Depression in the Medically Ill

Ira Lesser, M.D.Chair, Department of Psychiatry

Harbor-UCLA Medical CenterProfessor, Department of Psychiatry and

Biobehavioral SciencesGeffen School of Medicine at UCLA

Disclosures Grant support

National Institute for Mental Health Bristol-Myers Squibb Forest Pharmaceuticals Aspect Medical Systems

Disclosures None of my slides and/or handouts

contain any advertising, trade names or product-group messages. Any treatment recommendations I make will be based on clinical evidence or guidelines.

Ira Lesser, M.D.Harbor-UCLA Medical Center

The personal view

Depression is a disorder of mood, so mysteriously painful and elusive in the way it becomes known to the self--to the mediating intellect--as to verge close to being beyond description. It thus remains nearly incomprehensible to those who have not experienced it in the extreme mode.

William Styron, Darkness Visible

What I had begun to discover is that mysteriously and in ways that are totallyremote from normal experience, the graydrizzle of horror induced by depression takeson a quality of physical pain…it comes to resemble the diabolical discomfort of being imprisoned in a fiercely overheated room…

William Styron, Darkness Visible

Depressive Disorders Major depression Dysthymic disorder Bipolar disorder--depressed phase Mood disorder due to medical

condition Substance induced mood disorder Adjustment disorder with depressed

mood

Occurrence of Depression

Point prevalence 4–5% Women 5–6% Men 3%

1 year prevalence 11.3% Lifetime prevalence 12-

18% Majority have recurrences

50% after one episode 70% after two episodes 90% after three or more episodes

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Katon and Sullivan. J Clin Psychiatry. 1989;51(suppl 6):3.

Prevalence Of Major Depression by Locus of Care

Disease Burden in Established Market Economies, 1990

Ischemic heart disease 9.0 Unipolar major depression 6.8Cardiovascular disease 5.0 Alcohol use 4.7 Road traffic accidents 4.4 Lung & UR cancers 3.0 Dementia & degenerative CNS 2.9 Osteoarthritis 2.7 Diabetes 2.4

COPD 2.3

Barriers to Recognizing Depression in the Medically Ill Difficulty distinguishing psychological

symptoms from “realistic” response to physical illness

Confusion over whether physical symptoms of depression are due to medical illness

Stigma and negative attitudes about depression

Lack of time/training of physicians Patient’s unwillingness to discuss

depression

Major Depressive Episode

Depressed mood or anhedonia — at least 2 wks At least 5 of the following

Depressed mood Decreased interest or pleasure most of the time Insomnia or hypersomnia Anorexia or hyperphagia or 5% weight gain/loss in month Psychomotor agitation or retardation Fatigue Decreased concentration or thinking, indecisiveness Negative thinking — worthlessness, inappropriate guilt Recurring thoughts of death or suicide

Not organically caused Not uncomplicated bereavement

Diagnostic Approaches in the Medically Ill

Inclusion approach: “count” all symptoms

Etiological approach: exclude symptoms if physically-based

Substitutive approach modify criteria

Impact Of Depression In Chronic Medical Illness

EconomicImpact

TreatmentImplications

MaladaptiveEffects

MorbidityAnd

Mortality

Maladaptive Effects Of Affective Illness On Chronic Medical Illness

Amplification of somatic symptoms (especially pain) and functional disability

Direct maladaptive physiologic effects

Decreased self-care and adherence to medical regimens

Comorbidity increases functional impairment

Comorbidity increases mortality

Katon. Gen Hosp Psychiatry. 1996;18:215.

Organic Differential Diagnosis

Medication toxicities Cardiopulmonary disorders Neurological disorders Endocrine/Metabolic disorders Nutritional deficiencies Sleep disorders Infectious disorders Neoplasms

Prevalence of Depressive Disorders in Various Patient Populations*

* There is a range of percentages depending on the study.

Prevalence

General population

Chronically ill

Hospitalized

Geriatric inpatients

Cancer outpatients

Cancer inpatients

Stroke

MI

Parkinson’s disease 39.0%

45.0%

47.0%

42.0%

33.0%

36.0%

33.0%

9.4%

5.8%

0% 10% 20% 30% 40% 50%

Adapted from WPA/PTD Educational Program on Depressive Disorders

Apathy Diminished goal-directed behavior

Lack of effort, productivity, initiative, perseverance, time spent in activity

Diminished goal-directed cognition Lack of interest in new experiences, lack of

concern about personal welfare, diminished importance to socialization, recreation

Diminished emotional aspects Unchanging affect, lack of emotional

responsiveness, lack of excitement, response Overlaps with depressive illness, but can exist

independently

Depression vs. Apathy Disorder of mood Patient suffering

apparent Emotions are

strong and biased towards negative

Cognitions typically of negative triad

Disorder of motivation

Patient suffering less obvious

Emotions are attenuated to positive and negative

Cognitive bias toward negativity is absent

Conditions Associated with Apathy

Alzheimer disease Frontal lobe dysfunction Diseases of the basal ganglia Right hemisphere damage Apathetic hyperthyroidism Hypothyroidism

Apathy: Summary Can be quantified by rating scales Seems to be highly prevalent in

disorders involving sub-cortical frontal circuits (including anterior cingulate) in degenerative, TBI, and vascular conditions

Is associated with functional impairment Can appear both with and independent

of depressionVan Reekum et al: J Neuropsychiatry Clin Neurosci 17:2005

Treatment of Apathy Treat underlying medical problems Review medications (including psychotropics) Consider dopaminergic agonists (e.g.

amantadine, bromocriptine, buproprion, methylphenidate, etc.)

Possible use of atypical antipsychotics Consider use of anticholinesterases in cases

of dementia Behavioral/family interventions Environmental manipulations

Depression and Cardiovascular Disease Is there a relationship? If there is a relationship, which direction

does the “arrow go”? What effects, if any, does depression have

on course of CAD? What mechanism(s) explain the

relationship? Can treatment of depression affect

course/outcome of CAD?Excellent review: Psychosomatic Medicine, Suppl 67,

May/June 2005

Depression and Cardiovascular Disease Depression is a risk factor for development of CAD

Multiple long-term studies show a RR of > 1.6 for developing CAD in those who were depressed

Appears to be “dose related” with more severe depression leading to CAD

Increased prevalence of depression in patients with CAD 30-50% with depressive symptoms 15-20% with major depressionFrasure-Smith & Lesperance, Can J Psychiatry 51:2006

Depression and Cardiovascular Disease

Increased mortality post-MI in depressed patients RR for death is 2-2.5 among

depressed patients Some data that same is true for

post-bypass, angioplasty, or angiographically documented CAD

Frasure-Smith & Lesperance, Can J Psychiatry 51:2006

Cumulative Mortality for Depressed and Nondepressed Patients Months After An MI

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Depressed (n=35)

Non-depressed (n=187)

Depression and CAD: Why the Link?

Life style choices (e.g. smoking, exercise, dietary habits, etc.)

Poorer health care or non-compliance

Use of antidepressant or other psychotropic medications

Suicide

Depression and CAD: Why the Link? HPA axis and Sympathoadrenal system (role of

cortisol, CRF, NE) Autonomic nervous system dysregulation;

decreased heart rate variability (HRV) Low HVR is predictor of CAD mortality Low HVR lower in CAD patients with depression

Alterations in platelet receptors or reactivity Immuno-reactive factors Omega-3 Polyunsaturated Fatty Acids

Inverse relationship between Omega-3 FA and (1) CAD mortality, and (2) depression

Skala et al. Can J Psychiatry 51:2006

Treatment of Depression with CAD Newer antidepressants are treatment of

choice Medications improve mood, quality of life Do medications increase survival?

SADHEART (Sertraline & Depression Heart Attack Randomized Trial)

Does cognitive therapy increase survival? ENRICHD (Enhanced Recovery in Coronary

Heart Disease)

SADHEART Trial 369 patients with MDD, mean HAM-

D=19.6 74% had an MI; 26% had unstable angina Double-blind, flexible dose sertraline (50-

200mg) vs placebo for 24 weeks after two week placebo wash-out (mean dose was 68 mg)

Sertraline was safe in this population No difference in left ventricle ejection fraction No ECG changes No BP changes

SADHEART Trial No significant difference in severe

cardio-vascular events (MI, re-hospitalization, death), though there were less in Sertraline group

For all patients, non-significant difference on HAM-D change scores

For patients with previous depression, sertraline was more effective than placebo

There was a high placebo response rate

ENRICHD Study Almost 2500 participants post MI:

depressed and/or having low social support CBT vs. usual care; seriously depressed

patients also could receive sertraline Depression improved more in CBT group Up to 4-year survival showed no

differences in MI recurrence or death; those who received SSRI did better (but not randomly assigned)

JAMA 2003: 289

CREATE Trial Canadian Randomized Evaluation of

Antidepressant and Psychotherapy Efficacy Trial

Citalopram (up to 40 mg) superior to placebo in reducing depression in CAD patients with MDE, with very few adverse events

Interpersonal therapy (ITP) was no different than usual clinical care

Lespérance et al: JAMA 297:2007

Depression and Mortality 10 Years After a Stroke

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MinorDepression

(n=17)

MajorDepression

(n=20)

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MajorDepression

(n=20)Morris PLP, et al. 1993

Stroke and Depression

Depression increases the risk of stroke (by four-fold) in people under age 65

Up to 50% develop post stroke depression Probable relationship to left frontal brain area Treatable condition (antidepressants,

psychostimulants) Suggestion that when depression improves

with treatment, cognition may also improve

Berg et al: Stroke: 2003, 34Salaycik et al: Stroke: 2007, 38

Pain Depression

Bidirectional Relationship

Pain and Depression An average of 65% of depressed patients

have symptoms of pain Between 20-80% of patients with pain have

depression Pain makes recognition of depression more

difficult and treatment less successful Depression makes treatment of pain more

difficult and less successful Integrated treatments that address both

problems have best outcomesBair et al: Arch Internal Medicine 2003;163:2433

Pain and Depression Some data indicating that TCAs have

analgesic properties greater than seen with SSRIs

Dual action agents may also have analgesic properties (duloxetine and fibromyalgia)

Anticonvulsants (e.g. gabapentin) have analgesic properties (peripheral neuropathy) but have questionable effects on depression

Burden on Caregivers Emotional strain Physical demands Uncertainty Fear of patient dying Altered role/lifestyle Multiple demands of

others in household

Financial burdens Changes in sexual

relationship Questions about

adequacy of care Existential

concerns

Suicide Rates, 2003

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< 14 15-24 25-34 35-44 45-54 55-64 65-74 75-84 > 85

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Suicide Rates, 2003

Suicide Risk Factors Age Sex Race Hopelessness Previous suicide attempt Being alone Medical Illness Alcohol, drugs Unemployed

Santa Rosa: couple plan careful double suicide From the Associated Press

A husband and wife despondent over her failing health hanged themselves in a meticulously coordinated double suicide, shocking the couple's affluent Sonoma County community, authorities said.

The couple, who were married 26 years, wrote four suicide notes -two to police and one each to family members – according to investigators. They set out their wills, bills and keys, cleaned the house and unlocked their front door. A note inside the door discovered by a neighbor - concerned about the mounting mail and newspapers - described where the bodies could be found, police said.

Friends said Karen Andrews grew frail after a hysterectomy last year, and began suffering chronic pain, sleeplessness, and depression. The normally sociable pair, who volunteered with their homeowners association and local charities, had started to withdraw from others in recent months, friends said.The couple moved to Santa Rosa from Chicago five years ago after successful 'careers in the software industry settling in a new neighborhood, of 3,000-plus-square-foot homes selling for about $800,000.Each had a grown son from former marriages living in the San Francisco Bay Area. They also had a granddaughter.Santa Rosa police, said the couple's notes , clearly indicated that they had acted together. One addressed to police said that committing suicide is not a crime and that they had died together willingly.

Suicide and Medical Illness Specific illnesses have been reported

to have an increased rate of suicide CNS diseases: Huntington’s, MS,

Epilepsy, Spinal cord injury, DTs HIV/AIDS Cancer, particularly head/neck Chronic renal failure Systemic lupus erythematosus (SLE)

Suicide Risk and Medical Illness Population study of > 66 years of age Increased risk of suicide: CHF, COPD,

Seizures, Depression, BPD, Severe pain

Higher risk for patients with > 1 disorder

Majority of patients visited their MD in weeks before suicide

Juurlink et al: Arch Internal Medicine 2004;164:1179

Potential Predisposing Factors to Suicide in Medical Illness Chronic Debilitating Painful Downhill course Embarrassing Life-threatening

Stigmatizing Cognitively

impairing Dependency Irritability Inability to cope

Depressive Disorders:Treatment Goals

TreatmentTreatment

Reduce/RemoveReduce/RemoveSigns, SymptomsSigns, Symptoms

Minimize Relapse/Minimize Relapse/Recurrence RiskRecurrence RiskRestoreRestore

Role/Role/FunctionFunction

Adapted from WPA/PTD Educational Program on Depressive DisordersAdapted from WPA/PTD Educational Program on Depressive Disorders

Physical HealthCognition

Mood, Cognition and Health in Late Life

Complex InteractionsComplex Interactions

Age Mood

Therapeutic Approaches

Education and support Psychotherapies

PsychodynamicCognitiveGroupGrief Work

Family involvement Spiritual issues

Reaction to Medical Illness

Loss of sense of indestructibility (omnipotence)

Loss of connectedness to others and to one’s body

Loss of control over one’s life and world (helplessness)

Potential loss of logic, reasoning, perspective

Chronic Illness And Grieving

“A chronic disease or physical handicap, whatever else it may mean, also constitutes a loss--of time, function, appearance--and as such it has to be acknowledged and mourned…

Our braces, limps, drugs, weaknesses are a constant reminder. From this perspective it may be more remarkable that we are not crying all the time”.

Zola IK: Missing Pieces: A chronicle of living with disability. 1982.

Grief Work

Anticipatory Grief Losses

Bodily FunctionSocial StatusFinancial StabilitySexual Function

Psychological Considerations

Facilitation of grief and mourning accepting reality of the loss experiencing the pain of loss adjusting to new objective &

subjective reality of life re-investing energy into new self-

concept

Psychological Considerations

Achievement of mastery over feelings: dependency, abandonment, helplessness

Provision of meaning to the experience

Potential modifications

Cognitive Aspects Consider cognitive distortions vs

reality Examine long-lasting schemata Correct maladaptive thoughts Useful techniques include guided

imagery and behavioral tasks Advantages: Structure and short-

term

Psychiatric Disorders in Terminally Ill Patients

Depression Anxiety disorders Delirium Dementia Adjustment disorders

Anxiety may be related to: Underlying anxiety disorder

(panic disorder, generalized anxiety disorder or post-traumatic stress disorder)

Fear of death and the dying process itself

Spiritual or existential concerns

Anxiety and Terminal Illness

“the active total care of patients whosedisease is not responsive to curative treatment. Control of pain, of other symptoms and of psychological, social and spiritual problems is paramount. The goal of palliative care is achievement of the best possible quality of life for patients and their families.”

(WHO, 1990)

Supportive/Palliative Care

Adequate end of life care must expand beyond symptom control alone Psychiatric Psychosocial Spiritual Existential: the challenge of

finding meaning at the end of life

(Breitbart et al 2004)

Supportive Care

Treatment of “Spiritual Suffering”

Control physical symptoms Provide a supportive presence Encourage life review to assist in

recognizing purpose and meaning Explore guilt, remorse, forgiveness Reframe goals into what can be

accomplished Consider use of meditation, guided imagery,

and the arts with focus on healing not cureRousseau: J Clin Oncology 18:2000

Physician Assisted Dying (Suicide) Arguments for

Patient autonomy Relief of suffering

—life is intolerable Non-abandonment Not all who ask for

this are depressed

Quill & Battin: Physician Assisted Dying, 2004

Arguments against Killing is wrong Loss of M.D.

integrity Risk of abuse Seekers are

clinically depressed

Safeguards for Physician Assisted Dying Palliative care has become ineffective

or unacceptable to patient Informed consent has been given Diagnosis and prognosis are clear Independent 2nd opinion has occurred Accountability can be establishedQuill & Battin: Physician Assisted Dying, 2004

Pharmacologic Options Tricyclics (TCA): imipramine, desipramine,

nortriptyline, amitriptyline Serotonin reuptake inhibitors (SSRI):

fluoxetine, fluvoxamine, sertraline, paroxetine, citalopram, escitalopram

SNIRs (venlafaxine and duloxetine) Bupropion Nefazodone Mirtazapine Monoamine oxidase inhibitors (MAOI)

Use of Antidepressants in the Medically Ill No evidence-based studies showing

superiority of any antidepressant Be aware of AD’s with high side effect

burden (TCA) Make note of other medications taken

and possible drug-drug interactions (e.g. cytochrome P 450 enzyme system)

Be aware of decreased hepatic function and adjust dose

Antidepressant “Augmenters” An additional antidepressant

Bupropion, Tricyclic, SSRI, SNRI, Mirtazapine, MAOI

Lithium carbonate Thyroid hormone Stimulants Dopaminergic agents Buspirone Atypical antipsychotics

(IN-)Adequacy of Treatment

Many depressed patients receive inadequate treatment In one study, only 23% of trials used adequate

doses Nearly half improved once given adequate doses

Duration too brief is another source of failure In one study, 25% of previous nonresponders to

various antidepressants responded when trial was extended from 4 to 6 weeks (vs. 8% of placebo subjects)

Indications for ECT

Life-threatening depression

Inability to take medication

Contraindications to medication

Lack of response to medication

Conclusions Depression in the medically ill is frequent,

associated with increased medical and functional morbidity, and with suicide

Control of pain in medically ill is crucial Attention to physical, psychological, and

spiritual concerns are necessary Use of medication, psychotherapy or

counseling, family involvement, and complementary treatments in an integrated manner results in best outcomes