Download Modern Management of Sleep Disorders

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
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
Trends in Sleep Duration
1
Year
Avg Hours of Sleep
19101
9
19751
7.5
20002
6.9
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
Drugs That Cause Insomnia
• Alcohol
• Decongestants
• CNS stimulants
• Beta-blockers
• Stimulating
antidepressants
• Bronchodilators
• Thyroid hormones
• Calcium channel
blockers
• Nicotine
• Corticosteroids
Sleep-Disordered Breathing
(Sleep Apnea)
• Symptoms include loud snoring,
choking, gasping during sleep
• 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
45%
40%
P(trend)<.001 in
both men and
women
35%
30%
25%
Men
Women
20%
15%
10%
5%
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
Prevalent HTN by Quartiles of
RDI, Age  65
70%
60%
p(trend)=.004 in
women,
50%
NS in men
40%
Men
Women
30%
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
Odds for Prevalent CVD by
Quartiles of RDI*
1.60
1.40
1.20
1.00
P<.0003
0.80
0.60
0.40
0.20
0.00
Q1 (ref)
Q2
Q3
*Both sexes, all ages
Q4
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
- Unexplained sleep related CR
symptoms (e.g. pulmonary hypertension)
- Abnormal complex sleep behavior
- Unremitting chronic insomnia that
does not respond to therapy
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
• Cognititive 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)
• Anxiety, panic
- Benzodiazepines (suppress REM and
non REM stage 3 and 4)
• Idiopathic?
Treatment of Insomnia:
Pharmacologic
• Problems with benzodiazepine therapy
- Habit forming
- Tachyphylaxis
- Suppression of REM sleep
- Other side effects (cognitive, falls)
• Short-term 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, no 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 associated
with 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, nonpharmacologic treatment often
successful
• Primary care providers can diagnose and
treat most patients with insomnia
• Speciality referral (sleep study) for
selected patients with SDB or
hypersomnia