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Depression in the Medically Ill

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. Disclosures. Grant support National Institute for Mental Health

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Depression in the Medically Ill

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  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 pain…it 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 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

  8. Prevalence Of Major Depression by Locus of Care Percent of Population Katon and Sullivan. J Clin Psychiatry. 1989;51(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 • Patient’s 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. 1996;18:215.

  15. Medication toxicities Cardiopulmonary disorders Neurological disorders Endocrine/Metabolic disorders Nutritional deficiencies Sleep disorders Infectious disorders Neoplasms Organic Differential Diagnosis

  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% Parkinson’s 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. 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 Depression vs. Apathy

  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 17:2005

  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 > 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 51:2006

  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 51:2006

  25. Cumulative Mortality for Depressed and Nondepressed Patients Months After An MI Depressed (n=35) Non-depressed (n=187) 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 51:2006

  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-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

  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 297:2007

  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 2003;163:2433

  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. 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 Burden on Caregivers

  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 suicideFrom 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: Huntington’s, 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 > 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

  44. Chronic Debilitating Painful Downhill course Embarrassing Life-threatening Stigmatizing Cognitively impairing Dependency Irritability Inability to cope Potential Predisposing Factors to Suicide in Medical Illness

  45. Depressive Disorders:Treatment 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 Physical Health Age Mood 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 one’s body • Loss of control over one’s 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

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