modern management of sleep disorders douglas c. bauer, md university of california, san francisco no...
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Modern Management of Sleep Disorders
Douglas C. Bauer, MD
University of California,
San Francisco
No Disclosures
Introduction
• 40 million Americans suffer from sleep disorders
• 95% are undiagnosed and untreated
• Prevalence of sleep disorders increases with age
Percent Reporting Symptoms of Insomnia
0%
5%
10%
15%
20%
25%
30%
35%
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
19101 9
19751 7.5
20002 6.9
1 Webb WB et al. Bull Psychom Soc 1975; 6: 47-48
2 National Sleep Foundation. 2000 Sleep in America poll
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
• Until very recently, sleep loss was not believed to have any impact on human health
Van Cauter Laboratories:Sleep Debt Study*
• 11 healthy college-aged men
• Sleep restriction (4 hours per night) for 6 consecutive 24-hour periods
• Measured endocrine function before and after sleep restriction
* Spiegel et al, Lancet, 1999
Sleep Debt Study Results & Conclusions
Sleep restriction results in: Glucose tolerance, thyrotropin Evening cortisol levels Activity of sympathetic nervous system
Conclusions: – Sleep debt has a harmful impact on endocrine function and carbohydrate
metabolism.– These effects are similar to those seen in normal aging.
– Sleep debt may increase the severity of age-related chronic diseases including obesity, diabetes, CVD… and osteoporosis?
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%)
• More common in women than men
• Often secondary to a primary sleep disorder
• Commonly associated with psychiatric disorders or depression
Symptoms of Insomnia
• Difficulty initiating or maintaining sleep
• Wake after sleep onset
• Early morning awakening
• Awakening not rested
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
Drugs That Cause Insomnia
• Alcohol
• CNS stimulants
• Beta-blockers
• Bronchodilators
• Calcium channel blockers
• Corticosteroids
• Decongestants
• Stimulating antidepressants
• Thyroid hormones
• Nicotine
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/SDB
• 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
0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
<1.25 1.25-<4.0 4.0-<10.7 10.7+
Men
Women
Shahar, Am J Respir Crit Care Med. 2001 163(1):19-25
P(trend)<.001 in both men and women
Prevalent HTN by Quartiles of RDI, Age 65
0%
10%
20%
30%
40%
50%
60%
70%
<1.25 1.25-<4.0 4.0-<10.7 10.7+
Men
Women
p(trend)=.004 in women,
NS in men
Shahar, Am J Respir Crit Care Med. 2001 163(1):19-25
Odds for Prevalent CVD by Quartiles of RDI*
0.00
0.20
0.40
0.60
0.80
1.00
1.20
1.40
1.60
Q1 (ref) Q2 Q3 Q4
P<.0003
*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
• Treatment- Sinemet 25/100 qhs (70% respond)- 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
Insomnia Therapies
• Which of following is superior to benzodiazepine receptor agonists for primary insomnia?1) sleep hygiene2) cognitive behavioral therapy3) anti-histamines4) anti-depressants (TCA, SSRI, and trazadone)
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• Idiopathic?
Treatment of Insomnia: Pharmacologic
• Problems with anti-histamines: anti-cholinergic, 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 (OTC)- Secreted by pineal gland, receptors in hypothalamus- Low serum levels associatedwith poor sleep- Not FDA approved; safety?
• Ramelteon (Rozerem)– Melatonin receptor agonist. FDA approved
but no long-term safety data
Conclusions• Sleep disorders are common• Associated with significant morbidity• Drugs treatment over utilized, non-
pharmacologic 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
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