Depression in the Medically Ill

1
Depression in the Medically Ill

• Ira Lesser, M.D.
• Chair, Department of Psychiatry
• Harbor-UCLA Medical Center
• Professor, Department of Psychiatry and
  Biobehavioral Sciences
• Geffen School of Medicine at UCLA

2
Disclosures

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

3
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

4
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

5
What I had begun to discover is that
mysteriously and in ways that are totally remote
from normal experience, the gray drizzle of
horror induced by depression takes on a quality
of physical painit comes to resemble the
diabolical discomfort of being imprisoned in a
fiercely overheated room William Styron,
Darkness Visible
6
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

7
Occurrence of Depression

• Point prevalence 45
• Women 56
• 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

8
Prevalence Of Major Depression by Locus of Care
Percent of Population
Katon and Sullivan. J Clin Psychiatry.
198951(suppl 6)3.
9
Disease Burden in Established Market Economies,
1990

• Ischemic heart disease 9.0
• Unipolar major depression 6.8
• Cardiovascular 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

10
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
• Patients unwillingness to discuss depression

11
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

12
Diagnostic Approaches in the Medically Ill

• Inclusion approach count all symptoms
• Etiological approach exclude symptoms if
  physically-based
• Substitutive approach modify criteria

13
Impact Of Depression In Chronic Medical Illness
Morbidity And Mortality
Economic Impact
Treatment Implications
Maladaptive Effects
14
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. 199618215.
15
Organic Differential Diagnosis

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

16
Prevalence of Depressive Disorders in Various
Patient Populations
General population
5.8
Chronically ill
9.4
Hospitalized
33.0
Geriatric inpatients
36.0
Cancer outpatients
33.0
Cancer inpatients
42.0
Stroke
47.0
MI
45.0
Parkinsons disease
39.0
0
10
20
30
40
50
Prevalence
There is a range of percentages depending on
the study.
Adapted from WPA/PTD Educational Program on
Depressive Disorders
17
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

18
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

19
Conditions Associated with Apathy

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

20
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
  depression
• Van Reekum et al J Neuropsychiatry Clin Neurosci
  172005

21
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

22
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

23
Depression and Cardiovascular Disease

• Depression is a risk factor for development of
  CAD
• Multiple long-term studies show a RR of gt 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 depression
• Frasure-Smith Lesperance, Can J Psychiatry
  512006

24
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
  512006

25
Cumulative Mortality for Depressed and
Nondepressed Patients Months After An MI
Depressed (n35)
Non-depressed (n187)
Frasure-Smith et al., 1993
26
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

27
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 512006

28
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)

29
SADHEART Trial

• 369 patients with MDD, mean HAM-D19.6
• 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

30
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

31
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

32
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 2972007

33
Depression and Mortality 10 Years After a Stroke
Morris PLP, et al. 1993
34
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, 34
• Salaycik et al Stroke 2007, 38

35
Pain DepressionBidirectional
Relationship
36
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 outcomes
• Bair et al Arch Internal Medicine 20031632433

37
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

38
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

39
Suicide Rates, 2003
40
Suicide Risk Factors

• Age
• Sex
• Race
• Hopelessness
• Previous suicide attempt
• Being alone
• Medical Illness
• Alcohol, drugs
• Unemployed

41
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.

42
Suicide and Medical Illness

• Specific illnesses have been reported to have an
  increased rate of suicide
• CNS diseases Huntingtons, MS, Epilepsy, Spinal
  cord injury, DTs
• HIV/AIDS
• Cancer, particularly head/neck
• Chronic renal failure
• Systemic lupus erythematosus (SLE)

43
Suicide Risk and Medical Illness

• Population study of gt 66 years of age
• Increased risk of suicide CHF, COPD, Seizures,
  Depression, BPD, Severe pain
• Higher risk for patients with gt 1 disorder
• Majority of patients visited their MD in weeks
  before suicide
• Juurlink et al Arch Internal Medicine
  20041641179

44
Potential Predisposing Factors to Suicide in
Medical Illness

• Chronic
• Debilitating
• Painful
• Downhill course
• Embarrassing
• Life-threatening

• Stigmatizing
• Cognitively impairing
• Dependency
• Irritability
• Inability to cope

45
Depressive DisordersTreatment Goals
Treatment
Minimize Relapse/ Recurrence Risk
Reduce/Remove Signs, Symptoms
Restore Role/ Function
Adapted from WPA/PTD Educational Program on
Depressive Disorders
46
Mood, Cognition and Health in Late Life
Complex Interactions
Age
Mood

• Physical Health

Cognition
47
Therapeutic Approaches

• Education and support
• Psychotherapies
• Psychodynamic
• Cognitive
• Group
• Grief Work
• Family involvement
• Spiritual issues

48
Reaction to Medical Illness

• Loss of sense of indestructibility (omnipotence)
• Loss of connectedness to others and to ones body
• Loss of control over ones life and world
  (helplessness)
• Potential loss of logic, reasoning, perspective

49
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.

50
Grief Work

• Anticipatory Grief
• Losses
• Bodily Function
• Social Status
• Financial Stability
• Sexual Function

51
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

52
Psychological Considerations

• Achievement of mastery over feelings dependency,
  abandonment, helplessness
• Provision of meaning to the experience
• Potential modifications

53
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

54
Psychiatric Disorders in Terminally Ill Patients

• Depression
• Anxiety disorders
• Delirium
• Dementia
• Adjustment disorders

55
Anxiety and Terminal Illness

• 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

56
Supportive/Palliative Care

• the active total care of patients whose
• disease 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)

57
Supportive 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)

58
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 cure
• Rousseau J Clin Oncology 182000

59
Physician Assisted Dying (Suicide)

• Arguments for
• Patient autonomy
• Relief of sufferinglife 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

60
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 established
• Quill Battin Physician Assisted Dying, 2004

61
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)

62
Use of Antidepressants in the Medically Ill

• No evidence-based studies showing superiority of
  any antidepressant
• Be aware of ADs 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

63
Antidepressant Augmenters

• An additional antidepressant
• Bupropion, Tricyclic, SSRI, SNRI, Mirtazapine,
  MAOI
• Lithium carbonate
• Thyroid hormone
• Stimulants
• Dopaminergic agents
• Buspirone
• Atypical antipsychotics

64
(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)

65
Indications for ECT

• Life-threatening depression
• Inability to take medication
• Contraindications to medication
• Lack of response to medication

66
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