modern management of sleep disorders douglas c. bauer, md university of california, san francisco no...

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