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CHRONIC FATIGUE/DEPRESSION
THE MIND BODY CONNECTION
AIMGP Seminar Series
2003-2004
Tim Cook
(H. Abrams)
OUTLINE
1.
2.
3.
4.
5.
6.
7.
Case
Functional Somatic Syndromes
CFS Diagnostic Criteria
CFS Diagnostic Strategy
CFS Treatment Strategy: Evidence?
Depression Epidemiology
Depression Management
CASE

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33 yo woman VP HR
Referred from FDr c/o fatigue X 18 mos
MEDS
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multivits, CoE Q10, Gingko, glucosamine
Prn Zomig, Tylenol, Zelnorm
Non-smoker, daily glass wine, quit
exercising
Case Cont’d
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P/E – fit looking woman
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Few tender, “shotty” cervical nodes
5 trigger points tender
Upper abdo quadrants tender
Remainder normal
What additional history would be helpful?
What investigations should be done?
IMPORTANT HISTORY

FATIGUE
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Onset
Duration
Severity (% of N)
Provoking Factors
(exercise?)
Relieving Factors
(wkends, sleep?)
OTHER SYMPTOMS

Arthralgia, myalgia, sore
throat, neuro, depression
bowel habits,
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SLEEP
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Duration
Quality
Restorative?
Use of ETOH, caffeine
Narcolepsy “flags”
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Daytime napping
Hypnagogic hallucin.
Cataplexy
Sleep paralysis
Functional Somatic Syndromes

Several related syndromes characterized
by:
symptoms, suffering and disability
rather than
demonstrable tissue abnormality
Examples:
•
•
•
•
•
•
•
•
chronic fatigue syndrome (CFS)
multiple chemical sensitivities
sick building syndrome
fibromyalgia
silicone breast implant disease
chronic whiplash / other pain synd.
irritable bowel syndrome
others
Characteristics:
• explicit and highly elaborated
self-diagnosis
• symptoms may be refractory to
reassurance, explanation, and
standard treatments
Characteristics (cont’d)
• high rates of co-occurrence
• similar epidemiology
• higher than expected psychiatric
comorbidity
Characteristics (concl’d):
• suffering worsened by “self-perpetuating,
self-validating cycle in which common,
endemic , somatic symptoms are incorrectly
attributed to serious abnormality,
reinforcing the patient’s belief that he or she
has a serious disease”.
Barsky and Borus. Ann Intern Med 1999:130:910-921.
Incidence of somatic symptoms:
Typical adult has one common symptom
eg. Aching, every 4-6 days
81% of healthy college students report
> 1 somatic symptom q3days.
Amplification and Maintenance
of Somatic Symptoms
Five Factors:
1. The belief that one is sick
2. Future expectations and the Role of Suggestion
3. The Sick Role
4. Stress and Distress.
5. Political, Economic, and Legal issues
Amplification and Maintenance of
Somatic Symptoms
1. The belief that one is sick
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
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Effect of cognitive beliefs on interpretation of current
symptoms. e.g. hypertension and absenteeism
Effect of cognitive beliefs on interpretation and
recall of past symptoms
e.g. healthy volunteers given imaginary diagnosis
Amplified through self-scrutiny, medical scrutiny,
media / public health attention, advocacy groups
Amplification and Maintenance of
Somatic Symptoms
2. Future expectations and the Role of Suggestion

Cognitive processing of current bodily sensations
guided by expectations of what we will experience
next.
e.g. ASA for UAP – 6 X dropouts for GI symptoms (endoscopy) if consent form explicitly mentioned
Amplification and Maintenance
of Somatic Symptoms
3. The Sick Role
–
social labeling theory:
“… the connotations and implications of the label we
apply to a condition or state influence the outcome of
that condition or state.”
- changes interactions with family, employer & physician
Amplification and Maintenance
of Somatic Symptoms
4. Stress and Distress.
– Exacerbates and perpetuates physical symptoms
– lowers threshold for medical help seeking
– ambiguous body sensations more likely attributed to
disease.
Amplification and Maintenance
of Somatic Symptoms
5. Political, Economic, and Legal Issues


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political climate of entitlement
sense of belonging to a group
secondary gain e.g. prolonged rehab. in workers
compensation
2. Chronic Fatigue Syndrome
“…fatigue is very common, CFS is not ”.
Caplan. CMAJ 1998;159(5):519-520.
CDC Criteria for CFS:
1. Fatigue > 6 mos., resulting in decrease in
activities of > 50%.
and
2. All of:
- New or definite onset
- Not from ongoing exertion
- not alleviated by rest
and
CDC Criteria for CFS (concl’d):
> 4 of the following, present concurrently for > 6 mos.:
-
impaired memory/concentration
sore throat
tender cervical/axillary lymph nodes
myalgias
arthralgias
new headache
unrefreshing sleep
Post-exertional malaise
3.Diagnostic Strategy
A. Prolonged fatigue > 1 mo., < 6 mo.
- Hx and Px
- Mental status, psych, neuro as
indicated
- Lab: CBC, lytes, urea, Cr, glucose,
Ca++, phos, ALT, ALP, protein,
albumin, TSH, urinalysis,
?ESR ?Fe Sat
- Additional tests as indicated*
*Additional tests as indicated:
- ANA, RF, C3, C4, CH50
–
–
–
–
–
Quantitative Ig’s (serum, urine)
Cortisols, CK’s
HCV, HBV, HIV, CMV, toxo
TB skin test
Lyme serology
Sleep Study
Other cause of disease Identified?
YES: Manage as per disease
NO:
B. Chronic Fatigue > 6 mos.:
Meet the CDC criteria?
Yes: Do you really want to make this diagnosis?
No: Idiopathic chronic fatigue.
4. Treatment Strategies:
1. R/O diagnosable disease as per diagnostic strategy.
2. Treat psychiatric comorbidity.
3. Form therapeutic alliance with patient
4. Make restoration of function the goal of treatment
5. Provide limited reassurance
6. Cognitive Behavioral therapy?
7. Other options
4. Treatment Strategies:
1. R/O diagnosable disease (diagnostic strategy)
– Try not to foster sick role
– negative findings rarely reassure these patients
– risk of iatrogenesis.
4. Treatment Strategies:
2. Treat psychiatric comorbidity.
–
Major depression, panic disorder
–
 somatic symptoms =  probability of
psychiatric diagnosis
4. Treatment Strategies:
3. Form therapeutic alliance with patient
– acknowledge and legitimize patient’s suffering.
– discourage sick role.
– reassure that you will not abandon.
4. Treatment Strategies:
4. Make restoration of function the goal
– coping rather than curing
– realistic, incremental goals,
i.e. gently graduated exercise
– active rather than passive role
“not waiting to be cured” but “taking control of self-cure”
4. Treatment Strategies:
5. Provide limited reassurance
– “no life-threatening illness found”
– describe “amplification” process
4. Treatment Strategies:
What’s the Evidence?
6. Cognitive Behavioral therapy
–
Positive and negative randomized trials of varying
quality, and relatively small numbers.
– reexamines health beliefs and expectations
–
explores effects of sick role and stress on symptoms
– muscle relaxation, graduated exercise, desensitization
THE STRESS REACTION CYCLE
(adapted from
J. Kabat-Zinn)
External Stressors
Perceptual
Appraisal
Internal Stressors
STRESS
REACTION
acute hyperarousal
followed by normalization
Disregualation
= Chronic
Hyperarousal
HBP
Arrhythmias
sleep disprders
chronic pains
chronic illness
anxiety
Physical exhaustion
Psychological exhaustion
loss of energy, enthusiasm
depression
genetic predispositions
MI, cnacer, chronic illness
Maladaptive
Coping
Breakdown
Self-destructive
behaviours
overworking
hyperactivity
overeating
harmful conditionings
substance dependency
Improved Self-esteem
LETTING GO
Increased
Control
Improved
Motivation
Function Centred
Life
Pain Centred
Life
Improved
Function
Improved
Conditioning
Adequate Analgesia
Education
Exercise
Breath & Relaxation
Increased
Activities
CHRONIC MUSCLE CONTRACTION
Trauma
Emotions
Posture
Brain
Sensory
Feedback
Muscle & Fascia
Characteristics:
PAIN
Autonomic NS
Central NS
Hormonal system
(sex hormone, cortisol,
adrenaline, neuropeptides
etc.)
blood supply
metabolism
resting tone
contractility & power
flexibility & elasticity
Increased tone
Muscle tension
Exercise, Stretching, Breathing &
Relaxation Practices
4. Treatment Strategies:
7. Other options:
– low dose SSRI’s, TCA’s: no consistent response
– modafinil (alertec): few studies
– complementary therapies. No evidence from RCT’s
Depression
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Very common problem in primary
practice
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10% of men over lifetime
20% of women over lifetime
May be even more prevalent in medical
patients
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up to 40% with chronic illness
Depression in Medicine
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Depression more common in following
illnesses:
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stroke
dementia
diabetes
heart disease
renal disease
cancer
Depression and Drug Tx
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certain drugs have been linked to onset of
depressive symptoms
common offenders:
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steroids, calcium channel blockers, digoxin
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cohort studies
withdrawal of psycho-stimulants
benzos, barbituates, morphine, levo-dopa
perhaps ACEi, statins
B-blockers controversial
Why should we care?
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Prognosis of medical diseases worse in
depressed patients
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15 months post onset of depression,
mortality rates are 4 times that of age
matched controls!!!
Depressed patients admitted to NH are 1.5
times more likely to die within a year
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Post MI, depression is an important
marker of prognosis
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as important as LV function
incidence in stroke patients very high
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between 25-80%
range is large b/c difficult to make
diagnosis
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Cancer and depression
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estimates vary, but expect that depressed
patients have mortality rates 10-20%
greater than matched counterparts
Diagnosis
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often difficult
medical patients often have somatic
complaints
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important to r/o other causes for complaints
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GI upset, headache, fatigue etc.
hypothyroid, anemia etc.
rating scales available (+ we have them!)
DSM 4 Criteria
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Must have one of:
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depressed mood most of the time
decreased interest/pleasure in nearly all
activities
Plus, must have 5 of the following
during a 2 week period:
DSM 4 Criteria
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weight change
sleep change
observed agitation or retardation
fatigue or loss of energy
feelings of worthlessness or excessive guilt
unable to concentrate / indecisiveness
recurrent thoughts of death
Minor Depression
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patients and doctors may want to
attribute mood to current life stress
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I.e. adjustment disorder
this is characterized as a minor depression
most common type of depression
becomes problematic if leads to social
dysfunction, or persists longer than 2
months
Course and Prognosis
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untreated major depression:
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40% resolve spontaneously
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20% resolution is incomplete
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within 6 - 12 months
sub-clinical symptoms persist for years
40% depression continues
depression is usually recurrent
Course and Prognosis
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depression is usually recurrent
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70% recurrence after 2 episodes
90% recurrence after 3 episodes
thoughts of death are common
1 in 8 suicide attempts are successful
risk factors for suicide:
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medical illness, ETOH, male, Caucasian, presence of
psychotic symptoms, social isolation, history of
previous attempts, and a plan
Treatment
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main modalities include
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psychotherapy
drug treatment
electro-convulsant therapy
should be individualized
Psychotherapy
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recent studies do show it to be as
effective as medication
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40-50% improve
BMJ 2000;320:26-30
perhaps best suited to less severe forms
of depression in a highly motivated
patient
Medications
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three main groups of drugs:
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SSRI
TCAs
MAOI
occasionally for refractive forms:
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lithium
valproate
thyroid supplementation
Medications
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in general, need 6 week trial to see
effect
try to adjust dose to achieve benefits at
lowest possible dose
usually continue therapy for 6 months
to 2 years
relapses usually occur within 2 months
of discontinuation; taper slowly
SSRI
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Most commonly used
safer in overdose than TCAs
some meta-analyses say less effective
than TCAs: other say equal
fluoxetine (Prozac) safe in pregnancy
SSRI - Common Side Effects
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GI:
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neuro:
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nausea, diarrhea, weight gain
headache, sedation, paresthesia
insomnia, poor memory, agitation
other:
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sexual dysfunction
SSRI - Rare Side Effects
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Neuro:
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extrapyramdal - dystonias, akathesia
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Cardiac
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case reports of a fib, bradycardia, syncope
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b/c of serotonin mediated inhibition of
dopaminergic pathways
may have class 1,4 properties and be proarrhythmic
SIADH
SSRI - Serotonin Syndrome
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Insidious, may be fatal
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present as:
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usually seen when 2 or more drugs enhance
serotonin activity
confused, agitated, fever, shivering, diaphoretic,
diarrhea, ataxic, hyper-reflexic, myoclonus
tx: stop meds +/- anti-sertoninergics (BB)
SSRI - OD
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Rarely fatal
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if fatal, usually b/c of what it is combined
with
moderate OD - 30* dose - are
nauseated, drowsy
high - 75* - may have seizures, ECG
changes and further decreased LOC
supportive care mainstay of treatment
TCAs
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until recently, most common drugs used
to treat depression
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decrease use attributed to addition of SSRI
to market
very effective treatment
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approx. 50-60% improve
may still be 1st line for severe depression
TCAs
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inhibit re-uptake of mono-amines,
noradrenaline and serotonin at nerve
endings
many possible side effects, especially in
the elderly
TCAs - Side Effects
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anti-cholinergic:
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cardiovascular:
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dry mouth, nausea, constipation, urinary
retention, mydriasis and cycloplegia
postural hypotension, tachycardia
neurologic:
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fine tremor, dizziness, ataxia
drowsiness
TCA - Overdose
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can be rapidly fatal
were the 4th most common OD
within 6 hours:
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CNS depression, seizures
respiratory depression
CVcollapse, QRS prolongation and VT
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quinidine like effects
TCA - OD - Basic Treatment
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symptoms develop within 1-2 hours
undergoes entero-hepatic circulation
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repeated activated charcoal
correct acid-base - ventilator, NaHCO3
treat hypotension
arrhythmias - NaHCO3, lidocaine,
pacing
seizures - benzos or dilantin
MAOI
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increases levels of noradrenaline,
dopamine and 5-hydroxytryptamine
usually reserved for atypical depression:
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weight gain
excessive sleep
marked anxiety / obsessional features
MAOI - Side Effects

common:
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weight gain
drowsiness, agitation
postural hypotension
interactions may cause hypertension:
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tyramine in cheese, herring, red wines
dopamine - other antidepressants
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must give at least 2 week wash-out period
ECT
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usually reserved for:
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imminent suicide
psychotic depression
catatonia
very effective
usually need 6-8 treatments over 3
weeks
ECT - Side Effects

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can develop short-term retrograde
amnesia
also can get hypertensive surge

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sympathetic mediated
b/c done under general anaesthesia,
other potential complications include
aspiration pneumonia etc.
Special Considerations in
Elderly

age-related physiologic changes may
alter pharmacokinetics

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usually on multiple medications
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reduce flow to liver, kidney
decreased enzyme activity
increases potential for drug interactions
“start low and go slow”
Special Considerations in
Elderly

TCAs metabolized by P-450


common inhibitors cipro, biaxin, flagyl,
amiodarone, fluconazole
narrow therapeutic range

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increases possible side effects
SSRI

prozac, zoloft, paxil, luvox all inhibit P450

careful with haldol, coumadin, lithium
Conclusions

depression is common in our patient
population

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
elderly, chronic illnesses
often present with somatic complaints
therapy is effective


ideally managed by GP, or someone who can see
patient frequently
many side-effects, but SSRI generally well
tolerated