CHRONIC FATIGUE/DEPRESSION THE MIND BODY CONNECTION

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CHRONIC FATIGUE/DEPRESSIONTHE MIND BODY
CONNECTION

• AIMGP Seminar Series
• 2003-2004
• Tim Cook
• (H. Abrams)

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OUTLINE

1. Case
2. Functional Somatic Syndromes
3. CFS Diagnostic Criteria
4. CFS Diagnostic Strategy
5. CFS Treatment Strategy Evidence?
6. Depression Epidemiology
7. Depression Management

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CASE

• 33 yo woman VP HR
• Referred from FDr c/o fatigue X 18 mos
• MEDS
• multivits, CoE Q10, Gingko, glucosamine
• Prn Zomig, Tylenol, Zelnorm
• Non-smoker, daily glass wine, quit exercising

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Case Contd

• P/E fit looking woman
• 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?

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IMPORTANT HISTORY

• FATIGUE
• Onset
• Duration
• Severity ( of N)
• Provoking Factors (exercise?)
• Relieving Factors (wkends, sleep?)
• OTHER SYMPTOMS
• Arthralgia, myalgia, sore throat, neuro,
  depression bowel habits,

• SLEEP
• Duration
• Quality
• Restorative?
• Use of ETOH, caffeine
• Narcolepsy flags
• Daytime napping
• Hypnagogic hallucin.
• Cataplexy
• Sleep paralysis

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Functional Somatic Syndromes

• Several related syndromes characterized by
• symptoms, suffering and disability
• rather than
• demonstrable tissue abnormality

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• 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

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• Characteristics
• explicit and highly elaborated
• self-diagnosis
• symptoms may be refractory to reassurance,
  explanation, and standard treatments

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• Characteristics (contd)
• high rates of co-occurrence
• similar epidemiology
• higher than expected psychiatric
• comorbidity

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• Characteristics (concld)
• suffering worsened by self-perpetuating,
• self-validating cycle in which common,
• endemic , somatic symptoms are incorrectly
• attributed to serious abnormality,
• reinforcing the patients belief that he or she
• has a serious disease.
• Barsky and Borus. Ann Intern Med
  1999130910-921.

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Incidence of somatic symptoms Typical
adult has one common symptom eg. Aching, every
4-6 days 81 of healthy college students
report gt 1 somatic symptom q3days.
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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

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Amplification and Maintenance of Somatic Symptoms

• 1. The belief that one is sick
• 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

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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

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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

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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.

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Amplification and Maintenance of Somatic Symptoms

• 5. Political, Economic, and Legal Issues
• political climate of entitlement
• sense of belonging to a group
• secondary gain e.g. prolonged rehab. in workers
  compensation

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2. Chronic Fatigue Syndrome

• fatigue is very common, CFS is not .
• Caplan. CMAJ 1998159(5)519-520.

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CDC Criteria for CFS 1. Fatigue gt 6 mos.,
resulting in decrease in activities of gt
50. and 2. All of -
New or definite onset - Not from ongoing
exertion - not alleviated by rest
and
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CDC Criteria for CFS (concld) gt 4 of the
following, present con- currently for gt 6 mos. -
impaired memory/concentration - sore throat -
tender cervical/axillary lymph nodes -
myalgias - arthralgias - new headache -
unrefreshing sleep - Post-exertional malaise
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• Diagnostic Strategy
• A. Prolonged fatigue gt 1 mo., lt 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

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• Additional tests as indicated
• - ANA, RF, C3, C4, CH50
• - Quantitative Igs (serum, urine)
• Cortisols, CKs
• HCV, HBV, HIV, CMV, toxo
• TB skin test
• Lyme serology
• Sleep Study
• Other cause of disease Identified?
• YES Manage as per disease
• NO

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B. Chronic Fatigue gt 6 mos. Meet the CDC
criteria? Yes Do you really want to make this
diagnosis? No Idiopathic chronic fatigue.
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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
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• 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.

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• Treatment Strategies
• 2. Treat psychiatric comorbidity.
• Major depression, panic disorder
• ? somatic symptoms ? probability of
  psychiatric diagnosis

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• Treatment Strategies
• 3. Form therapeutic alliance with patient
• acknowledge and legitimize patients suffering.
• discourage sick role.
• reassure that you will not abandon.

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• 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

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• 4. Treatment Strategies
• 5. Provide limited reassurance
• no life-threatening illness found
• describe amplification process

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• 4. Treatment Strategies
• Whats 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

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THE STRESS REACTION CYCLE
(adapted from J. Kabat-Zinn)
External Stressors
Perceptual Appraisal
Internal Stressors
STRESS REACTION
Physical exhaustion Psychological exhaustion loss
of energy, enthusiasm depression genetic
predispositions MI, cnacer, chronic illness
Breakdown
acute hyperarousal followed by normalization
Self-destructive behaviours overworking hyperacti
vity overeating harmful conditionings substance
dependency
HBP Arrhythmias sleep disprders chronic
pains chronic illness anxiety
Disregualation Chronic Hyperarousal
Maladaptive Coping
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Improved Self-esteem
LETTING GO
Increased Control
Improved Motivation
Function Centred Life
Improved Function
Pain Centred Life
Improved Conditioning
Adequate Analgesia Education Exercise Breath
Relaxation
Increased Activities
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CHRONIC MUSCLE CONTRACTION
Trauma Emotions Posture
Brain
PAIN
Sensory Feedback
Autonomic NS Central NS Hormonal system (sex
hormone, cortisol, adrenaline, neuropeptides
etc.)
Muscle Fascia
Characteristics blood supply metabolism resting
tone contractility power flexibility
elasticity
Muscle tension
Increased tone
Exercise, Stretching, Breathing Relaxation
Practices
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• 4. Treatment Strategies
• 7. Other options
• low dose SSRIs, TCAs no consistent response
• modafinil (alertec) few studies
• complementary therapies. No evidence from RCTs

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Depression

• Very common problem in primary practice
• 10 of men over lifetime
• 20 of women over lifetime
• May be even more prevalent in medical patients
• up to 40 with chronic illness

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Depression in Medicine

• Depression more common in following illnesses
• stroke
• dementia
• diabetes
• heart disease
• renal disease
• cancer

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Depression and Drug Tx

• certain drugs have been linked to onset of
  depressive symptoms
• common offenders
• steroids, calcium channel blockers, digoxin
• cohort studies
• withdrawal of psycho-stimulants
• benzos, barbituates, morphine, levo-dopa
• perhaps ACEi, statins
• B-blockers controversial

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Why should we care?

• Prognosis of medical diseases worse in depressed
  patients
• 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
• as important as LV function
• incidence in stroke patients very high
• between 25-80
• range is large b/c difficult to make diagnosis

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• Cancer and depression
• estimates vary, but expect that depressed
  patients have mortality rates 10-20 greater than
  matched counterparts

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Diagnosis

• often difficult
• medical patients often have somatic complaints
• GI upset, headache, fatigue etc.
• important to r/o other causes for complaints
• hypothyroid, anemia etc.
• rating scales available ( we have them!)

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DSM 4 Criteria

• Must have one of
• 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

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DSM 4 Criteria

• 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

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Minor Depression

• patients and doctors may want to attribute mood
  to current life stress
• 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

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Course and Prognosis

• untreated major depression
• 40 resolve spontaneously
• within 6 - 12 months
• 20 resolution is incomplete
• sub-clinical symptoms persist for years
• 40 depression continues
• depression is usually recurrent

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Course and Prognosis

• depression is usually recurrent
• 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
• medical illness, ETOH, male, Caucasian, presence
  of psychotic symptoms, social isolation, history
  of previous attempts, and a plan

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Treatment

• main modalities include
• psychotherapy
• drug treatment
• electro-convulsant therapy
• should be individualized

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Psychotherapy

• recent studies do show it to be as effective as
  medication
• 40-50 improve
• BMJ 200032026-30
• perhaps best suited to less severe forms of
  depression in a highly motivated patient

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Medications

• three main groups of drugs
• SSRI
• TCAs
• MAOI
• occasionally for refractive forms
• lithium
• valproate
• thyroid supplementation

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Medications

• 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

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SSRI

• Most commonly used
• safer in overdose than TCAs
• some meta-analyses say less effective than TCAs
  other say equal
• fluoxetine (Prozac) safe in pregnancy

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SSRI - Common Side Effects

• GI
• nausea, diarrhea, weight gain
• neuro
• headache, sedation, paresthesia
• insomnia, poor memory, agitation
• other
• sexual dysfunction

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SSRI - Rare Side Effects

• Neuro
• extrapyramdal - dystonias, akathesia
• b/c of serotonin mediated inhibition of
  dopaminergic pathways
• Cardiac
• case reports of a fib, bradycardia, syncope
• may have class 1,4 properties and be
  pro-arrhythmic
• SIADH

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SSRI - Serotonin Syndrome

• Insidious, may be fatal
• usually seen when 2 or more drugs enhance
  serotonin activity
• present as
• confused, agitated, fever, shivering,
  diaphoretic, diarrhea, ataxic, hyper-reflexic,
  myoclonus
• tx stop meds /- anti-sertoninergics (BB)

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SSRI - OD

• Rarely fatal
• 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

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TCAs

• until recently, most common drugs used to treat
  depression
• decrease use attributed to addition of SSRI to
  market
• very effective treatment
• approx. 50-60 improve
• may still be 1st line for severe depression

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TCAs

• inhibit re-uptake of mono-amines, noradrenaline
  and serotonin at nerve endings
• many possible side effects, especially in the
  elderly

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TCAs - Side Effects

• anti-cholinergic
• dry mouth, nausea, constipation, urinary
  retention, mydriasis and cycloplegia
• cardiovascular
• postural hypotension, tachycardia
• neurologic
• fine tremor, dizziness, ataxia
• drowsiness

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TCA - Overdose

• can be rapidly fatal
• were the 4th most common OD
• within 6 hours
• CNS depression, seizures
• respiratory depression
• CVcollapse, QRS prolongation and VT
• quinidine like effects

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TCA - OD - Basic Treatment

• symptoms develop within 1-2 hours
• undergoes entero-hepatic circulation
• repeated activated charcoal
• correct acid-base - ventilator, NaHCO3
• treat hypotension
• arrhythmias - NaHCO3, lidocaine, pacing
• seizures - benzos or dilantin

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MAOI

• increases levels of noradrenaline, dopamine and
  5-hydroxytryptamine
• usually reserved for atypical depression
• weight gain
• excessive sleep
• marked anxiety / obsessional features

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MAOI - Side Effects

• common
• weight gain
• drowsiness, agitation
• postural hypotension
• interactions may cause hypertension
• tyramine in cheese, herring, red wines
• dopamine - other antidepressants
• must give at least 2 week wash-out period

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ECT

• usually reserved for
• imminent suicide
• psychotic depression
• catatonia
• very effective
• usually need 6-8 treatments over 3 weeks

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ECT - Side Effects

• can develop short-term retrograde amnesia
• also can get hypertensive surge
• sympathetic mediated
• b/c done under general anaesthesia, other
  potential complications include aspiration
  pneumonia etc.

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Special Considerations in Elderly

• age-related physiologic changes may alter
  pharmacokinetics
• reduce flow to liver, kidney
• decreased enzyme activity
• usually on multiple medications
• increases potential for drug interactions
• start low and go slow

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Special Considerations in Elderly

• TCAs metabolized by P-450
• common inhibitors cipro, biaxin, flagyl,
  amiodarone, fluconazole
• narrow therapeutic range
• increases possible side effects
• SSRI
• prozac, zoloft, paxil, luvox all inhibit P450
• careful with haldol, coumadin, lithium

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Conclusions

• depression is common in our patient population
• 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