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.