Publication
Article
Supplements and Featured Publications
Patient Identification
The homeostatic sleep drive and circadian arousal, each opposing the other, form theneurobiological bases of the sleep and wake states. Many factors can and do disrupt this cycle. Yet, excessive daytime sleepiness is not only common, and it often goes unrecognized. It can contribute to accidents, produce or exacerbate health conditions, reduce efficiency and productivity, interfere with social relationships, and diminish quality of life. The spectrum of common sleep disorders includes circadian rhythm changes, shiftwork requirements, obstructive sleep apnea, narcolepsy, and difficulty in initiating or maintaining sleep, also known as insomnia. In many cases, however, sleep deprivation is the choice of the patient, chosen in response to long commutes, academic rigor, or occupational matters. Regardless of the sleep disorder that a patient has, good sleep behavior or “sleep hygiene†is essential.
(Am J Manag Care. 2007;13:S132-S139)
Despite the high prevalence of excessive daytime sleepiness (EDS), it is still underrecognized and undertreated, despite the physical, mental, social, public health, and safety consequences. It can lead to or exacerbate health conditions, contribute to accidents, reduce efficiency and productivity, interfere with social relationships, and diminish quality of life. Therefore, EDS is a societal as well as a personal problem, with significant costs to the healthcare system, the workplace, and the wider society.
The purpose of this article is to delineate some of the ways to identify patients with EDS, show how the condition affects daily functioning, and evaluate the available pharmacologic and nonpharmacologic treatment methods. A case study will illustrate an approach to the problem, some of the clinical reasoning, and recommended treatment.
Physiological Basis of Sleep and Wakefulness
Given the biological sleep drive and the brain circuits for arousal, it is important to distinguish excessive sleepiness as a pathologic condition from a state of fatigue.3,4 Sleepiness is a normal function, based on time of day and circadian phase. A midafternoon lull or outright sleepiness at night are normal. Pathological or “excessive†sleepiness is a condition in which sleepiness interferes with activities of daily living, such as work, child care, or driving a car.
Fatigue is a state of tiredness, not a drive for sleep (ie, without the excessive sleepiness).5,6 A problem arises when people complain about fatigue but really mean sleepiness. They often do not make the distinction and just present with the final common pathway complaint of “I'm tired all of the time.†Physicians need to be aware of how patients present and what terms they may use for what amounts to excessive sleepiness. They then have to distinguish whether a patient is fatigued or sleepy.
Of course, fatigue and excessive sleepiness can coexist. A medical illness, for example, can cause either or both.7 If a person has fatigue, it is worth looking for an underlying cause, which may be as obvious as prolonged physical or mental activity. If a patient is sleepy during the day, one must consider the factors affecting nocturnal sleep and what else may be causing the pathologic daytime sleepiness, such as a medical illness, behavioral factors, or a specific sleep disorder like obstructive sleep apnea (OSA).
A patient with primary insomnia presents an interesting example of fatigue without sleepiness.8 While a lack of sleep at night may cause daytime fatigue and tiredness, it is the same pathologic mechanism that prevents sleep initiation at night that keeps the person from falling asleep at inappropriate times during the day. Still, the person is not fully refreshed and may perform poorly from lack of sleep. On the other hand, disorders that fragment nighttime sleep, such as OSA or periodic limb movement disorders, lead a person to have episodes of “microsleep†or unplanned naps.
Signs and Symptoms of Sleep Disturbance
Because physicians and patients may both think of sleepiness as normal in today's society, it falls on the primary care physician (PCP) to recognize the need to raise and evaluate the issue. Since many people are somewhat anxious and therefore more alert while at a physician's office, the PCP will probably miss a sleep problem unless he or she specifically asks. Therefore, every patient should be asked these 2 simple questions: (1) How well are you sleeping? and (2) How alert are you across the day? To determine if a patient has a significant impairment of alertness, a simple but slightly more detailed interview should reveal the problem.
1. Do you have difficulty falling asleep or remaining asleep at night?
3. Do you have discomfort in your legs that causes you to move them around in bed or at rest?
5. Are you often very restlessness during sleep at night?
7. Do you awaken feeling unrefreshed in the morning?
9. Do you doze in front of the TV or when reading?
Causes of excessive sleepiness may be behavioral, medical, or primary sleep disorders. Behavioral etiologies mainly relate to sleep deprivation (voluntary sleep restriction) and/or irregular timing of sleep (circadian rhythm not synchronized with the desired sleep-wake cycle, as in shift workers).9 Medical causes such as Parkinson's disease (PD), other central nervous system or metabolic and somatic diseases, movement disorders, chronic pain syndromes, psychiatric disorders, and side effects of a wide variety of medications are manifold.7,8 OSA, narcolepsy, insomnia, and shift-work sleep disorder (SWSD) are some examples of primary sleep disorders.7
According to sleep researcher Thomas Roth, PhD, nocturia may accompany disturbed sleep but is usually not the cause of it. If the patient awakes during the night, he or she may then go to the bathroom. But once the sleep disorder is corrected, he or she may sleep through to morning. If there is no sleep disorder and if one awakes to urinate, sleep is generally not disturbed much, and the person can get back to sleep relatively easily.
Physicians sometimes treat the obvious signs and symptoms and do not recognize the underlying sleep disturbance. The clinician should be aware that patients often do not complain of excessive sleepiness but may use terms such as tiredness, fatigue, or lack of energy.9 Other tip-offs may be complaints of the consequences of sleepiness (eg, difficulty concentrating or irritability) (Table 1).
Common Sleep DisordersAs listed by Thorpy,7 various common sleep disorders can be found in Table 2.
Insomnia. Insomnia, defined as difficulty in initiating or maintaining sleep, is more prevalent in women, the unemployed, and the elderly.13 Diagnosed or not, it is linked to a number of health problems, including comorbid physical conditions and psychiatric disorders. The National Health Interview Survey reports that people who sleep 7 or 8 hours per night make fewer doctor office visits and spend less days in the hospital than do those who sleep either more or fewer hours. Yet, according to one report, only about 5% of the more than 65 million persons with insomnia in the United States saw their doctor specifically for that complaint, and 69% did not mention insomnia when seeing their physicians for other reasons.12 In another study of people with insomnia, more than half of their PCPs had no idea that the patient had problems sleeping.12 It is here, especially, that PCP vigilance can be invaluable.
SWSD. Almost 20% of the American workforce works alternative schedules that are either permanent or rotating, and, of those, 32% have symptoms that fit the minimum criteria for SWSD,13 a disorder of excessive sleepiness and/or insomnia caused by misalignment of the sleep-wake schedule and a person's circadian sleep-wake patterns. Night shifts are primarily composed of 4 occupational groups: those in public safety, including police and firefighters; healthcare workers; global workers manning telephones in far-flung time zones; and newspaper publishers and other graveyard-shift workers. The problem with SWSD is that it cannot only mask other symptoms, but precipitate them. In addition, SWSD is a risk factor for such comorbidities as depression and breast cancer, gastrointestinal ulcers, and heart disease.14,15
Medical interns and residents subjected to long hours of work are considered vulnerable to SWSD. An early study found that interns reading electrocardiograms made up to twice the number of errors after working unrelieved for 24 hours or more than after a night's sleep.16 More recent studies have reported that, during simulated surgeries, surgical residents made up to twice the number of errors after working overnight than after a full night's sleep. Although few would doubt that sleep deprivation could lead to substantial decrements in performance and cognition in physicians, it was not until recently that serious inquiries into a system that routinely deprives medical personnel of sleep have begun. Of all hospital-based trainees, interns (physicians in their first postgraduate year of medical education) normally work the greatest number of weekly hours, with shifts often extended beyond 24 hours. A study was conducted that compared the number of errors made by interns working 2 different shift types. One shift was the more traditional extended-hours shift and the other was the “interventional†schedule that reduced work hours. Not surprising, interns made 22% more errors of a serious nature in the traditional work schedule. Potentially serious mistakes that were intercepted occurred 37% more frequently in the traditional schedule. Although the costs of medical errors made in critical care by sleep-deprived interns were not calculated in this study, few would argue that certain errors will translate into costs as well as endangering the lives of patients.
OSA. In the general population, the prevalence of OSA, defined as abnormal sleeping respirations from repeated episodes of obstruction in the upper airway associated with cessation or diminution of breathing, is about the same as that of asthma or diabetes, clinically significant in about 2% of women and 4% of men.17-20 The need to waken to reinnervate the upper airway disrupts their sleep, contributing to the EDS. Sufferers of OSA may, in addition to EDS, experience decreased libido, impotence, depression, and, although a less reliable symptom of sleep apnea than previously thought, morning headaches.18,20
Diagnosis is not straightforward. When considering OSA in the primary care setting as the cause of excessive sleepiness, a useful sign is the patient's neck size, with a neck circumference >17 inches in a male increasing the likelihood of OSA.21 Similarly, a crowded oropharynx with large tonsils and a small airway or even enlarged adenoids should raise suspicion of OSA. The condition is not confined to the obese, the elderly, and the postmenopausal, as OSA occurs in children, young women, and people with asthenic physiques.18,22 The expectation that OSA favors the overweight man abets its underdiagnosis in women and children.18 Men do, in fact, predominate, but that may occur at puberty, because before puberty numbers are approximately equal between the sexes.22 Risk factors for sleep-disordered breathing (SDB) in children include enlarged tonsils and adenoids; secondary risk factors were found to include exposure to secondhand smoke, chronic rhinitis, family history of snoring or SDB, obesity, and African-American race or ethnicity. Yet, many obese people do not suffer from OSA, and about one third of those with OSA are not obese.18 When OSA exists, however, it carries physiologic effects beyond EDS. The oxygen desaturation it engenders can provoke hypertension, right-sided heart failure, or polycythemia (the proliferation of red blood cells). In children, SDB has been associated with such behavior problems as attention-deficit hyperactivity disorder, with which some children may, in fact, present.22
Many studies report poor correlation between suspected and proven sleep apnea.18 Likewise, sleep questionnaires are often discrepant with objective measures. It is for these reasons that laboratory-conducted sleep studies, available for both adults and children, are required for positive diagnosis and determination of severity. Some people with OSA have measurably smaller and narrower upper airways than those without the disorder. Parallel to the smaller airways, they may have neck diameters of 17 inches or more.20 Thus far, techniques such as cephalometric roentgenography, somnofluoroscopy, flow-volume curves, acoustic-reflection studies, and Valsalva's and Müller's maneuvers, used to evaluate upper-airway anatomy and determine candidacy for such surgeries as uvulopalatopharyngoplasty, have not been as predictive as hoped.18 By far, the best way to diagnose OSA with certainty is with an overnight polysomnogram.20
Narcolepsy. In this sleep disorder, loss of the neuropeptide hypocretin (orexin), apparently through autoimmune activity, is associated with abnormal and displaced phenomena such as muscle paralysis that normally occurs only during rapid eye movement (REM) sleep.23 Documented narcolepsy is uncommon, with prevalence–0.09%–that approximates those of multiple sclerosis and PD.18 Although narcolepsy can manifest at any age, its usual age of onset is during adolescence or early adulthood. After onset it may progress for a short time and then stabilize, although it rarely or never clears up completely. Unanticipated sleep attacks last from seconds to minutes, usually occurring during times of reduced stimulation, such as when watching television or passively listening in on a conference call.
Narcolepsy is also associated with cataplexy, sleep paralysis, and hallucinations occurring at sleep onset (hypnagogic) or on awakening (hypnopompic).18 Although fewer than half of patients with narcolepsy report having all of these ancillary symptoms, EDS may precede their appearance, sometimes by decades. Between 65% and 70% of patients with narcolepsy also have cataplexy, defined as a sudden loss of muscle tone usually triggered by strong emotion. Sleep paralysis, a total paralysis of the body or selective muscle groups (eg, jaw, leg), occurs in up to 60% of patients with narcolepsy. Lasting from seconds to minutes, it can be very disturbing. The hallucinations that can accompany narcolepsy are reportedly vivid and often nightmarish and occur in 12% to 50% of patients. However, both sleep paralysis and hallucinations lurking on the frontiers of sleep have been reported in people who do not have narcolepsy.
Narcolepsy may have a genetic footprint, although nongenetic factors suggested through the increased risk of narcolepsy in first-degree relatives are also involved in this complex disorder.18,24 Many patients with narcolepsy carry a specific human leukocyte antigen (HLA) allele otherwise detected in less than 30% of people. However, although this linkage of HLA to disease is suggestive, it is neither necessary for nor predictive of the finding of narcolepsy. A variation in one gene cannot account for the spectrum of symptoms attributed to narcolepsy.
Narcolepsy is thought to be a reflection of disruptions in the normal boundaries among wakefulness, REM sleep, and non-REM sleep, which impair control of both REM and non-REM sleep.18 Relatively discrete components of the state of sleep become disordered, intruding inappropriately into wakefulness. Cataplexy and sleep paralysis are manifestations of the atonia of REM sleep, and hypnagogic and hypnopompic hallucinations are components of REM-related dreaming.
Psychiatric Conditions and Sleep. Although sleep disorders and depression commonly coexist in a person, some would not routinely consider depression a sufficient reason for EDS.18 Yet, depression can cause patients to increase their time needed to fall asleep, the amount of time between deciding to sleep and actually doing so.25 Depression can also increase nighttime wakefulness and early-morning awakening, and decrease the slow-wave sleep occurring during the deep sleep of stages 3 and 4. The prevalence of depression is high in people with EDS, and EDS is a risk factor for depression.18 In any case, depression can certainly interfere with the quality of sleep, as can anxiety, dementia, and posttraumatic stress disorder (PTSD).20
Dementia, particularly Alzheimer's disease, is associated with sleep disorders.25 Patients with dementia tend to have lower sleep efficiency, the ratio of total sleep time to time in bed, and more daytime napping. Dementia also alters the lengths of the stages of sleep. No effective therapy especially for sleep disorders arising from dementia has yet been devised.
PTSD and other anxiety disorders, schizophrenia, and bipolar disorder can cause problems in initiating or maintaining sleep.25 Also known as manic-depressive illness, bipolar disorder affects about 2.6% of the population older than the age of 18, typically developing late in adolescence or early in adulthood– although first symptoms have appeared in childhood as well as in later life.26 The daily amount of sleep a patient believes he/she requires during a manic episode is scant–maybe 3 hours, maybe none–and episodes will last a week or longer. In depressive episodes, a patient may sleep too much or, ironically, again be unable to sleep. Medication decisions can be complex and further complicated by sudden fluctuations in the patient's response; the expertise of a psychiatrist may be needed.
Medical Conditions Affecting Sleep. As anyone who has ever had nasal congestion can attest, breathing disruptions are even more difficult when trying to sleep. People with chronic obstructive pulmonary disease (COPD) have dips in oxygenation of arterial blood at night, producing hypoxia and arousals from sleep.25 Orthopnea, a form of dyspnea that allows comfortable breathing only when the patient is sitting erectly or standing, might understandingly impair sleep. Trauma to the heart or head can produce a Cheyne-Stokes breathing pattern, which makes it difficult to sleep. Nicotine disrupts sleep in a similar manner. People who smoke have more sleep disturbances, more difficulty falling asleep, and an increased risk of sleep apnea than those who don't smoke.
PD begets sleep/wake dysfunction in 98% of those who have it.27 In terms of EDS and other sleep events, it is difficult to separate the effects of PD pathophysiology from those of treatment with dopamine-agonist (DA) agents, which are discussed below. They may have urinary frequency and find it hard to turn in bed, thereby fragmenting sleep. Inability to initiate and maintain sleep, likely arising from neuropathologic PD manifestations, will surely amplify any EDS and sleep events that accompany DA agents.
Conditions such as asthma, arthritis, congestive heart failure, frequent nocturia, and any chronic pain can, if not frankly prevent sleep, at least interfere with its continuity.20 Constipation, gastroesophageal reflux disease, and pruritic skin conditions are not conducive to sleep, nor are such lower urinary tract disorders as benign prostatic hypertrophy or detrusor instability.25 Along with all of its other aches and pains, and because of some of them, advancing age also tends to create or amplify sleep dysfunctions. In addition, older patients consume a daily average of 5 to 9 medications, and some of these can interfere with sleep or wakefulness.
Drug-induced EDS
2. Ebert B,Wafford KA, Deacon S. Treating insomnia: current and investigational pharmacological approaches. Pharmacol Ther. 2006;112:612-629.
4. Hossain JL, Ahmad P, Reinish LW, Kayumov L, Hossain NK, Shapiro CM. Subjective fatigue and subjective sleepiness: two independent consequences of sleep disorders? J Sleep Res. 2005;14:245-253.
6. Vgontzas AN, Chrousos GP. HPA axis and sleep. http://www.endotext.org/adrenal/adrenal31/adrenal31.htm. Accessed October 10, 2007.
8. Kushida CA. Countermeasures for sleep loss and deprivation. Curr Treat Options Neurol. 2006;8:361-366.
10. Bitsios P, Schiza SE, Giakoumaki SG, Savidou K, Alegakis AK, Siafakas N. Pupil miosis within 5 minutes in darkness is a valid and sensitive quantitative measure of alertness: application in daytime sleepiness associated with sleep apnea. Sleep. 2006;29:1482-1488.
12. Hatoum HT, Kania CM, Kong SX, et al. Prevalence of insomnia: a survey of the enrollees at five managed care organizations. Am J Manag Care. 1998;4:79-86.
14. Davis S, Mirick DK, Stevens RG. Night shift work, light at night, and risk of breast cancer. J Natl Cancer Inst. 2001;93:1557-1562.
16. Landrigan CP, Rothschild JM, Cronin JW, et al. Effect of reducing interns’ work hours on serious medical errors in intensive care units. N Engl J Med. 2004;351:1838-1848.
18. Mahowald MW. What is causing excessive daytime sleepiness? Evaluation to distinguish sleep deprivation from sleep disorders. Postgrad Med. 2000;107:108-123. 19. Finlayson TL, Moyer CA, Sonnad SS. Assessing symptoms, disease severity, and quality of life in the clinical context: a theoretical framework. Am J Manag Care. 2004;10:336-344.
21. Davies RJ, Stradling JR. The relationship between neck circumference, radiographic pharyngeal anatomy, and the obstructive sleep apnoea syndrome. Eur Respir J. 1990;3:509-514.
23. Chemelli RM, Willie JT, Sinton CM, et al. Narcolepsy in orexin knockout mice. Cell. 1999;98:437-451.
25.Vij S, Gentili A. Sleep disorder, geriatric. emedicine. August 4, 2005. http://www.emedicine.com/med/topic3179.htm. Accessed September 11, 2007.
27. Simuni T. Diagnosis and management of Parkinson’s disease. Medscape Today. August 30, 2007. http://www.medscape.com/viewprogram/7698. Accessed September 5, 2007.
29. Homann CN, Suppan K,Wenzel K, et al. The Bradykinesia Akinesia Incoordination Test (BRAIN TEST), an objective and user-friendly means to evaluate patients with parkinsonism. Mov Disord. 2000;15:641-647.
