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Insomnia and Primary Care

Insomnia and Primary Care. Ruth Benca, MD PhD Wisconsin Sleep. Insomnia defined. Diagnosis requires one or more of the following: difficulty initiating sleep difficulty maintaining sleep waking up too early, or sleep that is chronically nonrestorative or poor in quality

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Insomnia and Primary Care

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  1. Insomnia and Primary Care Ruth Benca, MD PhD Wisconsin Sleep

  2. Insomnia defined • Diagnosis requires one or more of the following: • difficulty initiating sleep • difficulty maintaining sleep • waking up too early, or • sleep that is chronically nonrestorative or poor in quality • Sleep difficulty occurs despite adequate opportunity and circumstances for sleep. • Insomnia is not sleep deprivation, but the two may coexist. 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. Insomnia must be associated with daytime impairment • At least one daytime impairment related to the nighttime sleep difficulty must be present: • Fatigue/malaise • Attention, concentration, or memory impairment • Social/vocational dysfunction or poor school performance • Mood disturbance/irritability • Daytime sleepiness • Motivation/energy/initiative reduction • Proneness for errors/accident at work or while driving • Tension headaches, and/or GI symptoms in response to sleep loss • Concerns or worries about sleep 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. Comorbid insomnia • Impacts quality of life and worsens clinical outcomes1,2 • Predisposes patients to recurrence3 • May continue despite treatment of the primary condition4 • “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 1 Roth T, Ancoli-Israel S. Sleep. 1999;22:S354-S358. 2 Katz DA, McHorney CA. J FamPract. 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. Epidemiology of insomnia • General population: 10-15% • Clinical Practice: > 50% • The prevalence and treatment of primary insomnia have been the most studied (less than 20% of cases)1,2 • Comorbid insomnia accounts for >80% of cases 1 Simon GE,Vonkorff M. Am J Psychiatry. 1997;154:1417-1423. 2 Hajak G. Sleep. 2000; 23:S54-S63.

  6. At-risk populations for insomnia • Female sex • Increasing age • Comorbid medical illness (especially respiratory, chronic pain, neurological disorders) • Comorbid psychiatric illness (especially depression, depressive symptoms) • Lower socioeconomic status • Race (African American > White) • Widowed, divorced • Non-traditional work schedules

  7. Why insomnia is a disorder, not just a symptom • Relative consistency of insomnia symptoms and consequences across comorbid disorders • Course of insomnia does not consistently covary with the comorbid disorder • Insomnia responds to different types of treatment than the comorbid disorder • Insomnia responds to the sametypes of treatment across different comorbid disorders • Insomnia poses common risk for development of and poor outcome in different disorders Harvey, Clin Psychol Rev, 2001;Lichstein et al., Treating Sleep Disorders, 2004

  8. Increased prevalence of medical disorders in those with insomnia N=401 p<.001 N=137 % p<.001 p<.001 p<.001 p<.01 p<.05 p<.01 p<.05 Any medical problem Cancer GI Heart Disease Neuro-logic Breath-ing Urinary Diabetes Chronic Pain HTN 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. Taylor DJ., et al. Sleep. 2007;30(2):213-218.

  9. Increased prevalence of insomnia in those with medical disorders Survey Of Adults (N=2101) Living In Tucson, Arizona, Assessed Via Self-administered Questionnaires * * Prevalence, % * ** * *P ≤ .001, **P ≤ .005 vs. no health problem ASVD, arteriosclerotic vascular disease; OAD, obstructive airway disease. Klink ME et al. Arch Intern Med. 1992;152:1634-1637.

  10. 70 60 50 Percent of Respondents Reporting any Insomnia 40 30 20 10 0 2 or 3 4 0 1 Insomnia prevalence increases with greater medical comorbidity 80 Number of Medical Conditions Self-reported questionnaire data from 1506 community-dwelling subjects aged 55 to 84 years Foley D, et al. J Psychosom Res. 2004;56:497-502.

  11. Psychiatric disorder is the most common condition comorbid with insomnia 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%) Adjustment disorder (2%) Psychiatric Disorders (36%) Anxiety disorder (24%) Bipolar disorder (2%) Depressive disorder (8%) N=20,536. European meta-analysis Ohayon MM. Sleep Med Rev. 2002;6:97-111.

  12. Relative risk for psychiatric disorders associated with insomnia 1,2 1,2 1,2 1Breslau, 1996. N=1007 1,2 2Ford and Kamerow, 1989. N=811 2 1 1 2 1 1Breslau N, et al. Sleep disturbance and psychiatric disorders: a longitudinal epidemiological study of young adults. Biol Psychiatry. 1996;39:411-418. 2Ford DE, Kamerow DB. Epidemiologic study of sleep disturbances and psychiatric disorders. An opportunity for prevention? JAMA. 1989;262(11):1479-1484.

  13. Timing of insomnia related to onset of psychiatric illness N=14,915 Ohayon MM , Roth T. J Psychosom Res. 2003;37:9-15.

  14. Insomnia is a risk factor for later-life depression 40 Insomnia Total Cases 137 23 887 76 35 Yes No 30 25 P=.0005 Cumulative Incidence (%) 20 15 10 5 0 0 5 10 15 20 25 30 35 40 Follow-up Time (Years) Insomnia* Yes 137 135 133 127 117 106 99 27 9 No 887 877 859 838 799 740 616 382 216 * Number of men included at each time point. Chang P et al. Am J Epidemiol. 1997;146:105-114.

  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

  16. Bidirectional relationship between psychiatric disorders and insomnia ACTH, adrenocorticotropic hormone TST, total sleep time SOL, sleep onset latency SWS, slow wave sleep

  17. Sleep and menopause • Peri- and postmenopausal women have more sleep complaints1 • 41% of early perimenopausal women report sleep difficulties2 • Frequent awakenings suggest insomnia is secondary to vasomotor symptoms3 • However, waking episodes may occur in absence of hot flashes4 1Young T, et al. Sleep. 2003;26:667-672. 2Gold E, et al. Am J Epidemiol. 2000;152:463-473. 3Woodward S, Freedman RR. Sleep.1994;17:497-501. 4Polo-Kantola P, et al. Obstet Gynecol. 1999;94:219-224.

  18. Complaints of sleep problems with age 50 40 30 20 10 0 Percent 10-19 20-29 30-39 40-49 50-59 60-69 70+ Age Group, y “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. 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. Patients with pain report poor sleep • 287 subjects reporting to pain clinic • Mean age, 46.7 years; half with back pain • 89% reported at least 1 problem with sleep • Significant correlations between sleep and • Physical disability • Psychosocial disability • Depression • Pain McCracken LM, Iverson GL. Pain Res Manag. 2002;7:75-79.

  21. Insomnia comorbid with pain Control Any 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.

  22. Bidirectional relationship between pain and insomnia DIS, difficulty initiating sleep DMS, difficulty maintaining sleep

  23. Sleep and cancer • 30% to 75% of newly diagnosed or recently treated cancer patients complain of insomnia (double that of the general population) • Sleep complaints in cancer patients consist of • difficulty falling asleep • difficulty staying asleep • frequent and prolonged nighttime awakenings • Complaints occur before, during and after treatment Fiorentino L, Ancoli-Israel, S.Sleep dysfunction in patients with cancer. Curr Treat Opt Neurol. 2007;9:337–346.

  24. Risk factors for insomnia in cancer patients O'Donnell JF. Clin Cornerstone. 2004;6(Suppl 1D):S6-S14. 

  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. Insomnia and OSA or CSA • Studies have shown that 39% to 55% of patients with OSA have comorbid insomnia. Associated factors include: • female gender • psychiatric diagnoses • chronic pain • OSA patients with comorbid insomnia have • More severe sleep apnea • Increased depression, anxiety and stress • restless leg symptoms • lower AHI, lower DI AHI, apnea hypopnea index. CSA, central sleep apnea. DI, desaturation index. OSA, obstructive sleep apnea. Krell SB, Kapur VK. Sleep Breathing. 2005;9:104-10. Smith S, et al. Sleep Med. 2004;5:449-456.

  27. Insomnia and OSA or CSA • < 1% of 1,000 patients with OSA surveyed had been diagnosed with insomnia • Mood problems were not formally addressed • In a small study of patients with CSA (n=14): • 36% had sleep onset insomnia • 79% had maintenance insomnia • This rate was significantly higher than in patients with OSA (P =.016) MorganthalerTI,et al. Sleep. 2006;29:1203-1209. Smith S, et al. Sleep Med. 2004;5:449-456.

  28. Insomnia and COPD • >50% of patients with COPD have insomnia • 25% complain of excessive daytime sleepiness • Medications for COPD contribute to insomnia • Inhaled or PO; anticholinergics, corticosteroids, beta-2-agonists, theophylline; bupropion used for smoking cessation • Sleep deprivation may attenuate ventilatory response to hypercapnia in patients with COPD, leading to further desaturation and sleep disruption George CFP. Sleep. 2000;23:S31-S35. White DP, et al. Am Rev Respir Dis. 1983;128:984-986.

  29. Insomnia and COPD • Insomnia linked with comorbidities of COPD • Eg, depression, smoking, orthopnea, and nocturnal hypoxemia • Suggests multiple factors in pathogenesis of insomnia in COPD • Insomnia can impair pulmonary function • Spirometric decline is observed after one night of sleep deprivation • Despite importance of treating the underlying COPD, this may not lead to improvement of insomnia in clinical practice Cormick W, et al. Thorax. 1986;41:846-854. Kutty K. CurrOpinPulm 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. Insomnia may be a predictor of hypertension 95% CI: 1.45-2.45 95% CI: 1.42-2.70 HTN Incidence (%) n=192 n=286 n=4602 n=4157 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.

  31. Short sleep duration and hypertension: NHANES I and the Sleep Heart Health Study ≤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. Gangwisch et al. Hypertension. 2006;47:833-839. Gottlieb DJ, et al. Sleep. 2006;29(8):1009-1014.

  32. Relationships between sleep disorders* and obesity Factors associated with reduced sleep time* may contribute to obesity *Insomnia or sleep deprivation. 1Bjorvatn B, et al. J Sleep Res. 2007;16(1):66-76. 2Flint J, et al. J Pediatr. 2007;150(4):364-369. 3Chaput JP, et al. Obesity (Silver Spring). 2007;15(1):253-261. 4Gottlieb et al. Arch Intern Med. 2005;165:863-868.

  33. Management of insomnia • Treat any underlying cause(s)/comorbid conditions • Promote good sleep habits (improve sleep hygiene) • Consider cognitive behavior therapy • Consider medications to improve sleep Kupfer DJ and Reynolds CF III. N Engl J Med. 1997;336:341-346.

  34. Practicing good sleep hygiene • Avoid: • “watching the clock” • use of stimulants, eg, caffeine, nicotine, particularly near bedtime1,3 • heavy meals or drinking alcohol within 3 hours of bed1 • exposure to bright light during the night 1,3 • Enhance sleep environment: dark, quiet, cool temperature1,3 • Increase exposure to bright light during the day 2 • Practice relaxing routine 1-3 • Reduce time in bed; regular sleep/wake cycle 1-3 • Time regular exercise for the morning and/or afternoon 1,3 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. Behavioral techniques

  36. Drugs indicated for insomnia * Modified formulation. †No short-term use limitation.

  37. Antidepressants for Insomnia: Indications • Patients with psychoactive substance use disorder history • Patients with insomnia related to depression, anxiety • Treatment failures with BzRA • Suspected sleep apnea • Fibromyalgia • Primary insomnia (second-line agents) • Not FDA-approved for use as hypnotics

  38. Antidepressant drug effects on sleep

  39. When to refer an insomnia patient to Sleep Clinic: • Medical and psychiatric comorbidities have been assessed and are adequately treated • Patient has been instructed in sleep hygiene • Patient has failed trials of behavioral and/or pharmacological therapy

  40. Other common sleep disorders treated by sleep specialists: • Sleep apnea* • Restless legs/periodic limb movement disorder • Parasomnias • Circadian rhythm disorders • Narcolepsy* *Typically require sleep laboratory testing as well as clinical evaluation for diagnosis

  41. 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. Why high-density EEG in sleep? • Can now be done routinely; noninvasive and relatively inexpensive • What could be done with standard PSG has largely been done (NIH roadmap discourages it) • Sleep apnea PSG likely to migrate to home-monitoring • Spatial resolution is comparable to PET; temporal resolution is ideal • Sleep is a window on spontaneous brain function, unconfounded by attention, motivation, etc. • Broad patient population: sleep disorders, psychiatric disorders, neurological disorders (and connection to long-term epilepsy monitoring)

  43. Spontaneous brain rhythms during sleep reflect brain functioning unconfounded by attention and motivation slow wave activity spindle activity

  44. Fz Cz P4 Sleep Slow Wave Activity is Homeostatically Regulated Throughout the Cortex

  45. Slow waves originate more frequently in orbitofrontal and centroparietal regionsand propagate in an antero-posterior direction

  46. Diagnosis: Sleep spindle activity is reduced in schizophrenia Schizophrenics Schizophrenics vs. Controls Schizophrenics vs. Depressed P<.05 Controls Depressed Depressed vs. Controls 100 80 EEG spindle activity (13-15 Hz) 60 40 20 Ferrarelli et al., Am. J. Psychiatry, 2007

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