Overview and Risk Factors
Insomnia is characterized by difficulties in initiating sleep, maintaining sleep, or feeling restored after sleep. It is the most common sleep disorder in the United States, affecting about one-third of adults at some point in their lives. Approximately 10% of those with symptoms experience persistent insomnia.
Patients often report impairments in daytime function in addition to the nocturnal symptoms. They may experience daytime fatigue, inability to concentrate, irritability, anxiety, depression, and forgetfulness, and may have an increased risk of automobile accidents.1 Further, these patients often have associated psychosomatic symptoms, such as nonspecific aches and pains.
Insomnia has been described as transient (less than 1 week of symptoms), short-term (1-3 weeks), and chronic (longer than 3 weeks).2 Dozens of possible etiologies may explain each type. Sleep impairment lasting only a few days to a few weeks may be the result of poor or altered sleep environments, such as excessive noise or light and unpleasant room temperature. It may result from lifestyle changes, such as jet lag, change in work shift, acute illness, and stressful life events. Also, taking medications with stimulant properties (eg, bronchodilators, theophylline, antidepressants, caffeine-containing pain relievers, methylphenidate) and withdrawal from drugs or alcohol may contribute to impaired sleep. Insomnia lasting more than a few weeks may be associated with chronic drug or alcohol abuse, medical disorders, or psychiatric disorders, or it may result from primary sleep disorders, such as restless legs syndrome and sleep apnea.
Insomnia occurs disproportionately in women and in people who are divorced, widowed, or separated. Additional risk factors include:
Age. Prevalence increases with age. Age is the most important risk factor for developing insomnia.
Psychiatric comorbidities. Sleep disturbances are more common in patients with mood disorders such as major depression, dysthymia, and bipolar affective disorder, as well as in those with anxiety disorders, schizophrenia, and acute stress.
Drugs and alcohol. Abuse of these agents may be associated with impaired sleep.
Stimulants. Use of medications and other substances with stimulant properties is a common cause of insomnia. These include caffeine, theophylline, corticosteroids, thyroxine, and bronchodilators.
Nicotine withdrawal is associated with sleep fragmentation. Insomnia is also a frequent side effect of nicotine patches3 and of bupropion, an antidepressant often used for smoking cessation.4
Diagnosis and Treatment
History and physical examination, including a sleep history and psychiatric history, should include evaluation of sleep habits, sleep environment, drug and alcohol use, medical and medication history, and family medical history. It is often helpful to interview the patient's bed partner and to ask the patient to keep a sleep log.
Laboratory testing may identify medical disorders (such as endocrinopathies) that can contribute to sleep difficulties.
Sleep testing is used in some patients. Polysomnography can identify sleep-related breathing disorders. Multiple sleep latency testing evaluates for inappropriate daytime sleepiness. Actigraphy measures motion during sleep.
Underlying medical, surgical, or psychiatric disorders should be treated as appropriate.
It is helpful to ask the patient to maintain good sleep hygiene, the essentials of which are to exercise regularly but not before bedtime, avoid caffeine, and limit alcohol, particularly near bedtime.3 Exercise has been shown to improve total sleep duration, sleep onset latency, and global sleep quality.5 However, timing is important. Physical activity early in the day is generally not associated with improved sleep, and exercise taken shortly before bedtime can delay sleep onset.3
Other beneficial practices include sleeping only as much as necessary to feel rested, keeping a regular sleep schedule, avoiding smoking, and adjusting the bedroom environment as needed. Many individuals with insomnia report poorer sleep hygiene practices, including increased use of alcohol, smoking near bedtime, and taking frequent daytime naps.6 Proper sleep hygiene is an often overlooked high-yield, low-risk means of helping patients with insomnia.
Maladaptive behaviors or thought patterns can sustain insomnia symptoms, independent of the initial underlying cause. Cognitive-behavioral sleep therapy addresses these problems and has proven more effective over the long term than pharmacologic therapy.7 Although additional evidence from controlled trials is needed, cognitive-behavior therapy was also found effective for insomnia related to a spectrum of medical and psychiatric conditions (eg, cancer, chronic pain, human immunodeficiency virus (HIV), depression, posttraumatic stress disorder, alcoholism, bipolar disorder, eating disorders, generalized anxiety, and obsessive compulsive disorder).8
Although placebo-controlled trials are not possible, a review of available evidence indicated that warm-bath immersion to the mid-thorax, with water temperature at 40 to 41 degrees C, for 30 minutes in the evening can increase slow-wave sleep (deep sleep) in healthy elderly women with insomnia.9
Zolpidem, zaleplon, and eszopiclone are often the first drugs prescribed for sleep. Other frequently prescribed drugs are benzodiazepines (eg, temazepam, lorazepam, flurazepam), antihistamines (eg, diphenhydramine), and antidepressants (eg, amitriptyline, trazodone). In most cases, however, these drugs do not improve the quality of sleep.
Benzodiazepines are contraindicated in women who are pregnant and in patients with renal, hepatic, or pulmonary disease. They should be used with caution in patients who consume alcohol.
Ramelteon, a melatonin-receptor agonist, has recently been approved by the Federal Drug Administration (FDA) for insomnia treatment. Supplemental use of melatonin and valerian may also be effective for sleep disorders (see Nutritional Considerations).
Healthy natural sleep should follow as a consequence of the normal physical and mental fatigue people typically experience during an active life. However, sleep deprivation is increasingly common, and it may be attributed to poor lifestyle choices. Chief among these are excesses of caffeine and alcohol and inadequate physical activity. Steps to be considered are discussed below.
Avoiding alcohol. Small amounts of alcohol (eg, 1 standard drink per evening) may not have negative effects on sleep for most people. However, people soon develop tolerance to its sedative effects, thus making it less useful for inducing sleep.10 Alcohol may increase the risk of insomnia by several mechanisms. Excess or chronic alcohol intake (ie, alcohol abuse or dependence) can decrease REM phase sleep in a dose-dependent manner.11 Alcohol consumption in the amount of 0.5 or 1.0 g/kg (3- 6 standard drinks) also causes disruption of normal circadian rhythms,12 probably through inhibiting melatonin secretion by more than 40%.13 Alcohol may cause rebound excitation through an increase in the number or sensitivity of receptors for glutamate, an excitatory neurotransmitter.12 As alcohol is metabolized, it produces aldehydes, which can have stimulating effects.14 Alcohol hangover, an excitatory state despite its reputation as one involving malaise, may be related to acetaldehyde.12 Alcohol may also increase the level of histamine, a known excitatory neurotransmitter, in the central nervous system (CNS).15
Limiting caffeine. Caffeine produces varying effects in individuals. In middle-aged persons drinking up to 7 cups of coffee per day (600 mg) and in subjects to whom caffeine was acutely administered, few or no effects on sleep were noted.3,16 However, some persons are more sensitive to the effects of caffeine, particularly elderly persons, who often unknowingly consume caffeine in over-the-counter medications.17 Slower blood clearance and higher blood concentrations of caffeine at midnight have been found in individuals with caffeine-related insomnia than in those not adversely affected by caffeine, indicating that differences in caffeine metabolism may be a cause of sleep disturbance.18 In persons with suspected or documented caffeine-sensitive sleep insomnia, discontinuing coffee alone may not be effective. This strategy may underestimate total caffeine intake from all sources, which include cola beverages, tea, chocolate, and medications.19
Avoiding milk if intolerant. Infants with cow's milk allergy have been found to have frequent arousals during sleep, shorter sleep cycles, and larger amounts of non-rapid eye movement (NREM) sleep with easy awakening. After elimination of cow's milk for several weeks, a significant decrease in the number of arousals occurred, while total sleep time and time spent in NREM2 and NREM3 sleep all increased significantly.20 Further study by the same researchers using double-blind, crossover methodology also found normalization of sleep in a group of children < 5 years of age.21 Although confirmation from other investigators is indicated before cow's milk elimination can be deemed proven for children with sleep disorders, it is a low-cost, no-risk strategy that can be tried before more invasive evaluation methods.
Carbohydrates. Tryptophan and 5-hydroxytryptophan are precursors of melatonin through the serotonin pathway, and have some efficacy in the treatment of insomnia. However, neither can be recommended, due to previous findings of contamination with a compound that has caused eosinophilia-myalgia syndrome (EMS).22 The passage of tryptophan across the blood-brain barrier depends on the extent to which it must compete with other amino acids. In this context, carbohydrate-rich foods may prove helpful. Over the short-run, they stimulate the release of insulin, which reduces blood concentrations of competing amino acids, fostering tryptophan's passage across the blood-brain barrier.23
Avoiding over-the-counter weight-loss products. Products that contain ephedra alkaloids (eg, Ma huang) in combination with caffeine have been increasingly used for weight loss, but they have been found to cause insomnia when compared with a placebo.24
Rectifying poor iron status. Insomnia is a frequent problem in patients with restless legs syndrome. Iron deficiency, even at levels insufficient to cause anemia, has been associated with this syndrome, and iron deficiency anemia is also associated with insomnia in pregnancy.25 Although more research is needed, available evidence implicates low brain iron concentration caused by the inadequate transportation of iron from the blood to the central nervous system as a cause of dopaminergic dysfunction in these patients.26 Iron supplementation was found effective for improving insomnia in teens with low iron stores.27
The following 2 supplements are under investigation for their roles in treating insomnia:
Melatonin. Disturbances in circadian rhythm and melatonin production are more common among both the elderly and shift workers, and evidence suggests that this can be partly ameliorated by supplemental melatonin. Although studies suggest that melatonin is safe and effective for treating delayed sleep phase syndrome, most evidence does not support its effectiveness for the majority of primary and secondary sleep disorders.28 However, melatonin appears to help patients, particularly the elderly, discontinue their reliance on benzodiazepines. This was found to be an effective strategy in 78% of patients using melatonin, compared with 25% using a placebo.29
Valerian. Valerian's sedative and hypnotic effects probably result from increases in the secretion of the neurotransmitter ÃŽÂ³-aminobutyric acid (GABA) and inhibition of its uptake. Valerian binds to the same receptors as benzodiazepines, but with less efficiency and milder effects; this difference may account for the lack of residual morning sedation that is a common side effect of hypnotics.30 Doses of 400 to 500 mg/day have been found to significantly decrease sleep latency and improve subjective sleep quality. However, not all studies have found valerian to be effective. In addition, caution is warranted to avoid side effects, which may include headache, hangover, paradoxical stimulation, restlessness, and cardiac disturbances, as well as potentially dangerous interactions with barbiturates, benzodiazepines, opiates, and alcohol.30
What to Tell the Family
Insomnia can be caused by several factors, the most common involving caffeine and alcohol intake, lack of exercise, and poor sleep hygiene. When chronic, insomnia can adversely affect quality of life and should be discussed with a physician to rule out underlying medical or psychiatric etiologies.
1. National Sleep Foundation. 2005 Sleep in America Poll. National Sleep Foundation Web site. Available at: http://www.sleepfoundation.org/_content/hottopics/Sleep_Segments.pdf. Accessed December 2, 2005.
2. National Institutes of Health. Manifestations and Management of Chronic Insomnia in Adults. State-of-the-Science Conference, Final Statement: August 18, 2005. Available at: http://consensus.nih.gov/2005/2005InsomniaSOS026PDF.pdf.
Accessed April 10, 2006.
7. Morin CM, Colecchi C, Stone J, Sood R, Brink D. Behavioral and pharmacological therapies for late-life insomnia: a randomized controlled trial. JAMA. 1999;281:991-999.
9. Liao WC. Effects of passive body heating on body temperature and sleep regulation in the elderly: a systematic review. Int J Nurs Stud. 2002;39:803-810.
11. Brower KJ. Insomnia, alcoholism and relapse. Sleep Med Rev. 2003;7:523-539.
13. Ekman AC, Leppaluoto J, Huttunen P, et al. Ethanol inhibits melatonin secretion in healthy volunteers in a dose-dependent randomized double blind cross-over study. J Clin Endocrinol Metab. 1993;77:780-783.
14. von Wartburg JP, Buhler R. Biology of disease. Alcoholism and aldehydism: new biomedical concepts. Lab Invest. 1984;50:5-15.
15. Zimatkin SM, Anichtchik OV. Alcohol-histamine interactions. Alcohol. 1999;34:141-147.
22. Birdsall TC. 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev. 1998;3:271-280.
25. Sifakis S, Angelakis E, Papadopoulou E, Stratoudakis G, Fragouli Y, Koumantakis E. The efficacy and tolerability of iron protein succinylate in the treatment of iron-deficiency anemia in pregnancy. Clin Exp Obstet Gynecol. 2005;32:117-122.
30. Tesch BJ. Herbs commonly used by women: an evidence-based review. Am J Obstet Gynecol. 2003;188(suppl 5):S44-S55.