The American Journal of Managed Care
August 2010
Volume 16
Issue 08

Insomnia Risks and Costs: Health, Safety, and Quality of Life

This review article discusses the issues surrounding the risks and costs of sleep disturbance as they relate to society and the individual.

The effect of insomnia on next-day functioning, health, safety, and quality of life results in a substantial societal burden and economic cost. The annual direct cost of insomnia has been estimated in the billions of US dollars and is attributed to the association of insomnia with the increased risk of certain psychiatric and medical comorbidities that result in increased healthcare service utilization. It is well known that psychiatric conditions, anxiety and depression in particular, are comorbid with insomnia. However, emerging data have shown links with several common and costly medical conditions such as heart disease and diabetes. Furthermore, studies show that patients who have insomnia have more emergency department and physician visits, laboratory tests, and prescription drug use than those who do not have insomnia, increasing direct and indirect consumption of healthcare resources. Insomnia also has been shown to negatively affect daytime functioning, including workplace productivity, as well as workplace and public safety. These daytime effects of insomnia are translated into indirect costs that are reportedly higher than the direct costs of this disorder. These observations have significant implications for managed care organizations and healthcare providers. Improvements in diagnosing and treating insomnia can significantly reduce the healthcare cost of insomnia and its comorbid disorders, while providing additional economic benefits from improved daytime functioning and from increased productivity.

(Am J Manag Care. 2010;16(8):617-626)

This review describes the evidence associated with the direct and indirect economic costs of insomnia, as well as available and emerging therapeutic strategies.

  • The direct and indirect costs of insomnia are highlighted to impress on the reader a need for improvements in the management of insomnia.
  • Links between common costly medical conditions and insomnia are made, demonstrating the importance of improving the diagnosis and treatment of not only insomnia but also its comorbidities.
  • The benefits and drawbacks of current and future treatments are discussed to help healthcare providers make informed treatment decisions for their patients.

Insomnia is a disorder of inadequate sleep (poor quantity or quality) that can result in impairment of daytime function or in emotional distress.1,2 There are several types of insomnia, which are not mutually exclusive and include difficulty initiating sleep (sleep-onset insomnia), frequent or long nighttime awakenings (sleep-maintenance insomnia), and waking up too early without being able to return to sleep (also sleep-maintenance insomnia).1 The type of insomnia can vary over time in any individual and is classified based on its duration.3 Acute insomnia lasts 1 to 3 nights, short-term insomnia lasts 3 nights to 1 month, and chronic insomnia lasts longer than 1 month.4 Acute insomnia is often caused by emotional or physical discomfort and, if left untreated, may develop into chronic insomnia.5

Insomnia can exist as a primary disorder or as comorbid with another condition.6 Primary insomnia is commonly caused by life changes, including extended periods of stress or emotional upset.5 Comorbid insomnia (sometimes referred to as secondary insomnia) is the most common type of insomnia, afflicting more than 8 of 10 people with insomnia.5,7 The identification and diagnosis of insomnia are challenged by difficulty and ambiguity because of the variation in the ways insomnia can manifest in an individual, the potential overlap and changes in insomnia symptoms, and the possible disruption of sleep due to lifestyle or environmental factors unassociated with insomnia. Also, there is a discrepancy between subjective reporting and objective measuring of sleep, further complicating insomnia diagnosis and assessment. Generally, insomniacs tend to underestimate their ability to sleep.8

Determining the true prevalence of insomnia is further complicated due to patient underreporting and differences in operational definitions.1,9-11 In the United States, general population surveys consistently find that approximately one-third of adults report having sleep problems.12-15 Within this group, sleep-maintenance insomnia is reported more commonly than sleep-onset insomnia, as demonstrated by an international survey in which 73% of patients with insomnia reported problems with sleep maintenance, 61% reported difficulties falling asleep, and 48% reported poor sleep quality.16 In the 2009 Sleep in America Poll conducted by the National Sleep Foundation, 64% of individuals surveyed had complaints of frequent insomnia, with only 15% being formally diagnosed.15 In this poll, insomnia with nighttime awakenings and with waking up feeling unrefreshed characterized the most prevalent symptoms (46% and 45%, respectively).15

Certain populations have a higher likelihood for developing insomnia.7 Risk factors include female sex,17 increasing age,18,19 employment status,20,21 shift work,21 and a family history of insomnia.22,23 Among women, insomnia seems to be more prevalent in the perimenopausal years, and a gradual increase in insomnia is seen in early-to-late perimenopause transition.24,25 Although older age is associated with an increased risk of insomnia, reports of insomnia or trouble sleeping have been found to peak in middle age (range, 45-54 years), to decrease slightly during older age (range, 65-84 years), and to increase again at very old age (>85 years), suggesting that the relationship between insomnia or trouble sleeping and age may not be linear.26 Greater risk of chronic insomnia exists in shift workers, another group at high risk of insomnia, possibly due to the misalignment of their circadian sleep—wake patterns and sleep–wake schedules.21

This review will focus on the health and societal effects of insomnia as they relate to its economic cost burden. This issue is relevant to managed care organizations and healthcare providers because insomnia contributes to increased direct and indirect consumption of healthcare resources. Improvements in diagnosing and treating insomnia can relieve its cost burden by significantly reducing the associated direct and indirect healthcare costs.


Normal sleep consists of 2 alternating states, non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep.27 The NREM-REM cycle, beginning with NREM, generally occurs 3 to 7 times per night and normally lasts 90 to 120 minutes each time.28 The NREM sleep is composed of 4 stages (NREM1 through NREM4). Stage 1 is viewed as shallow or light sleep, having the lowest arousal threshold, and stage 2 is the transition from light sleep to deep sleep as the heart rate slows and body temperature decreases. Stages 3 and 4 are defined by high-voltage slow-wave activity, with stage 4 having a predominance of these wave-forms.29 Such high-voltage slow-wave activity is characteristic of slow-wave sleep (SWS) or deep sleep. These latter deep sleep stages have the highest arousal threshold and are believed to be required for physical restoration, while REM sleep is required for cognitive restoration.30,31

There are several determinants of a good night’s sleep, and these can be measured in different ways. Sleep efficiency is the ratio of time spent asleep (total sleep time) to the time spent in bed. A decrease in sleep efficiency typically reflects a decrease in total sleep time, which subsequently affects next-day alertness and performance.8 Sleep quality refers to the restorative and undisturbed quality of sleep. The depth of NREM sleep, the amount of REM sleep, and sleep continuity are major determinants of sleep quality.8 Refreshing sleep (ie, sleep that makes one feel refreshed the next day) requires sufficient total sleep time and sleep that is in synchrony with the sleep-wake circadian rhythm.32 Ultimately, good sleep manifests as an ability to function well the next day.

The sleep pattern of individuals with chronic insomnia demonstrates a marked deficiency in the SWS stage.33,34 Electroencephalographic data show that insomniacs have fewer waves that are characteristic of deep sleep and more higher-frequency lower-amplitude waves that are typical of wakefulness, REM sleep, and NREM1 and NREM2 light sleep.29,31,35


Insomnia has a negative association with health and quality of life (QoL) if left untreated. In a study36 that surveyed severe insomniacs, mild insomniacs, and good sleepers, insomniacs were reported to have a lower self-reported overall health status and higher bodily pain, both of which contribute to reduced QoL. Successful treatment of insomnia is expected to enhance QoL. However, treatment efficacy investigations in insomnia generally have a narrow range of outcome measures that tend to focus on short-term improvements and include mostly quantitative measurements of sleep improvements, with measures of QoL (if included) as secondary evaluations.37 A placebo-controlled study37 that included measurement of QoL demonstrated that long-term treatment of insomnia with eszopiclone enhanced QoL.


The potential negative effect that insomnia may have on health is further evidenced by its association with the increased risk of certain psychiatric and medical comorbidities, including anxiety and depression,1,38 obesity or weight gain,39 obstructive sleep apnea hypopnea syndrome,40 and alcoholism41 (). In addition, certain medical conditions are associated with an increased risk of insomnia.42 These include chronic pain, high blood pressure, gastrointestinal problems, urinary problems, osteoarthritis, hip impairment, fibromyalgia, peptic ulcer disease, and breathing problems (Figure).43-46 For example, more than 50% of patients with chronic obstructive pulmonary disease complain of difficulties initiating or maintaining sleep,47 and 50% of adults with diabetes are reported to have insomnia.48 Shorter sleep time is associated with impaired glucose regulation and with increased risk of diabetes.49 However, the cause—effect relationship of insomnia with psychiatric and medical comorbidities is unclear.46,50-52 Some evidence suggests a reciprocal cause—effect relationship between insomnia and psychiatric disorders such as depression, anxiety, and alcohol or drug abuse.53 Moreover, combined treatment of insomnia and depression or anxiety can augment the efficacy of antidepressants or antianxiolytics.54,55

Insomnia can affect daytime functioning by impairing one’s ability to perform common tasks. In the 2009 Sleep in America Poll, 40% of adults reported that daytime sleepiness interfered significantly with their daily activities.15 These daytime impairments are due to the negative effects of insomnia on memory, the ability to concentrate and focus, psychomotor function, and alertness. Such functional impairments can result in decreased productivity at home and at work.56

Decreased safety in the workplace is another consequence of daytime functional impairments resulting from insomnia. Workers with sleep disorder symptoms have a higher occupational injury rate than those without sleep problems.57 In a Swedish study,58 trouble sleeping was significantly associated with increased risk of fatal occupational accidents. Impaired performance due to reduced or inefficient sleep creates public safety risks when individuals with excessive daytime sleepiness are involved in potentially dangerous daily activities such as driving.59


It is difficult to determine exactly the direct cost of insomnia because there are varying degrees of overlapping expenditures with other medical conditions, and some cost attributed to insomnia may be due to other coexisting conditions.60 Nevertheless, patients with insomnia have been shown to have 60% higher mean total healthcare costs than those without insomnia.61 Patients with insomnia have more emergency department and physician visits, laboratory tests, and prescription drug use than those without insomnia, and patients with severe insomnia use more healthcare resources than their counterparts with less severe insomnia or those without insomnia.62 Other issues that contribute to the difficulty in assessing costs include differing definitions of insomnia and the fact that not all patients experiencing sleep problems may label or report themselves as insomniacs.

Direct Costs of Insomnia

Based on direct healthcare costs, insomnia is considered a significant economic burden for patients. The direct annual costs of insomnia treatment in the United States were estimated in 1990 to be $15.9 billion63 and in 1995 to be $13.9 billion.56 Another study64 examining the direct annual cost of insomnia in the United States for 1995 estimated the cost at $1.79 billion. Disparity between estimates is likely due to inflation, differences in the measuring methods used, and varying attributions of nursing home costs.56,65,66 Based on direct healthcare costs, insomnia is considered a significant economic burden for younger and older patients. A recent retrospective observational study61 conducted using medical claims for inpatient, outpatient, pharmacy, and emergency department services found the direct costs of insomnia treatment to be $924 per patient per 6 months for those aged 18 to 64 years and $1143 per patient per 6 months for those aged 65 years or older (2003 US dollar pricing).

Indirect Costs of Insomnia

It is generally accepted that the indirect costs of insomnia are higher than the direct costs.64,67 Based on a review of the literature, the combined direct and indirect estimated total costs for insomnia are likely to be at least $92 to $107 billion (1994 US dollars) annually, with indirect costs (including medical comorbidities, increased hospitalization, insomnia-related alcohol abuse, reduced workplace productivity, and motor vehicle crashes and other accidents) accounting for $77 to $92 billion.66 These data suggest a cost benefit to the treatment of insomnia.

Indirect costs of insomnia result primarily from its daytime effects. As such, the effect of insomnia on daily functioning is key to understanding its effect on cost burden, particularly indirect costs. Individuals with severe insomnia miss work twice as often and have a higher rate of work accidents and errors, as well as lower self-rated job performance scores, compared with those without insomnia.68,69 One retrospective analysis used the Human Capital Management Services Research Reference Database to compare the annual costs of insomnia between employees who have insomnia and those who do not have insomnia.70 The annual incremental costs, including medical and drug costs, sick leave, short-term disability, long-term disability, and workers’ compensation, were significantly higher for employees who have insomnia.70 In another study,71 the effect of insomnia on work productivity was found to result in a high cost to employers. It must be noted that cost estimates as they relate to work productivity are likely to be low because of the difficulty in accurately determining the economic burden of insomnia in the workplace.

A recent study72 conducted in the Canadian province of Quebec found that the indirect costs of untreated insomnia are much greater than the direct costs of treating it: For individuals meeting all diagnostic criteria for insomnia, the annual per-person insomnia-related costs averaged CaD $5010 (US $4388), with indirect costs (including costs associated with work absenteeism and productivity and motor vehicle crashes and other accidents) accounting for CaD $4717 (US $4131) and direct costs (including costs associated with healthcare visits, transportation to healthcare appointments, and alcohol and prescription medication to promote sleep) accounting for CaD $293 (US $257). Costs attributed to loss of work productivity and absenteeism were estimated using Statistics Canada Labour Force Survey data on mean salaries according to age group and sex. This study cited lost hours of work productivity, an estimated 27.6 days of work lost per person, as the highest cost of insomnia, accounting for 76% of all insomnia costs.72 The highest direct cost of treating insomnia was attributed to the use of alcohol as a sleep aid, accounting for 5% of all insomnia costs.72 It should be noted that these findings are in the context of Quebec’s centralized healthcare system, which keeps medical costs low and relies on a self-report method.


In a predictive analysis that used clinical literature and medical claims data, treatment of insomnia was associated with significant net savings in healthcare cost per patient per year (<$2362 [2007 US dollars] per patient per year for zolpidem tartrate extended-release treatment using total sleep time as the modeled efficacy measure).73 However, this study was limited to a national healthcare database, and the results may not be generalized to reflect all types of healthcare structures. Furthermore, information on long-term savings or trends was not obtained. In another model that used patient-level data from a 6-month clinical trial, assessment of the cost-effectiveness of eszopiclone for chronic primary insomnia demonstrated a net gain in quality-adjusted life-years (QALYs), with a cost-effectiveness of approximately $5000 per QALY gained, including indirect costs.74 However, these values may not translate to real-world cost-effectiveness, as patients receiving protocol-driven care in this trial had a low rate of physician visits and were healthier than the general population with insomnia, thereby reducing healthcare utilization.74

There are further economic benefits of treating insomnia that should be considered in the context of any associated comorbidity of the individual patient. In many cases, effective treatment of insomnia may reduce the indirect costs of treating comorbidities. In other cases, effective treatment of comorbidities may improve the insomnia symptoms and thereby reduce the economic burden.

Nonpharmacologic treatments of insomnia primarily include behavioral and cognitive techniques that modify the precipitating and perpetuating factors that contribute to insomnia.75 Pharmacologic treatments for insomnia include self-prescribed treatments such as over-the-counter sleep aids, alcohol, and “natural” treatments (eg, valerian, chamomile, and St John’s wort), as well as prescription agents.76-78 Although widely used, over-the-counter sleep aids such as those containing antihistamines (diphenhydramine or hydroxyzine), have negative adverse-effect profiles that include cognitive impairment and next-day sedation.75 Prescription agents most commonly used in the management of insomnia include benzodiazepines, nonbenzodiazepine hypnotics, and Ramelteon, as well as some antidepressants, particularly those that target the serotonergic system.14,75,77,79-82

Benzodiazepines (eg, estazolam, flurazepam hydrochloride, quazepam, temazepam, and triazolam) function as modulators of γ-aminobutyric acid A (GABAA) receptors and have been the first-line pharmacologic treatment option in the short-term management of insomnia.75 Benzodiazepines are known for their efficiency in reducing the time to sleep onset (sleep latency) and the number of nighttime awakenings, thereby increasing total sleep time.75 However, safety and tolerability concerns should be considered for their long-term use; for example, benzodiazepines can result in next-day “hangover” symptoms, including a negative effect on memory and recall and next-day sleepiness.75 Such adverse effects are likely attributed to the lack of differentiation of benzodiazepines between different GABAA receptors, some of which are located in areas of the brain involved in cognitive, memory, and psychomotor functions.83 Additional adverse effects of benzodiazepine use include addiction and tolerance to their sleep-promoting effects.84,85

Nonbenzodiazepine hypnotics (eg, zolpidem tartrate [sanofiaventis, Bridgewater, NJ], zolpidem tartrate extended-release [sanofi-aventis], zaleplon [King Pharmaceuticals, Bristol, TN], and eszopiclone [Sepracor, Marlborough, MA]) produce the same hypnotic effects as benzodiazepines, while offering more favorable safety and tolerability profiles.83 These drugs exhibit greater selectivity for GABAA receptor subtypes located in areas of the brain involved in sleep—wakefulness and sedation.75,83 As a result, they reduce the risk of next-day sedative (hangover) effects and do not exhibit the same propensity for tolerance and addictive properties as traditional benzodiazepines.83 Nevertheless, evidence for the addictive properties of nonbenzodiazepines exists, requiring these drugs to be scheduled.76,82,86,87

Ramelteon, a melatonin receptor agonist that is not scheduled, is indicated for the treatment of sleep-onset insomnia. It may have promise in the treatment of circadian disruptions such as those exhibited by shiftworkers and jet-lagged travelers.88,89

Although there is limited evidence for their efficacy in specifically treating insomnia, antidepressants such as amitriptyline hydrochloride, doxepin hydrochloride, trazodone hydrochloride, and mirtazapine have been prescribed off-label for the treatment of insomnia due to their sedative effects. Trazodone and mirtazapine elicit their sedative effects by acting as serotonergic serotonin receptor antagonists, with the former also having antihistaminergic properties.90 All of these drugs are associated with several adverse effects, including dizziness and psychomotor impairment.81,91-94 Furthermore, few studies have specifically examined the efficacy and safety of these antidepressants in the treatment of insomnia, and clinical trials that have examined the effect of antidepressants on insomnia have focused specifically on depression-associated insomnia.94,95


There is an evolving conceptual framework that views insomnia as a chronic disorder. Within this framework, therapeutic considerations would include the different types of insomnia and the potential need for their long-term treatment. The association of insomnia with increased risk of disease and with potential long-term health problems highlights the importance of using effective treatment modalities. This includes effectively treating the often underappreciated acute health risks associated with short-term insomnia, such as distress, anxiety, and the development of long-term insomnia.96 Treating short-term insomnia can alleviate acute health risks and has the potential to decrease the development of chronic insomnia.97 As such, early diagnosis and treatment action may benefit patients with insomnia and may improve individual and societal safety in the long term.98 Furthermore, studies73,74,99,100 have shown that treating insomnia can reduce direct healthcare costs for patients, as well as for healthcare plans.

Novel therapies are being developed to specifically treat different types of insomnia such as targeting serotonin receptor subtypes, with the aim of avoiding complicating adverse effects, while promoting SWS.101 Of particular interest have been the highly homologous 5-HT2a and 5-HT2c receptors. Antagonism of these receptors by the serotonin antagonist ritanserin has been shown to improve deep sleep and sleep quality in poor sleepers.102-104 Antagonists of 5-HT2a such as eplivanserin and pruvanserin are being investigated as therapeutics for sleep-maintenance insomnia.101

Other possible promoters of SWS are extrasynaptic GABA agonists such as gaboxadol, an investigated drug that was not approved,105 that function selectively via the extrasynaptic GABAA receptors.106 Prospective inducers of sleep initiation include orexin receptor antagonists, or orexinergics, which aim to inhibit the wake-promoting effects of endogenous orexins.107


Extensive data clearly demonstrate that insomnia is a significant clinical problem resulting in major societal costs. Insomnia has been shown to negatively affect workplace productivity and health-related QoL and increase healthcare utilization and costs.

The association of insomnia with increased consumption of healthcare resources has significant implications for managed care organizations and healthcare providers. Effective treatment of insomnia may reduce the indirect costs of treating comorbidities (summarized in the Table). Early diagnosis and treatment of insomnia may significantly decrease the US healthcare dollars spent on insomnia, with further benefits from improved daytime functioning and from increased productivity.


We thank Brigitte Teissedre, PhD, Medicus International, for her editorial assistance in the preparation of the manuscript.

Author Affiliations: From Alertness Solutions (MRR, KBG), Cupertino, CA.

Funding Source: Editorial support was funded by sanofi-aventis. The authors were fully responsible for all content and editorial decisions and received no financial support or other compensation related to the development of the article.

Author Disclosures: The authors (MRR, KBG) report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.

Authorship Information: Concept and design (MRR, KBG); drafting of the manuscript (MRR, KBG); and critical revision of the manuscript for important intellectual content (MRR, KBG).

Address correspondence to: Mark R. Rosekind, PhD, Alertness Solutions, 1601 S DeAnza Blvd, Ste 200, Cupertino, CA 95014. E-mail:

1. National Institutes of Health. NIH State-of-the-Science Conference: Manifestations and Management of Chronic Insomnia in Adults. June 13-15, 2005. Accessed June 9, 2010.

2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994.

3. Hohagen F, Käppler C, Schramm E, Riemann D, Weyerer S, Berger M. Sleep onset insomnia, sleep maintaining insomnia and insomnia with early morning awakening: temporal stability of subtypes in a longitudinal study on general practice attenders. Sleep. 1994;17(6):551-554.

4. Krystal AD. The effect of insomnia definitions, terminology, and classifications on clinical practice. J Am Geriatr Soc. 2005;53(7)(suppl):S258-S263.

5. National Heart, Lung, and Blood Institute and the NIH. Insomnia: key points. Accessed May 2009.

6. Morin CM, LeBlanc M, Daley M, Gregoire JP, Mérette C. Epidemiology of insomnia: prevalence, self-help treatments, consultations, and determinants of help-seeking behaviors. Sleep Med. 2006;7(2):123-130.

7. Schutte-Rodin S, Broch L, Buysse D, Dorsey C, Sateia M. Clinical guideline for the evaluation and management of chronic insomnia in adults. J Clin Sleep Med. 2008;4(5):487-504.

8. Keklund G, Akerstedt T. Objective components of individual differences in subjective sleep quality. J Sleep Res. 1997;6(4):217-220.

9. Roberts RE, Roberts CR, Duong HT. Chronic insomnia and its negative consequences for health and functioning of adolescents: a 12-month prospective study. J Adolesc Health. 2008;42(3):294-302.

10. Roberts RE, Roberts CR, Duong HT. Sleepless in adolescence: prospective data on sleep deprivation, health and functioning. J Adolesc. 2009;2(5):1045-1057.

11. Partinen M, Leger D, Hirshkowitz M, Chokroverty S, Hedner J. Frequency of insomnia symptoms in PCPs’ patients: results of the Equinox International Survey. Paper presented at: European Sleep Research Society Meeting; September 9-13, 2008; Glasgow, Scotland.

12. Ancoli-Israel S, Roth T. Characteristics of insomnia in the United States: results of the 1991 National Sleep Foundation Survey: I. Sleep. 1999;22(suppl 2):S347-S353.

13. Grandner MA, Kripke DF. Self-reported sleep complaints with long and short sleep: a nationally representative sample. Psychosom Med. 2004;66(2):239-241.

14. Rosenberg RP. Sleep maintenance insomnia: strengths and weaknesses of current pharmacologic therapies. Ann Clin Psychiatry. 2006;18(1):49-56.

15. National Sleep Foundation. Sleep in America Poll: data from 2002, 2003, 2004 and 2005 sleep polls. Accessed October 2009.

16. Leger D, Poursain B. An international survey of insomnia: underrecognition and under-treatment of a polysymptomatic condition. Curr Med Res Opin. 2005;21(11):1785-1792.

17. Owens JF, Matthews KA. Sleep disturbance in healthy middle-aged women. Maturitas. 1998;30(1):41-50.

18. Foley DJ, Monjan AA, Brown SL, Simonsick EM, Wallace RB, Blazer DG. Sleep complaints among elderly persons: an epidemiologic study of three communities. Sleep. 1995;18(6):425-432.

19. Webb WB. Sleep in older persons: sleep structures of 50- to 60-year-old men and women. J Gerontol. 1982;37(5):581-586.

20. Linton S, Bryngelsson I. Insomnia and its relationship to work and health in a working-age population. J Occup Rehabil. 2000;10:169-183.

21. Akerstedt T. Shift work and disturbed sleep/wakefulness. Sleep Med Rev. 1998;2(2):117-128.

22. Watson NF, Goldberg J, Arguelles L, Buchwald D. Genetic and environmental influences on insomnia, daytime sleepiness, and obesity in twins. Sleep. 2006;29(5):645-649.

23. Bastien CH, Morin CM. Familial incidence of insomnia. J Sleep Res. 2000;9(1):49-54.

24. Parry BL, Fernando Martínez L, Maurer EL, López AM, Sorenson D, Meliska CJ. Sleep, rhythms and women’s mood, part II: menopause. Sleep Med Rev. 2006;10(3):197-208.

25. Dennerstein L, Dudley EC, Hopper JL, Guthrie JR, Burger HG. A prospective population-based study of menopausal symptoms. Obstet Gynecol. 2000;96(3):351-358.

26. Pearson NJ, Johnson LL, Nahin RL. Insomnia, trouble sleeping, and complementary and alternative medicine: analysis of the 2002 National Health Interview Survey data. Arch Intern Med. 2006;166(16):1775-1782.

27. Fuller PM, Gooley JJ, Saper CB. Neurobiology of the sleep-wake cycle: sleep architecture, circadian regulation, and regulatory feedback. J Biol Rhythms. 2006;21(6):482-493.

28. Markov D, Goldman M. Normal sleep and circadian rhythms: neurobiologic mechanisms underlying sleep and wakefulness. Psychiatr Clin North Am. 2006;29(4):841-853, abstract vii.

29. Carskadon MA, Rechtschaffen A. Monitoring and staging human sleep. In: Kryger MH, Roth T, Dement WC, eds. Principles and Practice of Sleep Medicine. 4th ed. Philadelphia, PA: Saunders; 2005.

30. Roth T. Measuring treatment efficacy in insomnia. J Clin Psychiatry. 2004;65(suppl 8):8-12.

31. Carskadon MA. Sleep and circadian rhythms in children and adolescents: relevance for athletic performance of young people. Clin Sports Med. 2005;24(2):319-328, x.

32. Jamison JR. Maintaining Health in Primary Care: Guidelines for Wellness in the 21st Century. Edinburgh, Scotland: Elsevier Health Sciences; 2001.

33. Gaillard JM. Is insomnia a disease of slow-wave sleep? Eur Neurol. 1976;14(6):473-484.

34. Gaillard JM. Chronic primary insomnia: possible physiopathological involvement of slow wave sleep deficiency. Sleep. 1978;1(2):133-147.

35. Merica H, Blois R, Gaillard JM. Spectral characteristics of sleep EEG in chronic insomnia. Eur J Neurosci. 1998;10(5):1826-1834.

36. Léger D, Scheuermaier K, Philip P, Paillard M, Guilleminault C. SF-36: evaluation of quality of life in severe and mild insomniacs compared with good sleepers. Psychosom Med. 2001;63(1):49-55.

37. Walsh JK, Krystal AD, Amato DA, et al. Nightly treatment of primary insomnia with eszopiclone for six months: effect on sleep, quality of life, and work limitations. Sleep. 2007;30(8):959-968.

38. Winokur A, Gary KA, Rodner S, Rae-Red C, Fernando AT, Szuba MP. Depression, sleep physiology, and antidepressant drugs. Depress Anxiety. 2001;14(1):19-28.

39. Van Cauter E, Knutson KL. Sleep and the epidemic of obesity in children and adults. Eur J Endocrinol. 2008;159(suppl 1):S59-S66.

40. Smith S, Sullivan K, Hopkins W, Douglas J. Frequency of insomnia report in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Sleep Med. 2004;5(5):449-456.

41. Brower KJ. Insomnia, alcoholism and relapse. Sleep Med Rev. 2003;7(6):523-539.

42. Roth T. Comorbid insomnia: current directions and future challenges. Am J Manag Care. 2009;15(suppl):S6-S13.

43. Taylor DJ, Mallory LJ, Lichstein KL, Durrence HH, Riedel BW, Bush AJ. Comorbidity of chronic insomnia with medical problems [published correction appears in Sleep. 2007;30(7):table of contents]. Sleep. 2007;30(2):213-218.

44. Leigh TJ, Hindmarch I, Bird HA, Wright V. Comparison of sleep in osteoarthritic patients and age and sex matched healthy controls. Ann Rheum Dis. 1988;47(1):40-42.

45. Ancoli-Israel S. The impact and prevalence of chronic insomnia and other sleep disturbances associated with chronic illness. Am J Manag Care. 2006;12(8)(suppl):S221-S229.

46. Katz DA, McHorney CA. Clinical correlates of insomnia in patients with chronic illness. Arch Intern Med. 1998;158(10):1099-1107.

47. George CF, Bayliff CD. Management of insomnia in patients with chronic obstructive pulmonary disease. Drugs. 2003;63(4):379-387.

48. Skomro RP, Ludwig S, Salamon E, Kryger MH. Sleep complaints and restless legs syndrome in adult type 2 diabetics. Sleep Med. 2001;2(5):417-422.

49. Gottlieb DJ, Punjabi NM, Newman AB, et al. Association of sleep time with diabetes mellitus and impaired glucose tolerance. Arch Intern Med. 2005;165(8):863-867.

50. Riemann D, Berger M, Voderholzer U. Sleep and depression: results from psychobiological studies: an overview. Biol Psychol. 2001;57(1-3):67-103.

51. Roth T, Jaeger S, Jin R, Kalsekar A, Stang PE, Kessler RC. Sleep problems, comorbid mental disorders, and role functioning in the National Comorbidity Survey Replication. Biol Psychiatry. 2006;60(12):1364-1371.

52. Olson LG, Cole MF, Ambrogetti A. Correlations among Epworth Sleepiness Scale scores, multiple sleep latency tests and psychological symptoms. J Sleep Res. 1998;7(4):248-253.

53. Breslau N, Roth T, Rosenthal L, Andreski P. Sleep disturbance and psychiatric disorders: a longitudinal epidemiological study of young adults. Biol Psychiatry. 1996;39(6):411-418.

54. Fava M, McCall WV, Krystal A, et al. Eszopiclone co-administered with fluoxetine in patients with insomnia coexisting with major depressive disorder. Biol Psychiatry. 2006;59(11):1052-1060.

55. Fava M, Asnis GM, Shrivastava R, et al. Zolpidem extended-release improves sleep and next-day symptoms in comorbid insomnia and generalized anxiety disorder. J Clin Psychopharmacol. 2009;29(3):222-230.

56. Chilcott LA, Shapiro CM. The socioeconomic impact of insomnia: an overview. Pharmacoeconomics. 1996;10(suppl 1):1-14.

57. Nakata A, Ikeda T, Takahashi M, et al. Sleep-related risk of occupational injuries in Japanese small and medium-scale enterprises. Ind Health. 2005;43(1):89-97.

58. Akerstedt T, Fredlund P, Gillberg M, Jansson B. A prospective study of fatal occupational accidents: relationship to sleeping difficulties and occupational factors. J Sleep Res. 2002;11(1):69-71.

59. Pandi-Perumal SR, Verster JC, Kayumov L, et al. Sleep disorders, sleepiness and traffic safety: a public health menace. Braz J Med Biol Res. 2006;39(7):863-871.

60. Walsh JK. Clinical and socioeconomic correlates of insomnia. J Clin Psychiatry. 2004;65(suppl 8):13-19.

61. Ozminkowski RJ, Wang S, Walsh JK. The direct and indirect costs of untreated insomnia in adults in the United States. Sleep. 2007;30(3):263-273.

62. Hatoum HT, Kong SX, Kania CM, Wong JM, Mendelson WB. Insomnia, health-related quality of life and healthcare resource consumption: a study of managed-care organisation enrollees. Pharmacoeconomics. 1998;14(6):629-637.

63. National Commission on Sleep Disorders Research. Wake Up America: A National Sleep Alert: Executive Summary and Executive Report. Bethesda, MD: National Heart, Lung, and Blood Institute; 1993:1.

64. Walsh JK, Engelhardt CL. The direct economic costs of insomnia in the United States for 1995. Sleep. 1999;22(suppl 2):S386-S393.

65. Fullerton DS. The economic impact of insomnia in managed care: a clearer picture emerges. Am J Manag Care. 2006;12(8)(suppl):S246-S252.

66. Stoller MK. Economic effects of insomnia. Clin Ther. 1994;16(5):873-897, 854.

67. Martin SA, Aikens JE, Chervin RD. Toward cost-effectiveness analysis in the diagnosis and treatment of insomnia. Sleep Med Rev. 2004;8(1):63-72.

68. Léger D, Guilleminault C, Bader G, Lévy E, Paillard M. Medical and socio-professional impact of insomnia. Sleep. 2002;25(6):625-629.

69. Kuppermann M, Lubeck DP, Mazonson PD, et al. Sleep problems and their correlates in a working population. J Gen Intern Med. 1995;10(1):25-32.

70. Kleinman NL, Brook RA, Doan JF, Melkonian AK, Baran RW. Health benefit costs and absenteeism due to insomnia from the employer’s perspective: a retrospective, case-control, database study. J Clin Psychiatry. 2009;70(8):1098-1104.

71. Rosekind MR, Gregory KB, Mallis MM, Brandt SL, Seal B, Lerner D. The cost of poor sleep: workplace productivity loss and associated costs. J Occup Environ Med. 2010;52(1):91-98.

72. Daley M, Morin CM, LeBlanc M, Grégoire JP, Savard J. The economic burden of insomnia: direct and indirect costs for individuals with insomnia syndrome, insomnia symptoms, and good sleepers. Sleep. 2009;32(1):55-64.

73. Jhaveri M, Seal B, Pollack M, Wertz D. Will insomnia treatments produce overall cost savings to commercial managed-care plans? a predictive analysis in the United States. Curr Med Res Opin. 2007;23(6):1431-1443.

74. Snedecor SJ, Botteman MF, Bojke C, Schaefer K, Barry N, Pickard AS. Cost-effectiveness of eszopiclone for the treatment of adults with primary chronic insomnia. Sleep. 2009;32(6):817-824.

75. Morin AK. Strategies for treating chronic insomnia. Am J Manag Care. 2006;12(8)(suppl):S230-S245.

76. Lieberman JA. Update on the safety considerations in the management of insomnia with hypnotics: incorporating modified-release formulations into primary care. Prim Care Companion J Clin Psychiatry. 2007;9(1):25-31.

77. Ramakrishnan K, Scheid DC. Treatment options for insomnia. Am Fam Physician. 2007;76(4):517-526.

78. Taibi DM, Landis CA, Petry H, Vitiello MV. A systematic review of valerian as a sleep aid: safe but not effective. Sleep Med Rev. 2007;11(3):209-230.

79. Ebert B, Wafford KA, Deacon S. Treating insomnia: current and investigational pharmacological approaches. Pharmacol Ther. 2006;112(3):612-629.

80. Becker PM. Insomnia: prevalence, impact, pathogenesis, differential diagnosis, and evaluation. Psychiatr Clin North Am. 2006;29(4):855-870, abstract vii.

81. Owen RT. Ramelteon: profile of a new sleep-promoting medication. Drugs Today (Barc). 2006;42(4):255-263.

82. Roth T, Soubrane C, Titeux L, Walsh JK; Zoladult Study Group. Efficacy and safety of zolpidem-MR: a double-blind, placebo-controlled study in adults with primary insomnia. Sleep Med. 2006;7(5):397-406.

83. Wagner J, Wagner ML. Non-benzodiazepines for the treatment of insomnia. Sleep Med Rev. 2000;4(6):551-581.

84. Holbrook AM, Crowther R, Lotter A, Cheng C, King D. Metaanalysis of benzodiazepine use in the treatment of insomnia. CMAJ. 2000;162(2):225-233.

85. Chouinard G. Issues in the clinical use of benzodiazepines: potency, withdrawal, and rebound. J Clin Psychiatry. 2004;65(suppl 5):7-12.

86. Canaday BR. Amnesia possibly associated with zolpidem administration. Pharmacotherapy. 1996;16(4):687-689.

87. Drover DR. Comparative pharmacokinetics and pharmacodynamics of short-acting hypnosedatives: zaleplon, zolpidem and zopiclone. Clin Pharmacokinet. 2004;43(4):227-238.

88. Srinivasan V, Spence DW, Pandi-Perumal SR, Trakht I, Cardinali DP. Jet lag: therapeutic use of melatonin and possible application of melatonin analogs. Travel Med Infect Dis. 2008;6(1-2):17-28.

89. Erman M, Seiden D, Zammit G, Sainati S, Zhang J. An efficacy, safety, and dose-response study of Ramelteon in patients with chronic primary insomnia. Sleep Med. 2006;7(1):17-24.

90. Benca RM. Diagnosis and treatment of chronic insomnia: a review. Psychiatr Serv. 2005;56(3):332-343.

91. Winokur A, DeMartinis NA III, McNally DP, Gary EM, Cormier JL, Gary KA. Comparative effects of mirtazapine and fluoxetine on sleep physiology measures in patients with major depression and insomnia. J Clin Psychiatry. 2003;64(10):1224-1229.

92. Montgomery SA. Safety of mirtazapine: a review [published correction appears in Int Clin Psychopharmacol. 1996;11(2):153]. Int Clin Psychopharmacol. 1995;10(suppl 4):37-45.

93. Bon OL. Low-dose trazodone effective in insomnia [letter]. Pharmacopsychiatry. 2005;38(5):226.

94. Mendelson WB. A review of the evidence for the efficacy and safety of trazodone in insomnia. J Clin Psychiatry. 2005;66(4):469-476.

95. Walsh JK, Erman M, Erwin CW. Subjective hypnotic efficacy of trazodone and zolpidem in DSM-III-R primary insomnia. Hum Psychopharmacol. 1998;13:191-198.

96. White DP. Tragedy and insomnia. N Engl J Med. 2001;345(25):1846- 1848.

97. Reite M, Weissberg M, Ruddy J. Clinical Manual for Evaluation and Treatment of Sleep Disorders. Washington, DC: American Psychiatric Publishing; 2008.

98. Passarella S, Duong MT. Diagnosis and treatment of insomnia. Am J Health Syst Pharm. 2008;65(10):927-934.

99. Botteman MF, Ozminkowski RJ, Wang S, Pashos CL, Schaefer K, Foley DJ. Cost effectiveness of long-term treatment with eszopiclone for primary insomnia in adults: a decision analytical model [published correction appears in CNS Drugs. 2006;21(5):405]. CNS Drugs. 2007;21(4):319-334.

100. Botteman M. Health economics of insomnia therapy: implications for policy. Sleep Med. 2009;10(suppl 1):S22-S25.

101. Teegarden BR, Al Shamma H, Xiong Y. 5-HT(2A) inverse-agonists for the treatment of insomnia. Curr Top Med Chem. 2008;8(11):969-976.

102. Dukat M, Young R, Darmani NN, Ahmed B, Glennon RA. The 5-HT3 agent N-(3-chlorophenyl)guanidine (MD-354) serves as a discriminative stimulus in rats and displays partial agonist character in a shrew emesis assay. Psychopharmacology (Berl). 2000;150(2):200-207.

103. Sharpley AL, Williamson DJ, Attenburrow ME, Pearson G, Sargent P, Cowen PJ. The effects of paroxetine and nefazodone on sleep: a placebo controlled trial. Psychopharmacology (Berl). 1996;126(1):50-54.

104. Viola AU, Brandenberger G, Toussaint M, Bouhours P, Paul Macher J, Luthringer R. Ritanserin, a serotonin-2 receptor antagonist, improves ultradian sleep rhythmicity in young poor sleepers. Clin Neurophysiol. 2002;113(3):429-434.

105. Harrison NL. Mechanisms of sleep induction by GABAA receptor agonists. J Clin Psychiatry. 2007;68(suppl 5):6-12.

106. Szabadi E. Drugs for sleep disorders: mechanisms and therapeutic prospects. Br J Clin Pharmacol. 2006;61(6):761-766.

107. Nishino S. The hypocretin/orexin receptor: therapeutic prospective in sleep disorders. Expert Opin Investig Drugs. 2007;16(11):1785-1797.

108. Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62(6):617-627.

109. Katzelnick DJ, Kobak KA, DeLeire T, et al. Impact of generalized social anxiety disorder in managed care. Am J Psychiatry. 2001;158(12):1999-2007.

110. Greenberg PE, Sisitsky T, Kessler RC, et al. The economic burden of anxiety disorders in the 1990s. J Clin Psychiatry. 1999;60(7):427-435.

111. DuPont RL, Rice DP, Miller LS, Shiraki SS, Rowland CR, Harwood HJ. Economic costs of anxiety disorders. Anxiety. 1996;2(4):167-172.

112. Johnson EO, Roth T, Breslau N. The association of insomnia with anxiety disorders and depression: exploration of the direction of risk. J Psychiatr Res. 2006;40(8):700-708.

113. Taylor DJ, Lichstein KL, Durrence HH, Reidel BW, Bush AJ. Epidemiology of insomnia, depression, and anxiety. Sleep. 2005;28(11):1457-1464.

114. Ford DE, Kamerow DB. Epidemiologic study of sleep disturbances and psychiatric disorders: an opportunity for prevention? JAMA. 1989;262(11):1479-1484.

115. Henk HJ, Katzelnick DJ, Kobak KA, Greist JH, Jefferson JW. Medical costs attributed to depression among patients with a history of high medical expenses in a health maintenance organization. Arch Gen Psychiatry. 1996;53(10):899-904.

116. Simon GE, VonKorff M, Barlow W. Health care costs of primary care patients with recognized depression. Arch Gen Psychiatry. 1995;52(10):850-856.

117. Stensland MD, Jacobson JG, Nyhuis A. Service utilization and associated direct costs for bipolar disorder in 2004: an analysis in managed care. J Affect Disord. 2007;101(1-3):187-193.

118. Bryant-Comstock L, Stender M, Devercelli G. Health care utilization and costs among privately insured patients with bipolar I disorder. Bipolar Disord. 2002;4(6):398-405.

119. Harvey AG. Sleep and circadian rhythms in bipolar disorder: seeking synchrony, harmony, and regulation. Am J Psychiatry. 2008;165(7):820-829.

120. Rice DP. Economic costs of substance abuse, 1995. Proc Assoc Am Physicians. 1999;111(2):119-125.

121. Crum RM, Storr CL, Chan YF, Ford DE. Sleep disturbance and risk for alcohol-related problems. Am J Psychiatry. 2004;161(7):1197-1203.

122. Centers for Disease Control and Prevention. 2007 National diabetes fact sheet. September 2009.

123. Hoerger TJ, Ahmann AJ. The impact of diabetes and associated cardiometabolic risk factors on members: strategies for optimizing outcomes. J Manag Care Pharm. 2008;14(1)(suppl C):S2-S14.

124. Zhou H, Isaman DJ, Messinger S, et al. A computer simulation model of diabetes progression, quality of life, and cost. Diabetes Care. 2005;28(12):2856-2863.

125. Brandle M, Zhou H, Smith BR, et al. The direct medical cost of type 2 diabetes. Diabetes Care. 2003;26(8):2300-2304.

126. Amin SP, Mullins CD, Duncan BS, Blandford L. Direct health care costs for treatment of diabetes mellitus and hypertension in an IPA-group-model HMO. Am J Health Syst Pharm. 1999;56(15):1515-1520.

127. Laliberté F, Bookhart BK, Vekeman F, et al. Direct all-cause health care costs associated with chronic kidney disease in patients with diabetes and hypertension: a managed care perspective. J Manag Care Pharm. 2009;15(4):312-322.

128. Centers for Disease Control and Prevention. Obesity Among Adults in the United States: No Statistically Significant Change Since 2003-2004. Hyattsville, MD: National Center for Health Statistics; 2007.

129. Stone KL, Blackwell T, Ancoli-Israel S. Objective measures of sleep duration and obesity in older men and women [abstract]. Sleep. 2007;30:A106-A107.

130. Patel SR, Blackwell T, Redline S, et al; Osteoporotic Fractures in Men Research Group, Study of Osteoporotic Fractures Research Group. The association between sleep duration and obesity in older adults. Int J Obes (Lond). 2008;32(12):1825-1834.

131. Centers for Disease Control and Prevention. FastStats: Asthma. Accessed August 3, 2010.

132. Vgontzas AN, Liao D, Bixler EO, Chrousos GP, Vela-Bueno A. Insomnia with objective short sleep duration is associated with a high risk for hypertension. Sleep. 2009;32(4):491-497.

133. American Lung Association. Chronic obstructive pulmonary disease (COPD) fact sheet (chronic bronchitis and emphysema). Accessed June 10, 2010.

134. Menzin J, Boulanger L, Marton J, et al. The economic burden of chronic obstructive pulmonary disease (COPD) in a U.S. Medicare population. Respir Med. 2008;102(9):1248-1256.

135. Blanchette CM, Gutierrez B, Ory C, Chang E, Akazawa M. Economic burden in direct costs of concomitant chronic obstructive pulmonary disease and asthma in a Medicare Advantage population. J Manag Care Pharm. 2008;14(2):176-185.

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