Modern Management of Sleep Disorders Douglas C. Bauer, MD University of California, San Francisco No Disclosures Case 68 yr. old WF with >15 yr. of poor sleep Difficulty with both initiation and maintenance of sleep. Few daytime symptoms Bedtime 10PM, out of bed at 7AM. Naps Denies depression, anxiety, bad habits Previous MD prescribed valium 5-10mg 3-5 times per week What else would want to know and what do you want to do? Topics Covered Prevalence and potential consequences Sleep physiology (normal, elderly, and perimenopausal women) Sleep disordered breathing Evaluation/sleep studies Treatments Introduction 40 million Americans suffer from sleep disorders 95% are undiagnosed and untreated Occurs more frequently in women Prevalence of sleep disorders increases with age
Question: Which is the most commonly reported frequency of insomnia in older adults? 35% 30% Percent Reporting Symptoms of Insomnia 1. Almost every night 2. A few times a week 3. A few times a month 4. Rarely or never 33% 53% 25% 20% 15% 10% 14% 5% 0% 1 2 3 4 0% Almost Every Night Few times/week Few times/month Rarely/Never 2002 Sleep in America poll, National Sleep Foundation Trends in Sleep Duration Year Avg Hours of Sleep 1910 1 9 1975 1 7.5 2000 2 6.9 1 Webb WB et al. Bull Psychom Soc 1975; 6: 47-48 Consequences of Sleep Disorders Early research linked daytime sleepiness to Performance & productivity in the workplace Accidents and injuries Mood disorders & cognitive performance Quality of life Until recently, sleep disorders not believed to have significant impact on chronic disease Frequent complaint in primary care 2 National Sleep Foundation. 2000 Sleep in America poll
Definitions Insomnia (insufficient or poor quality sleep) Latency (time to fall asleep) Efficiency (proportion of time in bed asleep) Hypersomnia (excessive daytime sleepiness) - Sleep disordered breathing/sleep apnea - Narcolepsy Parasomnia (coordinated motor activity) -Restless leg syndrome Sleep Architecture REM (Rapid Eye Movement) - Characteristic eye movement - EEG resembles wakefulness Non REM - 75% of sleep - Four stages: correlate with depth of sleep - Progressive cortical inactivity Sleep architecture changes over age 65 - Reduced stage 3 and 4, phase advancement - total time, latency, efficiency Insomnia in the Elderly High prevalence (> 50%) Often secondary to a primary sleep disorder Commonly associated with psychiatric disorders or depression Question: Which of the following is true about perimenopausal insomnia? 1. Perimenopausal insomnia is primarily difficulty maintaining sleep 2. Insomnia is more common in peri- than postmenopausal women 3. Correlates with frequency of vasomotor symptoms 4. HRT fully relieves perimenopausal insomnia 29% 26% 42% 3% 1 2 3 4
Perimenopausal Insomnia Prospective study of >3000 women 42-52 followed for 7 yr (SWAN) Sleep complaints worse in both peri and postmenopausal women (40% vs. 22%) Both initiation and maintenance of sleep impaired Partly attributable to hot flushes Improved but not fully reversed with HRT Other neurocognitive effects? Kravitz et al, Sleep, 2008 Presentation and Screening for Insomnia Typical presentation Difficulty initiating or maintaining sleep Wake after sleep onset Early morning awakening Awakening not rested Recommended screening question: Do you have trouble falling asleep or staying asleep? If positive, consider sleep questionnaire Medical Conditions That Cause Insomnia Primary sleep disorder Hyperthyroidism Arthritis Chronic renal failure Chronic lung disease Heart failure Neurological disorders Dementia/AD Parkinson s disease Drugs That Cause Insomnia Alcohol CNS stimulants Beta-blockers Bronchodilators Calcium channel blockers Corticosteroids Decongestants Stimulating antidepressants Thyroid hormones Nicotine
Hypersominas: Sleep Apnea Obstructive more common than central Apnic episodes, loud snoring, choking, gasping during sleep Key feature: insomnia not common but usually associated with daytime sleepiness Risk factors include: Older age Male sex Obesity Craniofacial structure Definition of Sleep Apnea Apnea = cessation of respiration Hypopnea = partial decrease (>50%) of respiration Duration 10 seconds Respiratory Disturbance Index (RDI): # apneas + hypopneas / hour while asleep Normal RDI < 5, severe apnea 15 Prevalence of Sleep Disordered Breathing Heavily dependent on definition used 2-4% in younger adults (20-60 yrs) > 10% in elderly Consequences of Sleep Disordered Breathing Impaired QOL Increased risk of accidents & injuries Mild cognitive impairment/dementia 85% increased risk if RDI>15 in older women Increased risk of hypertension and cardiovascular events Sleep Heart Study Yaffe et al Jama, 2011
Sleep Heart Study: HTN by Quartiles of RDI 45% 40% 35% 30% 25% 20% 15% 10% 5% 0% <1.25 1.25-<4.0 4.0-<10.7 10.7+ P(trend)<.001 in both men and women Men Women Shahar, Am J Respir Crit Care Med. 2001 163(1):19-25 Sleep Heart Study: CVD by Quartiles of RDI* 1.60 1.40 1.20 1.00 0.80 0.60 0.40 0.20 0.00 Q1 (ref) Q2 Q3 Q4 *Both sexes, all ages P<.0003 Other Causes of Hypersomnia: Narcolepsy - Extreme daytime sleepiness, frequent brief naps, cataplexy - Rare, familial, presents in 20s and 30s - Requires sleep study and daytime Multiple Sleep Latency Test (MSLT) - Treatment: stimulants, anticholinergics Parasomnias: Restless Leg Syndrome Intense dysesthesias, repetitive jerking - Worse at bedtime, frequently awakens patient - Often familial, progresses with age Etiology unknown, associated with iron deficiency Treatment - Sinemet 25/100 qhs (70% respond) - Clonazepam 0.5-2 mg qhs - Dopamine agonists (rotingotine, pergolide, etc) effective but intolerance common Scholz et al, Cochrane Database, 2011
Evaluation of Sleep Disorders: History Sleep pattern (patient and bedroom partner) - Insufficient sleep time - Delayed onset - Frequent or early awakening Daytime correlates Medications and habits Associated nocturnal symptoms Evaluation of Sleep Disorders: Physical Exam and Routine Lab Less helpful than historical features Thorough exam of head and neck, and cardiorespiratory system Signs of coexisting disease or complications Consider thyroid function, Hct, UA, and glucose Evaluation of Sleep Disorders: Sleep Studies Polysomnography (oximetry, EEG, EKG, EMG, observation) Home monitoring (oximetry + 1-2 others) if not medically complicated Indications - Unexplained hypersomnia (esp. with snoring) - Unexplained sleep-related CV abn (pulm HTN) - Abnormal complex sleep behavior - Unremitting chronic insomnia that does not respond to therapy Flemons et al, Chest, 2003 Insomnia Therapies Which of following is superior to benzodiazepine receptor agonists for primary insomnia? 1. sleep hygiene 2. cognitive behavioral therapy 3. anti-histamines 4. anti-depressants (TCA, SSRI, and trazadone) 52% 23% 0% 26% 1 2 3 4
Treatment of Insomnia: Non-Pharmacologic Treat underlying disorders Begin with non-pharmacologic treatment - Sleep education (changes with aging) - Sleep hygiene (diet, exercise, habits, environment) - Establish optimal sleep pattern Non-Pharmacologic Therapy: Cognitive Behavioral Therapy Cognitive therapy Change maladaptive thought processes Behavioral therapy (stimulus control, sleep restriction, relaxation, good sleep hygiene) RCT of 46 adults with chronic insomnia Superior short and long-term (6 mo) outcomes with CBT compared to zopiclone or placebo Sivertsen et al, Jama 2006 Buysse et al, Arch Intern Med, 2011 Treatment of Insomnia: Pharmacologic Depression - TCA, trazadone, SSRI, combinations (suppress REM) - Not recommended if not depressed Anxiety, panic - Benzodiazepines (suppress REM and non REM stage 3 and 4) - Not recommended if not anxious What to use? Treatment of Insomnia: Pharmacologic Problems with anti-histamines: anticholinergic, sedation, cognitive dysfunction Problems with benzodiazepines: habit forming, tachyphylaxis, suppression of REM sleep, cognitive dysfunction, falls Short-term benzodiazepine use (<2 wk) may be helpful in some patients Alternatives to benzodiazepines?
Benzodiazepine Receptor Agonists Zolpidem (generic), zaleplon (Sonata), eszopiclone (Lunesta) - Activate 1 of 3 benzodiazepine receptors - No anxiolytic or muscle relaxing effects - No tolerance (studies up to one year) - Preserves REM, less withdrawal, little abuse - Rapid onset, half life 2-3 hours Longer and shorter half-life versions available CR zolpidem if awakens too early with generic Sublinguil zolpidem (Intermezzo) for middle of the night awakeing. Note women 1.75 mg, men 3.5 mg Other Drugs An unexpected side effect Melatonin (OTC) - From pineal gland, receptors in hypothalamus - Low serum levels = poor sleep - Poor evidence for insomnia, maybe for jet lag or phase delay - Not regulated; long term safety? Ramelteon (Rozerem) Melatonin receptor agonist. FDA approved but no long-term safety data AHRQ Evidence Report #108, 2011
Conclusions Sleep disorders are common Associated with significant morbidity Drugs treatment over utilized, nonpharmacologic treatment often successful Primary care providers can diagnose and treat most patients with insomnia Specialty referral (sleep study) for selected patients with unexplained hypersomnia or severe insomnia Suggested Approach to Insomnia In Primary Care Acute <4 wks Assess trigger Consider brief tx Hypersomia or parasomnia? Evaluate and treat Insomnia Primary? Sleep hygiene CBT Refer if persists Chronic >4 wks Secondary cause? Treat and reassess Case 68 yr. old WF with >15 yr. of poor sleep Difficulty with both initiation and maintenance of sleep. Few daytime symptoms Bedtime 10PM, out of bed at 7AM. Naps Denies depression, anxiety, bad habits Previous MD prescribed valium 5-10mg 3-5 times per week What else would want to know and what do you want to do?