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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.

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modern management of sleep disorders
Modern Management of Sleep Disorders

Douglas C. Bauer, MD

University of California,

San Francisco

No Disclosures

introduction
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
Percent Reporting Symptoms of Insomnia

2002 ‘Sleep in America’ poll, National Sleep Foundation

trends in sleep duration
Trends in Sleep Duration

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
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
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 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
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
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
‘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

Insomnia in the Elderly
symptoms of insomnia
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

Medical Conditions That Cause Insomnia

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

Drugs That Cause Insomnia
sleep disordered breathing sleep apnea
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
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
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
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
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
Prevalent HTN by Quartiles of RDI, Age < 65

P(trend)<.001 in both men and women

Shahar, Am J Respir Crit Care Med. 2001 163(1):19-25

prevalent htn by quartiles of rdi age 6521
Prevalent HTN by Quartiles of RDI, Age  65

p(trend)=.004 in women,

NS in men

Shahar, Am J Respir Crit Care Med. 2001 163(1):19-25

other causes of hypersomnia narcolepsy
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
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
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
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
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
Insomnia Therapies
  • Which of following is superior to benzodiazepine receptor agonists for primary insomnia?1) sleep hygiene2) cognitive behavioral therapy

3) anti-histamines

4) anti-depressants (TCA, SSRI, and trazadone)

treatment of insomnia non pharmacologic
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
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
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 pharmacologic32
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
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

slide35

An unexpected

side effect…

other drugs
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
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