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Insomnia

Highlights

What Is Insomnia?

Insomnia can be a short-term or long-term condition, but it always involves problems with falling asleep or staying asleep. Short-term (acute) insomnia can be caused by illness, stress, travel, or environmental factors. Long-term (chronic) insomnia may be due to underlying psychological or physical conditions.

Who Is at Risk?

Anyone can get insomnia, but it is generally more common in women than in men. The elderly are particularly at risk for insomnia.

Diagnosing Insomnia

A doctor will make a diagnosis of insomnia based on information about your sleep patterns. Your doctor may ask:

Your doctor may also ask you to keep a sleep diary to record specific sleep-related information.

Treating Insomnia

Non-benzodiazepine sedative hypnotics are usually the preferred type of drugs. They include zolpidem (Ambien, generic), zaleplon (Sonata, generic), and eszopiclone (Lunesta, generic). Newer types of sedative hypnotics include ramelteon (Rozerem, generic) and suvorexant (Belsomra). These drugs can cause side effects, so make sure that your doctor explains the risks of these drugs and the precautions you need to take.

New Drug Approval

In 2014, the FDA approved a new type of sleep drug called suvorexant (Belsomra). Suvorexant is an orexin receptor antagonist. Orexins are chemicals produced in the hypothalamus part of the brain. These chemicals are involved in regulating the sleep-wake cycle and keeping people awake. Suvorexant targets and blocks the action of orexin to promote sleep. The FDA approved four different dose strengths for suvorexant and advises people to use the lowest effective dose.

Introduction

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

Insomnia may be primary or secondary:

Duration of Insomnia

Insomnia is often categorized by how long it lasts:

Related Disorders

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

Healthy Sleep

In studies of human sleep behavior, 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. 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 about 24 hours. It usually takes the following daily patterns:

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

The Response in the Brain to Light Signals

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

Sleep Cycles

Sleep consists of REM and Non-REM sleep, two distinct states that alternate in cycles and reflect differing levels of brain nerve cell activity.

Non-Rapid Eye Movement (Non-REM) Sleep:

Non-REM (or NREM) sleep is also termed quiet sleep. Non-REM is divided into three stages of progression:

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 (REM) Sleep:

During REM sleep the brain is highly active. This stage is called active sleep in babies. Most vivid dreams occur in REM sleep. In REM sleep, brain activity is comparable to that in waking, but the muscles are virtually immobilized, which prevents people from acting out their dreams. Except for vital organs like lungs and heart, the only muscles not immobilized 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/Non-REM Cycle:

The cycle between quiet (Non-REM) and active (REM) sleep generally follows this pattern:

Causes of Temporary Insomnia

A reaction to change or stress is a common cause of short-term (several weeks) and transient (several days) insomnia. This condition is sometimes referred to as adjustment sleep disorder.

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

Temporary insomnia can also develop due to a relatively minor situational event, including:

In most cases, normal sleep almost always returns when the condition resolves, or when the person recovers from the event or 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. Some people never experience insomnia, even during very stressful situations while others may suffer from insomnia in response to very mild stressors.

Female Hormonal Fluctuations

Fluctuations in female hormones play a major role in insomnia in women over their lifetimes. This temporary insomnia may occur during:

Jet Lag

Air travel across time zones often causes temporary insomnia. After long plane trips, a day of adjustment is usually needed for each time zone crossed. Traveling from the east to an earlier time zone in the west seems to be less disruptive than traveling to a later time zone in the east because it is easier to lengthen a circadian phase than to shorten it.

Effect of Light and Other Environmental Disruptions

Light, noise, and uncomfortable temperatures can cause sleeplessness. Depending on the time of day, too much or too little light can disrupt sleep:

Other Causes of Temporary Insomnia

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

Nicotine: Nicotine is also a stimulant, but quitting smoking can lead to transient insomnia.

Partner's Sleep Habits: A partner's sleep habits, including snoring, can impair one's own sleep.

Medications: Insomnia is a side effect of many common medications, including over-the-counter preparations that contain caffeine or decongestants. If you suspect your medications are causing you to lose sleep, check with your doctor or pharmacist.

Causes of Chronic Insomnia

Sleep problems seem to run in families. Many people with chronic insomnia have a family history of insomnia, with the mother being the most commonly affected family member. Because there are so many factors involved in insomnia, a genetic component is difficult to define.

Anxiety, Depression, and Other Mental Health Disorders

Many cases of chronic insomnia cases have an emotional or psychological basis. The disorders that most often cause insomnia are:

Insomnia may also be the cause of emotional and mental health problems, such as depression and anxiety. It is often unclear which condition has triggered the other, or if the two conditions have a common source.

Psychophysiologic Insomnia

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 temporary insomnia disrupts your sleep patterns:

Medical Conditions and Their Treatments

Among the many medical problems that can cause chronic insomnia are allergies, benign prostatic hyperplasia (BPH), arthritis, gastroesophageal reflux disease (GERD), asthma, chronic obstructive pulmonary disorder (COPD), rheumatologic conditions, Alzheimer disease, Parkinson disease, hyperthyroidism, epilepsy, and fibromyalgia. Other types of sleep disorders, such as restless legs syndrome and sleep apnea, can cause insomnia. Many people with chronic pain sleep poorly.

Among the many medications that can cause insomnia are antidepressants (especially bupropion), beta-blockers, and beta-agonists.

Substance Abuse

Substance abuse can cause chronic insomnia. This is true for both stimulants such as cocaine and sedatives such as alcohol. One or two alcoholic drinks may help reduce stress and initiate sleep. However, excessive alcohol use 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 syndrome. People who are alcohol-dependent often suffer insomnia during withdrawal and, in some cases, for several years during recovery.

Risk Factors

More than a quarter of all Americans experience short-term (acute) insomnia at some point during a year, and nearly 10% have long-term (chronic) insomnia.

Gender

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

Hormonal fluctuations that occur during menstruation, pregnancy, and menopause put women at higher risk for insomnia. Women are also more likely than men to suffer from anxiety and depressive disorders, which can cause insomnia.

Age

Insomnia is more common in older people than younger people. As people grow older, sleep patterns change. Older adults tend to wake up frequently during the night, wake up earlier, and report waking up feeling unrefreshed.

Older people are also more likely than younger people to have medical conditions that cause pain or nighttime distress. These conditions include arthritis, gastrointestinal distress, frequent urination, lung disease, and heart conditions. Neurologic conditions, such as Parkinson disease and Alzheimer disease, can also affect sleep patterns. Consequences of poor sleep in the elderly include a higher risk of falling.

Shift Work

Shift workers are at considerable risk for insomnia. Workers over age 50 and those whose shifts are always changing are particularly susceptible to insomnia. Night-shift workers also have a high rate of sleeplessness.

Night-shift workers are at risk for falling 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 overall risk for health problems.

Complications

Insomnia itself is not life threatening, but it can increase the risk of accidents, psychiatric problems, and certain medical conditions. It can also affect school and work performance, and significantly interfere with quality of life. Lack of sleep can cause weight gain and lead to obesity.

Increased Risk of Accidents

Sleepiness increases the risk for motor vehicle and workplace accidents. Studies indicate that drowsy driving is as risky as drunk driving. Research also suggests that insomnia is associated with a higher proportion of workplace accidents than any other chronic health condition.

Quality of Life

Surveys show that people with severe insomnia have a quality of life that is almost as poor as those who have chronic medical conditions, such as heart failure. Daytime sleepiness can lead to decreased energy, irritability, mistakes at work and school, and poorer relationships.

Thinking and Performance

Insomnia makes it harder to concentrate and perform tasks. Deep sleep deprivation reduces concentration and impairs the brain's ability to process information.

Mood Disorders

Although stress and depression are major causes of insomnia, insomnia may also increase the activity of the hormones and pathways in the brain that are associated with mental health problems. Chronic insomnia may increase the risk of developing depression and anxiety.

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.

Obesity and Weight Gain

Lack of sleep causes hormonal, metabolic, and brain activity changes that affect weight and appetite regulation. Research increasingly suggests that people who are sleep-deprived are more likely to have problems with weight gain and obesity, which can increase the risk for other health conditions, such as heart disease and diabetes.

Heart Health

Evidence suggests that chronic insomnia may moderately increase the risk for heart disease, heart attack, and heart failure. In men, insomnia may possibly increase the chance of death from cardiovascular disease. Research continues on the relationship between insomnia and the chronic inflammation associated with heart disorders.

Diagnosis

Sleep Questionnaires

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

Sleep Diary: Keeping a sleep diary is a helpful diagnostic tool. Every day for 2 weeks, record all sleep-related information (including responses to questions listed above). Other information should include the time you went to bed, time spent falling asleep, number of nocturnal awakenings, and rising time. Your bed partner's observations of your sleep behavior can also help.

Measuring Sleepiness

Actigraphy: Actigraphy uses a portable device with a sensor to monitor movement. Actigraphy may be used in some situations to help give a doctor a better picture of a person's sleep pattern. It cannot, however, determine the severity of sleep problems. Most people with insomnia are diagnosed and treated without this test. However, actigraphy may help identify insomnia in some people.

Sleep Disorders Centers

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.

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

Most sleep disorders centers perform an in-depth analysis, which includes Polysomnography. Polysomnography is the technical term for an overnight sleep study that involves recording brain waves and other sleep-related activity. Its primary role is in diagnosing obstructive sleep apnea, restless leg syndrome/periodic limb movement disorder, or other abnormal sleep behaviors called parasomnias, such as nightmares, sleep walking, and acting out dreams.

Treatment

The American Academy of Sleep Medicine (AASM) recommends a number of behavioral methods 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.

Doctors agree that behavioral therapies should be the first-line treatment for insomnia. For children in particular, medications should rarely be used as initial treatment.

Behavioral Therapy

Various approaches are available to help people learn how to relax and sleep well. Although medications can help people with insomnia to sleep, they cannot cure the condition. Behavioral techniques can dramatically improve chronic insomnia in many cases, and the benefits of psychological and behavioral therapy are long lasting. Behavioral methods work for all age groups, including children and older adults.

Sleep hygiene practices, tips and techniques for ensuring a good night's sleep, should accompany any behavioral method. (For more on sleep hygiene, see the Lifestyle Changes section of this report.)

Behavioral methods include:

All behavioral approaches have the same basic goals:

Studies report that the majority of people who are treated with non-drug methods experience improved sleep. Furthermore, most of those who have been taking sleep medications are able to stop or reduce their use.

Stimulus Control

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

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. The goal is to change or correct misconceptions about the ability to fall and stay asleep. Emphasis is on reinforcing the need for 7 to 8 hours of sleep each night and addressing the anxiety that people with insomnia often develop around sleep. Many studies have shown CBT to work as well or better than drugs. According to several studies, adding medication to CBT does not provide additional benefit.

Relaxation Training and Biofeedback

Relaxation training includes breathing and guided imagery techniques. Progressive muscle relaxation is another technique for inducing sleep that works well for many people. It takes about 10 minutes to perform and involves the following:

Biofeedback may be combined with relaxation techniques. Biofeedback involves being monitored with an electroencephalogram (EEG), a device that measures brain waves. People are given feedback to recognize certain states of tension or sleep stages so that they can either avoid or repeat them voluntarily.

Paradoxical Intention and Sleep Restriction Therapies

Paradoxical intention is a type of cognitive technique that aims to conquer anxiety about insomnia by forcing the patient to stay awake. Not trying to fall asleep may help relieve performance anxiety associated with sleep.

Sleep restriction therapy is similar to paradoxical intention. It involves limiting the time spent in bed to the number of hours that are actually spent asleep. Eventually the sleep loss helps some people fall asleep faster and spend more time asleep. As sleep improves, the hours spent in bed are increased.

Treatment of Underlying Mental Health Problems

Disruption in sleep is commonly present in those with mental health problems, such as certain types of depression, bipolar disorder, anxiety disorders, attention deficit disorders, alcohol and substance abuse, psychosis and others.

When a sleep problem accompanies any of these disorders, it is important that the underlying mental health problem is treated also.

Drug Therapy

Unlike behavioral treatment, which can cure insomnia, sleeping pills produce only temporary improvement. Medications for insomnia can also have some serious side effects and risks, especially for older people. In general, the following considerations are important when using medications for the treatment of insomnia:

Lifestyle Changes

Sleep Hygiene Tips

Proper sleep hygiene should accompany any behavioral method. The term sleep hygiene is used to describe simple behaviors that may help everyone improve their sleep.

During the day:

Before and at bedtime:

If you are having problems falling asleep:

Medications

Many Americans use some form of herbal, over the counter, or prescription sleep aid pill. Over-the-counter (nonprescription) medications make use of the drowsiness caused by some common medications. Prescription drugs used specifically for improving sleeping are called sedative hypnotics.

Herbs and Supplements

More than 1.5 million Americans use complementary and alternative therapies to treat insomnia. Valerian and melatonin are among the most popular herbal and supplement remedies for insomnia. Chamomile tea and lemon balm are also popular. These substances are generally harmless for most people. However, other herbs and supplements have more serious side effects and interactions.

The American Academy of Sleep Medicine (AASM) advises 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.

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. People should always check with their doctors before using any herbal remedies or dietary supplements.

Melatonin

Melatonin is the most studied dietary supplement for insomnia. It appears to reduce the time to fall asleep (sleep onset) and increase the time spent asleep (sleep duration) and is not habit forming. There are no consistent standards on melatonin doses. General recommendations are to take 0.3 mg to 1 mg about 90 minutes before going to sleep. Taking higher doses may disrupt sleep and may cause daytime sleepiness, headaches, dizziness, nausea, and stomach cramps. Although melatonin may have limited benefits for people with chronic insomnia, studies suggest that it may help travelers with jet lag and people with delayed sleep syndrome.

Valerian root

Valerian is an herb that has sedative qualities and is commonly used by people with insomnia. Some studies have indicated that it may help improve the quality of sleep, but there have been few rigorous and well-conducted trials to prove it is effective.

Kava

Kava has been used to relieve anxiety and improve sleep. It is dangerous and associated with reports of liver failure and death, with highest risk in those with liver disease. Kava can interact 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. Do not use this herb.

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

Tryptophan is an amino acid used in the formation of the neurotransmitter serotonin, which is associated with healthy sleep. L-tryptophan used to be marketed for insomnia and other disorders but was withdrawn after contaminated batches caused a rare but serious, and even fatal, disorder called eosinophilia myalgia syndrome. A byproduct of tryptophan, 5-HTP, is still available as a supplement. There is little evidence that 5-HTP relieves insomnia.

Non-Prescription Sleep Medications

Brands with Antihistamines

Many over-the-counter sleeping medications use antihistamines, which cause drowsiness. Diphenhydramine (Benadryl, generic) is the most common antihistamine used in non-prescription sleep aids.

Some drugs marketed as sleep aids contain diphenhydramine alone, while others contain combinations of diphenhydramine with pain relievers (such as Tylenol PM and its generic forms). Doxylamine (Unison, generic) is another antihistamine used in sleep medications. Certain antihistamines indicated only for allergies, such as chlorpheniramine (Chlor-Trimeton, generic) or hydroxyzine (Atarax, Vistaril, generic) may also be used as mild sleep-inducers.

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

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

Common Pain Relievers

When sleeplessness is caused by minor pain, simply taking acetaminophen (Tylenol, generic) or a non-steroidal anti-inflammatory drug (NSAID) such as ibuprofen (Advil, Motrin, generic), 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.

Sedative hypnotics

Sedative hypnotics include benzodiazepines and non-benzodiazepines, which enhance the effects of the brain chemical (neurotransmitter) GABA. When GABA binds to GABA receptors, brain activity slows down, inducing calm and relaxation. There are also new types of sedative hypnotics that work in a different way by targeting receptors for melatonin or orexin.

Sedative hypnotics carry risks for dependence, tolerance, and rebound insomnia:

Non-Benzodiazepine Hypnotics

Non-benzodiazepines (also called "Z" drugs) are the preferred sedative hypnotic drugs for the treatment of insomnia. In general, non-benzodiazepine hypnotics are recommended for short-term use (7 to 10 days), and treatment should not exceed 4 weeks.

Non-benzodiazepine hypnotics currently approved in the United States are:

Dosage

Recommended dosage for zolpidem products:

Lower dose recommendations are also in place for eszopiclone, which can cause impairment in driving and cognitive skills up to 11 hours after an evening dose. The FDA is currently reviewing all sleep medications to evaluate how they affect next-day mental alertness.

Side Effects

Non-benzodiazepines tend to have fewer side effects than benzodiazepines because they target the GABA receptor in a more specific way. However, these drugs can still cause residual morning sedation even if you are feeling fully awake. When people 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 may include:

All non-benzodiazepine drugs carry labels warning that these drugs can cause strange sleep-related behavior, including driving, making phone calls, and preparing and eating food while asleep. Most cases of sleepwalking and sleep driving likely occur when people use the drug along with alcohol or other drugs or take more than the recommended dose.

Anyone who receives a prescription for these medicines will 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.

Carefully read the information labels for all drugs and follow the directions. Some sleeping pills take 30 to 60 minutes to take effect, while others (such as zolpidem) act quickly. For zolpidem, people should:

Interactions

As with any hypnotic, alcohol increases the sedative effects of these drugs. These hypnotics also interact with other drugs. Inform your doctor of all your medications.

Rebound Insomnia, Dependence, and Tolerance

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 to 10 days in a row or at higher than the recommended dose without a doctor's approval.

Benzodiazepine Hypnotics

Benzodiazepines used to be the most commonly prescribed sedative hypnotics. These drugs were originally developed in the 1960s to treat anxiety.

Commonly prescribed benzodiazepines are:

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 short-acting. They include:

Interactions

Benzodiazepines are potentially dangerous when combined with alcohol. Some medications, like the ulcer and acid reflux medication cimetidine (Tagamet, generic), can slow the metabolism of the benzodiazepine.

Withdrawal Symptoms

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

Other Types of Sedative Hypnotics

Ramelteon (Rozerem, generic)

Ramelteon is a type of sedative hypnotic called a melatonin receptor agonist. Unlike non-benzodiazepines or benzodiazepines, which target GABA receptors, ramelteon works by targeting melatonin receptors. Ramelteon is not habit forming and is the first sleep drug that is not designated as a controlled substance. A related melatonin receptor agonist, tasimelteon (Hetlioz), is approved for treating circadian rhythm disorders in people who are blind.

Suvorexant (Belsomra)

In 2014, the FDA approved suvorexant (Belsomra), the first orexin receptor antagonist sleep drug. Suvorexant targets and blocks orexin. Orexins are chemicals produced in the hypothalamus part of the brain, which are involved in regulating the sleep-wake cycle and keeping people awake. Suvorexant is a controlled substance, which means it can potentially be abused or cause dependence. Like other sleep medications, suvorexant may cause sleep-related behaviors such as sleep driving. The FDA approved four different dose strengths for suvorexant and advises people to use the lowest effective dose.

Antidepressants

Antidepressants are often helpful in treating insomnia even when anxiety or major depression are not present. Certain types of antidepressants have sedating properties are prescribed for the treatment of primary insomnia, generally in lower doses than used to treat depression.

For example, the antidepressant trazodone (Desyrel, generic) is prescribed in low doses as a hypnotic to help induce sleep. A very low dose formulation of the tricyclic antidepressant doxepin (Silenor) is approved for treatment of insomnia. Other antidepressants used for insomnia include the tricyclics trimipramine (Surmontil, generic) and amitriptyline (Elavil, generic) and the tetracyclic antidepressant mirtazapine (Remeron, generic).

Precautions should be taken in the use of trazodone and other sedating antidepressants in elderly people, due to the risk for side effects (daytime sleepiness, dizziness, priapism, and increased risk of falls) and drug interactions.

Resources

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Review Date: 3/25/2016
Reviewed By: Allen J. Blaivas, DO, Division of Pulmonary, Critical Care, and Sleep Medicine, VA New Jersey Health Care System, Clinical Assistant Professor, Rutger's New Jersey Medical School, East Orange, NJ. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the A.D.A.M. Editorial team.
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