the tired student… fatigue and sleep disorders in college students. david s. reitman, md, mba...

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)

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?

• Perceived sleep debt= (Desired sleep) – (Actual Sleep obtained)

• Vela-Bueno, 2007

SLEEP PHYSIOLOGY 101Back to the basics……

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: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

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• 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 (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”

• <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:• 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 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!”

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:

• 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!!!

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:• 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

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 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.

Case #5: Jan

• Thoughts?

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

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.