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Insomnia is a common malady. Half of the adult population has it over the course of a year; 35% experience insomnia on an occasional basis;12% on an ongoing basis. It is not surprising that sleep difficulties are also among the most frequently encountered problems in clinical medicine. Insomnia affects all ages, yet increases in prevalence with age. Women are twice as likely to have it compared to men. It is seen in all cultures and races.
Physicians often overlook the misery and debilitation associated with insomnia. Additionally, only 5% of all insomniacs approach their physicians specifically for insomnia as a primary complaint. Recent studies have shown, however, that insomnia can have profound negative effects on health and well being. Insomniacs report difficulties with memory and task completion, are often irritable, and have greater difficulty staying awake during daytime tasks than non-insomniacs. Inadequate sleep is associated with decreased work efficiency. Although the long-term risks of insomnia have not been adequately assessed, there is an emerging sense that unrelenting insomnia can bring on depression and other emotional difficulties.
Insomnia has long been assumed to be simply the result of tension or stress. However, key developments over the past four decades have helped tease apart and identify the many physical and emotional disorders that can be responsible for insomnia. The first of these was the discovery that sleep is not a uniform state, but a combination of five separate sleep stages. The second was the technical discovery of "polysomnography." the physiological study of sleep in a laboratory setting, which led to the establishment of the field of sleep disorders medicine. It is now clear that insomnia is not one entity, but can be a symptom of many different types of disorders, each with its own set of treatments. The first step in proper treatment, therefore, is accurate diagnosis.
Specific Causes of Insomia and Treatments
Adjustment Sleep Disorder
Sudden emotional stress, such as a job loss or a hospitalization, can induce transient insomnia. Sudden changes in work shift and travel across time zones can also cause difficulties with sleep. However, these difficulties usually resolve within a brief period of time, typically a few weeks. Many insomniacs, however, unknowingly intensify the effect of, or unnecessarily prolong, these insomnias by engaging in behaviors that make matters worse. Therefore, proper adherence to sleep hygiene rules can be helpful in producing a more rapid resolution to this type of insomnia. Examples of sleep hygiene measures include:
- Maintain a regular bedtime schedule.
- Avoid excessive time in bed.
- Avoid taking naps.
- Use the bed only for sleeping and sexual relations.
- Do not watch the clock.
- Do something relaxing before bedtime.
- Make the bedroom as quiet as possible.
- Avoid the consumption of alcohol and caffeine within 12 hours of bedtime
- Exercise moderately, regularly, and not within 4 hours of bedtime.
- Avoid going to bed hungry.
- Learn strategies to make bedtime as relaxing and tension-free as possible.
In general, no formal medical treatment is necessary for such short-lasting insomnia. In certain cases, however, such as when daytime fatigue begins to interfere with daily activities, seeking medical attention is warranted.
Medical treatment is also warranted if the insomnia lasts for more than just a few weeks. Although in many insomnia cases, self-help strategies such as those mentioned above are sufficient in overcoming insomnia rapidly, insomnia can escalate and become chronic. In this case, the causes of insomnia may represent more significant medical or emotional disorders. Therefore, sufferers should seek help if their own strategies do not relieve insomnia within a few weeks. The disorders below are examples of some of the more common chronic insomnia conditions that warrant further medical attention.
Psychophysiologic Insomnia
Psychophysiologic insomnia can follow a few nights of sleeplessness due to an adjustment sleep disorder. Concern regarding the prospect of facing yet another night of sleeplessness can result in an escalation of tension and anxiety with each successive night. The insomniac begins to dread going to bed and often feels tension increasing as bedtime approaches. He may become preoccupied with insomnia. Sufferers often spend hours in bed awake focused upon and brooding over their sleeplessness. In severe cases, the focus of their thoughts, and even conversations with others, may begin to revolve around insomnia. Curiously, sufferers often have little difficulty falling asleep during the course of the day when their minds are focused on other issues, such as during meetings. They also may experience relief from their own bedrooms as they fall asleep easily when away from home, such as on vacation on in a hotel room.
Psychophysiologic insomnia is often managed with a combination of behavioral measures and medications. The most commonly utilized behavioral measures are relaxation training with EMG biofeedback training, psychotherapy (cognitive and insight-oriented), and stimulus control therapy (asking patients to use the bed only for sleep and to not stay in bed trying to sleep for more than ten minutes at a time, but to go into another room and to return to bed only after feeling sleepy). Sleep hygiene measures should be closely adhered to during and after the termination of treatment, regardless of type.
Hypnotic Agents (Sleeping Pills)
Since sleeping pills are commonly used for the adjustment sleep disorder and psychophysiologic insomnia, I will discuss them in this section. Alcohol, one of the most widely utilized agents by insomniacs is a poor choice inasmuch as it alters sleep patterns and often results in further daytime sleepiness. Alcohol can also intensify breathing disorders during sleep, which may affect certain insomniacs. Many of the over-the-counter products contain antihistamines, which are also commonly used in cold preparations. However, these cannot be wholeheartedly recommended either, since they have unpredictable effects on sleep and since they can cause side effects such as constipation, rapid heart rates, urinary retention, and excessive daytime sedation. Although barbiturates and barbiturate-like drugs (chloral hydrate and glutethimide, among others) were utilized as hypnotic agents in the past, they also can no longer be recommended since they have a far greater potential for significant sedation and even death in overdoses when compared to other available medications.
Melatonin is a hormone which is released by the pineal gland and whose secretion peaks during sleep. Its blood levels decrease with
age. It has long been suspected as being helpful for sleep and has witnessed extraordinary popularity in recent years among insomniacs as an over-the-counter sleep aid. Unfortunately, the evidence for the efficacy of melatonin as a general sleep aid is scant. Melatonin may, however, be useful in circadian rhythm disorders such as jet lag or shift work sleep disorder, although more definitive studies are necessary in these areas as well. Concerns also exist regarding its safety and questions have been raised regarding the purity of certain melatonin preparations. Because of the lack of well-designed dosing studies, the proper dosage is also unknown. Therefore, despite the anecdotal reports of miraculous cures following its ingestion, its use cannot be fully supported by clinical evidence at the present time.
There are many prescription sleeping pills. Most of these agents fall into a class of medications called benzodiazepines. Benzodiazepines that are specifically marketed for sleep include flurazepam (Dalmane), quazepam (Doral), estazolam (ProSom), temazepam (Restoril), and triazolam (Halcion). These agents differ from each other by the length of time they stay in the body (referred to as elimination half-life) and selectivity. For example, agents with a longer half-life include flurazepam (Dalmane), and quazepam (Doral); those with an intermediate half-life include estazolam (ProSom) and temazepam (Restoril). The only short half-life benzodiazepine available in the United States is triazolam (Halcion).
Another medication, zolpidem (Ambien) is part of a different class of drugs called imidazopyridines. It also has a short half-life (approximately 2.5 hours). The most recently introduced hypnotic compound is zaleplon (Sonata), also a non-benzodiazepine hypnotic agent. It falls in the pyrazolopyrimidine class. It has the shortest half-life of all the hypnotic agents available in the United States (approximately 1 hour).
It is believed that zolpidem and zaleplon provide their hypnotic efficacy by their activity at GABA-Benzodiazepine receptor complex. This is the same receptor site at which the benzodiazepines act. The binding of hypnotic molecules at this site augments the activity of GABA, an inhibitory CNS neurotransmitter. However, these two non-benzodiazepine agents, and the benzodiazepine quazepam, preferentially act at a subset of GABA receptors that are distinguished by their geographic distribution in the brain. The possible clinical effects (if any) of this selectivity have yet to be conclusively determined.
Medications with longer elimination half-lives tend to be associated with a greater potential for daytime carryover effect and sleepiness on the day following administration. Triazolam, zolpidem and zaleplon have the least potential for residual daytime carryover effects if administered at bedtime. Furthermore, Zaleplon affords the possibility of being taken following middle-of-the-night awakenings without the production of residual next-day sedation if administered no later that 4 hours prior to morning awakening. Higher dosages of a medication may also contribute to daytime sleepiness, as do longer periods of continued use.
Sleeping pills have been known to have diminished effectiveness after prolonged use, a phenomenon called tolerance. They can also produce escalation of insomnia after rapid discontinuation, referred to as rebound insomnia. Short half-life agents may be more likely to produce tolerance and rebound insomnia, yet there is little evidence for either difficulty with extended use of the short half-life agents zolpidem and zaleplon. These difficulties, nevertheless, can be minimized by utilizing the medication at the lowest effective dose and for brief periods of time (days to weeks). If prolonged use is warranted, intermittent dosing, (i.e., administration on 4 or 5 nights per week only), may be beneficial.
With a few exceptions, hypnotic medications should be taken as a prophylactic at the beginning of the night, since taking them too close to morning awakening time may lead to daytime sedation. Zaleplon may be an exception to this rule since it can be effective as a "last-minute" medication for patients who wish to attempt to fall asleep of their own accord and take the hypnotic only if they have to. As stated above, however, a minimum of 4 hours in bed are necessary following its administration.
Most studies with zaleplon have focused on its ability to reduce sleep latency (the time it takes to fall asleep) following administration. Most of the other hypnotics, including zolpidem, have been shown to reduce not only the time to fall asleep but also the number and duration of awakenings during the course of the night and the duration of sleep.
Hypnotic agents should be utilized for brief periods of time and at the lowest effective doses. During the course of treatment, physicians should carefully monitor patients for side effects, such as daytime sleepiness, memory difficulties, and performance decrements, and habituation and tolerance. Hypnotics are contraindicated in patients suspected of having obstructive sleep apnea syndrome and other sleep-related breathing disorders, in pregnant women and heavy alcohol users, and should be utilized with caution in any chronic disorder. Although hypnotics can safely be combined with antidepressants, hypnotic agents alone are inappropriate for the treatment of the insomnia of depression.
Obstructive Sleep Apnea Syndrome
This sleep-related breathing disorder might occur in up to 10% of unsuspecting insomniacs. For reasons that are not entirely clear, the muscles in the throat that normally maintain an open upper airway during sleep do not function properly. This malfunction results in repetitive collapse of the upper airway during sleep causing intermittent cessation in breathing during sleep. Potentially dangerous changes in the body may take place during apneas, including decreased oxygen concentrations (hypoxemia), and increased carbon dioxide levels (hypercarbia). These can, in turn, cause abnormal heart rhythms. High blood pressure is also evident during apneas. Heart output falls during apneas and rises to normal levels following their termination.
Apneas are terminated by arousals--sudden generalized activations of the brain--which may be important in re-activating breathing. However, they also result in profound sleep fragmentation and poor sleep quality, which are thought to be responsible for the daytime sleepiness and emotional consequences of the disorder. Patients with OSA also complain of snoring, repeated nocturnal awakenings, unusual sleep positions, sleepwalking and nocturnal vocalizations, profuse sweating, enuresis (involuntary discharge of urine during sleep at night), heartburn, morning frontal headaches, and morning mouth dryness. Most patients are obese at the time of presentation and report gaining weight gradually over the years, often despite heroic attempts to curb this process through diet and exercise. However, normal weight does not preclude the diagnosis.
Cardiovascular diseases are common. Inhibited sexual desire, impotence, and ejaculatory problems are reported by nearly a third of patients. If left untreated, the illness may be associated with increased mortality. Depression, deterioration in interpersonal relationships, and academic difficulties are also common. Sedating medications such as sleeping pills tend to increase the duration and frequency of apneas and are contraindicated for untreated patients.
If the disorder is suspected, nocturnal polysomnography (study of sleep at night in a sleep lab) must be done to establish the diagnosis. This study would reveal obstructive apneas, defined as cessations in airflow through the nose or mouth lasting ten seconds or greater followed by the resumption of breathing. The syndrome is often defined by a frequency of breathing abnormalities (Respiratory Disturbance Index, RDI) of more than five per hour of sleep. However, this threshold is based on convention and is not a requirement for a diagnosis of OSA. Treatment options include continuous positive airway pressure (CPAP) laser-assisted uvuloplasty (LAUP), uvulopalatopharyngoplasty surgery (UPP), tracheostomy, nasal surgery, dental devices, drugs that suppress REM sleep, and weight management.
Periodic Limb Movement Disorder (Nocturnal Myoclonus)
Also referred to as nocturnal myoclonus, this disorder is characterized by the repetitive (usually every 20 to 40 seconds) twitching or kicking of the legs during sleep. Patients complain of either interrupted sleep or daytime sleepiness. In either case, they are unaware of the movements and the brief arousals that follow and have no lasting sensation in the legs. Therefore, if the disorder is suspected, bedpartners should be questioned. The disorder is more common in middle and older age. Although often of unknown causes, the disorder can be seen in association with drug withdrawal states, sleep apnea syndrome, narcolepsy, chronic kidney and liver failure, as well as during treatment with certain medications such as tricyclic antidepressants. Movements are often exacerbated by stress.
Patients having the disorder should receive a physical examination and blood tests. Polysomnography confirms the diagnosis. Medication options include benzodiazepines (especially clonazepam), carbidopa/levodopa, pergolide, and oxycodone, among others.
Restless Legs Syndrome is a related disorder characterized by a "creeping’’ sensation in the lower extremities and irresistible leg kicks that affect patients upon reclining prior to falling asleep. The disorder is more common in later age and is exacerbated by pregnancy, fatigue, environmental temperature extremes, the intake of caffeinated beverages and tricyclic antidepressants, and drug withdrawal states. The cause is usually unknown, but has been noted in association with a variety of medical disorders including pernicious anemia (vitamin B12 deficiency), iron deficiency, kidney failure, leukemia, rheumatoid arthritis, and fibromyositis (or fibromyalgia--a syndrome of nonspecific "aches and pains’’ without evidence of immune system dysfunction).
Polysomnography almost always reveals periodic leg muscle bursts during quiet wakefulness and sleep, the latter associated with arousals and awakenings. The syndrome should be distinguished from nocturnal leg cramps that involve pain in the deep muscles of the lower extremities whose occurrence is independent of sleep. The treatment of the Restless Legs Syndrome is essentially the same as periodic limb movement disorder.
Circadian Rhythm Sleep Disorders
Time zone change syndrome (jet lag) is caused by rapid travel across time zones that results in a mismatch between the sleep schedules of the body and that of the new environment. Eastward flight results in more severe symptoms than westward travel. The severity of symptoms is also related to the number of time zones crossed; travel across more than two to three times zones surpasses the adaptive capabilities of the body. This often affects the timing between internal body rhythms as well, such as those of temperature, sleep, and hormone secretion. When coupled with the curtailment of sleep length and the disturbance of sleep quality caused by any new environment, this leads to the symptoms of the disorder.
Jet lag countermeasures include the utilization of short-acting hypnotic agents for brief periods of time following arrival in the new locale. A safer and more effective method, however, is simply to maximize exposure to daylight in the new locale, which has the effect of resetting circadian rhythms with one another and with the environment. Individuals should also be urged to gradually shift their sleep/wake schedules prior to travel to coincide approximately with those of their destination.
Shift work sleep disorder. Most problematic is variable shift work in which shifts are changed frequently; sleep times typically must be changed accordingly. This often leads to poor sleep quality immediately following the new shift, which is followed by a period of adaptation. The severity of symptoms is proportional to the frequency with which shifts are changed, the magnitude of each change, as well as the frequency of counterclockwise changes. However, even fixed-shift workers who must sleep during the day experience difficulties since daytime noise and light often interfere with the quality of their sleep. They also frequently change their sleep times for social or family events.
Shift workers should be advised to maximize their exposure to sunlight at times when they should be awake and to ensure that the bedroom is as dark and quiet as possible when they are asleep, which is often during the day. Bright artificial light emanating from especially constructed boxes, when administered at critical times can enhance adaptation of internal rhythms to the new shift. If symptoms are not responsive to conventional countermeasures, it may be necessary to devise more rational shift schedules.
In delayed sleep phase syndrome, individuals fall asleep later than normal evening bedtime hours and awaken later than desired, often extending their bedtimes well into the afternoon. Thus, they typically complain of both insomnia and daytime sleepiness. Sufferers are usually young adults who present for treatment because of diminished school performance resulting from daytime sleepiness or missed morning classes. Prior history reveals a tendency for individuals to be "night owls." preferring to work and play well into the night. They can be distinguished from people who stay up late by choice because of social or occupational needs in that they cannot fall asleep earlier even if they were to try.
Attempts to advance the sleep/wake cycle by retiring earlier are uniformly unsuccessful. Instead, delaying bedtimes even further by increments of three hours per day are often successful, a process referred to as chronotherapy. An alternative is bright light therapy, administered for two hours early in the morning.
In advanced sleep phase syndrome, sleep/wake times are advanced in relationship to socially desired schedules. The disorder is more common in the elderly and is responsive to treatment with bright lights when administered in the evening.
Medical/Psychiatric Sleep Disorders
Most major medical and psychiatric conditions result in some degree of sleep interruption. In chronic pain, for example, patients may awaken multiple times each night and spend days feeling sleepy and washed out. Ultimately, the effective management of these sleep difficulties rests upon the conclusive management of the underlying medical or psychiatric condition. However, sleep hygiene and other behavioral methods, as well as sleeping pills, are appropriate if used judiciously and under medical supervision.
Depression is the one psychiatric syndrome that has received the most extensive attention by sleep physiologists. In fact, a depressive episode is usually accompanied by a characteristic set of changes to sleep patterns. These changes highlight the fact that depression leads to profound changes that affect not only psychology, but also brain biology.
Medications used to treat depression can also affect sleep. In general the sedating tricyclic antidepressants such as amitriptyline and doxepin enhance sleep continuity and depth, yet, because of long half-lives, tend to cause daytime drowsiness. Another type of antidepressant, the monoamine oxidase inhibitors, in contrast, can enhance nocturnal awakenings and diminish sleep continuity, yet their activating properties make them better suited for the depressed person with excessive drowsiness. The serotonin specific reuptake inhibitors (fluoxetine, paroxetine, sertraline) tend to worsen sleep discontinuity and, in the case of fluoxetine, produce an excessive amount of slow-rolling eye movements and arousals. Another drug in the SSRI category, citalopram, may be an exception in this regard since preliminary information suggests that it may not worsen sleep-related complaints. Bupropion also tends to have sleep-disruptive effects. In contrast, trazodone, nefazodone, and mirtazepine enhance sleep continuity. The effects of these antidepressants mentioned here apply, in general, to the acute (8-weeks) stage of treatment. Little is known about their effects on sleep when used over longer periods of time.
Medications
A number of medications treating a variety of conditions can cause insomnia. These include b-blockers, corticosteroids, ACTH, MAOI’s, SSRI’s, stimulating tricyclics, bronchodilators, thyroid hormone, oral contraceptives, some decongestants, among others. Additionally, rapid withdrawal from some sedatives, especially the short half-life benzodiazepines and opiates can produce a transient insomnia.
The Clinical Approach to Sleep-related Complaints
One of the most important points I always make with my patients is that insomnia is not a disorder in and of itself. Rather, it is best viewed as a symptom of a host of potential underlying sleep disorders. Therefore, a physician confronted with these complaints should strive to identify the underlying disorder(s) prior to treatment. Following the identification of an underlying disorder, a specific treatment can be instituted with confidence.
I follow the diagnostic process below in evaluating my patients:
- A thorough history with particular attention directed toward the hallmark symptoms of the major sleep disorders outlined above.
- Interview the bedpartner
- Patients almost invariably misjudge the extent of sleepiness; therefore, direct questioning regarding how sleepy an individual feels is often not helpful. The propensity for falling asleep is more accurate a measure; in severe cases, individuals fall asleep while actively engaged in complex tasks such as speaking, writing, or even eating. They may also experience sleep attacks, whose occurrence mandates rapid clinical intervention. Milder levels of daytime sleepiness result in falling asleep in passive situations such as while reading or watching television.
- Sleeping habits should be carefully reviewed including the patient’s usual bedtime, time spent awake in bed prior to and following the onset of sleep, and final morning awakening and arising time. Sleep logs, completed daily over two weeks prior to the evaluation, are often more revealing and accurate in this regard. The history should also include the pattern of drug, medication, and use of recreational substances, as well as potential sleep hygiene difficulties.
- Please see our "Sleep Hygiene" feature article which includes an example of a Sleep Log.
- A physical examination should be performed to assess the potential for medical and neurological illnesses that might be contributing to the sleep disorder.
- A thorough psychiatric history and mental status examination are also important.
- Serum laboratory tests including thyroid function studies should be considered if not performed within six months prior to the evaluation.
- When the diagnosis is in doubt, polysomnography in a sleep lab is recommended. Polysomnography is also warranted when seemingly adequate treatment of the presumed disorder does not result in the alleviation of symptoms. Polysomnography should always be performed when the office-based evaluation raises the possibility of intrinsic sleep disorders such as obstructive sleep apnea syndrome or narcolepsy. In these conditions, their presence and severity must be established prior to management.
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