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1 Depression in Primary Care Mourning or Melancholia? Financial Disclosures none Descartes Li, M.D. Clinical Professor University of California, San Francisco By Max Halberstadt - Public Domain, Outline Introduction and Epidemiology Trap of Meaning Depression with Apathy, r/o dementia Outline Introduction and Epidemiology Trap of Meaning Depression with Apathy, r/o dementia 1

2 Case Vignette 72yo man is depressed in the context of the death of his wife one month ago. Which of the following is the best diagnosis? a) Normal bereavement b) Major depressive disorder c) Bipolar depression d) Neurocognitive disorder with apathy Diagnosis of Depression Key issues 1) Rule out Medical conditions causing psychiatric symptoms 2) Rule out Substance abuse or iatrogenic medications 3) Rule out Bipolar disorder (ie, screen for mania or hypomania) The Three S s of the Psychiatric Interview 1) S Stressors/triggers 2)S Suicidality 3)S Substance Abuse Prevalence of Psychiatric Disorders* Disorder Lifetime prevalence(%) Any mood disorder Major depression Dysthymia 4.30 Bipolar I 3.31 Bipolar II 2.33 Any anxiety disorder Social anxiety 4.97 Any drug use disorder *Conway KP et al. Lifetime Comorbidity of DSM-IV Mood and Anxiety Disorders and Specific Drug Use Disorders: Results of the National Epidemiologic Survey on Alcohol and Related Conditions. J Clin Psychiatry 2006;67:

3 Prevalence of Psychiatric Disorders Disorder Lifetime prevalence(%) Post-traumatic stress disorder in women (1) 10.1 Post-traumatic stress disorder in men (1) 4.9 Suicidal ideation (2) 13.5 Suicidal plan (2) 3.9 Suicide attempt (2) 4.6 Why shouldn t I be depressed? 1. Bromet E et al. Risk Factors for DSM-III-R Posttraumatic Stress Disorder: Findings from the National Comorbidity Survey. Am J Epidemiol 1998; 147: Kessler RC et al. Prevalence of and Risk Factors for Lifetime Suicide Attempts in the National Comorbidity Survey. Arch Gen Psychiatry. 1999;56: Life means suffering 3

4 -glut-of-antidepressants/?_r=0 Is there a glut of coffee, alcohol? How about insulin, Lipitor? The Crazy State of Psychiatry, by Marcia Angell Turner E et al. Selective Publication of Antidepressant Trials and Its Influence on Apparent Efficacy. NEJM (3):252 4

5 In Defense of Antidepressants American Psychiatric Association Practice Guidelines for Depression Agency for Health Care Policy and Research, Clinical Practice Guidelines Cochrane Review 54.html In Defense of Antidepressants, by Peter Kramer (The New York Times, July 9, 2011) Bottom Line: For mild depression, watchful waiting is a reasonable option Outline Epidemiology Trap of Meaning Depression with Apathy, r/o dementia Case Vignette 72yo man is depressed in the context of the death of his wife. Pair discussion: How long would you wait before diagnosing MDD? a) One month b) Two months c) Six months d) One year or more 5

6 Mourning and Melancholia Major Depressive Episode Diagnostic Criteria Criterion A. Five or more of the following MDE = 2wks of d mood anhedonia 5 symptoms (with 1 sx in blue) signif wt ( or ) insomnia or hypersomnia Ψmotor agitation/retardation (PMA/PMR) fatigue or anergia guilt/worthlessness (G/W) d concentration recurrent thoughts of death or SI Sleep Interest Guilt Energy Concentration Appetite Psychomotor Suicide Major Depressive Episode Diagnostic Criteria (cont.) Criterion B. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. Criterion C. The episode is not attributable to the physiological effects of a substance or to another medical condition. Criteria A-C represent a major depressive episode Major Depressive Disorder Diagnostic Criteria (cont.) Criterion D. The occurrence of the MDE is not better explained by schizoaffective disorder, schizophrenia, etc. Criterion E. There has never been a manic episode or a hypomanic episode. *note: deletion of Bereavement exclusion in DSM 5 6

7 No Bereavement in DSM-5 No Bereavement exclusion in DSM-5 Grief is still exists Mild depressive episodes can be treated with psychotherapy alone %20Fact%20Sheet.pdf Normal Sadness Per Horvitz and Wakefield, 3 criteria: Has an environmental trigger Roughly proportionate in intensity to loss Ends when loss situation ends Horwitz AV, Wakefield JC. The Loss of Sadness: How Psychiatry Transformed Normal Sorrow into Depressive Disorder. New York, NY:Oxford University Press; (p.16) Problems with normal sadness What constitutes a trigger? Depression vs. Grief When is the response proportionate to the loss? Does the presence of a recent major loss somehow make it more likely that depression will spontaneously resolve? 7

8 Case Vignette 72yo man is depressed in the context of the death of his wife. He has had 6 prior episodes of depression in the past. Each episode lasted 2-9 months and he met DSM criteria for depression in each of them. Pair discussion: Which of the following is the best diagnosis? a) Normal bereavement b) Major depressive disorder c) Bipolar depression d) Neurocognitive disorder with apathy Depression vs. Grief Beware the Trap of Meaning! Individuals who fulfill MDD criteria after loss of significant other have NOT been shown to recover at a greater rate than MDD alone Specifiers for Major Depressive Episodes Atypical Catatonia Melancholic Mixed features Postpartum onset Psychotic features What is melancholic depression? Melancholic depression is characterized by significant psychomotor symptoms, insomnia, early morning awakening, worsening of mood in the morning (called diurnal variation in mood), significant anorexia, and a lack of reactivity to pleasurable stimuli. 8

9 Outline Epidemiology Trap of Meaning Depression with Apathy, r/o dementia Case vignette 28yo man, recently married 6m ago, appears well, but quickly breaks down: He says he s made a terrible mistake for imposing himself on his wife. I m a terrible person who cheated on my wife and on my taxes. He reports two months of depressed mood, crying spells, as well as oversleeping and not being able to get out of bed. In addition, his energy has been low, he has no appetite, and he can t focus at work. Would you diagnose him with Major Depressive Disorder? Would you prescribe an antidepressant? I cheated on my wife and on my taxes. Case vignette Do we accept his reasons as the causes of his depression? The Trap of Meaning Finding an explanation that appears meaningful and adopting it as causal. Even when confronted with an intuitively plausible set of reasons, we must look for objective causes. Lyketsos CG, Chisolm MS. The trap of meaning: a public health tragedy. JAMA Jul 22;302(4): doi: /jama

10 "...humans are incredibly good at linking cause and effect sometimes too good..." Reason vs. Cause "... it means that when you see something occur in a complex adaptive system, your mind is going to create a narrative to explain what happened even though cause and effect are not comprehensible in that kind of system." Embracing Complexity, An interview with Michael Mauboussin by Tim Sullivan Harvard Business Review 2011 Reason" and "cause" are not contradictory, nor are they synonymous Confusion between them: delays mental health care for mood disorders much more than care for diabetes, heart disease, stroke and cancer (?) Does the Trap of Meaning occur with mania or hypomania? Yes! Trap of Meaning references: Kendler KS, Gardner CO. Dependent Stressful Life Events and Prior Depressive Episodes in the Prediction of Major Depression: The Problem of Causal Inference in Psychiatric Epidemiology. Arch Gen Psychiatry. 2010;67(11): Kendler KS, Myers J, and Halberstadt LJ. Do reasons for major depression act as causes? Molecular Psychiatry (2011) 16, ; doi: /mp ; published online 8 March Kendler KS, Myers J, and Halberstadt LJ. Should the Diagnosis of Major Depression made Independent of or Dependent upon the Psychosocial Context? Psychol Med May ; 40(5): doi: /s Lyketsos CG, Chisolm MS. The trap of meaning: a public health tragedy. JAMA Jul 22;302(4): doi: /jama

11 What are the Validated Risk Factors for Depression? Major Depressive Episode: SIG E CAPS criteria Depressed mood (or anhedonia), plus: S Sleep symptoms I lack of Interest. G feelings of Guilt E lack of Energy. C--lack of Concentration. A--lack of Appetite. P--Psychomotor changes S--thoughts of Suicide Take Home Message Be aware of "explaining away" mood episodes. Outline Epidemiology Trap of Meaning Depression with Apathy, r/o dementia Lyketsos CG, Chisolm MS. The trap of meaning: a public health tragedy. JAMA Jul 22;302(4): doi: /jama

12 Cyclothymic Disorder Bipolar I Disorder Bipolar II Disorder Major Depressive Disorder Dysthymic Disorder National Comorbidity Study (NCS) 2007 Lifetime (and 12-month) prevalence estimates: [9282 Respondents] for BP-I 1.0% (0.6%), for BP-II, 1.1% (0.8%) for subthreshold BPD 2.4% (1.4%). Subthreshold BPD was defined as recurrent hypomania without a major depressive episode or with fewer symptoms than required for threshold hypomania. Merikangas, K. R. et al. Arch Gen Psychiatry 2007;64: Bipolar Disorder Symptoms Are Chronic and Predominantly Depressive 146 Bipolar I Patients followed 12.8 yrs 6% 9% 86 Bipolar II Patients followed 13.4 yrs 1%2% 32% 53% % of Weeks 50% 46% Asymptomatic Depressed Hypo/manic Cycling/mixed Study 1 Study 2 1. Judd LL, et al. Arch Gen Psychiatry : Judd LL, et al. Arch Gen Psychiatry 2003;60: Conversion refers to when individuals previously diagnosed with unipolar depression develop a mania or hypomania. The individual converts to bipolar disorder. St Paul s Conversion 12

13 Test Question A 22yo woman is admitted to the hospital for severe depression with suicidal ideation. What is the likelihood that she will have a hypomanic or manic episode in the next five years? 1) 3-5% 2) 6-10% 3) 11-20% 4) 25-50% 5) Greater than 50% Summary study n Conversion rate: (per year) Akiskal HS; et al 1995 Coryell et al Goldberg JF et al Angst J et al % (1.1%) % (1.0%) 74 41% (2.7%) % (3.0%) Years of f/u comment 11 Mood lability predictive 10 Avg. age >35 15 Younger pts (<25yo) and hospitalized 13 Linear rate of conversion, severely ill Specifiers (that are risk factors for bipolar disorder) Atypical Catatonia Melancholic (not a risk factor) Mixed features Postpartum onset Psychotic features Take home messages Several studies looking at the course of major depressive disorder are fairly consistent: Patients initially diagnosed with unipolar depression are at high risk for converting to bipolar disorder. Several risk factors are associated with conversion: Age of onset (ie, <25yo) Family history of bipolar disorder Number of depressive episodes (ie, > six) Post-partum onset Psychotic features Severity (eg, hospital admission) The conversion rate is about 1-2% per year, perhaps slightly higher in the first 4 years, but really no obvious plateau ing of risk (see Angst) 13

14 Outline Epidemiology Trap of Meaning Depression with Apathy, r/o dementia Case Vignette 71yo man complains of poor memory and depressed mood. How would you differentiate between dementia and depression? Major Depressive Episode: SIG E CAPS criteria Depressed mood (or anhedonia), plus: S Sleep symptoms I lack of Interest. G feelings of Guilt E lack of Energy. C--lack of Concentration. A--lack of Appetite. P--Psychomotor changes S--thoughts of Suicide Major Neurocognitive Disorder Cognitive impairment due to depression Insight Not aware Aware and concerned Course Slow, often subtle (onset over month/years) More rapid(onset over days and weeks) Social skills Maintained Lost Memory Loss of recent, not remote memory. Random memory loss Effort Fair Poor, or variable *May not be distinguishable, or may be co-morbid 14

15 Dementia vs. Depression Depression requires either sad mood or anhedonia Depression may be the prodrome of dementia Depression, even the context of dementia, may respond well to antidepressants or behavioral activation/socialization Outline Epidemiology Trap of Meaning Depression with Apathy, r/o dementia Outline Epidemiology Trap of Meaning Depression with Apathy, r/o dementia 15

16 Or so What? My treatment fails only in curable cases. -Galen 129 AD c. 216 Situation treatment Life stressor or Identify predisposing factors normal sadness Psychotherapy, CBT or existential? Major Depressive disorder Bipolar depression Depression with apathy Psychotherapy Antidepressants Avoid antidepressants Mood stabilizers refer to psychiatrist? Rule out neuropsychiatric disorder (dementia, Parkinson s, etc) The person who takes medicine must recover twice, once from the disease and once from the medicine. Case Vignette 72yo man is depressed in the context of the death of his wife one month ago. Attributed to William Osler Which of the following is the best diagnosis? a) Normal bereavement b) Major depressive disorder c) Bipolar depression d) Neurocognitive disorder with apathy By Unknown - [1], CC BY 4.0, 16

17 Outline Epidemiology Trap of Meaning Depression with Apathy, r/o dementia Jaspers: No single method or technique in psychiatry is sufficient to completely understand the patient, we must use them all separately, with a clear knowledge of when they are most useful, based on their strengths, and when they are inaccurate guides, based on their weaknesses