SLEEP DISORDERS
From the University of California, San Francisco, School of Medicine’s 35th Annual Advances in
Internal Medicine
David M. Claman, MD, Clinical Professor, Department of Medicine, and Director, Sleep Disorders Center,
University of California, San Francisco, School of Medicine
| Sleep deprivation: most common sleep disorder; as individual gets older, less able to handle sleep deprivation;
when obtaining sleep history, important to know what time patient goes to bed and gets up, and how many hours of
sleep patient getting; in truck drivers, sleep deprivation more common than sleep apnea; also important to know
how often patient napping during daytime or accidentally dozing off during day
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| Insomnia: most common sleep complaint; approximately one-third of population in United States has occasional or
chronic insomnia, according to surveys taken in any particular year; what insomnia means differs with individual;
may mean inability to fall asleep at beginning of night (sleep-onset insomnia), early-morning awakening (consider
depression and anxiety), or waking up periodically throughout night (due to, eg, chronic pain, respiratory disorders,
prostatism); must ask for details; case—man, 40 yr of age, complained of sleep-onset insomnia; worries about
sleep at night and takes 2 to 3 hr to fall asleep; once asleep, able to sleep through night; naps at lunch or after work
to “catch up”; has occasional alcohol and drinks coffee in morning; first intervention for insomnia should be behavior
modification (not medication); start with sleep hygiene and prevention
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| Differential diagnosis of insomnia: first question whether insomnia sleep-onset type or sleep-maintenance type;
causes—include psychiatric or psychologic; in those with chronic insomnia, one-fourth to one-third have some degree
of depression or anxiety as major contributor; in those with medical illnesses (eg, chronic pain, respiratory issues),
focus on primary medical problem (eg, relieving pain); more medical conditions person has, more prevalent
insomnia becomes; drugs (prescription or illicit), caffeine, and alcohol affect sleep; ask patient when he or she
drinks caffeinated beverages (caffeine stays in system 6-8 hr); for some people, alcohol near bedtime induces sleep,
but tends to become cause of sleep-maintenance insomnia; psychophysiologic insomnia—psychologic reaction
that causes physiologic response (eg, worry leading to tension that keeps person awake); treatment spending less
time in bed and focusing on relaxation techniques; eliminating naps; circadian rhythm issues—another cause of insomnia;
jet lag predictable and temporary; shift work (because ongoing) causes more problems
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| Sleep hygiene: most important; refers to behavior modifications designed to encourage better sleep and avoid
things detrimental to sleep; keep regular bedtime and wake-up time; sleep restriction often helps people to sleep
better in short term; keep bedroom quiet, comfortable, and dark (conducive to sleep); find something relaxing to do
10 to 30 min (eg, reading, listening to soft music, taking bath or shower) before bedtime; regular exercise helps (but
not too close to bedtime); avoid—naps, especially for persons with insomnia; lying in bed feeling worried, anxious,
or frustrated (makes patient more tense and awake); lying awake in bed for long periods; alcohol, caffeine,
and nicotine; cell phone, computer, and television
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| Hypnotics and other sedatives: zolpidem (Ambien) has short half-life; zaleplon (Sonata) has extremely short
half-life (can wake up at 2:00 AM and take dose); rare reports of transient amnesia from triazolam (Halcion);
temazepam (Restoril) has longer half-life; eszopiclone (Lunesta)—S-isomer of zopiclone; 1-, 2-, and 3-mg doses;
half-life longer; 6-mo randomized placebo-controlled trial showed persistent benefit; approved for long-term use
by Food and Drug Administration (FDA); Ambien CR also has long-term indication; both medications tend to be
better for sleep-maintenance insomnia or early-morning awakening; ramelteon (Rozerem)— melatonin receptor
agonist; half-life 2 to 5 hr; 8-mg dose; takes 7 to 10 days before effect achieved (geting patient to sleep; warn patient);
speaker believes better for drug-naive patient (has more patience to wait for benefit); cannot be combined
with fluvoxamine, due to hepatic interaction; not schedule drug (all others Schedule 4 medications); for sleep maintenance,
use shorter-acting medications (eg, over-the-counter [OTC] zolpidem); other sedatives—diphenhydramine
(eg, Benadryl) and acetaminophen and diphenhydramine (Tylenol PM) most commonly used medications for sleep;
benzodiazepines—help with anxiety; have active metabolites that stay in system (more habit-forming);
trazodone—sedating antidepressant; used by many people for years; still has role; available as generic and inexpensive;
some people report hangover drowsiness; nonsedating antidepressants—to help patient worry less and
cope better with stress; agents most commonly used by speaker include paroxetine and citalopram; summary for
insomnia—start with sleep hygiene; reserve hypnotic medications for times of clear need; sleep hygiene interventions
essential and provide longer duration of benefit
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| Leg movements at night: periodic kicking activity during night detected on polysomnography; hypnic
myoclonus—“sleep starts”; normal; restless legs syndrome (RLS)—awake sensation of discomfort; insomnia most
common symptom; most people have kicking activity on polysomnography; can initiate trial of treatment based on
clinical impression; periodic limb movements of sleep (PLMS)—usually leg kicking (or arm); usually sleep study
diagnosis to ensure primary problem; primary or secondary phenomenon; treatment—RLS worse with iron deficiency;
if serum ferritin in low–normal range (<50 ng/mL), iron replacement recommended to raise ferritin to >100
ng/mL; iron involved in dopamine metabolism; RLS and PLMS worsen with antidepressants; if medications necessary,
first choice dopaminergic agents; pramipexole (Mirapex) and ropinirole (Requip) FDA-approved for this; single
dose at bedtime; carbidopa-levodopa (Sinemet) available as generic medication, but lasts only 3 to 4 hr;
clonazepam—also used for both conditions; used less commonly now, but helpful if restlessness causing insomnia;
gabapentin (Neurontin) effective for RLS with pain and discomfort; opiates also used, but effect nonspecific (similar
to clonazepam)
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| Sleep apnea: airflow initially present but stops; effort from rib cage and abdomen shows muscle activity trying to
generate air flow; clearly, obstructive apnea (as opposed to central apnea) occurs in presence of effort; for most
adults without history of heart failure (increases chances of Cheyne-Stokes respiration), 95% of sleep apnea obstructive;
apnea followed by O2 desaturation and ends with interruption in sleep (electroencephalography [EEG]
arousal); patient usually tired and sleepy next day from interrupted sleep quality; hypopneas—shallow breathing
events in which airflow still present but clearly diminished; effort at breathing present; followed by O2 desaturation
and EEG arousal, interrupting sleep quality; apnea-hypopnea index (AHI)—average number of episodes per hour;
benchmark when looking at sleep study; in apnea, breathing stopped for 10 sec; in hypopnea, shallow breathing for
10 sec; classically associated with 4% desaturation; also called respiratory disturbance index (RDI); average number
of respiratory events per hour of sleep; in Medicare population, if AHI >15, patients qualify for continuous positive
airway pressure (CPAP) therapy; if patient in mild category (5-15 episodes/hr) and has symptoms attributable
to sleep apnea (eg, sleepiness during daytime, hypertension, history of heart failure or stroke), patient could qualify
for treatment, depending on insurance provider; Wisconsin Sleep Cohort Study—ongoing epidemiologic and prospective
study; 600 working subjects; defined middle age as 30 to 60 yr; performed overnight sleep studies and
characterized breathing pattern during sleep; for prevalence study, obstructive sleep apnea (OSA) defined as combination
of AHI >5 and hypersomnolence (excessive daytime sleepiness) on written questionnaires; in middle-aged
women in Wisconsin, 9% had AHI >5 and 22% complained of excessive sleepiness; prevalence in women 2%; in
men in Wisconsin, 24% had abnormal AHI (>5); higher prevalence in men, but only 15% of men complained of
daytime sleepiness; overall, 9% to 24% have sleep-disordered breathing, and 2% to 4% have clinical OSA on basis
of abnormal breathing and subjective daytime sleepiness; clinical predictors—from Sleep Heart Health Study (ongoing);
data show predictors include male sex, advancing age, higher body mass index (BMI), and neck circumference
(may be better measure of risk for sleep apnea than truncal obesity; airway more collapsible as neck gets
bigger); any measure of obesity predictive; snoring present in almost all people with sleep apnea, unless they had
previous uvulopalatopharyngoplasty (UPPP), but not specific; presence of apnea predictive; male sex, older age,
overweight, snoring, and witnessed apnea predicted AHI >15; other clinical predictors published in New England
Journal of Medicine include daytime sleepiness, snoring, drowsiness while driving, obesity, and hypertension; parameters
not specific
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 | Conservative measures: weight loss—has role, since most patients with sleep apnea obese; losing 10% of body
mass reduces AHI by ≈25% (10% gain in body mass increases AHI by similar amount); avoidance of alcohol before
bed—alcohol relaxes airway-dilating muscles during sleep; postural training—sleeping on side improves
sleep apnea; promoting nasal patency—in patients with seasonal or perennial allergic rhinitis; breathing through
mouth worsens snoring and sleep apnea; allergy treatments help make CPAP more effective
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| Mechanical methods: CPAP—most consistently effective treatment; lower pressure adjustments, eg, C-Flex (expiratory
pressure relief) or Bilevel CPAP (BiPAP) may be helpful; problem with compliance; oral or dental
appliances—pull jaw forward; fit behind lower incisors and in front of upper incisors (has effect of pulling
tongue forward to increase breathing space posteriorly); best ones individually fitted by dentists and adjustable;
concern about temporomandibular joint symptoms; for patients with severe sleep apnea, CPAP recommended;
study—showed highest compliance rate with CPAP if AHI >30 (severe sleep apnea); moderate sleep apnea
(AHI 15-30 ) has moderate compliance; mild sleep apnea has lower compliance; improvement of daytime sleepiness
motivates compliance; Spanish study—observational study of 1300 men with control group; those with
AHI <5 labeled “simple snorers”; those with severe sleep apnea (AHI >30) always given CPAP; those with mild
to moderate sleep apnea and daytime sleepiness or heart failure given CPAP; severe sleep apnea group had
higher rate of fatal and nonfatal cardiovascular events than other groups, and CPAP treatment did not reduce this
risk; data show that severe untreated sleep apnea has more associated cardiovascular risk
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| Surgical treatment: nasal surgery—rarely curative; indicated in nasal obstruction; UPPP—most common surgery;
reduces AHI in only 50% of patients; not first-line treatment; performed in patients unable or unwilling to use
CPAP; snoring procedures—laser, radiofrequency, or Pillar procedures; no documented effect on sleep apnea;
mandibular advancement—available in specialized centers; pulling jaw forward for genioglossus advancement or
performing osteotomies on mandible and maxilla; success rate for improving sleep apnea 75% to 95%;
tracheotomy—much less frequently performed after CPAP became available; still gold standard of treatment
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| Questions and answers: not lying in bed for long periods—applies for sleep-onset and sleep-maintenance insomnia;
individual variations; dosage of gabapentin for RLS—speaker uses 300-mg dose at bedtime; for elderly patients,
start with 100 mg; if 300 mg inadequate, can increase to 600 mg; melatonin for insomnia and jet lag—used
for long time; available OTC; very short acting; not regulated by FDA; not effective for sleep maintenance;
ramelteon—more expensive but has better quality-control measures; binds receptor more actively than melatonin;
no comparison studies with melatonin; follow-up for patients on CPAP for sleep apnea—determine whether daytime
sleepiness better and any change in weight; speaker asks for sleeping partner report on whether snoring disappears
completely when mask on (desired end point) and whether breathing pattern completely regularized, without
episodes of apnea or snoring; role for repeated sleep studies—not on routine basis if symptoms better and patient
not snoring through mask; yes, under certain circumstances (if sleepiness recurs or worsens, patient has apnea even
with mask on, or with any significant weight change); supplements available in health food stores—no studies
looking at tryptophan and valerian as treatment for insomnia; placebo arm of insomnia treatment studies always
shows improvement during 1, 2, or 6 mo of treatment trial; in general, most people feel insomnia waxing and waning
condition (worsening with stress and improving when away from stress); placebo treatment often helpful; supplements
not regulated, so caution needed; efficacy of C-Flex and bilevel CPAP—classically, CPAP had steady
pressure; only 10% to 20% of patients have such high CPAP pressure that bilevel treatment better; bilevel CPAP
gives higher pressure on inspiration and lower pressure on expiration; difficulty breathing out against pressure
causes discomfort with CPAP; 2 companies manufacture devices that lower CPAP pressure during exhalation, promoting
idea that this improves compliance and treatment benefit (no data to support); automatic CPAP devices
available; still working to make CPAP more comfortable
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Suggested Reading
American Academy of Family Physicians: Information from your family doctor. Insomnia: how to get a good
night's sleep. Am Fam Physician 72:1309, 2005; Basner RC: Continuous positive airway pressure for obstructive
sleep apnea. N Engl J Med 356:1751, 2007; Basner RC: Shift-work sleep disorder–the glass is more than half
empty. N Engl J Med 353:519, 2005; Bradley TD et al: Continuous positive airway pressure for central sleep apnea
and heart failure. N Engl J Med 353:2025, 2005; Craig TJ et al: The correlation between allergic rhinitis and
sleep disturbance. J Allergy Clin Immunol 114:S139, 2004; Garcia-Borreguero D et al: Treatment of restless legs
syndrome with gabapentin: a double-blind, cross-over study. Neurology 59:1573, 2002; Hallowell PT et al: Potentially
life-threatening sleep apnea is unrecognized without aggressive evaluation. Am J Surg 193:364, 2007; Hening
WA: Current guidelines and standards of practice for restless legs syndrome. Am J Med 120:S22, 2007; Johnson
MW et al: Ramelteon: a novel hypnotic lacking abuse liability and sedative adverse effects. Arch Gen Psychiatry
63:1149, 2006; Kono M et al: Obstructive sleep apnea syndrome is associated with some components of metabolic
syndrome. Chest 131:1387, 2007; Lin CC et al: Effect of uvulopalatopharyngoplasty on work of breathing during
wakefulness in obstructive sleep apnea syndrome. Ann Otol Rhinol Laryngol 116:271, 2007; Mulgrew AT et al:
Diagnosis and initial management of obstructive sleep apnea without polysomnography: a randomized validation
study. Ann Intern Med 146:157, 2007; Patil SP et al: Adult obstructive sleep apnea: pathophysiology and diagnosis.
Chest 132:325, 2007; Pennestri MH et al: Nocturnal blood pressure changes in patients with restless legs syndrome.
Neurology 68:1213, 2007; Phillips B et al: Prevalence and correlates of restless legs syndrome: results from
the 2005 National Sleep Foundation Poll. Chest 129:76, 2006; Silber MH et al: An algorithm for the management
of restless legs syndrome. Mayo Clin Proc 79:916, 2004; Summers MO et al: Recent developments in the classification,
evaluation, and treatment of insomnia. Chest 130:276, 2006; Thurnheer R: Diagnosis of obstructive sleep
apnea: alternatives to polysomnography. Chest 130:1625; author reply 1625, 2006; Virkkula P et al: Snoring is not
relieved by nasal surgery despite improvement in nasal resistance. Chest 129:81, 2006; Wessell AM et al: Eszopiclone
(Lunesta) for treatment of transient and chronic insomnia. Am Fam Physician 71:2359, 2005.
Educational Objectives
| The goal of this program is to improve the management of sleep disorders. After hearing and assimilating this program,
the clinician will be better able to:
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| 1. Identify the types of insomnia and recognize the causes.
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| 2. Recommend sleep hygiene measures and prescribe medications to improve sleep.
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| 3. Distinguish restless legs syndrome from periodic limb movements of sleep.
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| 4. Prescribe appropriate conservative and mechanical treatments for sleep apnea.
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| 5. Describe surgical measures for treating sleep apnea.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty members to disclose
relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any
identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary
business or commercial interest. For this program, the faculty reported nothing to disclose.
Acknowledgements
Dr. Claman was recorded at 35th Annual Advances in Internal Medicine, held May 21-25, 2007, in San Francisco,
CA, and sponsored by the University of California, San Francisco, School of Medicine. The Audio-Digest Foundation
thanks Dr. Claman and the sponsor for their cooperation in the production of this program.
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