Modern Management of Sleep Disorders

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Modern Management of Sleep Disorders

• Douglas C. Bauer, MD
• University of California,
• San Francisco

No Disclosures
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Introduction

• 40 million Americans suffer from sleep disorders
• 95 are undiagnosed and untreated
• Prevalence of sleep disorders increases with age

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Percent Reporting Symptoms of Insomnia
2002 Sleep in America poll, National Sleep
Foundation
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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
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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

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Van Cauter LaboratoriesSleep 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

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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?

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Definitions

• Insomnia (insufficient or poor quality sleep)
• Hypersomnia (excessive daytime sleepiness)-
  Sleep disordered breathing/sleep apnea-
  Narcolepsy
• Parasomnia (coordinated motor activity)-Restless
  leg syndrome

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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

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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

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Insomnia in the Elderly

• High prevalence (gt 50)
• More common in women than men
• Often secondary to a primary sleep disorder
• Commonly associated with psychiatric disorders or
  depression

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Symptoms of Insomnia

• Difficulty initiating or maintaining sleep
• Wake after sleep onset
• Early morning awakening
• Awakening not rested

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Medical Conditions That Cause Insomnia

• Primary sleep disorder
• Hyperthyroidism
• Arthritis
• Chronic renal failure
• Chronic lung disease

• Heart failure
• Neurological disorders
• Dementia/AD
• Parkinsons disease

Note sleep disordered breathing is not a common
cause of insomnia
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Drugs That Cause Insomnia

• Alcohol
• CNS stimulants
• Beta-blockers
• Bronchodilators
• Calcium channel blockers
• Corticosteroids

• Decongestants
• Stimulating antidepressants
• Thyroid hormones
• Nicotine

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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

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Definition of Sleep Apnea/SDB

• Apnea cessation of respiration
• Hypopnea partial decrease (gt50) of respiration
• Duration ?10 seconds
• ? Respiratory Disturbance Index (RDI)
• apneas hypopneas / hour slept
• typical cutpoint is RDI ? 15

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Prevalence of Sleep Disordered Breathing

• Heavily dependent on definition used
• 2-4 in younger adults (20-60 yrs)
• gt 10 in elderly

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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

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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
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Prevalent HTN by Quartiles of RDI, Age lt 65
P(trend)lt.001 in both men and women
Shahar, Am J Respir Crit Care Med. 2001
163(1)19-25
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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
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Odds for Prevalent CVD by Quartiles of RDI
Plt.0003
Both sexes, all ages
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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

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ParasomniasRestless 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

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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

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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

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Evaluation of Sleep DisordersSleep 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

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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)

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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

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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
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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?

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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 (lt2 wk) may be
  helpful in some patients
• Alternatives to benzodiazepines?

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(No Transcript)
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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

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An unexpected side effect
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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

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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