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? 1. Almost every night 2. A few times a week 3. A few times a month 4. Rarely or never
Percent Reporting Symptoms of Insomnia 35% 30% 25% 20% 15% 10% 5% 0% Almost Every Night Few times/week Few times/month Rarely/Never 2002 Sleep in America poll, National Sleep Foundation
Consequences of Sleep Disorders Research has focused on daytime sleepiness, resulting in: Performance & productivity in the workplace Accidents and injuries Mood disorders & cognitive performance Quality of life Traditionally sleep loss was not believed to have any impact on human health
Sleep Debt Study Young men restricted to 4 hr/night for 6 days: - Before and after serum measurements Sleep restriction resulted in: Glucose tolerance, thyrotropin Evening cortisol levels Activity of sympathetic nervous system Implications: Effects similar to normal aging Sleep debt may increase the severity of age-related chronic diseases including obesity, diabetes, CV Spiegel et al, Lancet, 1999
Definitions Insomnia (insufficient or poor quality sleep) Hypersomnia (excessive daytime sleepiness) - Sleep disordered breathing/sleep apnea - Narcolepsy Parasomnia (coordinated motor activity) -Restless leg syndrome
Normal Sleep 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 with aging
Normal Age-Related Changes in Sleep Decreased total sleep time Alterations in sleep architecture slow wave (stages 3 & 4) sleep sleep latency sleep efficiency Alterations in circadian rhythms phase advance amplitude of rhythm Increased fatigue and daytime napping
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 perithan postmenopausal women 3. Correlates with frequency of vasomotor symptoms 4. HRT fully relieves perimenopausal insomnia
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?
Drugs That Cause Insomnia Alcohol CNS stimulants Beta-blockers Bronchodilators Calcium channel blockers Corticosteroids Decongestants Stimulating antidepressants Thyroid hormones Nicotine
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 Note: sleep disordered breathing is not a common cause of insomnia
Sleep-Disordered Breathing (Sleep Apnea) Symptoms include loud snoring, choking, gasping during sleep Usually associated with daytime sleepiness Risk factors include: Older age Male sex CVD risk factors such as 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 slept typical cutpoint is RDI 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 Excessive daytime sleepiness Increased risk of accidents & injuries Cognitive impairments Increased risk of hypertension and cardiovascular events? Via hypoxemia, sympathetic activation, acute hypertension and decreased stroke volume
Sleep Heart Health Study 6000+ participants from existing cohort studies: CHS, Framingham, ARIC Men & women, mean age 63y (min 40y) In-home polysomnography & ongoing ascertainment of CVD events Aim: to test whether SDB/apnea increases risk for incident CVD events Shahar, Am J Respir Crit Care Med. 2001 163(1):19-25
Prevalent HTN by Quartiles of RDI, Age < 65 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
Prevalent HTN by Quartiles of 70% RDI, Age 65 60% 50% 40% 30% p(trend)=.004 in women, NS in men Men Women 20% 10% 0% <1.25 1.25-<4.0 4.0-<10.7 10.7+ Shahar, Am J Respir Crit Care Med. 2001 163(1):19-25
Risk of Prevalent CVD by Quartiles of RDI* 1.60 1.40 1.20 1.00 0.80 P<.0003 0.60 0.40 0.20 0.00 Q1 (ref) Q2 Q3 Q4 *Both sexes, all ages
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 - Often awakens patient - Often familial, progresses with age Etiology unknown, associated with iron deficiency Treatment - Dopamine agonists (70% respond to Sinemet 25/100 qhs) - Clonazepam 0.5-2 mg qhs
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) Indications - Unexplained hypersomnia (esp. with snoring) - Unexplained sleep-related CV findings (e.g. pulmonary hypertension) - Abnormal complex sleep behavior - Unremitting chronic insomnia that does not respond to therapy
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) 25% 25% 25% 25% sleep hygiene cognitive beha... anti histamine... anti depressan...
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, 295(25): 2851
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 (Ambien), 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 sleep, less withdrawal, little abuse potential - Rapid onset, half life 2-3 hours
An unexpected side effect
Other Drugs Melatonin (5 mg qhs, OTC) - Secreted by pineal gland, receptors in hypothalamus - Low serum levels associated with poor sleep - Not FDA approved; little data Ramelteon (Rozerem) Melatonin receptor agonist. FDA approved but no long-term safety data
Suggested Approach to Insomnia In Primary Care Acute <4 wks Insomnia Chronic >4 wks Assess trigger Consider brief tx Hypersomia or parasomnia? Evaluate and treat Primary? Sleep hygiene CBT Refer if persists Secondary cause? Treat and reassess
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 Speciality referral (sleep study) for selected patients with unexplained hypersomnia or severe insomnia
Case 68 yr. old WF with >15 yr. of poor sleep Difficulty with both initiation and maintenance of sleep. Few daytime sx. 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 do you want to know what do you want to do?