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The Tired Student…
Fatigue and Sleep Disorders in
college students.
David S. Reitman, MD, MBA
George Washington University
Washington, DC
Objectives
• Define “fatigue” and “sleep disorder.”
• Understand Sleep Physiology as an
active biological process
• Review the clinical workup of a
fatigued/sleep disordered student
• Use cases to discuss major
diagnoses and treatment modalities
What is “Fatigue”
Three Main types:
• Weakness
• Inability to initiate activity
• Decreased ability to maintain activity
• Mental Fatigue
• Problems with concentration, memory,
emotions
Epidemiology of Fatigue
• Prevalence: ~7% of Adults
• 7 million office visits annually
• Chronic Fatigue (not CFS):
• Medical or Psych Dx cause fatigue in 67%
• Of patients with fatigue 60-80% have psych
diagnosis.
Causes of Fatigue and sleep problems in
college students (broad categories)
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Infection
Inflammatory
Sleep disorders
Neoplasm
Nutritional
Endocrine
Cardiovascular
Neurologic
• Psychiatric
Disorders
• Stress
• Substance abuse
• Medications
• Caffeine
Role of the College Health
Professional
Physiologic / Psychologic Disorder
vs
Environmental Disorder
Vs
Sleep Disorder
Sleep in College Students
• Recommendations (National Sleep Foundation):
8hr 30m – 9hr 15min
• The reality (Lund et al, 2009):
7.02 hrs mean sleep time
(25% of students: <6.5 hrs)
(only 29% get 8+ hrs)
Sleep times and Rise times
National Sleep Foundation 2006
Sleep Bedtimes in College Students
• Vela-Bueno et al 2008
How does this affect College Students?
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Perceived sleep debt= (Desired sleep) – (Actual Sleep obtained)
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Vela-Bueno, 2007
Back to the basics……
SLEEP PHYSIOLOGY 101
3 Principle Sleep Regulators
1. Circadian Rhythms
2. Homeostatic Drive
3. Ultradian Rhythms
Circadian Rhythm
Circadian Rhythms
• Allow organisms to anticipate a 24
hour light-dark cycle.
• Human Circadian rhythm is 24.2 hrs.
• Requires adjustment
• Accounts for sleep differences
• Infants/Toddlers
• Children
• Adolescents
• Balanced by Homeostatic Drive
Homeostatic Sleep Drive
• Sleep drive reflects time period of
wakefulness
Ultradian Rhythms
• Occur within the context of sleep.
• Common Sleep Myths
– “It’s a time for the brain to rest”
NO!!!!!
• Very active process
• Brain extremely involved
– “Sleep is a static process once you fall
asleep”
NO!!!!
• Sleep is a dynamic process
• REM vs NREM
Sleep Architecture
• Sleep Cycles 90 min-2 hrs
• Normal Sleep must follow these
cycles
NREM Sleep
• Stage 1:
– Transition to sleep from wakefulness
– 2-5% of sleep time in young adults
• Stage 2:
– Slowing frequency on EEG
– 40-50% of sleep time in young adults
NREM Sleep
• Stage 3 / Stage 4
– Deepest sleep. Hardest to wake.
– May serve a restorative function
• Eg. Energy levels, wakefulness
– 20% sleep time in young adults
REM Sleep
Probably functions for Memory Consolidation
Key Features:
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Rapid Eye movements
2.
Active, fast frequency EEG
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3.
(similar to wakefulness)
Virtual Paralysis of voluntary muscles (except EOMs)
REM Sleep Characteristics (ANS)
• Predominantly Vagal
• Sympathetic Bursts
• Associated with body-wide sympathetic
events
»  BP
»  HR
»  RR
• Can be accompanied by long asystoles
Putting it all together
Question…
• Overnight “working?”
Back to the clinic….
Diagnosing the problem: History
• Define “fatigue”
• Frequency of
Fatigue?
• Onset?
• Abrupt
• Gradual
• Related to illness
• Daily Pattern
• Factors that
alleviate or worsen
• Impact on Daily life
• History of Medical
issues
• History of Psych
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Depression
Anxiety
Bipolar
Somatoform d/o’s
• Recent stresses or
changes
• Medications
• Drug/EtOH use
• Exercise
Diagnosis- Physical Examination
• General appearance
• Agitation?
• Body Habitus
• Eye Exopthalmos
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Thyroid exam
Oropharyngeal exam
Cardio-respiratory examination
Neurologic evaluation
• Cognitive abilities
• Tremors
Lab Studies
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Tailor Studies to your suspicions….
CBC
ESR
Comprehensive Metabolic Panel
TSH
CK (if muscle weakness suspected)
Other ID workup if indicated
Case #1: Greg
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19 y.o. College Sophomore.
Complains about “Insomnia.”
Falls asleep at 3 a.m.
Gets up at 8 a.m. for a 9 a.m. class
Drinks coffee to stay awake
2-3 hour nap after lunch
Weekends- out with friends until 3
a.m., then sleeps until 1 p.m.
Diagonosis????
Circadian Rhythm Disorders
• Delayed sleep phase syndrome
(DSPS)
• Disconnect between sleep times and
societal demands
• Seen in 17% College Students
• Mean age 20 yrs
• Different from “Motivated Sleep Phase
Delay” (non-volitional)
• Sleep Architecture?
Maintained
Delayed Sleep Phase Syndrome
(DSPS)
Delayed Sleep Phase Syndrome –
Treatment
• Treatments
• Chronotherapy
» Gradual (2 hour increments)
» Dramatic (24 hour)
• Bright Light therapy
• Melatonin
– ? Long term safety
– Give 0.3mg-3 mg 5-7 hours prior to desired sleep
onset
Sleep Hygiene
• Caffeine Intake
• Pre-bedtime activity
• Studying
• Computer / TV
• Exercise (early)
• Weekend Sleep patterns
• Eating before bed
• EtOH
• Stress Management
• Naps…
Napping…
The good, the bad, and the sleepy
Case #2: Peter
• “My girlfriend won’t sleep with
me…because I snore!”
• 20 yo. Average build (not overweight)
• No significant health problems in past
• States that he tries to get 8-9 hours of
sleep/night. Rarely naps.
• But, complains about “feeling tired”
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<8: Normal
8-11 mild sleepiness
12-15 moderate sleepiness
15-18 severe sleepiness
Case#2 :
What data do you want to know?
• Polysomnography
Obstructive Sleep Apnea Syndrome Anatomy
• Compromised upper airway patency
• REM sleep Atonia!
Obstructive Sleep Apnea Syndrome
• Risks:
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Age 18+
African Americans
Obesity
Craniofacial abnormalities
Current smokers (3X)
Nasal Congestion (2X)
Snorers (7X)
Obstructive sleep Apnea
Manifestations
• Short Term
– Daytime Sleepiness
– Poor Concentration
– Increased errors and
accidents
– Headaches and
somatic complaints
• Long Term
– Hypertension
– Pulmonary Htn.
• Cor Pulmonale
– Sudden Cardiac
arrythmia
OSA Treatments
• Behavioral
• Weight Loss
• Sleep Position
• EtOH Avoidance
• Continuous Positive Airway
Pressure (CPAP)
OSA Treatments
• Oral Appliance
• Surgical Repair
Case #3: Marsha
Case #3: Marsha
• 19 y.o….“Tired all the time.”
• Needs a note to take two incompletes.
• Fatigue for the last 5 months
• Sleep doesn’t help
• Tried to exerciseslept 18 hours!
• Started last fall when she had H1N1.
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No fever, but “still feels like she has the flu.”
• Myalgias intermittently
• Sore throat
Case #3: Marsha
• Physical Exam
• Tired appearing, otherwise unremarkable
• Labs:
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CBC 8.6>42/13<210
Comp Met Panel – all WNL
ESR 8
TSH/T4 all WNL
EBV IgG/IgM – non-reactive
CMV IgG/IgM – non-reactive
Case #3: Marsha
• Other notes:
• Always a Straight-A student.
• Supportive parents.
• No history of depression or other mental
health issues
» But, very frustrated that she can’t stay awake
to succeed in classes.
• Starts to cry… “I need to get at least an Aminus in my classes or I will be a “failure!”
Thoughts? Diagnoses???
Chronic Fatigue Syndrome (CFS)
• CDC Definition:
– Unexplained, persistent fatigue that is not due to ongoing exertion, is
not substantially relieved by rest, is of new onset (not lifelong) and
results in a significant reduction in previous levels of activity.
– Four or more of the following symptoms are present for six months or
more:
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Impaired memory or concentration
Postexertional malaise (extreme, prolonged exhaustion and exacerbation of symptoms
following physical or mental exertion)
Unrefreshing sleep
Muscle pain
Multi-joint pain without swelling or redness adults
Headaches of a new type or severity
Sore throat that’s frequent or recurring
Tender cervical or axillary lymph nodes
Is CFS a real diagnosis?
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No Lab Tests or markers
Similar symptoms to other illnesses
Patient’s frequently do not look sick
Symptoms vary by type, number and
severity
• Symptoms vary within a given
individual
Proposed Etiologies for CFS
• Infectious?
• Immune dysfunction?
• Neurally-mediated
hypotension?
• Lower levels of NK cells,
immune complexes,
autoantibodies.
• (May indicate
inflammatory process)
• Elevated titers of
antiviral antibodies
against measles, HHV6, EBV, CMV
• Depression?
• Sleep Dysruption?
• Endocrine?
• Non-specific cortisol
depressions.
• Tilt table testing
abnormal in 1 series
• Resolution with
fludrocortisone,
atenolol
• Lower sleep times,
efficiency and REM
sleep
Treatment of CFSWhat has (not) been shown to work?
• Medications
– Antidepressants
– small studies, conflicting
– Methylphenidate
– Small studies, ?improved concentration/fatigue
– Steroids
– Conflicting studies
– IVIG
– Small, conflicting studies
– Galantamine (ACTase inhibitor)
– No benefits
– Acyclovir
– No benefits
– Others
• Amantadine, doxycycline, Mg, exclusion diets
– No benefits noted
Treatment of CFS- What does work?
• Cognitive Behavioral Therapy
• Graded exercise therapy
• Physician/Provider Support
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Honesty
Review the data
Psych versus Organic – not important!
Assess for depression as secondary development
Case #4: Bobby
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18 yo freshman “I can’t stay awake”
“Always tired”
Falls asleep during classes at least once/week.
Gets 8-9 hours sleep/night. Feels rested in the
morning.
• Has fallen asleep while biking, at a party etc.
• Last week, working out and fell asleep doing arm
curls!!!
Thoughts?
• Differential?
• Labs / Workup?
Case#4: Bobby
• Referred for PSG
and for multiple
sleep latency test
(MSLT)
• PSG: Normal
• MSLT:
• 3 minutes to nap
• Rapid onset REM
sleep during
multiple naps
Narcolepsy
• 250,000 Americans
• Genetic: HLA-DR2/DQ1 Gene
– Lack of Hypocretin-1 (orexin) Production by
hypothalamus
• REM sleep intrudes into the awake state.
• Symptoms:
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Excessive Daytime Sleepiness
Cataplexy (60-70% of narcoleptics)
Hypnogogic Hallucinations
Sleep Paralysis
Narcolepsy- Treatments
• Modafenil
• Stimulant Medications
(methylphenidate)
• Possible treatments:
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Tricycylic Antidepressants
Gamma Hydroxybuterate
SSRIs
Venlafaxine
Case #5: Cindy
• “I can’t sleep!”
• Goes to bed at night, stares at ceiling for 4-5
hours.
• Feels exhausted in the morning
• No problems with roommates or outside noise
• Hard to concentrate in classes due to fatigue.
• Denies symptoms of depression/anxiety.
Insomnia- ICSD-2 Definition
• Difficulty with sleep
• Initiation
• Maintenance
• Non-restorative
• No external factors impeding sleep
• Daytime deficits
Insomnia- ICSD -2 Classifications
• Acute insomnia
• Stress-related
• Adjustment related
• Short term insomnia
• Psychophysiological
insomnia
• Primary, Chronic
• Learned
• Idiopathic insomnia
• Childhood onset
• Paradoxical insomnia
• Sleep state
misperception
• Subjective insomnia
• Pseudoinsomnia
• Insomnia from
medical condition
• Psych disorder
• Drugs
• Medications
• Unspecified insomnia
Insomnia- Clinical features
• Extremely variable
• 30+ minutes to fall
asleep
• <6 hours
sleep/night
• No sleep at all
Insomnia – Why do we care?
• Cardiac
– HTN: RR=5 (for <5 hrs
sleep/night)
– CAD
• Psychiatric Disease
– Depression
– Anxiety
– Substance abuse
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Respiratory disease
Neurologic Disease
Pain syndromes
GI disorders
Urologic disorders
Diagnosing Insomnia
• History
• Sleep Logs (2 weeks)
Insomnia - Treatments
• Behavioral Therapies
• Sleep Hygiene
• Stimulus Control
» In bed ONLY when tired
» Avoid stimulating activities (eg.
Computer)
• Progressive Relaxation
(May improve sleep time but not
daytime functioning)
• Cognitive Behavioral therapy
• 8-10 week intervention
• Very effective, if available
Insomnia- Treatments (Medications)
Benzodiazepines
(Clonazepam,
lorezepam etc)
• Reduce sleep latency
• Increase stage 2
sleep
• Reduce REM sleep
• Anxiolytic effects
Non-Benzodiazepines
(Zolpidem, Zaleplon,
Eszopiclone)
• Target GABA Type-A
receptors
• No anxiolytic effects
• Shorter halflivesBetter for sleep
initiation
– (except Zolpidem ER)
• Decreased post-Benzo
“hangover”
Other medications NOT approved for
Insomnia
• Antidepressants (tricyclic)
• Antipsychotics
• Diphenhydramine
• OTC Cold medicines?
– “Hangover”
• REM sleep inhibition
• Anticholinergic effects (long T½)
Herbal Products?
• Valerian
• Few studies- all short
term
• Published placebo
controlled studies do not
indicate efficacy
• Melatonin
• Scant evidence for
efficacy except:
– Circadian rhythm
disturbances
• Short term use safe,
Long term???
Case#6: Jan
• 21 year-old college junior
• “tired all the time”
• Goes to sleep at 11pm.
– Wakes at 3 am.
• Lives alone with cat.
• Boyfriend recently shipped to Iraq.
Case #5: Jan
• Thoughts?
Mood Disorders and Sleep
• 65-75% of Patients with mood d/o’s
report insomnia or hypersomnia
• Sx:
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Frequent nocturnal awakenings
Non-restorative sleep
Nightmares
Decreased Sleep quantity
• Mania: Total decrease in need to sleep
Mood disorders and Sleep
• Insomnia
– ↑depression risk 9x
– RR=39.8 for major
depression at 1 yr f/u
• Depression + Insomnia=
– ↑risk for suicidality
Sleep Abnormalities in Depression
Role of Treatment of Sleep issues
in Depression
• SSRIs ↑serotonin
• ↑REM sleep latency
• ↑Stage 3-4 sleep
• Reversing
architectural
abnormalities
• Trazadone
• Sedating
antidepressant
– Low doses treat
insomnia (not FDA
approved)
– Higher doses will
treat depression
• Other hypnotics
• Zolpidem
• Esczolpiclone
• Tend to improve
symptoms of
depression.
• No rebound on
discontinuation
• Do not work well
alone
Conclusion…
• Sleep and fatigue common complaints.
• History is key to diagnosis.
• Sleep hygiene is key to treatment.