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The Tired Student…Fatigue and Sleep Disorders in college students.
David S. Reitman, MD, MBAGeorge 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)
• 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)
How does this affect College Students?
• Perceived sleep debt= (Desired sleep) – (Actual Sleep obtained)
• Vela-Bueno, 2007
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
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
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:1. Rapid Eye movements
2. Active, fast frequency EEG – (similar to wakefulness)
3. 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
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• 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
• Thyroid exam• Oropharyngeal exam• Cardio-respiratory examination• Neurologic evaluation
• Cognitive abilities• Tremors
Lab Studies
• Tailor Studies to your suspicions….• CBC• ESR• Comprehensive Metabolic Panel• TSH• CK (if muscle weakness suspected)• Other ID workup if indicated
Case #1: Greg
• 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 –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…
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”
Obstructive Sleep Apnea Syndrome
• Risks:• 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)
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 exerciseslept 18 hours!
• Started last fall when she had H1N1.
• No fever, but “still feels like she has the flu.”
• Myalgias intermittently
• Sore throat
Case #3: Marsha
• Physical Exam• Tired appearing, otherwise unremarkable
• Labs:• 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 A-
minus in my classes or I will be a “failure!”
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:
• 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?
• 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?
• Lower levels of NK cells, immune complexes, autoantibodies.
• (May indicate inflammatory process)
• Elevated titers of antiviral antibodies against measles, HHV-6, EBV, CMV
• Endocrine?• Non-specific cortisol
depressions.
• Neurally-mediated hypotension?
• Tilt table testing abnormal in 1 series
• Resolution with fludrocortisone, atenolol
• Depression?• Sleep Dysruption?
• Lower sleep times, efficiency and REM sleep
Treatment of CFS- What 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• Honesty• Review the data• Psych versus Organic – not important!• Assess for depression as secondary development
Case #4: Bobby
• 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!!!
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:• Excessive Daytime Sleepiness• Cataplexy (60-70% of narcoleptics)• Hypnogogic Hallucinations• Sleep Paralysis
Narcolepsy- Treatments
• Modafenil• Stimulant Medications
(methylphenidate)• Possible treatments:
• 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
• Respiratory disease• Neurologic Disease• Pain syndromes• GI disorders• Urologic disorders
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 half-
livesBetter 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.
Mood Disorders and Sleep
• 65-75% of Patients with mood d/o’s report insomnia or hypersomnia
• Sx:• 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
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.