CHRONIC FATIGUE/DEPRESSIONTHE MIND BODY CONNECTION

AIMGP Seminar Series

2003-2004

Tim Cook

(H. Abrams)

OUTLINE1. Case2. Functional Somatic Syndromes3. CFS Diagnostic Criteria 4. CFS Diagnostic Strategy5. CFS Treatment Strategy: Evidence?6. Depression Epidemiology7. Depression Management

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

Case Cont’d

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?

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

Functional Somatic Syndromes

Several related syndromes characterized by:

symptoms, suffering and disability

rather than

demonstrable tissue abnormality

Examples:Examples:

• chronic fatigue syndrome (CFS)chronic fatigue syndrome (CFS)• multiple chemical sensitivitiesmultiple chemical sensitivities• sick building syndromesick building syndrome• fibromyalgiafibromyalgia• silicone breast implant diseasesilicone breast implant disease• chronic whiplash / other pain synd.chronic whiplash / other pain synd.• irritable bowel syndromeirritable bowel syndrome• othersothers

Characteristics:Characteristics:

• explicit and highly elaboratedexplicit and highly elaborated

self-diagnosisself-diagnosis

• symptoms may be refractory to symptoms may be refractory to reassurance, explanation, and reassurance, explanation, and standard treatmentsstandard treatments

Characteristics (cont’d)Characteristics (cont’d)

• high rates of co-occurrencehigh rates of co-occurrence

• similar epidemiologysimilar epidemiology

• higher than expected psychiatrichigher than expected psychiatric

comorbiditycomorbidity

Characteristics (concl’d):Characteristics (concl’d):

• suffering worsened by “self-perpetuating,suffering worsened by “self-perpetuating, self-validating cycle in which common,self-validating cycle in which common, endemic , somatic symptoms are incorrectlyendemic , somatic symptoms are incorrectly attributed to serious abnormality, attributed to serious abnormality, reinforcing the patient’s belief that he or shereinforcing the patient’s belief that he or she has a serious disease”.has a serious disease”.

Barsky and Borus. Ann Intern Med 1999:130:910-921.Barsky and Borus. Ann Intern Med 1999:130:910-921.

Incidence of somatic symptoms:Incidence of somatic symptoms:

Typical adult has one common symptomTypical adult has one common symptom eg. Aching, every 4-6 days eg. Aching, every 4-6 days

81% of healthy college students report81% of healthy college students report>> 1 somatic symptom q3days. 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 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

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 con-currently 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 diseaseNO:

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

External Stressors

Internal Stressors

Perceptual Appraisal

STRESSREACTION

acute hyperarousal followed by normalization

Disregualation = ChronicChronic HyperarousalHyperarousal

HBPArrhythmiassleep disprderschronic painschronic illnessanxiety

Maladaptive Coping

Self-destructive behaviours

overworkinghyperactivityovereating

harmful conditioningssubstance dependency

BreakdownBreakdown

Physical exhaustionPsychological exhaustionloss of energy, enthusiasmdepressiongenetic predispositionsMI, cnacer, chronic illness

(adapted fromJ. Kabat-Zinn)

Pain Centred Life

Function CentredLife

Adequate AnalgesiaEducationExerciseBreath & Relaxation

IncreasedActivities

Improved Conditioning

Improved Function

IncreasedControl

Improved Self-esteem

Improved Motivation

LETTING GO

Brain

Muscle & Fascia

SensoryFeedback

Characteristics:blood supply

metabolism

resting tone

contractility & power

flexibility & elasticity

Autonomic NSCentral NSHormonal system (sex hormone, cortisol, adrenaline, neuropeptides etc.)

TraumaEmotionsPosture

Muscle tensionIncreased tone

PAIN

CHRONIC MUSCLE CONTRACTION

Exercise, Stretching, Breathing & Relaxation Relaxation Practices

Exercise, Stretching, Breathing & Relaxation 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 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

Depression in Medicine Depression more common in

following illnesses: stroke dementia diabetes heart disease renal disease cancer

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

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

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

Cancer and depression

estimates vary, but expect that depressed patients have mortality rates 10-20% greater than matched counterparts

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!)

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:

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

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

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

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

Treatment main modalities include

psychotherapy drug treatment electro-convulsant therapy

should be individualized

Psychotherapy recent studies do show it to be as

effective as medication 40-50% improve BMJ 2000;320:26-30

perhaps best suited to less severe forms of depression in a highly motivated patient

Medications three main groups of drugs:

SSRI TCAs MAOI

occasionally for refractive forms: lithium valproate thyroid supplementation

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

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

SSRI - Common Side Effects GI:

nausea, diarrhea, weight gain neuro:

headache, sedation, paresthesia insomnia, poor memory, agitation

other: sexual dysfunction

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

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)

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

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

TCAs inhibit re-uptake of mono-amines,

noradrenaline and serotonin at nerve endings

many possible side effects, especially in the elderly

TCAs - Side Effects anti-cholinergic:

dry mouth, nausea, constipation, urinary retention, mydriasis and cycloplegia

cardiovascular: postural hypotension, tachycardia

neurologic: fine tremor, dizziness, ataxia drowsiness

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

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

MAOI increases levels of noradrenaline,

dopamine and 5-hydroxytryptamine

usually reserved for atypical depression: weight gain excessive sleep marked anxiety / obsessional features

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

ECT usually reserved for:

imminent suicide psychotic depression catatonia

very effective usually need 6-8 treatments over 3

weeks

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.

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”

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

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