, these drugs may be used on a daily basis. (Rebound effect is the worsening of symptoms over time; augmentation means the appearance of symptoms earlier in the day. About 30% of patients who take dopamine receptor agonists have reported augmentations symptoms. As the newer drugs are taken for longer periods and at higher doses, however, their augmentation rates may become closer to those of L-dopa.)

Dopamine agonists have been shown to relieve symptoms in 70 - 90% of patients. Dopamine agonists can be ergot-derived (such as cabergoline) or non-ergot derived (such as pramipexole and ropinirole). The newer non-ergotamine derivatives may induce fewer side effects than ergot-derived drugs. Studies on these medications report the following:

Ropinirole (Requip) is a non-ergotamine dopamine agonist. Approved in 2005, ropinirole is the first drug approved specifically for treatment of moderate-to-severe RLS (more than 15 RLS episodes a month). Side effects are generally mild but may include nausea, vomiting, drowsiness, and dizziness.
The Food and Drug Administration (FDA) approved pramipexole (Mirapex) for use in moderate-to-severe RLS in November 2006. However, patients may fall asleep, without warning, while taking this drug, even while performing activities such as driving.

Cabergoline (Dostinex) is also showing promise in clinical trials. In one study, cabergoline was used for RLS after levodopa had either failed or resulted in increased symptoms. Patients in the study reported relief or freedom from symptoms after 4 weeks of use. A 2006 study indicated that a single evening dose of cabergoline improved both day and nighttime limb movements, and sleep disturbances.The FDA announced in March 2007 that the dopamine agonist pergolide (Permax) was voluntarily withdrawn from the market. Studies confirmed that this drug could cause serious damage to the heart valves of patients who take it. These problems have not been reported with ropinirole or pramipexole, which are chemically different then pergolide.

Other Dopamine Agonists. Rotigotine is a unique dopamine agonist that is being developed in patch form for RLS. In May 2007, the FDA approved this patch for treatment of early Parkinson's disease. Other dopamine agonists that have shown some promise in small studies include alpha-dihydroergocryptine, or DHEC (Almirid), and piribedil (Trivastal).

Regimens. The effects of L-dopa are apparent in 15 - 30 minutes. Dopamine receptor agonists, meanwhile, take at least 2 hours to start working. Some doctors recommend regular use of dopamine receptor agonists for patients who experience nightly symptoms, and L-dopa for those whose symptoms occur only occasionally.

Side Effects. Common side effects of dopaminergic drugs vary but may include feeling faint or dizzy (especially when standing up), headaches, abnormal muscle movements, rapid heartbeat, insomnia, bloating, chest pain, and dry mouth. Nausea may be especially common. Adding the drug domperidone may help to relieve this side effect. In rare cases, dopaminergic drugs can cause hallucinations or lung disease.

Because these drugs may cause daytime drowsiness, patients should be extremely careful while driving or performing tasks that require concentration.

Long-term use of dopaminergic drugs can lead to loss of effectiveness (tolerance). Adding a drug called entacapone (Comtan) may prolong the duration of action of carbidopa-levodopa therapy (Sinemet), but it can cause nausea.

Rebound effect, augmentation, and tolerance can reduce the value of dopaminergic drugs in the treatment of RLS. Using the lowest dose possible can minimize these effects.

Withdrawal Symptoms. Patients who withdraw from these drugs typically experience very severe RLS symptoms for the first 2 days after stopping. RLS eventually returns to pre-treatment levels after about a week. The longer a patient uses these drugs, the worse their withdrawal symptoms.

Benzodiazepines, such as clonazepam (Klonopin), are known as sedative hypnotics. Doctors prescribe them for insomnia and anxiety. They may be helpful for some patients with restless legs syndrome (RLS) that disrupts sleep. Clonazepam may be particularly helpful for children with both periodic limb movement disorder and symptoms of attention deficit hyperactivity disorder. The medicine also may be helpful for patients with RLS who are undergoing dialysis.

Side Effects. Elderly people are more susceptible to side effects. They should usually start at half the dose prescribed for younger people, and should not take long-acting forms. Side effects may differ depending on whether the benzodiazepine is long-acting or short-acting.

The drugs may increase depression, a common condition in many people with insomnia.
Breathing problems may occur with overuse or in people with pre-existing respiratory illness.
Long-acting drugs have a very high rate of residual daytime drowsiness compared to others. They have been associated with a significantly increased risk for automobile accidents and falls in the elderly, particularly in the first week after taking them. Shorter-acting benzodiazepines do not appear to pose as high a risk.
There are reports of memory loss (so-called traveler's amnesia), sleepwalking, and odd mood states after taking triazolam (Halcion) and other short-acting benzodiazepines. These effects are rare and probably enhanced by alcohol.
Because benzodiazepines cross the placenta and enter breast milk, pregnant and nursing women should not use them. There are some reports of an association between the use of benzodiazepines in the first trimester of pregnancy and the development of cleft lip in newborns. Studies are conflicting at this point, but, due to other known side effects of benzodiazepines, pregnant women should not use these drugs, if possible.
In rare cases, overdoses have been fatal.

Interactions. Benzodiazepines are potentially dangerous when used in combination with alcohol. Some drugs, such as the ulcer medication cimetidine, can slow the breakdown of benzodiazepine.

Withdrawal Symptoms. Withdrawal symptoms usually occur after prolonged use and indicate dependence. They can last 1 - 3 weeks after stopping the drug and may include:

Gastrointestinal distress
Sweating
Disturbed heart rhythm
In severe cases, patients might hallucinate or experience seizures, even a week or more after they stop taking the drug.

Rebound Insomnia. Rebound insomnia, which often occurs after withdrawal, typically includes 1 - 2 nights of sleep disturbance, daytime sleepiness, and anxiety. The chances of rebound are higher with the short-acting benzodiazepines than with the longer-acting ones.

Narcotics are pain-relieving drugs that act on the central nervous system. They are sometimes prescribed for severe cases of restless legs syndrome (RLS). They may be a good choice if pain is a prominent feature. Some evidence also suggests that narcotics reduce the frequency of periodic leg movements.

There are two types of narcotics, both of which have been used for severe RLS:

Opiates (such as morphine and codeine) come from natural opium. Some patients report relief with the use of the opiate fentanyl (Duragesic), available in skin patch form. An implanted pump that uses morphine and an anesthetic called bupivacaine is showing promise for patients with severe RLS. The pump delivers the drugs to the fluid surrounding the spinal cord (cerebrospinal fluid).
Opioids are synthetic drugs. The most common example is oxycodone (Percodan, Percocet, Roxicodone, Oxycontin). Apomorphine is a morphine derivative. In one study, when injected under the skin at night, it reduced nocturnal discomfort and leg movements in some patients.

Although the use of narcotics for severe RLS is controversial, some studies have suggested that even when the treatments are long-term, they are rarely addictive for pain sufferers except among patients with a history of substance abuse.

The use of such drugs may be beneficial when included as part of a comprehensive pain management program. Such a program involves screening prospective patients for possible drug abuse, and regularly monitoring those who are taking narcotics. Doses should be adjusted as necessary to achieve an acceptable balance between pain relief and side effects. Patients on long-term opiate therapy should also be monitored periodically for sleep apnea, a condition that causes breathing to stop for short periods many times during the night. Sleep apnea may worsen symptoms of RLS, insomnia, and other complaints.

Tramadol. Tramadol (Ultram) is a pain reliever that has been used as an alternative to opioids. In one study, tramadol was very effective for RLS and produced few or no side effects. It has opioid-like properties, but is not as addictive. (However, there are reports of dependence and abuse with this drug as well.) Withdrawal after long-term use (longer than a year) can cause intense symptoms, including diarrhea, insomnia, and even restless legs syndrome itself.

Antiseizure drugs -- such as gabapentin (Neurontin), valproic acid (valproate, divalproex, Depakote, Depakene), and carbamazepine (Tegretol) -- relax blood vessels and are being tested for restless legs syndrome (RLS). Gabapentin, a newer antiseizure drug, is showing particular promise for mild-to-moderate RLS. One study reported that it improved RLS symptoms and sleep, particularly in patients who also experienced pain. It was also effective for periodic leg movement disorder. A new gabapentin product is in phase III clinical trials for the treatment of RLS. The new drug, known as XP13512, converts to gabapentin in the intestines, and therefore may reduce some of the side effects experienced by patients taking antiseizure medications.

Side Effects. All antiseizure drugs have potentially severe side effects. Therefore, patients should try these medications only after non-drug methods have failed. Side effects of many anti-seizure drugs include nausea, vomiting, heartburn, increased appetite with weight gain, hand tremors, irritability, and temporary hair thinning and hair loss (taking zinc and selenium supplements may help reduce this last effect). Some antiseizure drugs can also cause birth defects and, in rare cases, liver toxicity. Gabapentin may have fewer of these side effects than valproic acid or carbamazepine.

Antidepressants. Bupropion (Wellbutrin), a newer antidepressant, may be helpful for restless legs syndrome (RLS). Bupropion is a weak dopamine reuptake inhibitor -- it causes a slight increase in the availability of dopamine in the brain. The drug is not addictive and does not have the severe side effects of other RLS drugs, but more research is needed to determine if it is useful.

Clonidine. Clonidine (Catapres), a drug used for high blood pressure, is helpful for some patients and may be an appropriate choice for patients who have RLS accompanied by hypertension. It also may help patients with RLS who are undergoing hemodialysis.

Baclofen. The anti-spasm drug baclofen (Lioresal) appears to reduce intensity of RLS (although not frequency of movements).

Resources

www.aasmnet.org -- American Academy of Sleep Medicine
www.sleepfoundation.org -- National Sleep Foundation
www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
www.nhlbi.nih.gov/about/ncsdr/ -- National Center on Sleep Disorders Research
www.rls.org -- Restless Legs Syndrome Foundation
www.wemove.org -- Worldwide Education and Awareness for Movement Disorders

References

Bogan RK, Fry JM, Schmidt MH, Carson SW, Ritchie SY. Ropinirole in the treatment of patients with restless legs syndrome: a US-based randomized, double-blind, placebo-controlled clinical trial. Mayo Clin Proc. 2006 Jan;81(1):17-27.

Claman DM; Redline S; Blackwell T, Ancoli-Israel S, Surovec S, Scott N, et al. Prevalence and correlates of periodic limb movements in older women. J Clin Sleep Med. 2006 Oct;2(4):438-445.

Merlino G, Fratticci L, Valente M, et al. Association of restless legs syndrome in type 2 diabetes: a case-control study. Sleep. 2007; 30(7): 866-71.

Oertel WH, Benes H, Bodenschatz R, Peglau I, Warmuth R, Happe S, et al. Efficacy of cabergoline in restless legs syndrome: a placebo-controlled study with polysomnography (CATOR). Neurology. 2006 Sep 26;67(6):1040-6.

Partinen M, Hirvonen K, Jama L, Alakuijala A, Hublin C, Tamminen I, et al. Efficacy and safety of pramipexole in idiopathic restless legs syndrome: a polysomnographic dose-finding study--the PRELUDE study. Sleep Med. 2006 Aug;7(5):407-17.

Picchietti D, Winkelman JW. Restless legs syndrome, periodic limb movements in sleep, and depression. Sleep. 2005 Jul 1;28(7):891-8.

Picchietti D. Restless legs syndrome: prevalence and impact in children and adolescents--the Peds REST study. Pediatrics. 2007; 120(2): 253-66.

Stefansson H, Rye DB, Hicks A, et al. A Genetic Risk Factor for Periodic Limb Movements in Sleep. N Engl J Med. 2007;357:639-47.

Winkelman JW, Sethi KD, Kushida CA, Becker PM, Koester J, Cappola JJ, et al. Efficacy and safety of pramipexole in restless legs syndrome. Neurology. 2006 Sep 26;67(6):1034-9.

Winkelmann J, Schormair B, Lichtner P, et al. Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions. Nat Genet (in press). [cited in: Winkelmann J. Periodic Limb Movements in Sleep - Endophenotype for Restless Legs Syndrome? N Engl J Med. 2007; 357:703-05.]

Review Date:
10/22/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

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Ability to Survive on Six Hours of Sleep Is Pipe Dream

FitSugar — Fri, 14 Aug 2009 12:30:50 -0700

One way that busy folks try to increase their productivity level is to sleep less, and many boast that they can survive with six or so hours of sleep. A good night's sleep, between seven and nine hours, has been found to be vital for our overall health. Chronic undersleeping can lead to diabetes, high blood pressure, and some cancers, not to mention depression and short-term memory loss. However, new research from University of California San Francisco has found a mutation in the gene that governs the sleep/wake pattern known as the circadian rhythm. The mother and daughter, who share the mutation, only require six to six and half hours of sleep a night but still feel well rested, proving that it is possible to sleep less and stay healthy. Unfortunately, it is estimated that only three percent of the population has this genetic mutation.

I, for one, run better, both literally and figuratively, on eight hours of sleep. What about you? Do you think you're one of the small percentage of people who requires less sleep?