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Insomnia Last Updated: September 7, 2005 |
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| Synonyms and related keywords: sleep disorder, sleep problem, sleep symptom, sleep complaint, sleeplessness, inability to sleep, transient insomnia, short-term insomnia, chronic insomnia
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AUTHOR INFORMATION
| Section 1 of 11   |
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| Author: James A Rowley, MD, Fellowship Program Director, Associate Professor of Medicine, Division of Pulmonary, Critical Care & Sleep Medicine, Department of Med, Wayne State University School of Medicine Coauthor(s): Nicholas Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants |
| James A Rowley, MD, is a member of the following medical societies:
American Academy of Sleep Medicine,
American College of Chest Physicians,
American College of Physicians, and
American Thoracic Society |
| Editor(s): Carmel Armon, MD, MSc, MHS, Professor of Neurology, Tufts University School of Medicine; Chief, Division of Neurology, Baystate Medical Center; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine;
Jose E Cavazos, MD, PhD, Assistant Professor, Departments of Medicine (Neurology) and Pharmacology, University of Texas Health Science Center at San Antonio;
Matthew J Baker, MD, Consulting Staff, Collier Neurologic Specialists, Naples Community Hospital;
and Helmi L Lutsep, MD, Associate Director, Oregon Stroke Center; Associate Professor, Department of Neurology, Oregon Health and Science University |
Disclosure
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INTRODUCTION
| Section 2 of 11   |
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Background: Insomnia is the most common sleep complaint. It is a perception that sleep quality is inadequate or nonrestorative, despite the adequate opportunity to sleep. That insomnia is a symptom, not a disease, is important to note; it is associated with a variety of medical, psychiatric, and sleep disorders (see Causes). A comprehensive history and physical examination are essential to determine the etiology of the insomnia.
The complaint of insomnia encompasses many sleep problems. These include difficulty falling asleep, sleeping too lightly, being easily disrupted with multiple spontaneous awakenings, or early morning awakenings with inability to fall back asleep. The timing of insomnia is important in determining its etiology. Therefore, having each patient define what he or she means by insomnia is essential.
To be considered a disorder, the complaint of insomnia should be accompanied by distress and/or impairment in daytime functioning (see Morbidity).
On the basis of duration, insomnia is commonly divided into the following 3 types:
- Transient insomnia lasts up to 1 week and often is referred to as adjustment sleep disorder because it most often is caused by an acute situational stress, such as a new job, upcoming deadline, or exam. It often recurs with new or similar stresses.
- Short-term insomnia lasts for 1-6 months and is usually associated with more persistent stressful situational (death or illness of a loved one) or environmental (noise) factors.
- Chronic insomnia is any insomnia lasting more than 6 months and is associated with a wide variety of disorders (to be discussed later).
Pathophysiology: Insomnia usually results from an interaction of biological, physical, psychological, and environmental factors.
Although transient insomnia can occur in any person, chronic insomnia appears to develop only in a subset of patients who may have predisposing factors. Evidence for this theory includes the following:
- When compared to control subjects, individual with insomnia (1) have higher rates of depression and anxiety, (2) score higher on scales of arousal, (3) have longer daytime sleep latency, (4) have an increased 24-hour metabolic rate, (5) have more night-to-night variability in their sleep, and (6) may have more beta EEG activity (an EEG pattern seen during memory processing/performing tasks) at sleep onset.
- In experimental models of insomnia, control subjects deprived of sleep do not demonstrate the same abnormalities in metabolism, daytime sleepiness, and personality as persons with insomnia.
- In an experimental model of giving control subjects caffeine, causing a state of hyperarousal, the control subjects did have changes in metabolism, daytime sleepiness, and personality similar to those seen in individuals with insomnia.
These results support a theory that insomnia is a manifestation of hyperarousal. In other words, the poor sleep may not itself be the cause of the daytime dysfunction but merely the nocturnal manifestation of a general disorder of hyperarousability.
Therefore, chronic insomnia is believed to primarily occur in patients with predisposing factors. These factors may cause the occasional night of poor sleep, but in general, the patient sleeps well until the occurrence of a precipitating event, such as death or other life stress. Then, acute insomnia develops. If poor sleep habits or other perpetuating factors occur, chronic insomnia develops despite the removal of the precipitating factor. This theory is illustrated in Image 1. Frequency:
- In the US: In a 1991 survey, 30-35% of adult Americans reported difficulty sleeping in the past year and 10% reported the insomnia to be chronic and/or severe. Despite the high prevalence, only 5% of persons with chronic insomnia visited their physician specifically to discuss their insomnia. Only 26% discussed their insomnia during a visit made for another problem.
- Internationally: A study from Quebec indicated an overall prevalence of insomnia of approximately 20% of French Canadians. A study of young adults in Switzerland indicated a 9% prevalence of chronic insomnia. A World Health Organization (WHO) study conducted in 15 centers found a prevalence of approximately 27% for the complaint "difficulty sleeping."
Mortality/Morbidity: Insomnia is associated with a variety of complaints in daytime functioning.
- Insomniacs complain of impaired ability to concentrate, poor memory, difficulty coping with minor irritations, and decreased ability to enjoy family and social relationships.
- Insomniacs are more than twice as likely as the general population to have a fatigue-related motor vehicle accident.
- The mortality rate appears to be higher in patients who get less than 5 hours of sleep per night than in the general population.
Sex: The prevalence of the complaint of insomnia is higher in women—approximately 40% as against 30% in men.
Age: The frequency of the complaint of insomnia increases with age.
History: The history is the most important part of evaluating insomnia. It must include a complete sleep history, medical history, social history, and careful medication review. - Sleep history: Determining the timing of insomnia, the patient's sleep habits (commonly referred to as sleep hygiene), and symptoms of sleep disorders associated with insomnia is important.
- Timing of insomnia: Patients should be asked about any difficulty falling asleep, frequent awakenings or early morning awakening, problems in sleep onset, and whether they feel sleepy when getting into bed.
- Sleep schedule: Patients must be asked what time they go to bed and rise from bed in the morning. Determine whether the sleeping schedule is consistent and if the schedule has changed recently.
- Sleep environment: Patients should be asked about temperature, bed comfort, noise, and light levels. Ask whether the patient sleeps better in his or her own bed or in a chair or a foreign environment (like a hotel).
- Sleep habits: Patients with insomnia often have poor sleep hygiene. They should be asked about activities prior to bedtime (ie, relaxation or work), whether they read or watch TV in bed, and whether the TV or light is kept on during the night. Also, ask patients what they do if unable to fall asleep and whether they fall asleep after waking up in the middle of the night. Ask patients about daytime naps and whether they exercise and the time of exercise.
- Patients should be asked about symptoms of other sleep disorders such as obstructive sleep apnea (eg, snoring, witnessed apneas, gasping) and restless leg syndrome/periodic limb movement disorder (ie, restless feeling in legs on lying down, which improves with movement; rhythmic kicking during the night; very messy sheets in the morning).
- Daytime effects: Patients should experience daytime effects if they truly are not sleeping at night. In fact, if a patient is having no daytime effects, he or she probably is getting adequate sleep and the complaint of insomnia is truly subjective. Common complaints are fatigue, tiredness, lack of energy, irritability, reduced work performance, and difficulty concentrating. These complaints should be distinguished from the complaint of excessive sleepiness, which is rare in insomnia.
- Medical history: A thorough medical history and review of systems should be performed, with particular emphasis on those disorders mentioned in Causes.
- Psychiatric history: A thorough psychological review should be done to screen for psychiatric disorders (see Causes).
- Social history: For transient or short-term insomnia, inquire about new situational stresses such as a new job or school, or bereavement. For chronic insomnia, attempt to relate the onset of insomnia to past stresses or medical illnesses. A thorough history of the use of tobacco, caffeinated products, alcohol, and illegal drugs should be obtained.
- Medication history: Medications that commonly cause insomnia include beta-blockers, clonidine, theophylline (acutely), certain antidepressants (protriptyline or fluoxetine), decongestants, and stimulants.
Physical: The physical examination is rarely helpful in the evaluation of insomnia, with the following exceptions: - If the patient complains of sleep apnea, a careful head and neck examination should be performed. Common anatomic features associated with sleep apnea include lateral narrowing of the oropharynx, oropharyngeal crowding secondary to increased tongue and soft tissue volume, enlarged tonsils, micrognathia, and retrognathia
- If the patient complains of symptoms of restless leg syndrome or any other neurologic syndrome, a careful neurologic examination should be performed.
- If the patient has daytime complaints consistent with any of the medical causes of insomnia listed in Causes, a careful examination of the affected organ system (eg, the lungs in chronic obstructive pulmonary disease [COPD]) may be helpful.
Causes: As stated previously, insomnia is a symptom; an accurate differential diagnosis is essential for the proper management of this complaint in any given patient.- Transient and short-term insomnia: Etiologies can be divided into 2 broad categories, as follows:
- Environmental - Unfamiliar or unconducive sleep environment due to factors such as too much noise or light, extremes of temperature, or poor bed
- Stress - Primarily life events such as new job or school, deadlines or exams, or death of a relative or close friend
- Chronic insomnia: Differential diagnosis is broader and includes the following categories:
- Medical disorders - Include chronic pain syndromes from any cause (eg, arthritis, cancer), advanced COPD, chronic renal disease (especially if on hemodialysis), chronic fatigue syndrome, and fibromyalgia
- Neurologic disorders - Include Parkinson disease and other movement disorders, as well as headache syndromes, particularly cluster headaches, which frequently are triggered by sleep
- Psychiatric disorders - Most chronic psychiatric disorders
- Depression most commonly is associated with early morning awakenings and inability to fall back asleep; studies also have shown that insomnia can lead to depression. (The presence of insomnia for longer than 1 year is associated with an increased risk of depression.)
- Schizophrenia and the manic phase of bipolar illness frequently are associated with sleep-onset insomnia.
- Anxiety disorders (including nocturnal panic disorder and posttraumatic stress disorder) are associated with both sleep-onset and sleep-maintenance complaints.
- Drug-related insomnia: Sleep disruption is common with excessive use of stimulants, alcohol, or sedative-hypnotics.
- Restless leg syndrome (RLS)/periodic limb movement disorder (PLMD) is a sleep disorder characterized by unpleasant physical sensations in the legs, often described as a motor restlessness; relief of symptoms through movement, with worsening in a recumbent position; and occurrence only in the evening, primarily at bedtime. It is frequently relieved by movement (in the case of RLS) and is usually (but not necessarily) associated with frequent and rhythmic leg kicking once asleep (in the case of PLMD). If RLS is predominant, sleep-onset insomnia is the rule; if PLMD is predominant, sleep-maintenance insomnia or daytime hypersomnolence is more likely.
- In obstructive sleep apnea, a minority of patients complain of insomnia rather than hypersomnolence. They frequently complain of multiple awakenings or sleep-maintenance difficulties.
- Circadian rhythm disorders, such as sleep phase advance (patient goes to bed early and rises early) and sleep phase delay (patient goes to bed late and rises late) syndromes can present as insomnia when the patient wants to either stay in bed later or go to bed earlier but cannot and then believes he or she has a problem sleeping. Shift workers also frequently have problems with insomnia, particularly when they want to sleep during the day.
- Primary insomnia: If all the disorders already discussed have been ruled out, the patient has primary insomnia. Most primary insomnia is psychophysiologic insomnia; rarely, primary insomnia is caused by idiopathic insomnia (long-standing insomnia beginning in childhood without antecedent psychiatric or medical trauma) or sleep state misperception (insomnia with objective evidence of a sleep disorder).
- Psychophysiologic insomnia is a disorder of somatized tension and learned sleep-preventing associations resulting in a complaint of insomnia and daytime fatigue.
- Psychophysiologic insomnia begins with a prolonged period of stress in a person with previously adequate sleep. The patient responds to stress with somatized tension and agitation, causing physiologic arousal. The bedroom and/or sleep routine becomes associated with frustration and arousal; poor sleep hygiene follows.
- In a normal sleeper, as the initial stress abates, the bad sleep habits are extinguished gradually, as they are not reinforced. However, in a sleeper with a tendency toward occasional poor sleep nights, bad habits are reinforced, the individual "learns" to worry about his or her sleep, and chronic insomnia follows.
- History in these patients frequently reveals excessive daily worries about not being able to fall asleep, evidence of trying too hard to sleep with apprehension if unable to fall asleep, an ability to fall asleep during monotonous pursuits (such as watching TV or reading) and in inappropriate situations (at a lecture or while driving) but not when desired, improvement of sleep in unusual sleep environments, and increased agitation and muscle tension prior to bed.
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DIFFERENTIALS
| Section 4 of 11 |
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Obstructive Sleep Apnea-Hypopnea Syndrome
Other Problems to be Considered:
Circadian rhythm disorder
Improper sleep hygiene
Depression |
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Lab Studies:
- Patients with a history suggestive of sleep apnea or RLS/PLMD should be referred to a sleep center for polysomnography.
- Patients with a history suggestive of COPD and insomnia should have an arterial blood gases (ABG) study performed to determine if they are hypoxemic.
- Insomnia in COPD frequently begins with the development of nocturnal hypoxemia (though nocturnal, hypoxemia is not required for insomnia to occur).
- Treatment with oxygen may improve but rarely eliminates the insomnia.
- Nocturnal hypoxemia is present if the patient has daytime hypoxemia or, frequently, exercise-related hypoxemia.
- If the ABG is negative for hypoxemia, an exercise desaturation study or overnight oximetry may be helpful to determine if the patient needs oxygen.
- Neurologic testing may be indicated in patients with signs and symptoms of neurologic disease.
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TREATMENT
| Section 6 of 11 |
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Medical Care: - The management of insomnia depends upon its etiology.
- If the patient has a medical, neurologic, or sleep disorder, treatment should be directed at the disorder. In particular, adequate pain control can greatly relieve insomnia associated with pain syndromes.
- In case of a psychiatric disorder, treatment should be directed at the disorder. This may involve medications, psychotherapy, and if possible referral to a psychiatrist, psychologist, or therapist.
- If the insomnia is related to medication or drug abuse, the offending medication or drug must be withdrawn.
- The treatment of psychophysiologic insomnia begins with education about the sleep problem and appropriate sleep hygiene (elements of good sleep hygiene are described in Patient Education).
- Before instituting therapy, most patients are asked to maintain a sleep log for 2-4 weeks. In the sleep log, the patient records bed and wake times, how much sleep is obtained, and daytime naps and activities. It gives the physician a clearer picture of the degree of sleep disturbance and allows him or her to better tailor the treatment.
- Behavioral therapy now is considered the most appropriate treatment for patients with primary insomnia. The therapies are based on the fact that primary insomnia is associated with physiologic, emotional, and cognitive arousal and conditioning to arousal in bed. The 3 primary behavioral therapies are as follows:
- Relaxation therapy: In progressive relaxation, the patient is taught to recognize and control tension through a series of exercises that consist of first tensing and then relaxing each muscle group in a systematic way.
- Guided imagery and meditation teach the patient how to focus on neutral or pleasant targets in place of racing thoughts.
- Biofeedback techniques also can be used. They have the advantages of providing the patient with immediate feedback regarding his or her level of tension and rapidly teaching the patient how to relax.
- Stimulus control therapy works to reassociate the bed with sleepiness instead of arousal. Rules for its use include the following:
- Using the bed only for sleeping and sexual activity (no reading, TV, eating, or working in bed)
- Lying down only when sleepy
- If unable to fall asleep in 15-20 minutes, getting out of bed to do something relaxing until sleepy; this can be repeated as often as needed
- Not spending more time in bed than is needed
- Sleep-restriction therapy is based upon the fact that excessive time in bed often perpetuates the insomnia. Limiting time in bed leads to more efficient sleep that is both consolidated, and more regular and predictable. Time in bed is allowed to increase as the patient demonstrates a continuing ability to sleep in an efficient and consolidated fashion.
Consultations: Primary care physicians should be able to diagnose and treat transient or short-term insomnia. Chronic insomnia is often more difficult to treat and when primary or associated with a sleep or psychiatric disorder, referral to an appropriate specialist may be indicated. - Patients should be referred to a sleep specialist in the following cases:
- If any history suggestive of obstructive sleep apnea or RLS/PLMD
- In cases of primary insomnia, particularly if it is psychophysiologic insomnia and of long duration
- Many sleep centers have a staff psychologist who specializes in treating insomnia. The advantages include experience in behavioral techniques and providing sleep education, greater available time for the often-frequent follow-up that is needed, and the ability to ascertain if other psychological factors are present that may need further evaluation by a psychiatrist.
- Patients with a history of depression should be referred to a psychiatrist based on the usual referral pattern of the primary care physician.
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MEDICATION
| Section 7 of 11 |
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Sedative-hypnotic medications do not cure insomnia but may provide symptomatic relief. The most appropriate use of these drugs is for transient and short-term insomnia in combination with nonpharmacologic treatment. Most authorities now agree that they should never be the sole therapy for chronic insomnia. However, for patients with chronic insomnia, a sedative-hypnotic may play an adjunctive role in the early states of treatment when behavioral therapies are being introduced.
Some general precautions should be followed for the use of sedative-hypnotics, as follows:
- Therapy should be instituted with a small dose and maintained at the smallest effective dose.
- Continued nightly use should be avoided; patients should be encouraged to use them only when truly necessary.
- Use for more than 2-3 weeks should be avoided.
- A hypnotic free of residual effects in the morning is preferable (eg, zolpidem, zaleplon, triazolam).
- Hypnotics with a rapid onset of action, such as zolpidem, zaleplon, and triazolam, are preferable when the problem is falling asleep. If the problem is staying asleep, a hypnotic with a slower rate of elimination may be more appropriate (eg, temazepam, estazolam, flurazepam). If the patient is depressed, an antidepressant with sedative properties, such as trazodone or amitriptyline, may be useful.
- Hypnotics never should be used with alcohol.
- In general, pregnancy is a contraindication.
- Benzodiazepines should be avoided in patients with known or possible sleep apnea.
- Smaller doses should be used in elderly patients.
- In most patients, the risk of dependency is low (most rarely escalate the dose or use more frequently than prescribed). However, avoid use in patients with a history of substance abuse.
- Rebound insomnia may develop when the medication is withdrawn abruptly. This is more likely to occur with large doses and short-acting agents. Using smaller doses and tapering the drug can avoid rebound insomnia.
Note that most studies of the efficacy of sedative-hypnotics have been short-term trials, generally less than 4 weeks. Use longer than 4 weeks was thought to result in tolerance and decreased efficacy, although there is a paucity of supportive literature and epidemiologic literature suggests that patients report continued efficacy with continued use. However, because of the addictive nature of benzodiazepines, most authorities believe that the length of use should be limited.
Recently, a new drug, eszopiclone was the first sedative-hypnotic to be tested over a 6-month period (see Krystal et al in the Bibliography). This study showed continued efficacy over the 6-month period. Recent evidence, presented in abstract form, shows continued efficacy at 12 months. Eszopiclone is believed to be less addictive than benzodiazepines and, therefore, represents an important advance in the long-term treatment of chronic insomnia. Eszopiclone is likely to become a first choice agent for the treatment of insomnia. However, further study is needed to determine its role relative to nonpharmacologic therapies outlined above.
Common OTC antihistamines (eg, diphenhydramine, hydroxyzine) are not indicated for the treatment of sleeplessness. Antihistamines are the major ingredient of OTC sleep aids and are the ingredient in cold and sinus formulas sold as bedtime-use medications. While H1-antihistamines have sedative effects in healthy individuals, no study has established a dose range over which the hypnotic effect is effective in patients with insomnia. Thus, their regular use in individuals with insomnia is not advised. These agents may have some subjective benefit, but long-term efficacy has not been demonstrated and they are not recommended.
Melatonin has become a popular OTC sleep aid. Melatonin is a naturally occurring hormone secreted by the pineal gland. The concentration of melatonin is highest in the blood during normal times of sleep and lowest during normal times of wakefulness. The general consensus is that melatonin given during normal waking hours has hypnotic properties. However, the timing of evening administration is critical as to whether a hypnotic effect occurs. Melatonin given early in the evening appears to increase sleep time; however, administration 30 minutes before a normal bedtime has not resulted in a decreased sleep latency or sleep time.
However, studies of melatonin in individuals with chronic insomnia have not demonstrated objective changes in patient sleep habits or changes in mood or alertness the day after treatment. In addition, a dose-response relationship has not been determined. OTC melatonin is also sold at doses much higher than those that naturally occur in the blood. Therefore, at this time, most authorities do not recommend melatonin for the treatment of chronic insomnia.
Drug Category: Sedative-hypnotics -- These agents are excellent choices for treatment of sleep-onset insomnia. Drug Name
| Zaleplon (Sonata) -- Sedative-hypnotic of pyrazolopyrimidine class; rapid onset of action with ultra-short duration of action; good choice for treatment of sleep-onset insomnia. Second dose can be used during middle of night without residual sedation in morning (believed to be an advantage of this hypnotic over others). |
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| Adult Dose | 10 mg PO hs; 5 mg PO hs in elderly adults |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity |
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| Interactions | Cimetidine significantly increases levels |
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| Pregnancy |
C - Safety for use during pregnancy has not been established.
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| Precautions | Failure of insomnia to remit after 7-10 d of treatment may indicate need for evaluation of primary psychiatric or medical illness; limit treatment to 7-10 d of use, and reevaluate patient if to be taken for >2-3 wk (do not prescribe in quantities exceeding 1-month supply); in hepatic function impairment, reduce dose to 5 mg PO hs; caution in patients exhibiting signs or symptoms of depression; headaches may occur if taking 20 mg hs |
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Drug Name
| Zolpidem (Ambien, Ambien CR) -- Sedative-hypnotic of imidazopyridine class; has rapid onset and duration of action; good first choice for treatment of sleep-onset insomnia; has no significant residual sedation in morning. The extended-release product (Ambien CR) consists of a coated 2-layer tablet and is useful for insomnia characterized by difficulties with sleep onset and/or sleep maintenance. The first layer releases drug content immediately to induce sleep; the second layer gradually releases additional drug to provide continuous sleep. |
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| Adult Dose | 10 mg PO hs; 5 mg PO hs in elderly adults
Extended-release: 12.5 mg PO hs
Extended-release in elderly patients: 6.25 mg PO hs| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; lactation |
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| Interactions | Increases toxicity of alcohol and CNS depressants; effect may be delayed if taken with food or shortly after a meal |
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| Pregnancy |
B - Usually safe but benefits must outweigh the risks.
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| Precautions | Monitor elderly persons for impaired cognitive or motor performance; extended-release dosage form must be swallowed whole (do not divide, chew, or crush) |
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Drug Name
| Eszopiclone (Lunesta) -- Nonbenzodiazepine hypnotic pyrrolopyrazine derivative of the cyclopyrrolone class. The precise mechanism of action is unknown but is believed to interact with GABA-receptor at binding domains close to or allosterically coupled to benzodiazepine receptors. Indicated for insomnia to decrease sleep latency and improve sleep maintenance. Short half-life of 6 h. Higher doses (ie, 2 mg for elderly adults and 3 mg for nonelderly adults) are more effective for sleep maintenance, whereas lower doses (ie, 1 mg for elderly adults and 2 mg for nonelderly adults) are suitable for difficulty in falling asleep. |
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| Adult Dose | Nonelderly adults: 2 mg PO hs; may increase to 3 mg PO hs prn
Elderly adults: 1 mg PO hs initially; not to exceed 2 mg PO hs
Severe hepatic impairment: Do not exceed 2 mg PO hs| Pediatric Dose | <18 years: Not established
>18 years: Administer as in adults| Contraindications | Documented hypersensitivity |
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| Interactions | CYP3A4 and CYP2E1 substrate; potent CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, nefazodone, ritonavir, nelfinavir) increases AUC, Cmax, and t1/2 and therefore potential toxicity (decrease dose); potent CYP3A4 inducers (eg, rifampicin) increase clearance; coadministration with alcohol or other CNS depressants may increase effect and toxicity (decrease dose); coadministration with olanzapine may decrease DSST scores; sleep onset may be delayed if taken with or immediately after a high-fat or heavy meal |
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| Pregnancy |
C - Safety for use during pregnancy has not been established.
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| Precautions | May cause dysgeusia, headache, or coldlike symptoms; rare adverse effects associated with hypnotics include short-term amnesia, confusion, agitation, hallucinations, worsened depression, or suicidal thoughts; high doses (ie, 6-12 mg) produce euphoric effects similar to those of diazepam 20 mg; anxiety, abnormal dreams, nausea, and upset stomach may occur within 48 h after discontinuing; alertness may be affected the following day, use caution while operating machinery or driving a car |
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Drug Category: Benzodiazepine hypnotics -- These agents have been the hypnotics of choice for many years because of their relative safety compared to the barbiturates. By binding to specific receptor sites, these agents appear to potentiate the effects of GABA and facilitate inhibitory GABA neurotransmission and other inhibitory transmitters.Drug Name
| Triazolam (Halcion) -- Short acting; good agent for sleep-onset insomnia; has no significant residual effects in morning. |
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| Adult Dose | 0.125-0.25 mg PO hs; 0.125 mg PO hs in elderly persons |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; narrow-angle glaucoma; untreated obstructive sleep apnea; history of substance abuse |
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| Interactions | Phenothiazines, barbiturates, alcohols, and MAOIs increase CNS toxicity |
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| Pregnancy |
D - Unsafe in pregnancy
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| Precautions | High incidence of rebound insomnia; adverse effects include dizziness, drowsiness, and headache, all of which are dose related; use cautiously in depressed patients; caution and close monitoring needed in hepatic dysfunction, low albumin levels, renal or pulmonary disease; may cause residual daytime sedation, impair cognition, and increase risk of falls, especially in older people |
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Drug Name
| Estazolam (ProSom) -- Intermediate acting with slow onset of action and long duration; good agent for sleep-maintenance insomnia. |
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| Adult Dose | 1-2 mg PO hs; 0.5-1 mg PO hs in elderly persons |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; narrow-angle glaucoma; untreated obstructive sleep apnea; history of substance abuse |
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| Interactions | Phenothiazines, barbiturates, alcohols, and MAOIs increase CNS toxicity |
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| Pregnancy |
D - Unsafe in pregnancy
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| Precautions | Caution in depressed patients; most common adverse effects include drowsiness, hypokinesia, dizziness, and abnormal coordination; may have more significant respiratory depressive effects than other agents in its class; caution and close monitoring needed in hepatic dysfunction, low albumin levels, renal or pulmonary disease; may cause residual daytime sedation, impair cognition, and increase risk of falls, especially in older people |
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Drug Name
| Flurazepam (Dalmane) -- Long-acting metabolites; residual effects in morning are likely, but if tolerated, good drug for sleep-maintenance insomnia. |
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| Adult Dose | 15-30 mg PO hs; 15 mg PO hs in elderly persons |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; narrow-angle glaucoma; preexisting CNS depression; respiratory depression |
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| Interactions | Phenothiazines, barbiturates, alcohols, and MAOIs increase CNS toxicity |
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| Pregnancy |
D - Unsafe in pregnancy
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| Precautions | Caution with other CNS depressants, low albumin levels, or hepatic disease (may increase toxicity) |
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Drug Name
| Temazepam (Restoril) -- Short to intermediate acting with longer latency to onset and half-life; may be more helpful in sleep-maintenance insomnia. |
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| Adult Dose | 15-30 mg PO hs; 7.5-15 mg PO hs in elderly persons |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; narrow-angle glaucoma; untreated obstructive sleep apnea; history of substance abuse; severe uncontrolled pain |
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| Interactions | Phenothiazines, barbiturates, alcohols, and MAOIs increase CNS toxicity |
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| Pregnancy |
D - Unsafe in pregnancy
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| Precautions | Use cautiously in depressed patients; adverse effects are generally mild and include drowsiness, headache, nervousness, and dizziness; caution with other CNS depressants, low albumin levels, or hepatic disease (may increase toxicity) |
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Drug Category: Antidepressants -- The side effect of drowsiness seen with some antidepressants can be used to benefit the patient in the treatment of sleep-maintenance insomnia or insomnia associated with depression.Drug Name
| Trazodone (Desyrel) -- Nontricyclic antidepressant with short onset of action; consolidates sleep. Antagonist at 5-HT2 receptor and inhibits reuptake of 5-HT. Also has negligible affinity for cholinergic and histaminergic receptors. |
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| Adult Dose | 50-100 mg PO hs |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity |
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| Interactions | May enhance response to alcohol, barbiturates, and other CNS depressants; may increase digoxin and phenytoin serum levels; may decrease hypoprothrombinemic effects of warfarin |
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| Pregnancy |
C - Safety for use during pregnancy has not been established.
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| Precautions | Common adverse effects include dry mouth, blurred vision, constipation, and urinary retention; priapism has been reported; hypotension, including orthostatic hypotension and syncope, have occurred; may produce drowsiness or dizziness; patients taking this medication should observe caution while driving or performing other tasks requiring alertness, coordination, or dexterity |
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Drug Name
| Nefazodone (Serzone) -- Inhibits serotonin reuptake and is potent antagonist at type 2 serotonin (5-HT) receptor. Also has negligible affinity for cholinergic, histaminic, or alpha-adrenergic receptors. |
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| Adult Dose | 50-150 mg PO qhs |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; use of MAOIs within 14 d of initiating treatment; concurrent use with astemizole, carbamazepine, cisapride, or terfenadine |
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| Interactions | Decreases effects of anticoagulants, oral hypoglycemics, diuretics, clonidine, and methyldopa; increases effects of digoxin, carbamazepine, and MAOIs; toxicity of may increase when used concurrently with amiodarone, cimetidine, fluoxetine, fluvoxamine, grapefruit juice, indinavir, itraconazole, ketoconazole, metronidazole, zafirlukast, or zileuton |
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| Pregnancy |
C - Safety for use during pregnancy has not been established.
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| Precautions | Caution in cardiac disease, cerebrovascular disease, or seizures; discontinue therapy and reevaluate if priapism occurs |
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Drug Name
| Amitriptyline (Elavil) -- Tricyclic antidepressant with sedative effects. Inhibits reuptake of serotonin and/or norepinephrine at presynaptic neuronal membrane, which increases concentration in CNS. |
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| Adult Dose | 50-100 mg PO hs |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; MAOIs in past 14 d; history of seizures, cardiac arrhythmias, glaucoma, or urinary retention |
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| Interactions | Phenobarbital may decrease effects; CYP2D6 enzyme system inhibitors (eg, cimetidine, quinidine) may increase levels; inhibits hypotensive effects of guanethidine; may interact with thyroid medications, alcohol, CNS depressants, barbiturates, and disulfiram |
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| Pregnancy |
B - Usually safe but benefits must outweigh the risks.
|
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| Precautions | Most common adverse effects are anticholinergic -- urinary retention, constipation, and blurred vision; caution in cardiac conduction disturbances and history of hyperthyroidism, renal or hepatic impairment; avoid using in elderly persons |
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Drug Category: Melatonin agonists -- Indicated for insomnia characterized by difficulty with sleep onset.Drug Name
| Ramelteon (Rozerem) -- Melatonin receptor agonist with high selectivity for human melatonin MT1 and MT2 receptors. MT1 and MT2 are thought to promote sleep and be involved in maintenance of circadian rhythm and normal sleep-wake cycle. |
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| Adult Dose | 8 mg PO 30 min before bedtime on empty stomach |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; strong cytochrome P450 CYP1A2 inhibitors (eg, fluvoxamine); severe hepatic impairment |
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| Interactions | Major substrate of cytochrome P450 CYP1A2 and minor substrate of CYP2C and CYP3A4; strong CYP1A2 inhibitors (eg, fluvoxamine) increase AUC up to 190-fold and Cmax 70-fold; strong CYP inducers (eg, rifampin) decrease total exposure by mean of 80%; strong CYP3A4 inhibitors (eg, ketoconazole) and strong CYP2C9 inhibitors (eg, fluconazole) may increase serum levels |
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| Pregnancy |
C - Safety for use during pregnancy has not been established.
|
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| Precautions | Caution with mild hepatic impairment; adverse effects leading to discontinuation in clinical trials included dizziness, nausea, fatigue, headache, and worsening insomnia |
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FOLLOW-UP
| Section 8 of 11 |
|
Patient Education:
- Developing regular sleep habits: This means keeping a regular bedtime and wake time, sleeping as much as needed to feel refreshed the following day, but not spending more time in bed than needed.
- Slowing down and unwinding before bedtime (beginning at least 30 minutes before bedtime); a light snack may be helpful.
- Keeping the bedroom dark, quiet, and at a comfortable temperature.
- Exercising daily: This is best performed in the late afternoon or early evening (but not later than 7-8 pm).
- Not forcing oneself to sleep: Advise the patient that if unable to fall asleep within 15-30 minutes, he or she should get up and do something relaxing until sleepy.
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MISCELLANEOUS
| Section 9 of 11 |
|
Special Concerns:
- The satisfaction of sleep declines with age. This probably is related to changes in sleep associated with age, such as a decrease in slow wave sleep, increased time awake after sleep onset, and a tendency to go to bed early and rise early.
- However, aging should not be assumed to be the explanation for insomnia. Multiple factors affect sleep in the elderly, including nocturia, pain syndromes, and many medical disorders (eg, heart failure, COPD, Parkinson disease). Other factors include RLS, PLMD, and sleep apnea (all of which have increased frequency in the elderly), dementia and, frequently, changing situational factors, such as retirement, bereavement, or financial difficulties, leading to anxiety and depression.
- As in younger patients, nonpharmacologic treatment should take precedence over pharmacologic treatment.
- Hypnotics should be prescribed cautiously and in lower doses than for younger patients. Drugs tend to have longer duration of effect due to changes in metabolism and elimination. This can lead to increased incidence of falls and bone fractures at night (if the patient gets up to use the bathroom not fully awake or ataxic) and decrements in daytime alertness and performance (including increased incidence of motor vehicle accidents).
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PICTURES
| Section 10 of 11 |
|
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BIBLIOGRAPHY
| Section 11 of 11 |
|
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Zorick FJ, Walsh, JK: Evaluation and Management of Insomnia: An overview. In: Kryger MH, Roth T, Dement WC, eds. Principles and Practice of Sleep Medicine. New York: McGraw-Hill; 2000: 615-23.
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