UPDATE ON SLEEP DISORDERS
| GENERAL ASPECTS OF SLEEP DISORDERS —William Mariencheck, MD, Director, Sleep Center, St. Francis Hospital,
and Physician, Mid-South Pulmonary Specialists, Memphis, TN
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| Introduction: hours of sleep needed depends on age and lifestyle; 7.5 to 8.0 hr usually acceptable
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| States of sleep: rapid eye movement (REM) sleep—dream sleep; characterized by absence of muscle tone; patients
awakened quickly and easily; stages of non-REM sleep—drowsy period (stage 1) followed by longer stage of sleep
(stage 2; 50% of night); delta sleep (deep sleep; delta waves [high voltage, low frequency] seen on electroencephalography
[EEG])
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| Normal sleep cycle: sleep onset within 2 to 20 min; alternating cycles of non-REM sleep (75% of sleep time) and REM
sleep (occurs after 90-120 min); delta sleep cycles decrease early in night; REM sleep periods become longer and closer
together later in night
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| Sleep deprivation: voluntary insufficient sleep syndrome; patients develop problems due to sleep deprivation; can be
due to specific sleep disorder, resulting in excessive daytime sleepiness or common symptoms of most sleep disorders;
commonly associated with automobile accidents
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| Sleep debt: patients who miss 30 to 60 min of sleep per night accumulate debt of sleep that must be repaid; even after 8-
hr night of sleep, patients remain sleepy due to accumulated debt; controversial concept
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| Questions to ask patients: 1) “do you have to rely on a loud alarm clock to get up in the morning, and is arising a
struggle?” 2) “do you experience waves of drowsiness during the day, especially during sedentary activities?” 3) “do you
sometimes fall asleep without intending to?” 4) “has your get-up-and-go gotten-up-and-gone?” 5) “does drinking a single
beer or glass of wine seem to hit you very hard?”
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| Symptoms of sleep disorders: perception of disturbed sleep or insomnia; patients do not feel refreshed in morning;
daytime drowsiness or fatigue; loud snoring; abnormal behaviors during sleep—associated with arousals from sleep;
parasomnias (eg, teeth grinding, sleepwalking); occur often in children but become less common as child grows
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| Characteristics: loud snoring associated with apneas or hypopneas (tidal volume becomes shallow for 30-60 sec); decreased
O2 level in blood; affects blood pressure (BP) and circulation (patients at increased risk for stroke, myocardial infarction,
and heart failure); inappropriate dozing and excessive fatigue; affects 2% to 4% of population; likelihood
increases with obesity; best evaluated in sleep laboratory; treated with continuous positive airway pressure (CPAP)
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| Diagnosis: based on polysomnography and respiratory disturbance index (RDI) of >5 respiratory events (eg, hypopnea or apnea
lasting >10 sec) per hour of sleep; severity based on frequency and duration of respiratory events, degree of hypoxemia,
number of arousals, and number of awakenings; upper airway resistance syndrome—sleepiness out of proportion to RDI;
patients alter effort, but not flow rate; insert esophageal balloon to detect patient’s effort and breathing; consider comorbidities
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| Treatment: CPAP to eliminate apneas and hypopneas, abolish hypoxemia, silence snoring (requires greater CPAP pressure),
and reduce arousals; for patients who continue to have excessive daytime sleepiness, stimulant medication (eg,
modafinil [Provigil]) initial choice because of fewer side effects and complications; O2 saturation study provides good
screening data but not as precise as sleep laboratory study; improves hypertension and arrhythmias; reduces incidence of
automobile accidents; can improve mood, cognition, impotence, fibromyalgia, and gastroesophageal reflux disease
(GERD); surgery—uvulopalatopharyngoplasty (UPPP) with palate resection, tonsilloadenoidectomy, and resection of
tissue at back of throat treats snoring, but fails to treat obstructive sleep apnea >50% of time; more aggressive procedures
(eg, maxillary and mandibular advancement procedures) can be curative; weight loss, avoiding sedatives and alcohol
within 4 hr of bedtime, lying on side in bed, and good sleep hygiene important
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| Characteristics: patients complain about inability to fall asleep (sleep-onset insomnia), frequent awakenings, or waking
up too soon (sleep-maintenance insomnia); adjustment sleep disorder—most common cause of acute insomnia; affects
patients experiencing stressful event; responds to hypnotic medication; chronic insomnia affects 9% of population; symptoms
include problems with concentration and irritability; higher incidence of automobile accidents
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| Classification: primary or psychophysiologic insomnia—long history of difficulty sleeping; may have positive family
history; secondary or comorbid insomnia—more common; related to psychiatric or medical condition; associated with
poor sleep hygiene
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| Associated disorders: depression; medical and neurologic conditions; restless leg syndrome; periodic limb movement
disorder; sleep-related breathing disorders; ≈10% of patients with obstructive sleep apnea present with insomnia; circadian
rhythm disorders
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| Treatment: treat comorbid conditions; improve sleep hygiene (eg, clean bedroom); multiple sessions of cognitive behavioral
therapy; pharmacotherapy for selected patients; phototherapy for phase-shifted patients
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| Selective benzodiazepine-receptor agonists: for sleep-onset, maintenance, and early-awakening insomnia; fewer
problems with rebound and addiction; zaleplon (Sonata)—short half-life; can be used in middle of night for additional
2 to 3 hr of sleep; zolpidem (Ambien, Ambien CR)—prevents awakenings; used throughout night; eszopiclone
(Lunesta)—fewer side effects (eg, rebound or hangover); some patients complain about bad taste in mouth
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| Melatonin agonist: more potent than melatonin; may be useful to patients with sleep-onset insomnia or delayed sleep-
phase syndrome; little data available; undergoing research
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| RESTLESS LEG SYNDROME AND PERIODIC LIMB MOVEMENT DISORDER
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| Restless leg syndrome: commonly seen; ropinirole (Requip) approved by Food and Drug Administration (FDA); sensorimotor
disorder; patients experience sensations in legs described as creepy, crawly, numbness, and aching associated
with overwhelming urge to move legs; occurs at rest and relieved with walking; worse at night; rapid involuntary leg
movements during wakeful periods; 80% of patients develop periodic limb movements during sleep
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| Periodic limb movement disorder: for 15 min to 2 hr, patients have 3- to 4-sec rhythmic leg movements characterized
by flexions of ankle and knee; may or may not interfere with sleep; can cause arousals and result in impaired sleep
and daytime sleepiness; some patients have periodic limb movements without restless leg syndrome; treated same way as
restless leg syndrome; treatment effective; rule out secondary disorders (eg, iron deficiency [serum ferritin <50 µg/L]);
common in pregnancy but resolves after delivery; commonly seen in patients on dialysis and patients on certain drugs
(eg, tricyclic antidepressants or selective serotonin reuptake inhibitors [SSRIs]); restless leg syndrome and periodic limb
movements rarely seen in blacks unless on dialysis
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| Medications: ropinirole; pramipexole (Mirapex) not approved by FDA; clonazepam (Klonopin) effective hypnotic sedative
and decreases arousals during sleep, but does not stop movements as some dopamine agonists do; opiates effective;
antiepileptic drugs (eg, gabapentin) effective in patients with coexisting neuropathy or significant sensory complaints;
iron; some patients have symptoms every few nights and can be given opiate prn or levodopa and carbidopa (Sinemet;
dopamine precursor; latency 30 min); augmentation—can develop if Sinemet used nightly; medication effective initially,
but disease worsens and need for medication escalates; medication becomes ineffective, and restless leg syndrome becomes
more complex to control; not seen with newer agents (but may develop)
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| Characteristics: 2 to 3 cases per 10,000 people; excessive sleepiness; some patients have uncontrollable sleep attacks;
perform sleep study to distinguish from idiopathic hypersomnia; sleep paralysis (inability to move muscles for 30-40
sec); intrusion of REM sleep into wakefulness; cataplexy (sudden loss of muscle tone) associated with excessive sleepiness;
loss of muscle tone in jaw, arms, or knees, often with excitement
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| Diagnosis: established in sleep laboratory by multiple sleep latency test after overnight sleep test to rule out pathologic
sleep disorder; pathologically short sleep latency (≤5 min of head hitting pillow in series of 5 naps); REM sleep usually
intrudes into naps; pathogenesis complex
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| Treatment: stimulants; medications for improving sleep quality (including antidepressants); γ-hydroxybutyrate (sodium
oxybate [Xyrem]; date-rape drug) used at night to improve sleep quality and to prevent cataplexy next day
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| Characteristics: lesions around REM sites in central nervous system (CNS) identified in cats and later seen in humans;
dream-enacting behavior during REM sleep disrupts sleep in patient or bed partner; seen commonly in patients with Parkinson’s
disease or neurodegenerative processes; destroys area where REM sleep generated and allows muscle tone to
persist during REM sleep; diagnosis established by patient history; patient remembers events (eg, getting up and swinging
club)
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| Treatment: easily treated with clonazepam; doses can be titrated; other sedatives may be helpful; worsens with use of
SSRIs and venlafaxine (Effexor)
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| DOCTOR, CAN YOU HELP ME SLEEP ?—Lois Krahn, MD, Professor and Chair, Department of Psychiatry and Psychology,
Mayo Clinic College of Medicine, Scottsdale, AZ
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| What controls sleep: homeostatic pressure—“the longer we are awake, the sleepier we are”; influences adults and
children; does not exist in isolation; circadian pacemaker—24-hr cycle promotes sleep and wakefulness; in healthy
sleepers, pressure to sleep and circadian pacemaker aligned
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| Diagnosis of insomnia: patient complains about trouble sleeping, not getting enough sleep, or poor sleep quality; be
sure patient sets aside sufficient time for sleep
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| Definition of insomnia: patients remain awake ≥30 min past time they want to fall asleep; patients awaken ≥3 times during
night (1-2 times to use bathroom normal); wakefulness after trip to bathroom or in isolation; <6.5 hr of sleep; poor sleep
quality; mild insomnia resolves without treatment in 2 yr; chronic or severe insomnia less likely to resolve spontaneously
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| Conditions associated with insomnia: inability to sleep well increases at time of perimenopause due to hot flushes,
possible sleep-disordered breathing, mood and anxiety disorders, and primary insomnia; cognitive compromise; decrease
in quality of life; chronic pain syndromes (eg, fibromyalgia); psychiatric disorders; workplace issues and risk for motor
vehicle accidents; alcohol use
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| Factors that lead to insomnia: certain personality types (eg, obsessive patients); older age; perimenopause; irregular
sleep and wake cycles; poor coping skills after stressful event; self-medication with alcohol; poor choices at bedtime;
poor sleep hygiene; conditioning (patients believe they will never sleep again); consider hot flushes, patient history, snoring
bed partner, medical illnesses (eg, thyroid disease, urinary frequency), primary sleep disorders (eg, restless leg syndrome),
caffeine use, diabetes, and heart failure; psychiatric disorders—depression; mood and anxiety disorders; 90%
of patients in psychiatric in-patient units have insomnia; positive dexamethasone-suppression testing in patients with primary
insomnia without depression suggests alteration of hypothalamic-pituitary-adrenal (HPA) axis; study found people
who do not sleep well generally perceive events as more stressful; stress-related insomnia linked to depression; persistent
insomnia may be indicator that depression or anxiety disorder not fully treated and may recur; aggressive management of
mood or anxiety disorder while treating insomnia may be helpful
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| Treatment: address sleep as separate issue in patients with secondary or primary insomnia; goals—improve sleep quality;
enhance daytime alertness and cognition; decrease pain; augment other therapies being used for depression; decrease arousals
and awakenings at night; take time with patients and try to obtain as much information about sleep environment and attitude
as possible; separate insomnia from more significant conditions; provide sleep education; refer to sleep specialist if
indicated
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| Causes: caffeine—in bottled water and candy; patients should consider quantity and timing (eg, after dinner) of consumption;
alcohol—metabolized quickly; does not promote good quality sleep; activities—intellectually or physically
stimulating activities; environmental disruptions—snoring bed partner; pets on bed
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| Helpful techniques for patients: advise patients to go to bed later than usual and to turn attention to relaxing activity
(eg, reading) if unable to sleep; sleep restriction—reduce time in bed severely (eg, to 4.0 hr); gradually extend period to
7.5 hr; patients regain confidence in body’s ability to sleep; belief system—patients convinced body broken; use cognitively
oriented therapy to help patients change expectations; reassure patients that 1 to 2 nights of inadequate sleep not
catastrophic
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| Psychotherapy: data show cognitive behavorial therapy and hypnotic medication beneficial in decreasing time to fall
asleep; can reduce amount of medication needed
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| Medications: long-acting agents—flurazepam (Dalmane; detected 6 wk after dose); may cause hangover effects, cognitive
impairment, or increased risk for falls; newer short-acting agents—triazolam (Halcion) causes confusion and
amnesia (withdrawn from market in United Kingdom; similar issues with zolpidem); antidepressants—useful for patients
with addictions; fairly long half-life; consider cost (trazodone good choice); duration of action—Ambien ER released
continuously during night; Sonata short-acting and helpful for patients who awaken during night; ramelteon
(melatonin-receptor agonist) helps patients fall asleep, but not as helpful at keeping patients asleep; intermediate-acting
agents (eg, Lunesta) help patients fall asleep and stay asleep; recent studies found Ambien and Lunesta for 6 mo safe and
efficacious without tolerance and significant side effects; Lunesta, ramelteon, and Ambien CR approved for longer-term
use; consider sleep specialist if medications ineffective
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Educational Objectives
| The goal of this program is to educate the listener about the causes and management of sleep disorders. After hearing and
assimilating this program, the participant will be better able to:
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 | 1. Choose effective therapy for obstructive sleep apnea.
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| 2. Distinguish restless leg syndrome from periodic limb movement disorder.
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| 3. List characteristics of narcolepsy.
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| 4. Counsel patients about techniques for relieving insomnia.
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| 5. Select appropriate sleep agents for patients with insomnia.
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Discussed on This Program
Clonazepam [Klonopin]
Ferrous fumarate [Feostat, Ferretts, Ferro-Sequels, Nephro-Fer]
Flurazepam HCl [Dalmane]
Levodopa and carbidopa [Parcopa, Sinemet-10/100, Sinemet-25/100, Sinemet-25/250, Sinemet CR]
Modafinil [Provigil]
Pramipexole [Mirapex]
Ramelteon [Rozerem]
Ropinirole HCl [Requip]
Sodium oxybate [Xyrem]
Trazodone HCl [Desyrel, Desyrel Dividose]
Triazolam [Halcion]
Venlafaxine HCl [Effexor, Effexor XR]
Zaleplon [Sonata]
Zolpidem tartrate [Ambien, Ambien CR]
Suggested Reading
Culebras A: Update on idiopathic narcolepsy and the symptomatic narcolepsies. Rev Neurol Dis 2:203, 2005; Dinges
DF: Can habitual sleep duration harbor sleep debt? Sleep 28:1209, 2005; Ferri R et al: New approaches to the study of
periodic leg movements during sleep in restless legs syndrome. Sleep 29:759, 2006; Gagnon JF et al: Rapid-eye-movement
sleep behaviour disorder and neurodegenerative diseases. Lancet Neurol 5:424, 2006; Hornyak M et al: Periodic
leg movements in sleep and periodic limb movement disorder: Prevalence, clinical significance and treatment. Sleep Med
Rev 10:169, 2006; Kim H et al: Subjective daytime sleepiness: dimensions and correlates in the general population.
Sleep 28:625, 2005; Krahn LE: Psychiatric disorders associated with disturbed sleep. Semin Neurol 25:90, 2005;
Krahn LE: Sleep disorders. Semin Neurol 23:307, 2003; Lin SW et al: A comparison of the long-term outcome and
effects of surgery or continuous positive airway pressure on patients with obstructive sleep apnea syndrome. Laryngoscope
116:1012, 2006; Maher MJ et al: Sleep disturbances in patients with post-traumatic stress disorder: epidemiology, impact
and approaches to management. CNS Drugs 20:567, 2006; Montplaisir J et al: New trends in restless legs syndrome
research. Sleep Med Rev 10:147, 2006; Ohayon MM: Severe hot flashes are associated with chronic insomnia.
Arch Intern Med 166:1262, 2006; Sforza E et al: Event-related potentials in patients with insomnia and sleep-related
breathing disorders: evening-to-morning changes. Sleep 29:805, 2006; Sivertsen B et al: Cognitive behavioral therapy
vs zopiclone for treatment of chronic primary insomnia in older adults: a randomized controlled trial. JAMA 295:2851,
2006; Szabadi E: Drugs for sleep disorders: mechanisms and therapeutic prospects. Br J Clin Pharmacol 61:761, 2006;
Wise MS: Objective measures of sleepiness and wakefulness: application to the real world? J Clin Neurophysiol 23:39,
2006; Wu R et al: Comparison of sleep condition and sleep-related psychological activity after cognitive-behavior and
pharmacological therapy for chronic insomnia. Psychother Psychosom 75:220, 2006.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial relationship
with the manufacturer or provider of any commercial product or service discussed. For this issue, the faculty reported
nothing to disclose.
Dr. Mariencheck spoke in Memphis, TN, on February 28, 2006, at the 39th Annual Review Course for the Family Physician,
presented by the University of Tennessee Health Science Center, College of Medicine. Dr. Krahn was recorded in
Phoenix, AZ, at Clinical Reviews 2006: A Primary Care and Internal Medicine Update, presented April 26-29, 2006,
by Mayo Clinic College of Medicine at Scottsdale, AZ. The Audio-Digest Foundation thanks the speakers and the sponsors
for their cooperation in the production of this program.
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