There may be more than one causal factor playing a role in the pathogenesis of poor sleep.

Insomnia is inadequate or poor sleep quality characterized by difficulty falling asleep, difficulty maintaining sleep, waking up too early in the morning, and nonrefreshing sleep.¹ Daytime consequences of insomnia include fatigue, lack of energy, difficulty concentrating, and irritability.¹ Acute insomnia involves periods of sleeping difficulty lasting between 1 night and a few weeks. Chronic insomnia involves sleep difficulty occurring at least 3 nights per week for 1 month or more¹; 30% to 40% of adults have some level of insomnia within any given year and about 10% to 15% have chronic insomnia, severe insomnia, or both.² This translates to insomnia affecting one in three American adults; in other words, more than 20 million people complain of chronic insomnia. The prevalence of insomnia increases with age and is more common in women.² This widespread prevalence of insomnia and its association to numerous underlying medical conditions would dictate that insomnia first be addressed in the primary care setting³; however, primary care providers rarely ask about insomnia in the review of systems.³ Because of time constraints and limited resources, optimal management of insomnia by a primary care physician is not as feasible as in a specialized sleep disorders clinics.³ Sleep specialists usually concentrate on sleep disorders other than insomnia and often refer their patients to a psychologist or psychiatrist to manage insomnia. In June, the American Academy of Sleep Medicine offered its first examination in behavioral sleep medicine to stress the importance of this field in the practice and understanding of sleep medicine. In a Gallup Poll survey of the general population, individuals with insomnia infrequently asked their primary care providers for medical advice about their sleeping problems, and most tended to self-medicate themselves with nonprescription drugs or alcohol.⁴

There are many factors that affect insomnia, and in chronic insomnia, there may be more than one causal factor playing a role in the pathogenesis of poor sleep.⁵ If the insomnia cannot be related to a causal factor, it is classified as primary insomnia.⁵ Precipitating events such as acute stress, illness, jet lag, or a psychiatric condition (an episode of depression) may lead to poor sleep⁶; however, insomnia may persist after the precipitating event has resolved.⁵

Spielman et al⁷ described a behavioral perspective on insomnia and predisposing, precipitating, and perpetuating factors and their role in the natural history and progression of insomnia. Several of these factors may contribute to insomnia and the roles may vary over time.

Predisposing Factors
An individual may have some predisposition to developing insomnia. Individuals with low predisposition may sleep well despite exposure to chronic pain, anxiety, caffeine intake, or stress,⁵ whereas those with a high predisposition may develop insomnia with almost any precipitating event.⁵ A person who has had insomnia for a few weeks or months develops perpetuating factors like changes in their sleep behavior and cognition, which may further contribute to insomnia. Trying hard to sleep and excessive rumination about poor sleep are some perpetuating factors.⁷

The proposed predisposing factors for insomnia include physiological hyperarousal, cognitive arousal, emotional arousal, and decreased homeostatic sleep drive.^8-10 In physiological hyperarousal, basal heart rate and temperature, metabolic rate, and heart rate reactivity with stress are increased in individuals with insomnia when compared to those without.^8,11-13 This type of arousal has been found prior to sleep, during sleep, and during the day in insomnia patients.^8,11-13 Bonnet and Arand⁸ proposed an arousal system set at a high basal level and independent of the sleep system in chronic insomnia. Researchers found a significant correlation between levels of urinary-free cortisol and catecholamine metabolites, and wakefulness at night in chronic insomnia¹⁴; hence, the physiological hyperarousal is mediated by increased sympathetic nervous system activity.

Cognitive arousal includes worry and excessive rumination about sleep, fear related to consequences of insomnia, unrealistic expectations about sleep, and self-induced pressure to sleep, which leads to performance anxiety.^10,15 Second, insomnia is a conditioned response to cues in the bedroom and associated with bedtime that occurs once a person experiences poor sleep.¹⁶ Certain personality types predispose individuals to develop these cognitive changes in chronic insomnia.⁵ Patients with obsessive-compulsive personalities have a ruminative thought process and a high need for control that increases the risk for development of these cognitive features.⁵ These cognitive factors are also perpetuating factors for insomnia in conditioned or “learned” insomnia.^5,15

Emotional arousal factors may also cause insomnia. Abnormal scores on psychometric tests measuring anxiety, depression, and personality are demonstrated in chronic insomnia.⁹ Emotions are internalized, leading to poor sleep, and stressful events in life can precipitate insomnia.¹⁷ Emotional arousal in psychiatric disorders associated with insomnia is well known.^5,8

Patients with insomnia do not show excessive daytime sleepiness (EDS) on the Multiple Sleep Latency Test despite reduced total amount of sleep at night,¹⁸ which may represent a neurophysiological abnormality in such individuals. Besset and coworkers¹⁹ demonstrated significantly less change in patients’ slow sleep activity (a measure of homeostatic sleep drive) on their recovery night following sleep deprivation in those with chronic insomnia, hence demonstrating a diminished homeostatic response to sleep loss in insomnia.⁵

Precipitating Factors
Medical or psychiatric illness, use of drugs, or a sleep disorder like sleep apnea or periodic limb movement disorder (PLMD) may precipitate insomnia by interacting with a predisposing factor.⁵ More than one precipitating factor may be active in an individual with insomnia.⁵

Insomnia may be secondary to a medical condition, which may go undiagnosed, therefore a complete medical evaluation is imperative in patients with chronic insomnia. Chronic pain at night may cause frequent awakenings in neurodegenerative conditions disrupting neurophysiologic pathways that produce sleep-wake function.⁵ In patients with neurodegenerative diseases like Parkinson’s disease, sleep-initiating insomnia and reduced total sleep are detected.20 Alzheimer’s disease is associated with reduced sleep efficiency, increased stage 1 sleep, and increased microarousals.²¹ A rare prion disease causes atrophy of the thalamus and absence of non-rapid eye movement (n-REM) sleep leading to fatal familial insomnia.²² Autonomic dysfunction and motor and cognitive abnormalities are also present in this disease.²²

Patients with emphysema have frequent arousals, increased stage 1 sleep, and decreased total sleep time.²³ Oxygen hemoglobin desaturation during REM sleep is often significant.²³ Patients with osteoarthritis, rheumatoid diseases, and fibromyalgia often complain of insomnia or nonrefreshing sleep.²⁴ Patients with fibromyalgia have disturbed sleep and daytime fatigue, and their sleep is associated with increased transient arousals and alpha-delta sleep.²⁵ Sleep disturbance in fibromyalgia may be inherent to this disorder rather than nighttime pain causing sleep abnormality²⁵; however, alpha-delta sleep, transient arousals, and decreased total sleep time are also seen in other medical disorders and chronic pain syndromes.^24,25 The presence of phasic alpha activity during n-REM sleep may predict the severity of daytime pain.²⁶ Hyperthyroidism and Cushing’s disease have been linked with insomnia (by stimulation of the central nervous system).⁵ There is a potential role of hormone changes in insomnia in peri- and post-menopausal women. These women self-report more insomnia complaints compared to premenopausal women.²⁵ Women with hot flashes and night sweats in menopause have lower sleep efficiencies.²⁵ Gastroesophageal reflux disease (GERD) is associated with frequent nocturnal awakenings and disturbed sleep pattern.¹ Many medical disorders worsen at night from sleep, circadian influence (asthma), or recumbency (GERD).¹

Although psychiatric illnesses are a common cause of chronic insomnia, they account for less than 50% of cases.¹ Poor sleep is one of the main symptoms of major depression, generalized anxiety disorder, and post-traumatic stress disorder (PTSD).⁵ There may be a direct relationship between insomnia and psychiatric disorders, such as central nervous system dysregulation causing poor sleep, as well as personality disorders that contribute to a chaotic lifestyle with irregular sleep-wake schedules.⁵ Major depression can lead to insomnia, and hypersomnia may also occur.⁵ Polysomnographic abnormalities include frequent electroencephalographic arousals and awakenings, decreased slow-wave sleep, decreased latency to REM sleep, increased duration of the first REM period, and increased REM density.²⁸ Decreased homeostatic sleep drive, circadian dysregulation, and increased REM pressure are the proposed theories/mechanisms to explain the sleep disturbances in depression.^5,28 On the other hand, persistent insomnia may precipitate an episode of depression.⁵ Epidemiologic survey data²⁹ suggest that individuals with insomnia have an increased risk for subsequent development of depression. Generalized anxiety disorder, obsessive-compulsive disorder, PTSD, and panic disorder have all been associated with insomnia. Patients with PTSD have increased latency to sleep, decreased sleep efficiency, decreased REM sleep, and sleep-disrupting nightmares.³⁰

A variety of prescription and nonprescription drugs, and drugs with abuse potential (heroin or cocaine), cause increased wakefulness and poor quality sleep.^1,5,31 Poor sleep is a side effect of these medications, which may be dose-dependent, and insomnia symptoms may vary among the individuals who use them. Stimulant medications such as amphetamines, methylphenidate, pemoline, and caffeine reduce total sleep time, delay sleep onset, and increase sleep fragmentation.⁵ Antidepressants like monoamine oxidase inhibitors (MAOI) or some selective serotonin reuptake inhibitors (SSRI) have stimulant effects and lead to insomnia complaints.⁵ Fluoxetine, paroxetine, and fluvoxamine use has resulted in documented poor sleep.³¹ Antidepressants may disturb nighttime sleep and cause daytime fatigue. Venlafaxine and bupropion may disrupt sleep.^5,31 Antihypertensives and antiarrhythmics also may disrupt sleep.^5,21 b blockers (particularly most lipophilic ones) cause insomnia. Propranolol and pindolol are important drugs in this category.³¹ Corticosteroids, theophylline, and lovastatin are also implicated in insomnia.^5,31 Misuse of sleeping pills may contribute to insomnia. Alcohol may help patients to fall asleep, but its breakdown in the later part of the night disrupts the sleep architecture. Patients with chronic alcoholism have a “prematurely aged” sleep pattern. Their sleep is fragmented and shallow, and they may have excessive daytime sleepiness. Delirium tremens may be the result of prolonged sleep deprivation.³²

Primary sleep disorders such as restless legs syndrome results in sleep-initiating insomnia (prolonged sleep-onset latency and marked reduction in total sleep time),³³ whereas periodic limb movement disorder (PLMD), obstructive sleep apnea (OSA), and obesity-hypoventilation syndrome cause sleep maintenance insomnia.⁵ Central sleep apnea causes insomnia in contrast to OSA, where a patient mainly has excessive daytime sleepiness (EDS) or loud snoring. Sleep fragmentation and increased stage 1 sleep are seen in OSA.⁵ Patients who have PLMD may present with insomnia or EDS. Circadian rhythm sleep disorders lead to insomnia. Delayed sleep phase syndrome (DSPS) has a long sleep-onset latency (sleep-onset insomnia), whereas advanced sleep phase syndrome (ASPS) is noted by early morning awakenings (sleep maintenance insomnia).⁵ In other words, the patient is trying to sleep at a time when his or her circadian clock is promoting wakefulness.⁵ Moreover, any sleep that occurs “out of phase” has frequent awakenings and increased stage 1 sleep.³⁴ Shift work (a work schedule that requires a person to work outside the standard daytime hours, 8 am to 5 pm) and an irregular sleep-wake schedule disorder (erratic hours of sleep) also cause insomnia.⁵ Shift workers do not get the same amount of sleep as workers on day shifts, and sleep deprivation is the worst in those working rotating shifts. Because a large amount of sleep occurs out of phase, the sleep quality is poor.^5,34 Circadian rhythm disorders may also act as perpetuating factors. Patients with insomnia due to medical or psychiatric illnesses may alter their sleep-wake schedule in such a fashion that leads to a shift in the endogenous circadian schedule.^5,34

Perpetuating Factors
Behavioral and cognitive factors that develop after the onset of insomnia may perpetuate or further contribute to insomnia. The original precipitant of insomnia may have resolved, but insomnia continues due to behavioral and/or cognitive changes. Sedentary lifestyle, poor sleep hygiene, or sleep-related behaviors, like leaving the television on in the bedroom, playing computer games, surfing the Internet, and eating snacks in the middle of the night, can contribute to insomnia.⁵ Increased consumption of caffeinated beverages, daytime or afternoon naps, going to bed early, or staying in bed late are compensatory mechanisms/habits for daytime fatigue.⁵ Sleep-incompatible behaviors in bed establish a conditioned response (increased arousal) to the sleep environment and interfere with sleep.⁵ Drinking caffeinated beverages in the evening directly increases arousal at night, whereas afternoon naps decrease homeostatic drive for sleep.⁵

Patients with insomnia exhibit excessive worry about their sleep and are preoccupied with their sleep and have fears about not sleeping well.³⁵ This increases tension and arousal throughout the day and evening, resulting in sleep-initiating difficulty. Cognitive arousal is more important than physiological arousal in the causation of poor sleep.³⁶

Patients with primary insomnia do not have an obvious medical or psychiatric (precipitating) cause.^5,8,13 It is not a symptom of another primary disorder. Patients have cognitive and behavioral factors that act as precipitating and perpetuating factors in the development and maintenance of their insomnia.⁵ The International Classification of Sleep Disorders (ICSD) uses the term psychophysiological insomnia (15% of all insomnia patients presenting to a sleep clinic), inadequate sleep hygiene, sleep state misperception (less than 5% of patients) and idiopathic insomnia in place of primary insomnia.³⁷

Consequences of Insomnia
The primary consequences of acute insomnia are sleepiness, negative mood, and impairment of performance. The severity of these consequences is related to the amount of sleep lost on one or more nights.¹ Insomnia appears to contribute to increased rates of absenteeism, health care utilization, and social disability.³⁸ Sleep disturbance is a reliable predictor of psychological ill health, physical ill health, or both. Insomnia is often associated with psychiatric or medical illness, sometimes as the primary or initial symptoms of a problem.¹ Insomnia has been statistically associated with various medical conditions, including disorders of the cardiovascular, respiratory, gastrointestinal, renal, and musculoskeletal systems.³⁹

An epidemiological survey demonstrated that subjects with continuing insomnia had significantly higher rates of new onset depression and anxiety disorder.⁴⁰ People with insomnia also report more health concerns, limited physical activity, less vitality, and more emotional difficulties.^3,5

Balter and Uhlenhuth⁴¹ found that insomniacs had a 3.5 to 4.5 times greater risk of accidents than controls. Direct inquiry about sleeping habits is important because more than one half of patients with chronic insomnia have never discussed the problem with a physician.¹ Its detection may be enhanced by incorporating sleep-related questions into the general review of patient systems.¹

Taj M. Jiva, MD, is clinical assistant professor of medicine and director of Sleep Medicine Clinics, Buffalo Medical Group PC, Buffalo, NY.

References
1. NHLBI Working Group on Insomnia. Insomnia: assessment and management in primary care. Am Fam Physician. 1999;59:3029-39.
2. Mellinger GD, Balter MB, Uhlenhuth EH. Insomnia and its treatment. Prevalence and correlates. Arch Gen Psychiatry. 1985;42:225-232.
3. Richardson GS. Managing insomnia in the primary care setting: raising the issues. Sleep. 2000;23:S9-S12.
4. Ancoli-Israel S, Roth T. Characteristic of insomnia in the United States: results of the 1991 National Sleep Foundation Survey. Sleep. 1992;22:S347-S353.
5. Stepanski EJ. Behavioral therapy for insomnia. In: Kryger MH, Roth T, Dement WC, eds. Principles and Practice of Sleep Medicine. Philadelphia: WB Saunders; 2000:647-655.
6. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text revision. Washington, DC: American Psychiatric Association; 2000.
7. Spielman AJ, Caruso L, Glovinsky P. A behavioral perspective on insomnia. Psychiatric Clin North Am. 1987;10:541-553.
8. Bonnet MH, Arand D. Hyperarousal and insomnia. Sleep Med Rev. 1997;1:97-108.
9. Kales A, Kales JD. Evaluation and Treatment of Insomnia. New York: Oxford University Press; 1984.
10. Morin CM. Insomnia: Psychological Assessment and Management. New York: Guilford Press; 1993.
11. Freedman RR, Sattler HL. Physiological and psychological factors in sleep-onset insomnia. J Abnorm Psychol. 1982;91:380-389.
12. Stepanski E, Glinn M, Zorick F, et al. Heart rate changes in chronic insomnia. Stress Med. 1994;10:261-266.
13. Bonnet M, Arand D. 24-hour metabolic rate in insomniacs and matched normal sleepers. Sleep. 1995;18:581-588.
14. Vgontzas A, Tsigos C, Bixler E, et al. Chronic insomnia and activity of the stress system: a preliminary study. J Psychosom Res. 1998;45:21-31.
15. Hauri P. Persistent psychophysiological (learned) insomnia. Sleep. 1986;9:38-53.
16. Bootzin RR, Nicassio PM. Behavioral treatments for insomnia. In: Hersen M, Eissler R, Miller P, eds. Progress in Behavior Modification. New York: Academic Press; 1978:1-45.
17. Healey ES, Kales A, Monroe LJ, Bixler EO, Chamberlin K, Soldatos CR. Onset of insomnia: role of life-stress events. Psychosom Med. 1981;43:439-451.
18. Stepanski E, Zorick F, Roehrs T, Young D, Roth T. Daytime alertness in patients with chronic insomnia compared with asymptomatic control subjects. Sleep. 1988;11:54-60.
19. Besset A, Villemin E, Tafti M, Billiard M. Homeostatic process and sleep spindles in patients with sleep-maintenance insomnia: effect of partial (21 h) sleep deprivation. Electroencephalogr Clin Neurophysiol. 1998;107:122-132.
20. Kryger MH, Roth T, Dement WC, eds. Principles and Practice of Sleep Medicine. Philadelphia: WB Saunders; 2000.
21. Prinz PN, Vitaliano PP, Vitiello MV, et al. Sleep, EEG, and mental function changes in senile dementia of the Alzheimer type. Neurobiol Aging. 1982;3:361-370.
22. Lugaresi E, Medori R, Montagna P, et al. Fatal familial insomnia and dysautonomia with selective degeneration of thalamic nuclei. N Engl J Med. 1986;315:997-1003.
23. Sandek K, Andersson T, Bratel T, Hellstrom G, Lagerstrand L. Sleep quality, carbon dioxide responsiveness and hypoxaemic patterns in nocturnal hypoxaemia due to chronic obstructive pulmonary disease (COPD) without daytime hypoxaemia. Respir Med. 1999;93:79-87.
24. Mahowald ML, Mahowald MK. Nighttime sleep and daytime functioning (sleepiness and fatigue) in well-defined chronic rheumatic diseases. Sleep Med. 2000;1:179-193.
25. Mahowald ML, Mahowald MK. Nighttime sleep and daytime functioning (sleepiness and fatigue) in less well-defined chronic rheumatic diseases with particular reference to the alpha-delta NREM sleep anomaly. Sleep Med. 2001;1:195-207.
26. Roizenblatt S, Moldofsky H, Benedito-Silva A, Tufik S. Alpha sleep characteristics in fibromyalgia. Arthritis Rheum. 2001;44:222-230.
27. Shaver JL, Zenk SN. Sleep disturbance in menopause. J Womens Health Gend Based Med. 2000;9:109-118.
28. Benca RM, Obermeyer WH, Thisted RA, Gillin JC. Sleep and psychiatric disorders: a meta-analysis. Arch Gen Psychiatry. 1992;49:651-668.
29. Chang PP, Ford DE, Mead LA, Cooper-Patrick L, Klag MJ. Insomnia in young men and subsequent depression: the Johns Hopkins Precursors Study. Am J Epidemiol. 1997;146:105-114.
30. Mellman TA, Nolan B, Hebding J, Kulick-Bell R, Dominguez R. A polysomnographic comparison of veterans with combat-related PTSD, depressed men, and non-ill controls. Sleep. 1997;20:46-51.
31. Schweitzer P. Drugs that disturb sleep and wakefulness. In: Kryger MH, Roth T, Dement WC, eds. Principles and Practice of Sleep Medicine. Philadelphia: WB Saunders; 2000:441-461.
32. Bates RC. Delirium tremens and sleep deprivation. Mich Med. 1972;71:941-944.
33. Zorick FJ, Roth T, Hartse KM, Piccione PM, Stepanski EJ. Evaluation and diagnosis of persistent insomnia. Am J Psychiatry. 1981;138:769-773.
34.Carskadon MA, Wolfson AR, Acebo C, Tzischinsky O, Seifer R. Adolescent sleep patterns, circadian timing, and sleepiness at a transition to early school days. Sleep. 1998;21:871-881.
35. Moldofsky H, Scarisbrick P, England R, Smythe H. Musculoskeletal symptoms and non-REM sleep disturbance in patients with “fibrositis syndrome” and healthy subjects. Psychosom Med. 1975;37:341-351.
36. Lichstein K, Rosenthal T. Insomniacs’ perceptions of cognitive versus somatic determinants of sleep disturbances. J Abnorm Psychol. 1980;89:105-107.
37. American Sleep Disorders Association. The International Classification of Sleep Disorders, Revised, Diagnostic and Coding Manual. Rochester, Minn: American Sleep Disorders Association; 1997.
38. Simon GE, VonKorff M. Prevalence, burden and treatment of insomnia in primary care. Am J Psychiatry. 1997;54:1417-1423.
39. Zorick FJ. Insomnia. In: Kryger MH, Roth T, Dement WC, eds. Principles and Practice of Sleep Medicine. Philadelphia: WB Saunders; 2000:615-623.
40. Ford DE, Kamerow DB. Epidemiologic study of sleep disturbances and psychiatric disorders. JAMA. 1989;262:1479-1484.
41. Balter MB, Uhlenhuth EH. New epidemiologic findings about insomnia and its treatment. J Clin Psychiatry. 1997;171:382-388.