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Managing Sleep Health in Primary Care Managing Sleep Health in Primary Care Paul P. Doghramji, MD, FAAFP Family Practice Physician Collegeville Family Practice & Pottstown Medical Specialists, Inc. Medical Director of Health Services,
Managing Sleep Health in Primary Care 1
Paul P. Doghramji, MD, FAAFP Family Practice Physician Collegeville Family Practice & Pottstown Medical Specialists, Inc. Medical Director of Health Services, Ursinus College – Collegeville, PA Attending Family Practice Physician, Pottstown Memorial Medical Center – Pottstown, PA
Managing Sleep Health in Primary Care 2
▪ Behavioral ▪ Reversible ▪ Perceptual disengagement from, and unresponsiveness to, the environment ▪ Neurophysiological ▪ Two distinct states: REM sleep and NREM ▪ Actively produced, not a result of passive inactivity ▪ Highly regulated by homeostatic and circadian processes ▪ Produces changes in the entire organism, not just the CNS ▪ Teleological ▪ Necessary for survival; deprivation leads to functional impairments and eventual death ▪ Important for clearance of neurotoxic waste products (e.g., beta amyloid) that accumulate in the brain during wakefulness
NREM = non-rapid eye movement Carskadon MA, Dement WC (2005), Normal human sleep: an overview. In: Principles and Practice of Sleep Medicine, 4th ed., Kryger MH et al., eds. Philadelphia: Elsevier/Saunders, pp13-23. Science vol 342, 18 Oct 2013.
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Managing Sleep Health in Primary Care 4
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Rapid eye movement (REM) sleep ▪ When dreaming occurs ▪ “Active brain in a paralyzed body”
Hours 1 N 1 & REM N 2 N3 2 3 4 5 6 7 8
Non-REM sleep ▪ 3 stages ▪ Based primarily on EEG
Typical Sleep Architectural Pattern of a Young Human Adult
Adapted from Hauri P. The Sleep Disorders. Kalamazoo, Mich: Upjohn;1982:8.
Stage I & REM sleep (red) are graphed on the same level because their EEG patterns are very similar
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NREM REM
Heart rate Steady Variable Blood pressure Steady Labile Respirations Regular Irregular Skeletal muscle tone Normal Decreased Thermoregulation Waking modes Decreased Penile tumescence Infrequent Frequent Mental activity Limited Dreaming Brain O2 consumption Decreased Waking level
Lee-Chiong T, ed. Sleep: A Comprehensive Handbook. Hoboken, NJ: Wiley & Sons; 2006.
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100 200 300 400 500 600 700 Total Sleep Time (min) Age (years) Total Time in Bed Awake in Bed NREM N 1 REM NREM N 2 NREM N 3 10 20 30 40 50 60 70 80 5
Adapted from Williams RL, et al. Electroencephalography of Human Sleep: Clinical Applications. New York, NY: John Wiley & Sons; 1974.
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Managing Sleep Health in Primary Care 9
Peyron et al. J Neurosci. 1998;18:9996. Moore et al. Arch Ital Biol. 2001;139:195. Silber & Rye. Neurology. 2001;56:1616.
Modified from Saper CB, et al. Nature. 2005;437(7063):1257-1263.
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Managing Sleep Health in Primary Care 11
Foulkes D. Dreaming: a cognitive-psychological analysis. Hillsdale, N.J.: Erlbaum, 1985.
N1 & N2 N3 REM Simpler, shorter and have fewer associations than REM sleep dreams More diffuse (e.g., about a color or an emotion) Tend to be bizarre and detailed, with storyline plot associations Highest recall during sleep stages with EEG patterns most like those in the waking state D R E A M S
TYPE OF DREAM INCIDENCE SYMPTOMS SLEEP STAGE ASSOCIATED FACTORS Frequent nightmares in children 20% to 30%, declines with age Frightening, detailed plots Difficult return to sleep REM sleep, usually late in sleep (4 - 6 a.m.) Usually no pathology Frequent nightmares in adults 5% to 8% Increased awakenings Daytime memory impairment and anxiety REM sleep “Thin-boundary” / creative personality May have associated psychopathology PTSD 8% - 68% of veterans >25% of trauma victims Stereotypic dreams of the trauma Intense rage, fear, grief REM sleep and sleep
Significant trauma Daytime hyper- arousability & anxiety REM sleep behavior disorder Most common in late middle age and in men Acting out of dreams Nocturnal injuries REM sleep REM EMG tone Degenerative neurologic illness in 50% Night terrors 1% to 4% of children Declines with age Rare in adults Blood-curdling screams Autonomic discharge Limited recall Deep sleep, early (1- 3 a.m.) Stages 3 & 4 arousals on PSG No pathology in children Psychiatric & neurologic disorders in adults
PAGEL JF, Nightmares and Disorders of Dreaming. Am Fam Physician. 2000 Apr 1;61(7):2037-2042.
REM = rapid eye movement; EMG = electromyography
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The International Classification of Sleep Disorders: Diagnostic and Coding Manual. 2nd ed. Westchester, IL: American Academy of Sleep Medicine; 2005. Chervin RD. Chest 2000;118:372-379. Shen J, et al. Sleep Med Rev 2006;10:63-76.
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Sleepiness Fatigue Lack of motivation
Tendency to fall asleep or inability to stay awake Sensation of weariness, tiredness, exhaustion, loss of energy; the desire to rest “I don’t feel like doing anything…” Improved by sleep Improved by rest, exertion makes it worse
37% 16% 0% 10% 20% 30% 40% At least a few days per month At least a few days per week
% of US Adults Reporting that They Are So Sleepy it Interferes with Their Daily Activities
National Sleep Foundation. “Sleep in America” Poll. March 2002.
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▪ Epworth ▪ Insomnia Severity Scale ▪ Diaries ▪ Often do not reflect objective sleep measures
▪ Not reimbursable, not validated in clinical practice
Johns MW. Sleep. 1991;14:540-545.
Rate the chances of dozing in sedentary situations
Never Slight Moderate High Sitting and reading 1 2 3 Watching television 1 2 3 Sitting, inactive in a public place (eg, a movie theater or a meeting) 1 2 3 As a passenger in a car for an hour without a break 1 2 3 Lying down to rest in the afternoon when circumstances permit 1 2 3 Sitting and talking to someone 1 2 3 Sitting quietly after lunch without alcohol 1 2 3 In a car, while stopped for a few minutes in the traffic 1 2 3
Score >=10 Prompts Further Evaluation
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US women 20.8%, US men 29.7%2
South Africa1 24.5% Japan1 12.4% China1 6.2% Austria1 17.5% Belgium1 17.5% Brazil1 14.3% Germany1 7.2% Portugal1 18.3% Slovakia1 13.7% Spain1 12.7% Norway3 17.7%
N=35,327 survey respondents aged 39 ± 15.3 years.1 ESS, Epworth Sleepiness Scale
▪ Insufficient sleep ▪ Factitious ▪ Insomnia ▪ Poor quality sleep ▪ Obstructive sleep apnea ▪ Restless Legs Syndrome ▪ Disturbed timing of sleep ▪ Circadian rhythm disorders ▪ Medications and substances ▪ Rx, OTC, herbals ▪ Illicit drugs, alcohol ▪ Brain “damage” ▪ MS, Parkinson’s, TBI, stroke, Alzheimer's ▪ Narcolepsy
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Restless Legs Syndrome6
10%-15%
Comorbid Insomnias4
6%
Narcolepsy5
0.06%†
Obstructive Sleep Apnea1
3%-28%
*Among night and rotating shift workers; †Prevalence of hypersomnias such as narcolepsy without cataplexy may be higher.
†Mignot E, et al. Brain. 2006;129:1609-1623. †Singh M, et al. Sleep. 2006;29:890-895.
Shift Work Disorder2
8%-32%*
Insufficient Sleep Syndrome3
26%
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▪ Determine whether sleepy, fatigue, or depression
▪ Insufficient Sleep Syndrome: doesn’t get enough sleep ▪ OSA: loud snoring, waking up choking, witnesses apneas, waking with sore throat, headache, enuresis, nocturia ▪ RLS: uncomfortable feelings in legs prevent sleep, need to move them to relieve symptoms ▪ PLMD: no clues except excessive sleepiness ▪ Narcolepsy: hypnogogic/hypnopompic hallucinations, sleep paralysis, cataplexy
Symptoms
▪ Loud Snoring ▪ Gasping, choking ▪ Witnessed apneas ▪ Morning headaches, sore throat ▪ Enuresis/nocturia
Physical Findings
▪ Large neck ▪ Crowded pharynx ▪ Obesity ▪ Micrognathia, short chin
Treatment
▪ CPAP/BiPAP/Auto-AP ▪ Oral appliance ▪ Surgery ▪ Weight loss ▪ Positioning ▪ “Provent” ▪ “Inspire”
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STOP Questionnaire* ▪ Snoring ▪ Tiredness (daytime) ▪ Observed you stop breathing during sleep ▪ High blood Pressure BANG† ▪ BMI > 35 ▪ Age > 50 years ▪ Neck circumference > 40 cm (~ 16 in) ▪ Gender: Male * High risk = Yes to > 2 of 4 STOP items † High risk = Yes to > 3 of 8 STOP-BANG items
Chung F, et al. Anesthesiology 2008;108:812-821.
Nuckton TJ, et al. Sleep. 2006;29:903-908.
Odds of OSA increase >2-fold for every 1-point increase
Class I Class II Class III Class IV
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Symptoms
▪ Irresistible urge to move legs usually with unpleasant sensations ▪ Relief with movement ▪ Worse at night ▪ Worse with rest
Etiology
▪ Dopaminergic dysfunction ▪ Iron deficiency ▪ Renal insufficiencies ▪ Peripheral neuropathies ▪ 25% secondary
Treatment
▪ Dopaminergic agents ▪ Iron if deficient ▪ Sedative hypnotics ▪ Anticonvulsants ▪ Opiates ▪ Sleep hygiene
Allen RP, Sleep Med, 2003.
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Managing Sleep Health in Primary Care 21
▪ Very prevalent in primary care ▪ But patients don’t tell you ▪ Serious consequences ▪ Day to day life ▪ Poor outcome on mental and physical health ▪ Insomnia is a clue ▪ Most insomnia is co-morbid ▪ Easy to identify Treatment ▪ Relieves an upsetting symptom ▪ Improves next day consequences ▪ Improves outcome of co-morbidity ▪ Psychiatric ▪ Medical ▪ Majority is done by PCP
▪ Age (older) ▪ Sex (especially post-1 and perimenopausal2 females) ▪ Divorce / separation / widowhood ▪ Psychiatric illness (mood and anxiety disorders) ▪ Medical conditions ▪ Cigarette smoking ▪ Alcohol and coffee consumption ▪ Certain prescription drugs
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▪ Sleep Schedule: Do you have trouble getting to sleep, staying asleep, or waking up too early? ▪ Daytime consequences: Do you feel like you have slept well throughout the day? ▪ Sleep timing: When do you go to bed? …Wake up? …Middle of the night awakening? …How long does it take you to fall back to sleep? ▪ Treatments: What remedies have you tried? Any previous Rx’s? ▪ Sleep hygiene/lifestyle issues: Alcohol? Smoking? Exercise? Medications that cause insomnia? ▪ Duration, frequency, prior: How long has this been going on?...How often?... Have you had it before?...
Sateia MJ, Doghramji K, Hauri PJ, Morin MM. Sleep. 2000;23:1-66. Erman MK. In: Sleep Disorders: Diagnosis and Treatment. Totowa, NY: Humana Press; 1998:21-51.
Terzano MG, et al. Sleep Med. 2004;5:67-75. Katz DA, McHorney CA. (1998). Clinical correlates of insomnia in patients with chronic illness. Arch Intern Med 158(10):1099-1107.
35 28 19 17 15 14 11
10 20 30 40 50
30 47 37 39 50 38 42
10 6 17 25 22 12 15
10 20 30 40 50
Insomnia Severe insomnia
Prevalence %
Medical Conditions in Primary Care Patients with Insomnia Insomnia with Medical Conditions
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▪ Total sleep time (TST) < 5 hours compared to TST > 5 hours ▪ Higher glucose & cortisol levels ▪ HPA-associated endocrine & metabolic imbalances ▪ Hypercholesterolemia even after controlling for other risk factors ▪ Night time BP: Nighttime SBP higher and day-to-night SBP dipping was lower (-8% vs -15%, P < 0.01) in insomniacs ▪ Atherosclerosis: Total sleep time (P = 0.005), and sleep quality (P = 0.05) contributed to increased carotid intima-media thickness ▪ Inflammation: Serum CRP levels higher and increased at a steeper rate
Lanfranchi, PA, et al. (2009). Nighttime blood pressure in normotensive subjects with chronic insomnia: implications for cardiovascular risk. Sleep 32(6): 760-766. Nakazaki, C, et al. (2012). Association of insomnia and short sleep duration with atherosclerosis risk in the elderly."Am J Hypertens 25(11): 1149-1155. Parthasarathy, S, et al. (2015). Persistent insomnia is associated with mortality risk. Am J Med 128(3): 268-275 e262. Lin, CL, et al. (2016). The relationship between insomnia with short sleep duration is associated with hypercholesterolemia: a cross-sectional study. J Adv Nurs 72(2): 339-347. Farina, B., et al. (2014). Heart rate and heart rate variability modification in chronic insomnia patients. Behav Sleep Med 12(4): 290-306. de Zambotti, M., et al. (2011). Sleep onset and cardiovascular activity in primary insomnia. J Sleep Res 20(2): 318-325.
Lewis, P. E., et al. (2014). Risk of type II diabetes and hypertension associated with chronic insomnia among active component, U.S. Armed Forces, 1998-2013. MSMR 21(10): 6-13.
Prospective Follow-up
▪ Active duty in US Military ▪ Excluded: Chronic insomnia prior to 1/1/1998 ▪ Without hypertension at baseline ▪ Chronic insomnia led to higher risk of hypertension (aHR 2.00)
Rate of Developing Hypertension
(per 10,000 person-years)
46.2 95.6 20 40 60 80 100
Controls Insomnia
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1.68 1.85 1.4 1.3
0.5 1 1.5 2
0.96 1.35 4.53 1 2 3 4 5
1 2 3
1st CV Event
# Insomnia Symptoms
Hsu, CY , et al. (2015). The Association Between Insomnia and Increased Future Cardiovascular Events: A Nationwide Population-Based Study. Psychosom Med 77(7): 743-751. Laugsand, LE, et al. (2014). Insomnia and the risk of incident heart failure: a population study. Eur Heart J 35(21): 1382-1393. Canivet, C, et al. (2014). Insomnia increases risk for cardiovascular events in women and in men with low SES: a longitudinal, register- based study. J Psychosom Res 76(4): 292-299.
Health Professionals Follow-Up Study ▪ US men free of cancer ▪ Insomnia symptoms in 2004, followed through 2010 ▪ Adjusted for age, lifestyle factors, and common chronic conditions Metaanalysis of 13 Prospective Studies ▪ 122,501 subjects followed for 3-20 yrs ▪ Insomnia increased risk by 45% of developing or dying from CVD
▪ (RR 1.45, 1.29-1.62; p < 0.00001)
Li, Y , et al. (2014). "Association between insomnia symptoms and mortality: a prospective study of U.S. men." Circulation 129(7): 737-746. Sofi, F, et al. (2014). Insomnia and risk of cardiovascular disease: a meta-analysis. Eur J Prev Cardiol 21(1): 57-64.
1.25 1.09 1.04 1 1.25 1.5
Total Mortality CVD Mortality
Difficulty Initiating & Nonrestorative
Difficulty initiating Difficulty maintaining Early-morning awakenings
1.55 (1.19-2.04) 1.32 (1.02-1.72) Health Professionals Follow-Up Study
Adjusted Hazards Ratio
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Insulin Resistance Associated with Subjective Sleep Complaints In Those without Diabetes
ORs Adjusted for Insomnia Daytime Sleepiness Sex and age 1.68 (1.09–2.58) 1.80 (1.22–2.66) Fully* 1.24 (0.74–2.09) 1.75 (1.10–2.77) *Adjusting for sex, age, alcohol consumption, smoking, exercise, occupational status, BMI, and family history of diabetes
Pykkönen A-J, et al. (2012) Subjective Sleep Complaints Are Associated With Insulin Resistance in Individuals Without Diabetes. Diabetes Care 35:2271–8.
aORs for HbA1c >= 6.0%
6.79 3.96 2.33 2 4 6 8
Kachi, Y ., et al. (2011). Association between insomnia symptoms and hemoglobin A1c level in Japanese men. PLoS One 6(7): e21420.
Males 22-69 years old with no hx of diabetes Difficulty maintaining sleep
Lasting 2+wks
Early AM awakening
Some- times Some- times
Japanese company annual health check-up
Standard BP treatment + estazolam vs. Standard BP treatment + placebo ▪ Insomnia treatment efficacy
▪ Estazolam: 67.3% (P < 0.001) ▪ Placebo: 14.0%
▪ Goal BP(< 140/90 mmHg)
▪ Estazolam: 74.8% (P < 0.001) ▪ Placebo: 50.5%
Li, Y , et al. (2017). "The impact of the improvement of insomnia on blood pressure in hypertensive patients." J Sleep Res 26(1): 105-114.
Blood Pressure Reduction from Baseline
7 14 21 28 7 14 21 28
Placebo Estazolam
Systolic Diastolic
N = 202 N = 200
Days of Treatment
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31.1 35.9 30 14.4 5 21 18 10 5 10 15 20 25 30 35 40
Patients (%)
Incidence (%) over 3.5 years
Insomnia (n=240) No Insomnia (n=739) Breslau N, Roth T, Rosenthal L, Andreski P. Sleep disturbance and psychiatric disorders: a longitudinal epidemiological study of young adults. Biol Psychiatry. 1996;39:411-418.
20 40 60 80 100 4 Months 16 Months Poor Good 20 40 60 80 100 4 Months 16 Months Control Tai Chi
By Sleep Quality
% 4 months CBT .21 (.03-1.47)
p<.10
TCC NS 16 months CBT .06 (.005-.669)
p<.01
TCC .10 (.008-1.29)
p<.05 ORs of Remaining at High Risk 2-hour group sessions weekly for 4 mo with a 16-mo evaluation
Risk score based on 8 biomarkers: HDL, LDL, triglycerides, C-reactive protein, fibrinogen, HA1c, glucose, insulin
By Intervention
% Remaining at High Risk
Carroll, JE, et al. (2015). Improved sleep quality in older adults with insomnia reduces biomarkers of disease risk: pilot results from a randomized controlled comparative efficacy trial. Psychoneuroendocrinology 55: 184-192.
Managing Sleep Health in Primary Care 27
▪ Genetic: heritability 42% - 57% in chronic insomnia ▪ Final common pathway: Autonomic and CNS hyperarousal
▪ Greater whole-brain metabolism during both sleep and wake periods ▪ Increased secretion of corticotropin and cortisol throughout sleep-wake cycle
▪ Sleep-wake regulation imbalance
▪ Overactivity of arousal systems ▪ Hypoactivity of sleep-inducing systems ▪ Both
▪ Failure of wake-promoting structures to deactivate during the transition from waking to sleep states
Riemann D., et al. (2015). The neurobiology, investigation, and treatment of chronic insomnia. Lancet Neurol 14(5): 547-558. Vgontzas, AN, et al. (2013). Insomnia with objective short sleep duration: the most biologically severe phenotype of the disorder. Sleep Med Rev 17(4): 241-254. Vgontzas et al. Nofzinger et al. Am J of Psychiatry. 2004;161:2126-2128.
Discuss With Patient How They Sleep
Diagnosis1, 2 Education, Including Good Sleep Practices1, 2 Nonpharma- cologic and/or Pharma- cologic Therapy1, 2 Referral to Sleep Specialist (In Cases of Treatment Failure)1
Managing Sleep Health in Primary Care 28
▪ Consequences
▪ Wake up same time every day ▪ Naps usually not a good idea
▪ Can’t catch up on weekends
▪ Alcohol, exercise, smoking, caffeine, diet (no large meals)
▪ Address the co-morbid condition as well as the insomnia ▪ Discuss with patient pros and cons of meds and CBT ▪ Medications: ▪ Which are best applicable? ▪ Habit forming? ▪ How long to use? ▪ Side effects? ▪ CBT: at your discretion—ability, time, interest ▪ Allow patient to voice his/her concerns, fears, and needs
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Adapted from: Jacobs GD, et al. Arch Intern Med. 2004;164:1888-1896. Schutte-Rodin S et al. J Clin Sleep Med. 2008;4(5):487-504. Morin CM, et al. Sleep 1999;22:1134-56.
CBT-I Components ▪ Sleep hygiene education ▪ Cognitive therapy ▪ Sleep restriction therapy ▪ Stimulus control therapy ▪ Relaxation training Sleep Hygiene ▪ Regular wake time ▪ Limit time awake and in bed ▪ Limit napping during the day ▪ Avoid clock watching if awake ▪ Avoid caffeine (after 2 PM), alcohol after dinner, or eating dinner just before bedtime ▪ Avoid stressful activities in the evening
▪ Trouble with sleep initiation only: rapid and short acting
▪ Ramelteon, triazolam, zaleplon, zolpidem
▪ Trouble staying asleep with sleep initiation problems: rapid and long acting
▪ Eszopiclone, temazepam, zolpidem ER, zolpidem (if awakes early in evening), suvorexant
▪ Trouble staying asleep withOUT sleep initiation problems
▪ Doxepin (taken at sleep onset), sublingual zolpidem (taken if one awakens)
▪ Issues with controlled substances: both of these unscheduled
▪ Ramelteon, doxepin
▪ Generic medications
▪ Temazepam, triazolam, zaleplon, zolpidem, eszopiclone
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