
|
InsomniaHighlightsSedative 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:
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
Complementary and Alternative Medicine
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. IntroductionInsomnia comes from the Latin words for “no sleep.” Insomnia is characterized by:
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:
Duration of InsomniaInsomnia, usually temporary, is often categorized by how long it lasts:
Forms of InsomniaInsomnia may also be defined in terms of inability to sleep at conventional times. The following examples are referred to as circadian rhythm disorders:
Healthy SleepIn 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:
In addition, daily rhythms intermesh with other factors that may interfere or change individual patterns:
The Response in the Brain to Light SignalsThe response to light signals in the brain is an important key factor in sleep:
Sleep CyclesSleep 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:
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:
Causes of Short-Term or Transient InsomniaA 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:
Temporary insomnia could also develop after a relatively minor event, including:
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. Female Hormonal FluctuationsFluctuations in female hormones play a major role in insomnia in women over their lifetimes. This insomnia is usually temporary.
Jet LagAir 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. Effect of Light and Other Environmental DisruptionsIn 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.
Other Causes of Short-Term or Transient InsomniaCaffeine. 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 InsomniaSleep 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. Brain Chemicals and Hormones Affecting Chronic InsomniaAbnormal levels of certain brain chemicals have been observed in some people with chronic insomnia.
Chronic Insomnia and the Immune SystemChronic 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. Emotional DisordersMany cases of chronic insomnia cases have a psychologic or psychiatric basis. The disorders that most often cause insomnia are:
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. Psychophysiologic InsomniaIn 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:
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. Medical Conditions and TreatmentsIn 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. Alcohol OveruseAn 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 and Chronic InsomniaShift work throws off the body's circadian rhythm and may lead to chronic insomnia. Risk FactorsStudies 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. Seven Significant Risk FactorsA 2003 study suggested that there were seven significant factors that predicted high risk for insomnia:
Negative ThinkingStressful 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. Depression and Chronic PainStudies 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. Gender FactorsOverall, 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:
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. Risk Factors in Elderly AdultsAs 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:
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:
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 WorkersShift 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. Other Risk FactorsAmong the many conditions that pose a high risk for insomnia are:
PrognosisA 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. Increased Risk for AccidentsSleepiness 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.) Effect on Mood and Quality of LifeSurveys 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.
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 Physical HealthEffects 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. DiagnosisDiagnosing 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. Sleep QuestionnairesA number of questionnaires are available for determining whether a patient has insomnia or other sleep disorders. For example, the doctor may ask:
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. Measuring SleepinessThe Epworth Sleepiness Scale. The Epworth Sleepiness Scale (ESS) uses a simple questionnaire to measure excessive sleepiness during eight situations.
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:
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. Sleep Disorders CentersIf 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:
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. TreatmentThe 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. Behavioral MethodsPrevention 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:
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:
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:
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:
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.
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:
To achieve this goal, the patient takes the following actions:
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. Sleep Hygiene Tips
ExerciseExercise 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. Light TherapyThe 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:
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:
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. MedicationsAccording 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:
Common Non-Prescription DrugsBrands 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:
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. Benzodiazepine HypnoticsBenzodiazepines, 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:
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:
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:
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. Non-Benzodiazepine HypnoticsNewer 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).
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:
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:
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. AntidepressantsAntidepressants 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. Older, Rarely Used DrugsChloral 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. Investigational DrugsIndiplon. The FDA is reviewing indiplon, a new non-benzodiazepine hypnotic. Natural RemediesAccording 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:
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:
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. Herbs and SupplementsGenerally, 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
ReferencesBliwise 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. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-
A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited. |
||||||||||||||||||||||
