More than a drug is required for insomnia

Persistent sleeplessness stems from a variety of factors, all of which should be addressed if a treatment plan is to succeed long-term.

While many patients (10%-40% of the population) complain about insomnia, few actually seek help. In a recent survey, almost 30% of respondents complained about symptoms of insomnia, yet only 13% discussed them with their clinicians.1

Insomnia frequently leads to excessive daytime sleepiness. The condition has three forms: psychophysiologic, sleep state misperception, and idiopathic.

Psychophysiologic insomnia: This has two key elements: somatized tension and learned sleep-preventing associations.2

Somatized tension refers to the manifestation of psychological stresses as bodily complaints, which are often alerting and activating. This may cause increased heart rate, muscle tension, and agitation. Learned sleep-preventing associations may result from various causes, such as an episode of pain or an illness. External associations could include stress from employment, relationships, shift work, and/or environmental factors.

Many patients who are affected by external factors can sleep normally in different environments, e.g., on vacation or when traveling on business. At home, however, they develop an increased concern and preoccupation with being able to fall asleep. Increased worrying becomes mentally and physiologically activating. Patients typically complain only about the difficulty falling asleep and will often deny other issues. Risk factors for psychophysiologic insomnia include light sleeping, anxiety, depression, and relationship concerns. Patients often avoid any changes in routine, especially during the evening hours, for fear such changes will further interfere with sleep.

Onset of psychophysiologic insomnia is usually in the third and fourth decades of life, with a female preponderance. While there is no definite inheritance pattern, parents and other relatives can pass “learned” behaviors to subsequent generations. Light sleeping, which may predispose to insomnia, can have a genetic basis.

Sleep state misperception insomnia: This form often begins in early or middle adulthood in women more than men. Patients complain about excessive daytime sleepiness or an inability to fall or remain asleep as well as dramatically reduced sleep time.

Diagnosis requires an objective and quantifiable measure of actual sleep time. Nocturnal polysomnography, the most reliable technique, will be normal with at least 6.5 hours of sleep.

Actigraphy, a portable wrist device that senses and records movement over several days, produces a chart of activity that correlates well with the awake and asleep states.3 Insurance companies usually do not reimburse for it. An inexpensive technique is a sleep diary in which patients chart sleep patterns over two weeks. Limitations include patient compliance and ability to chart. Some patients experience increased anxiety with these tasks, which may lead to increased insomnia.

Idiopathic insomnia: This begins in early childhood and has no medical or psychiatric explanation. Many patients will develop secondary problems, such as depression, anxiety, and other maladaptive coping mechanisms. Establishing the early childhood onset, which may be difficult, is essential.

Diagnosis

The history is key to diagnosis. All primary-care clinicians, and even specialists, should do a simple screening. Examples of questions to ask are provided in Table 1.

Having the bed partner present facilitates accurate history-taking, since he/she may provide valuable information and observations. Any positive response requires further assessment. The most relevant questions in cases of suspected insomnia are 1, 2, and 8.

Patients may have more than one sleep disorder. A complete medical history is essential, including review of prescription and OTC medications, alcohol and recreational drug use, work hours, and psychosocial stresses. Medications and other agents that can cause or exacerbate insomnia appear in Table 2.

While alcohol is a soporific in naïve subjects, it frequently has rather complex effects. It decreases sleep-onset latency as well as rapid eye movement (REM) sleep time in the early part of the night and increases non-REM sleep. After the patient has been asleep for a few hours, a rapidly declining blood alcohol leads to withdrawal symptoms, including REM rebound, increased dreaming, and sympathetic activation, which often results in arousals.

Some patients experience the urge to void because of the diuretic effect of the alcohol, GI irritation and upset, and “rebound wakefulness.” Patients with chronic alcohol dependence often must drink to stave off the sleep-onset insomnia. Alcohol also increases periodic leg movements of sleep, which can lead to sleep fragmentation, arousals, and excessive daytime somnolence. Opioid use in naïve patients tends to reduce total sleep time and REM sleep, but in patients with significant pain, these agents tend to increase sleep.

Differential diagnosis

A number of disorders may lead to secondary insomnia. For example, obstructive sleep apnea and restless legs syndrome (RLS) can cause nocturnal arousals and fragmentation of sleep, which result in excessive daytime somnolence. Many patients with RLS have problems falling asleep because they cannot find a comfortable position for their limbs.

Circadian rhythm disorders result from a disassociation between real-world time and the patient’s own sleep rhythm. In delayed sleep phase syndrome, an internal clock keeps patients up later than a “normal” real-world bedtime. Attempts to go to sleep according to the “real-world clock time” often result in insomnia because of reduced sleep drive. Delayed sleep syndrome occurs most commonly in adolescents and young adults. In advanced sleep phase syndrome, which is more common in the elderly, the internal sleep clock is set such that patients fall asleep very early in the evening but awaken in the middle of the night, a situation that may mimic sleep-maintenance insomnia.

Poor sleep hygiene refers to maladaptive sleep-related behaviors that may lead to irregular sleep times, variable awakening times, use of medications (both prescription and OTC), consumption of caffeine-containing beverages, and pre-bedtime behaviors not conducive to sleep. Noise, hot environments, increased fluid consumption at bedtime, stress, and other factors often accompany these “bad habits.” Shift work can result in significant insomnia. Travel-related insomnia, or jet lag, is really a desynchronization of the patient’s internal clock and real-world time.

REM behavior disorder (RBD) usually occurs in older adults, especially those with Parkinson disease or dementia. During normal REM sleep, all muscles except the diaphragm, extraocular, and chin muscles are paralyzed. In RBD, the paralysis of somatic muscles is absent or incomplete, which can result in patients’ actually acting out their dreams. This often includes thrashing about and jumping out of the bed, making it difficult to return to sleep.

Medical conditions can interfere with normal physiologic functions, thereby preventing sleep or causing awakening. Patients with congestive heart failure often experience central apnea (cessation of central drive for respiration) with secondary arousals. Asthma, bronchospasm, secondary adrenergic activity, and hypoxia may lead to arousals. Painful conditions, such as pruritus, arthritis, fibromyalgia, renal colic, etc., interrupt sleep. Perimenopausal symptoms include vasomotor phenomena and sleep disturbances.

Many neurologic conditions can lead to insomnia. Patients with dementia and Parkinson disease often experience sleep disturbances because of decreased daytime physical activities and medication effects. Psychiatric conditions associated with insomnia include depression, anxiety, mood disorders, post-traumatic stress disorder, and psychoses.

Evaluation

Background information on the patient’s sleep habits is essential. Inquire about the following characteristics of sleep disturbance to help identify the problem and devise an appropriate intervention:
• Description — Have patients describe exactly what they experience when trying to fall or stay asleep. Inquire about sleep in different environments, such as work-related travel, vacation, and other family homes.
• Onset of insomnia (age and details)
• Daily pattern — Have patients delineate the following times in detail (use the sleep diary): (a) morning awakening; (b) getting out of bed for the day; (c) all naps: time to bed, sleep, awakening; (d) caffeine use; (e) alcohol use; (f) dinner; (g) activities after dinner (in detail); (h) pre-bed activities (showering/bathing can be alerting, smoking, reading, TV, computer use, etc.); (i) bed activities before lights out: reading, computer use, sex, and (j) nocturnal awakenings: number, duration, activities
• Environmental factors — Do family members coming home late or leaving early, neighborhood noises, or construction interfere with sleep?
• Course of insomnia (i.e., worsening, with exacerbating factors, or improving, with ameliorating factors)
• Screening for depression, anxiety, sexual or physical abuse, trauma, and post-traumatic stress disorder
• Review of medical problems
• Work history (shift work and occupation)
• Treatments (self-medication, behavioral interventions, and pharmacologic interventions and responses)

Laboratory testing should include a complete blood count, complete metabolic panel, and a high-sensitivity thyroid- stimulating hormone level. If there is any possibility of RLS or depression, include ferritin, vitamin B12, folate, and magnesium levels.

A thorough physical examination is essential, particularly an assessment of craniofacial proportions, tongue size, palate width and height, uvular descent, tonsillar tissue, and an estimate of the adequacy of the oropharyngeal airway. Auscultation of the chest and heart, measurement of the neck circumference, and evaluation of pedal edema are important components of the examination.

In general, nocturnal polysomnography is not necessary for the diagnosis of insomnia if the clinician does not suspect any other sleep disorders.

Management of insomnia

Some patients treat insomnia by reading or watching television in bed “until they fall asleep.” Many patients attempt self-medication, which can lead to serious secondary problems. Patients frequently use alcohol, OTC preparations, hypnotics, sedatives, and anxiolytics to fall asleep and daytime caffeine to promote alertness.

Treatment should reduce factors that adversely affect sleep with minimum medication.

Behavioral approaches begin with obtaining complete information about the patient’s insomnia. Improving sleep hygiene is essential. Early-morning exposure to sunlight is necessary for resetting the body’s internal clock. On weekends and holidays, patients should awaken no more than one hour later than on weekdays. This, along with minimizing daytime naps, will increase sleep pressure at bedtime. Morning exercise facilitates nighttime sleeping. Evening exercise often exacerbates insomnia.

Sleep hygiene also includes avoidance of medications and other agents, especially caffeine, that may worsen insomnia. Many patients take their worries and stresses to bed. Techniques such as meditation, yoga, making “to-do lists,” packing backpacks and briefcases, and selecting clothes for the next day can decrease ruminative thoughts in bed. Avoiding activating behaviors, such as watching television, arguments, and using a computer, as well as keeping the bedroom quiet, cool, and dimly lit can also promote sleep.

The “bed rule” restricts use of the bed to sleep and sex. The “20-minute rule” requires patients who are still awake after 20 minutes to leave their bed for a cool, dimly lit, quiet room and to perform nonstimulating activities.

Pharmacologic interventions

Unless patients also apply behavioral interventions, pharmacologic treatment will probably not provide significant or optimal results. Helping patients and their families understand this at the outset of treatment can increase the probability of success and reduce unrealistic expectations. During therapeutic trials, all patients should maintain a sleep diary to assist the clinician in monitoring their response as they attempt various interventions.

The efficacy of OTC medications is limited. These usually contain an antihistamine such as diphenhydramine (Benadryl or Nytol). Antihistamines do help initiate sleep but often lead to sedation and drowsiness the next day. They can also interfere with cognitive function and memory. In elderly patients, such medications as well as other sleep preparations may increase the risk of falling.

Other OTC agents, e.g., chamomile tea and valerian root, may facilitate sleep. Magnesium and calcium may also be helpful. Melatonin, a naturally occurring hormone that is a precursor of serotonin, may facilitate sleep when taken 60-90 minutes before retiring. Typical doses range from 0.5-5 mg. Some patients experience a decrease in beneficial response over time.


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Table 3 outlines the key properties of the major medications.

If the patient’s main problem is the initiation of sleep, then choose among short-acting zolpidem (Ambien), zaleplon (Sonata), and ramelteon (Rozerem). If the primary complaint is awakening in the middle of the night, a very short-acting preparation, such as zaleplon or perhaps zolpidem, is effective. For the patient who has difficulty falling and remaining asleep, extended-release zolpidem (Ambien CR), eszopiclone (Lunesta), and ramelteon (Rozerem) would be better choices.

Whichever medication the clinician chooses to prescribe, patients should try it first on at least one night when they will not need to drive or operate potentially dangerous machinery the following day. Potential complications of the medications previously noted can include development of tolerance, morning sedation, cognitive dysfunction, a bad taste in the mouth, and headaches.

Other classes of medications have been used for the management of chronic insomnia. These include benzodiazepines, tricyclic and quarternary antidepressants, which include diazepam and congeners, trazodone, as well as nortriptyline and related compounds. Tolerance, excessive daytime somnolence, and cognitive dysfunction may occur with these agents. Many of the problems are more serious in older patients. Clinicians should carefully monitor all patients who are using any sleep-inducing medications.

Additional information is available from the American Insomnia Association (www.americaninsomniaassociation.org) and the National Library of Medicine (www.nlm.nih.gov/medlineplus/sleepdisorders.html). Patients whose insomnia is complex or does not respond to therapy should be referred to a sleep specialist.

Dr. Selman is a board-certified neurologist with special interest and training in sleep medicine. He is clinical associate professor of neurology at Columbia University College of Physicians and Surgeons in New York City, where he also has a private practice.

References

1. Morin CM, LeBlanc M, Daley M, et al. Epidemiology of insomnia: prevalence, self-help treatments, consultations, and determinants of help-seeking behaviors. Sleep Med. 2006;7:123-130.

2. The International Classification of Sleep Disorders, Revised: Diagnostic and Coding Manual. Westchester, Ill.: American Academy of Sleep Medicine; 2001.

3. Lichstein KL, Stone KC, Donaldson J, et al. Actigraphy validation with insomnia. Sleep. 2006;29:232-239.

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