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