Insomnia and Primary Care


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  • Taylor DJ; Mallory LJ; Lichstein KL et al. Comorbidity of chronic insomnia with medical problems. SLEEP 2007;30(2):213-218.
  • ARE THERE ANY STATISTICS FOR THESE DATA, TO SHOW WHETHER THESE BARS SHOW SIGNIFICANT DIFFERENCES? Sleep Problems and Multiple Medical Conditions The objective of the study undertaken by Foley and colleagues was to assess the association between sleep problems and chronic disease in older adults. A majority of the participants (83%) reported 1 or more of 11 medical conditions and nearly 1 in 4 elderly respondents (age 65–84 years) had major comorbidity (ie,  4 conditions). As shown on the slide, there was a correlation between reports of insomnia and the number of medical conditions reported. Depression, heart disease, bodily pain, and memory problems were associated with more prevalent symptoms of insomnia (not shown). The authors concluded that the sleep complaints common in older adults are often secondary to their comorbidities and not to the aging process itself. Furthermore, the authors suggest that these types of studies may be useful in promoting sleep awareness among health professionals and among older adults, especially those with heart disease, depression, chronic bodily pain, or major comorbidity. Foley D, et al. J Psychosomatic Res . 2004;56:497-502.
  • AS LONG AS THE NUMBERS REPRESENT THE SAME THING, IT IS PROBABLY OK. HOWEVER, I’D INDICATE ON THE SLIDE THAT THE BRESLAU STUDY REPRESENTS LIFETIME RISK IN YOUNG ADULTS, WHEREAS THE FORD AND KAMEROW IS PREVALENCE DATA OVER A 6 MOS PERIOD IN ADULTS (VERIFY FOR BOTH, PLS). Ruth, part of me thinks I’m possibly violating some kind of thermodynamic statistical laws by doing this, but I thought it would be a good way to condense the data from both papers and provide a snapshot. Calling it “relative risk” sort of crosses over the causation-correlation line, though, doesn’t it? Unless there’s something else you can call a RR graph that isn’t “relative risk.” I made standard RR calculations to make this graph, but I’m not sure it’s “legal.” Considering that this graph contains data from two papers, I think it’d be a good idea to include the full references at the bottom of the slide, too?
  • What about creating a single, new slide regarding the predictive value of insomnia for psychiatric disorders and put data from several studies on there? Could then list a bunch of the key studies, with the points that insomnia most highly predictive of new or recurrent mood episode, but also predictive of onset of other psych disorders (could specify and reference) Ruth: do you mean include the Breslau paper (1996) and the relapse stuff from this same (Ohayon and Roth) paper? Not quite sure what you want here; if you want a lot of information like this, you’re talking about a table or bullets, right? Not a graph?
  • FINE TO INCLUDE THE SUICIDE DATA FOR THE TWO GROUPS, PERHAPS IN THE LEGEND, IN A COLUMN AFTER “CASES” Ruth: if you mention the 13 suicides in here, maybe we can ditch slide 17 (suicidal ideation) Key point: Insomnia is a risk factor for long-term psychiatric distress. Notes : The Johns Hopkins Precursors Study, a long-term prospective study, was used to study the relation between self-reported sleep disturbances and subsequent clinical depression and psychiatric distress. 1,053 men provided information on sleep habits during medical school at The Johns Hopkins University (classes of 1948-1964) and have been followed since graduation. During a median follow-up period of 34 years (range 1-45), 101 men developed clinical depression (cumulative incidence at 40 years, 12.2%), including 13 suicides. After adjusting for multiple variables, relative risk (RR) of clinical depression was greater in those who reported insomnia in medical school (RR 2.0, 95% CI 1.2-3.3) compared with those who did not and greater in those with difficulty sleeping under stress in medical school (RR 1.8, 95% CI 1.2-2.7) compared with those who did not report difficulty. Similar associations were observed between reports of sleep disturbances in medical school and psychiatric distress assessed in 1988 by the General Health Questionnaire. These findings suggest that insomnia in young men is indicative of a greater risk for subsequent clinical depression and psychiatric distress that persists for at least 30 years. [Chang, p. 105, abstract; graph from p. 110, Figure 1 a, top of page] Reference : Chang PP, Ford DE, Mead LA, Cooper-Patrick L, Klag MJ. Am J Epidemiol . 1997 Jul 15;146(2):105-114.
  • Ruth: this is kind of like the preceding slide; going for your “leitmotif request”
  • Something doesn’t look right here. All of the graphs are identical. Perhaps something could be done combining this with the data from the prev slide. Ruth: Your comment alarmed me, since this was a slide I had taken from a program I made for Tom! I went back and checked, though; these are the correct data (Ohayon 2005); data are extremely close to each other. Ohayon MM. Relationship between chronic painful physical condition and insomnia. J Psychiatr Res . 2005 Mar;39(2):151-159
  • v1 I AGREE, WHERE DOES THE ABSENCE OF REG ETOH USE COME FROM? DO YOU HAVE THIS ARTICLE? Ruth: Desaturation Index. Also, is “absence of regular alcohol use” correct? It seems counterintuitive to me?
  • v1
  • v1
  • PLS USE A BLACK LINE WITH END BARS TO SHOW THE CI’S Ruth: redone to your specs Key point: Insomnia has been demonstrated to be associated with an increased risk of hypertension. Notes : A recent study has shown insomnia to be significantly associated with a risk for the development of hypertension in Japanese men. 9237 male Japanese workers were assessed for insomnia (difficulty initiating sleep and difficulty maintaining sleep) and followed up for four years or until the development of hypertension. Subjects with persistent difficulty initiating sleep (n=192) were significantly more likely to develop hypertension than subjects with no difficulty initiating sleep (n=4602). Incidence of hypertension in the subjects with persistent difficulty initiating sleep was 40.1% (130.7/1000 person-years) as compared with subjects with no difficulty initiating sleep (30.6%, 89.9/1000 person years). Subjects with persistent difficulty maintaining sleep (n=286) were significantly more likely to develop hypertension than subjects with no difficulty initiating sleep (n=4157). Incidence of hypertension in the subjects with persistent difficulty initiating sleep was 42.3% (136.7/1000 person-years) as compared with subjects with no difficulty initiating sleep (30.7%, 90.8/1000 person years). After adjusting for BMI, tobacco and alcohol use, and job stress, persistent complaints of both persistent difficulty in initiating and maintaining sleep were significantly associated with an increased risk of hypertension (OR=1.96 and 1.88, respectively). [Suka p 344 c1 abstract] Reference : Suka M, Yoshida K, Sugimori H. Persistent insomnia is a predictor of hypertension in Japanese male workers. J Occup Health . 2003 Nov;45(6):344-350.
  • NHANES information; ALL of the confounders are listed below. Hazard Ratio. Sleep duration and increased risk of HTN in subjects 32-59y; adjusted for daytime sleepiness, depression, physical activity, alcohol and salt consumption, smoking, pulse rate, gender, education, age, ethnicity overweight/obesity, and diabetes. Gangwisch 2006 Hypertension 2006;47;833-839; originally published online Apr 3, 2006; Dolores Malaspina Buijs, Felix Kreier, Thomas G. Pickering, Andrew G. Rundle, Gary K. Zammit and James E. Gangwisch, Steven B. Heymsfield, Bernadette Boden-Albala, Ruud M. National Health and Nutrition Examination Survey Short Sleep Duration as a Risk Factor for Hypertension: Analyses of the First Sleep durations of 5 hours per night were associated with a significantly increased risk of hypertension (hazard ratio, 2.10; 95% CI, 1.58 to 2.79) in subjects between the ages of 32 and 59 years, and controlling for the potential confounding variables only partially attenuated this relationship. The increased risk continued to be significant after controlling for obesity and diabetes, which was consistent with the hypothesis that these variables would act as partial mediators. Short sleep duration could, therefore, be a significant risk factor for hypertension. ] Gottlieb DJ; Redline S; Nieto FJ et al. Association of usual sleep duration with hypertension: the sleep heart health study. SLEEP 2006;29(8):1009-1014 Sleep duration above or below the median of 7 to < 8 hours/night is associated with an increased prevalence of hypertension,
  • IS THIS REALLY SLEEP DISORDERS OR REDUCED SLEEP TIME, AS MAY OCCUR IN INSOMNIA? ALSO, SHOULD THE CIRCLE IN THE MIDDLE BE REDUCED SLEEP WITH ARROWS POINTING OUT TO THE INDIVIDUAL BOXES, WHICH ARE THE EFFECTS? Ruth, this is new; sort of an obesity-insomnia lit review References: The association between sleep duration, body mass index and metabolic measures in the Hordaland Health Study. Bjorvatn B, Sagen IM, Oyane N, Waage S, Fetveit A, Pallesen S, Ursin R. J Sleep Res . 2007 Mar;16(1):66-76. Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway. Several studies show that short self-reported sleep duration is associated with elevated body mass index (BMI). Short sleep duration may change appetite hormones, but whether this also influences metabolic measures like cholesterol and triglycerides is less clear. Furthermore, obesity is linked to increases in blood pressure, and recently, short sleep duration has been shown to be an independent risk factor for hypertension. This is a population-based cross-sectional study (The Hordaland Health Study). A subgroup of 8860 subjects, aged 40-45 years, answered a sleep questionnaire. Body weight, height and blood pressure were measured, and non-fasting blood samples were collected and analyzed for total cholesterol, HDL-cholesterol and triglycerides. Sleep duration was divided into the following subgroups: < 5, 5-5.99, 6-6.99, 7-7.99, 8-8.99 and > or = 9 h. The results show that short sleep duration was associated with elevated BMI and increased prevalence of obesity. Similar to BMI, levels of cholesterol, triglycerides, systolic and diastolic blood pressure were higher in subjects with short sleep duration. This co-variation seemed to be attributed to variables like gender, smoking and BMI. In conclusion, our study confirms a clear association between short sleep duration and elevated BMI and obesity. Furthermore, levels of total cholesterol, HDL-cholesterol, triglycerides and blood pressure were associated with sleep duration. Flint J, Kothare SV, Zihlif M, Suarez E, Adams R, Legido A, De Luca F. Association between inadequate sleep and insulin resistance in obese children. J Pediatr . 2007 Apr;150(4):364-9. Chaput JP, Despres JP, Bouchard C, Tremblay A. Short sleep duration is associated with reduced leptin levels and increased adiposity: Results from the Quebec family study. Obesity (Silver Spring) . 2007 Jan;15(1):253-61. Gottlieb et al. Arch Intern Med . 2005;165:863-868 Association of sleep time with diabetes mellitus and impaired glucose tolerance. Gottlieb DJ, Punjabi NM, Newman AB, Resnick HE, Redline S, Baldwin CM, Nieto FJ. Arch Intern Med . 2005 Apr 25;165(8):863-7.
  • I added your sleep hygiene slide since you listed it in the previous “Management of insomnia” slide
  • Cognitive behavior
  • SMEI 10/18/10 12:45 Optional Slides
  • Put the first bullet last, as a caveat
  • Ruth: This OK? I LIKE THE IDEA. PERHAPS MORE COLORFUL SOMEHOW, AND HAVE THE TEETER-TOTTER MORE ANGLED UP TO THE RIGHT? Have a slide that introduces next group, which is that Rx of insomnia seems to improve comorbid conditions.
  • Discuss up-state/down-state EEG vs. LFP issue?
  • Discuss up-state/down-state EEG vs. LFP issue?
  • Insomnia and Primary Care

    1. 1. Ruth Benca, MD PhD Wisconsin Sleep Insomnia and Primary Care
    2. 2. <ul><li>Diagnosis requires one or more of the following: </li></ul><ul><ul><li>difficulty initiating sleep </li></ul></ul><ul><ul><li>difficulty maintaining sleep </li></ul></ul><ul><ul><li>waking up too early, or </li></ul></ul><ul><ul><li>sleep that is chronically nonrestorative or poor in quality </li></ul></ul><ul><li>Sleep difficulty occurs despite adequate opportunity and circumstances for sleep. </li></ul><ul><li>Insomnia is not sleep deprivation, but the two may coexist. </li></ul>Insomnia defined American Academy of Sleep Medicine. International classification of sleep disorders, 2nd ed.: Diagnostic and coding manual. Westchester, Illinois: American Academy of Sleep Medicine, 2005.
    3. 3. <ul><li>At least one daytime impairment related to the nighttime sleep difficulty must be present: </li></ul><ul><ul><li>Fatigue/malaise </li></ul></ul><ul><ul><li>Attention, concentration, or memory impairment </li></ul></ul><ul><ul><li>Social/vocational dysfunction or poor school performance </li></ul></ul><ul><ul><li>Mood disturbance/irritability </li></ul></ul><ul><ul><li>Daytime sleepiness </li></ul></ul><ul><ul><li>Motivation/energy/initiative reduction </li></ul></ul><ul><ul><li>Proneness for errors/accident at work or while driving </li></ul></ul><ul><ul><li>Tension headaches, and/or GI symptoms in response to sleep loss </li></ul></ul><ul><ul><li>Concerns or worries about sleep </li></ul></ul>Insomnia must be associated with daytime impairment American Academy of Sleep Medicine. International classification of sleep disorders, 2nd ed.: Diagnostic and coding manual. Westchester, Illinois: American Academy of Sleep Medicine, 2005.
    4. 4. Comorbid insomnia <ul><li>Impacts quality of life and worsens clinical outcomes 1,2 </li></ul><ul><li>Predisposes patients to recurrence 3 </li></ul><ul><li>May continue despite treatment of the primary condition 4 </li></ul><ul><li>“ Comorbid insomnia” more appropriate than “secondary insomnia,” because limited understanding of mechanistic pathways in chronic insomnia precludes drawing firm conclusions about the nature of these associations or direction of causality. Considering insomnia to be “secondary” may also result in undertreatment. 5 </li></ul>1 Roth T, Ancoli-Israel S. Sleep . 1999;22:S354-S358. 2 Katz DA, McHorney CA. J Fam Pract . 2002;51:229-235. 3 Chang PP, et al. Am J Epidemiol . 1997;146:105-114. 4 Ohayon MM, Roth T. Psychiatr Res . 2003;37:9-15. 5 National Institutes of Health State of the Science Conference Statement on Manifestations and Management of Chronic Insomnia in Adults, June 13-15, 2005. National Institutes of Health. Sleep . 2005 Sep 1;28(9):1049-1057.
    5. 5. Epidemiology of insomnia <ul><li>General population: 10-15% </li></ul><ul><li>Clinical Practice: > 50% </li></ul><ul><li>The prevalence and treatment of primary insomnia have been the most studied (less than 20% of cases) 1,2 </li></ul><ul><li>Comorbid insomnia accounts for > 80% of cases </li></ul>1 Simon GE,Vonkorff M. Am J Psychiatry . 1997;154:1417-1423. 2 Hajak G. Sleep . 2000; 23:S54-S63.
    6. 6. At-risk populations for insomnia <ul><li>Female sex </li></ul><ul><li>Increasing age </li></ul><ul><li>Comorbid medical illness (especially respiratory, chronic pain, neurological disorders) </li></ul><ul><li>Comorbid psychiatric illness (especially depression, depressive symptoms) </li></ul><ul><li>Lower socioeconomic status </li></ul><ul><li>Race (African American > White) </li></ul><ul><li>Widowed, divorced </li></ul><ul><li>Non-traditional work schedules </li></ul>
    7. 7. Why insomnia is a disorder, not just a symptom <ul><li>Relative consistency of insomnia symptoms and consequences across comorbid disorders </li></ul><ul><li>Course of insomnia does not consistently covary with the comorbid disorder </li></ul><ul><li>Insomnia responds to different types of treatment than the comorbid disorder </li></ul><ul><li>Insomnia responds to the same types of treatment across different comorbid disorders </li></ul><ul><li>Insomnia poses common risk for development of and poor outcome in different disorders </li></ul>Harvey, Clin Psychol Rev , 2001; Lichstein et al., Treating Sleep Disorders, 2004
    8. 8. Increased prevalence of medical disorders in those with insomnia Taylor DJ., et al. Sleep. 2007;30(2):213-218 . p values are for Odds Ratios adjusted for depression, anxiety, and sleep disorder symptoms. From a community-based population of 772 men and women, aged 20 to 98 years old. Heart Disease Cancer HTN Neuro-logic Breath-ing Urinary Diabetes Chronic Pain GI Any medical problem % N=137 N=401 p <.05 p <.05 p <.01 p <.01 p <.001 p <.001 p <.001 p <.001
    9. 9. Increased prevalence of insomnia in those with medical disorders Prevalence, % Survey Of Adults (N=2101) Living In Tucson, Arizona, Assessed Via Self-administered Questionnaires * * ** * * Klink ME et al. Arch Intern Med . 1992;152:1634-1637. * P ≤ .001, ** P ≤ .005 vs. no health problem ASVD, arteriosclerotic vascular disease; OAD, obstructive airway disease.
    10. 10. Insomnia prevalence increases with greater medical comorbidity Foley D, et al. J Psychosom Res . 2004;56:497-502. Self-reported questionnaire data from 1506 community-dwelling subjects aged 55 to 84 years 80 Number of Medical Conditions 0 10 20 30 40 50 60 70 Percent of Respondents Reporting any Insomnia 0 1 2 or 3 4
    11. 11. Psychiatric disorder is the most common condition comorbid with insomnia Adjustment disorder (2%) Anxiety disorder (24%) Bipolar disorder (2%) Depressive disorder (8%) Psychiatric Disorders (36%) Other DSM-IV Distribution of Insomnia(64%) No DSM-IV diagnosis (24%) Other sleep disorders (5%) Insomnia due to a general medical condition (7%) Substance-induced insomnia (2%) Insomnia related to another mental disorder (10%) Primary insomnia (16%) Ohayon MM. Sleep Med Rev . 2002;6:97-111. N=20,536. European meta-analysis
    12. 12. Relative risk for psychiatric disorders associated with insomnia 1 Breslau N, et al. Sleep disturbance and psychiatric disorders: a longitudinal epidemiological study of young adults. Biol Psychiatry . 1996;39:411-418. 2 Ford DE, Kamerow DB. Epidemiologic study of sleep disturbances and psychiatric disorders. An opportunity for prevention? JAMA . 1989;262(11):1479-1484. 1 Breslau, 1996. N=1007 2 Ford and Kamerow, 1989. N=811 1 1 1 2 2 1,2 1,2 1,2 1,2
    13. 13. Timing of insomnia related to onset of psychiatric illness Ohayon MM , Roth T. J Psychosom Res . 2003;37:9-15. N=14,915
    14. 14. Insomnia is a risk factor for later-life depression * Number of men included at each time point. Chang P et al. Am J Epidemiol . 1997;146:105-114. Insomnia* Yes 137 135 133 127 117 106 99 27 9 No 887 877 859 838 799 740 616 382 216 Cumulative Incidence (%) Yes No Total Cases 137 23 887 76 Insomnia P =.0005 Follow-up Time (Years) 0 5 10 15 20 25 30 35 40 0 5 10 15 20 25 30 35 40
    15. 15. Objective sleep abnormalities are seen in psychiatric patients Comparison of sleep EEG in groups of patients with psychiatric disorders or insomnia to age-matched normal controls. Benca RM et al. Arch Gen Psych . 1992;49:651-668 TST SE SL SWS REM L Mood Alcoholism Anxiety Disorders Schizophrenia Insomnia
    16. 16. Bidirectional relationship between psychiatric disorders and insomnia ACTH, adrenocorticotropic hormone TST, total sleep time SOL, sleep onset latency SWS, slow wave sleep
    17. 17. Sleep and menopause <ul><li>Peri- and postmenopausal women have more sleep complaints 1 </li></ul><ul><li>41% of early perimenopausal women report sleep difficulties 2 </li></ul><ul><li>Frequent awakenings suggest insomnia is secondary to vasomotor symptoms 3 </li></ul><ul><ul><li>However, waking episodes may occur in absence of hot flashes 4 </li></ul></ul>1 Young T, et al. Sleep . 2003;26:667-672. 2 Gold E, et al. Am J Epidemiol . 2000;152:463-473. 3 Woodward S, Freedman RR. Sleep .1994;17:497-501. 4 Polo-Kantola P, et al. Obstet Gynecol . 1999;94:219-224.
    18. 18. Complaints of sleep problems with age Age Group, y 50 40 30 20 10 0 Percent 10-19 20-29 30-39 40-49 50-59 60-69 70+ “ Trouble With Sleeping” Assessed in a comprehensive survey of 1645 individuals in Alachua County, Florida Karacan I et al. Soc Sci Med . 1976;10:239-244.
    19. 19. Prevalence of insomnia by age group % Age Group, years Large-scale community survey of non-institutionalized American adults, aged 18 to 79 years Mellenger GD, et al. Arch Gen Psychiatry . 1985;42:225-232.
    20. 20. Patients with pain report poor sleep <ul><li>287 subjects reporting to pain clinic </li></ul><ul><ul><li>Mean age, 46.7 years; half with back pain </li></ul></ul><ul><li>89% reported at least 1 problem with sleep </li></ul><ul><li>Significant correlations between sleep and </li></ul><ul><ul><li>Physical disability </li></ul></ul><ul><ul><li>Psychosocial disability </li></ul></ul><ul><ul><li>Depression </li></ul></ul><ul><ul><li>Pain </li></ul></ul>McCracken LM, Iverson GL. Pain Res Manag . 2002;7:75-79.
    21. 21. Insomnia comorbid with pain N=18,980; p <.001. Based on survey data. *Pain categories included limb pain, backaches, joint pain, GI pain, and headaches. Ohayon MM. J Psychiatr Res . 2005 Mar;39(2):151-159. Control Any pain* %
    22. 22. Bidirectional relationship between pain and insomnia DIS, difficulty initiating sleep DMS, difficulty maintaining sleep
    23. 23. Sleep and cancer <ul><li>30% to 75% of newly diagnosed or recently treated cancer patients complain of insomnia (double that of the general population) </li></ul><ul><li>Sleep complaints in cancer patients consist of </li></ul><ul><ul><li>difficulty falling asleep </li></ul></ul><ul><ul><li>difficulty staying asleep </li></ul></ul><ul><ul><li>frequent and prolonged nighttime awakenings </li></ul></ul><ul><li>Complaints occur before, during and after treatment </li></ul>Fiorentino L, Ancoli-Israel, S. Sleep dysfunction in patients with cancer. Curr Treat Opt Neurol. 2007;9:337–346.
    24. 24. Risk factors for insomnia in cancer patients O'Donnell JF. Clin Cornerstone . 2004;6(Suppl 1D):S6-S14.  Risk Factor Examples Disease factors Tumors that increase steroid production, symptoms of tumor invasion (pain, dyspnea, fatigue, nausea, pruritis) Treatment factors Frequent monitoring, corticosteroid treatment, hormonal fluctuations, fatigue Medications Narcotics, chemotherapy, neuroleptics, sympathomimetics, sedative/hypnotics, steroids, caffeine/nicotine, antidepressants, diet supplements Environmental factors Disturbing light and noise, temperature extremes Psychosocial disturbances Depression, anxiety, delirium, stress Physical disorders Headaches, seizures, snoring/sleep apnea
    25. 25. Bidirectional relationship between insomnia and cancer SDB, sleep-disordered breathing Fiorentino L, Ancoli-Israel, S. Sleep dysfunction in patients with cancer. Curr Treat Opt Neurol. 2007;9:337–346.
    26. 26. Insomnia and OSA or CSA <ul><li>Studies have shown that 39% to 55% of patients with OSA have comorbid insomnia. Associated factors include: </li></ul><ul><ul><li>female gender </li></ul></ul><ul><ul><li>psychiatric diagnoses </li></ul></ul><ul><ul><li>chronic pain </li></ul></ul><ul><li>OSA patients with comorbid insomnia have </li></ul><ul><ul><li>More severe sleep apnea </li></ul></ul><ul><ul><li>Increased depression, anxiety and stress </li></ul></ul>Krell SB, Kapur VK. Sleep Breathing. 2005;9:104-10. Smith S, et al. Sleep Med. 2004;5:449-456. AHI, apnea hypopnea index. CSA, central sleep apnea. DI, desaturation index. OSA, obstructive sleep apnea. <ul><ul><li>restless leg symptoms </li></ul></ul><ul><ul><li>lower AHI, lower DI </li></ul></ul>
    27. 27. Insomnia and OSA or CSA <ul><li>< 1% of 1,000 patients with OSA surveyed had been diagnosed with insomnia </li></ul><ul><ul><li>Mood problems were not formally addressed </li></ul></ul><ul><li>In a small study of patients with CSA (n=14): </li></ul><ul><ul><li>36% had sleep onset insomnia </li></ul></ul><ul><ul><li>79% had maintenance insomnia </li></ul></ul><ul><ul><ul><li>This rate was significantly higher than in patients with OSA ( P =.016) </li></ul></ul></ul>Morganthaler TI,et al. Sleep . 2006;29:1203-1209. Smith S, et al. Sleep Med. 2004;5:449-456.
    28. 28. Insomnia and COPD <ul><li>>50% of patients with COPD have insomnia </li></ul><ul><ul><li>25% complain of excessive daytime sleepiness </li></ul></ul><ul><li>Medications for COPD contribute to insomnia </li></ul><ul><ul><li>Inhaled or PO; anticholinergics, corticosteroids, beta-2-agonists, theophylline; bupropion used for smoking cessation </li></ul></ul><ul><li>Sleep deprivation may attenuate ventilatory response to hypercapnia in patients with COPD, leading to further desaturation and sleep disruption </li></ul>George CFP. Sleep . 2000;23:S31-S35. White DP, et al. Am Rev Respir Dis. 1983;128:984-986.
    29. 29. Insomnia and COPD <ul><li>Insomnia linked with comorbidities of COPD </li></ul><ul><ul><li>Eg, depression, smoking, orthopnea, and nocturnal hypoxemia </li></ul></ul><ul><ul><li>Suggests multiple factors in pathogenesis of insomnia in COPD </li></ul></ul><ul><li>Insomnia can impair pulmonary function </li></ul><ul><ul><li>Spirometric decline is observed after one night of sleep deprivation </li></ul></ul><ul><li>Despite importance of treating the underlying COPD, this may not lead to improvement of insomnia in clinical practice </li></ul>Cormick W, et al. Thorax . 1986;41:846-854. Kutty K. Curr Opin Pulm Med. 2004;10:104-112. Maggia S, et al. J Am Geriatric Soc. 1998;46:161-168. Phillips BA, et al. Chest . 1987;91:29-32. Wetter DW, et al. Prev Med. 1994;23:328-334.
    30. 30. Insomnia may be a predictor of hypertension N=9237 male Japanese workers assessed for difficulty initiating and/or maintaining sleep and followed up for 4 years or until the development of HTN (initiation of anti-HTN therapy or a SBP of ≥140 mmHg or a DBP of ≥140 mmHg). Results adjusted for BMI, tobacco and alcohol use and job stress. Suka M, et al. J Occup Health . 2003;45:344-350. HTN Incidence (%) n=4602 n=192 n=4157 n=286 95% CI: 1.42-2.70 95% CI: 1.45-2.45
    31. 31. Short sleep duration and hypertension: NHANES I and the Sleep Heart Health Study Gangwisch et al. Hypertension. 2006;47:833-839. Gottlieb DJ, et al. Sleep . 2006;29(8):1009-1014. ≤ 5h 6h 7-8h ≥ 9h ≤ 6h 6-7h 7-8h 8-9h ≥ 9h (1.0; referent) (1.0; referent) Hazard Ratios. N=4180. Subjects 32-59y. Sleep duration and increased risk of HTN, adjusted for multiple confounders including physical activity, alcohol/salt consumption, smoking, age, overweight/obesity, and diabetes. Odds Ratios . N=5910. Subjects 40-100y. Sleep duration and increased risk of HTN adjusted for age, sex, race, apnea-hypopnea index and BMI.
    32. 32. Relationships between sleep disorders* and obesity * Insomnia or sleep deprivation. 1 Bjorvatn B, et al. J Sleep Res . 2007;16(1):66-76. 2 Flint J, et al. J Pediatr . 2007;150(4):364-369. 3 Chaput JP, et al. Obesity (Silver Spring) . 2007;15(1):253-261. 4 Gottlieb et al. Arch Intern Med . 2005;165:863-868. Factors associated with reduced sleep time* may contribute to obesity
    33. 33. Management of insomnia <ul><li>Treat any underlying cause(s)/comorbid conditions </li></ul><ul><li>Promote good sleep habits (improve sleep hygiene) </li></ul><ul><li>Consider cognitive behavior therapy </li></ul><ul><li>Consider medications to improve sleep </li></ul>Kupfer DJ and Reynolds CF III. N Engl J Med . 1997;336:341-346.
    34. 34. Practicing good sleep hygiene <ul><li>Avoid: </li></ul><ul><ul><li>“ watching the clock” </li></ul></ul><ul><ul><li>use of stimulants, eg, caffeine, nicotine, particularly near bedtime 1,3 </li></ul></ul><ul><ul><li>heavy meals or drinking alcohol within 3 hours of bed 1 </li></ul></ul><ul><ul><li>exposure to bright light during the night 1,3 </li></ul></ul><ul><li>Enhance sleep environment: dark, quiet, cool temperature 1,3 </li></ul><ul><li>Increase exposure to bright light during the day 2 </li></ul><ul><li>Practice relaxing routine 1-3 </li></ul><ul><li>Reduce time in bed; regular sleep/wake cycle 1-3 </li></ul><ul><li>Time regular exercise for the morning and/or afternoon 1,3 </li></ul>1 NHLBI Working Group on Insomnia. 1998. NIH Publication . 98-4088. 2 Kupfer DJ, Reynolds CF. N Engl J Med . 1997;336:341-346. 3 Lippmann S et al. South Med J . 2001;94:866-873.
    35. 35. Behavioral techniques Technique Aim Stimulus control therapy Imprint bed and bedroom as sleep stimulus Sleep restriction Restrict actual time spent in bed to enhance sleep depth & consolidation Cognitive therapy Address dysfunctional beliefs and attitudes about sleep Relaxation training Decrease arousal and anxiety Circadian rhythm entrainment Reinforce or reset biological rhythm using light and/or chronotherapy Cognitive behavior therapy Combination of behavioral and cognitive approaches listed above
    36. 36. Drugs indicated for insomnia * Modified formulation. † No short-term use limitation. Generic Brand T 1/2 (Hours) Dose (mg) Drug Class Flurazepam Dalmane 48-120 15-30 BZD Temazepam Restoril 8-20 15-30 BZD Triazolam Halcion 2-6 0.125-0.25 BZD Estazolam Prosom 8-24 1-2 BZD Quazepam Doral 48-120 7.5-15 BZD Zolpidem Ambien 1.5-2.4 5-10 non-BZD Zaleplon Sonata 1 5-20 non-BZD Eszopiclone † Lunesta 5-7 1-3 non-BZD Zolpidem Ex Rel † Ambien CR 1.5-2.4* 6.25-12.5 non-BZD Ramelteon † Rozerem 1.5-5 8 MT agonist
    37. 37. Antidepressants for Insomnia: Indications <ul><li>Patients with psychoactive substance use disorder history </li></ul><ul><li>Patients with insomnia related to depression, anxiety </li></ul><ul><li>Treatment failures with BzRA </li></ul><ul><li>Suspected sleep apnea </li></ul><ul><li>Fibromyalgia </li></ul><ul><li>Primary insomnia (second-line agents) </li></ul><ul><li>Not FDA-approved for use as hypnotics </li></ul>
    38. 38. Antidepressant drug effects on sleep Sleep continuity Slow wave sleep REM sleep Other Tricyclic  To   To   To     PLMs  Apnea SSRI  To   To   To   Eye movements in NREM  PLM  apnea Trazodone, Nefazodone   To   To  Trazodone more sedating Bupropion   To   No increase in PLM Mirtazapine    Low doses sedating
    39. 40. When to refer an insomnia patient to Sleep Clinic: <ul><li>Medical and psychiatric comorbidities have been assessed and are adequately treated </li></ul><ul><li>Patient has been instructed in sleep hygiene </li></ul><ul><li>Patient has failed trials of behavioral and/or pharmacological therapy </li></ul>
    40. 41. Other common sleep disorders treated by sleep specialists: <ul><li>Sleep apnea* </li></ul><ul><li>Restless legs/periodic limb movement disorder </li></ul><ul><li>Parasomnias </li></ul><ul><li>Circadian rhythm disorders </li></ul><ul><li>Narcolepsy* </li></ul><ul><li>*Typically require sleep laboratory testing as well as clinical evaluation for diagnosis </li></ul>
    41. 45. High density-EEG / TMS studies in health and disease pioneered by Giulio Tononi, MD, PhD High density EEG (256 electrodes) recorded across entire night, TMS in wakefulness and sleep
    42. 46. Why high-density EEG in sleep? <ul><ul><li>Can now be done routinely; noninvasive and relatively inexpensive </li></ul></ul><ul><ul><li>What could be done with standard PSG has largely been done (NIH roadmap discourages it) </li></ul></ul><ul><ul><li>Sleep apnea PSG likely to migrate to home-monitoring </li></ul></ul><ul><ul><li>Spatial resolution is comparable to PET; temporal resolution is ideal </li></ul></ul><ul><ul><li>Sleep is a window on spontaneous brain function, unconfounded by attention, motivation, etc. </li></ul></ul><ul><ul><li>Broad patient population: sleep disorders, psychiatric disorders, neurological disorders (and connection to long-term epilepsy monitoring) </li></ul></ul>
    43. 47. Spontaneous brain rhythms during sleep reflect brain functioning unconfounded by attention and motivation slow wave activity spindle activity
    44. 48. Fz Cz P4 Sleep Slow Wave Activity is Homeostatically Regulated Throughout the Cortex
    45. 49. Slow waves originate more frequently in orbitofrontal and centroparietal regions and propagate in an antero-posterior direction
    46. 50. P<.05 100 80 60 40 20 Schizophrenics Controls Depressed Schizophrenics vs. Controls Schizophrenics vs. Depressed Depressed vs. Controls EEG spindle activity (13-15 Hz) Diagnosis: Sleep spindle activity is reduced in schizophrenia Ferrarelli et al., Am. J. Psychiatry, 2007
    47. 51. Treatment: Sleep slow oscillations can be triggered by TMS Massimini et al., submitted
    48. 52. <ul><li>Sleep Clinic and 16 Bed Sleep Laboratory </li></ul><ul><ul><li>UWMF clinic </li></ul></ul><ul><ul><li>Sleep Laboratory joint venture with Meriter </li></ul></ul><ul><li>Open with 12 beds, 5 nights/week </li></ul><ul><li>Clinic operates 5 days/week </li></ul><ul><li>Staff model - approx 30 FTE </li></ul><ul><li>Sleep Equipment of Wisconsin - UWHC/Meriter joint venture </li></ul>
    49. 53. <ul><li>Psychiatry </li></ul><ul><ul><li>R. Benca, MD, PhD </li></ul></ul><ul><ul><li>M. Rumble, PhD </li></ul></ul><ul><li>Pulmonary </li></ul><ul><ul><li>M. Klink, MD </li></ul></ul><ul><ul><li>S. Cattapan, MD </li></ul></ul><ul><ul><li>J. McMahon, MD </li></ul></ul><ul><ul><li>G. DoPico, MD </li></ul></ul><ul><ul><li>Mihaela Teodorescu, MD </li></ul></ul><ul><li>Geriatrics </li></ul><ul><ul><li>S. Barczi, MD </li></ul></ul><ul><ul><li>Mihai Teodorescu, MD </li></ul></ul><ul><li>Pediatrics </li></ul><ul><ul><li>C. Green, MD </li></ul></ul><ul><li>Neurology </li></ul><ul><ul><li>J. Jones, MD </li></ul></ul>Interdisciplinary Clinical Expertise
    50. 54. Clinical Practice Model: Clinic <ul><li>Referral-based practice. </li></ul><ul><li>Improve access. </li></ul><ul><li>Standardized assessments of all patients using validated questionnaires, comprehensive evaluations, outcomes measures. All information on electronic database. </li></ul><ul><li>Development of behavioral sleep medicine program. </li></ul><ul><li>Outreach to primary care. </li></ul>
    51. 55. Clinical Practice Model: Laboratory <ul><li>Encourage referring providers to request studies with management. </li></ul><ul><li>Laboratory studies read the next morning. Timely communication with referring physicians; reports sent and/or available electronically within 24 hours of completion. </li></ul><ul><li>Sleep Equipment of Wisconsin on-site to provide immediate availability of treatment. </li></ul>
    52. 56. Educational program <ul><li>Directed by Steven Barczi, MD </li></ul><ul><li>ACGME-accredited fellowship </li></ul><ul><ul><li>Currently only 1 position; application for up to 3 slots per year pending </li></ul></ul><ul><li>Plan to coordinate medical school and residency training in sleep </li></ul><ul><ul><li>Lectures in medical school and residency curricula </li></ul></ul><ul><ul><li>Clinical electives </li></ul></ul>
    53. 57. Translational research opportunity <ul><li>Brand new program </li></ul><ul><li>Standardized assessment and outcomes measures </li></ul><ul><li>State-of-the-art neurophysiological recording techniques </li></ul><ul><li>Every patient a potential research subject </li></ul>