Depression in Medical Settings

1. Depression in Medical Settings APM Resident Education Curriculum Pamela Diefenbach, MD, FAPM Lead Psychiatrist, Mental Health Integration in Primary Care Veterans Affairs Greater Los Angeles Healthcare System Clinical Professor of Psychiatry & Biobehavioral Sciences UCLA David Geffen School of Medicine & UCLA Semel Institute of Neuroscience Updated Summer 2011 Robert C. Joseph, MD, MS Summer 2013 SermsakLolak, MD

2. Learning Objectives By the end of the lecture, the viewer will be able to: • Describe the types and characteristics of depression in a variety of medical settings • Appreciate the diverse medical conditions, medication therapies and psychiatric conditions that contribute to depressive symptoms • List the evidence-based therapies for depression in the medically ill

3. Overview • Classification of depression • Prevalence in medical Settings • Evaluation • Time course and associations • Treatment

4. Depression in medical illness • Coexistence • Induced by illness or medications • Cause or exacerbate somatic symptoms

5. Classification of Depression Major depression Persistent Depressive Disorder (DSM5) Adjustment disorder Mood disorder due to general medical condition, with depressive features Substance-induced mood disorder Mixed anxiety depression (moved to Section III in DSM5)

6. Some Medical Conditions Closely Associated with Depressive Symptoms Stroke Parkinson’s disease Multiple sclerosis Huntington’s disease Pancreatic cancer Diabetes Heart disease Hypothyroidism Hepatitis C HIV/AIDS

7. Difficulties in Diagnosing Depression in the Medically Ill • Medical symptoms can overlap with depressive symptoms • Fatigue • Anorexia and/or weight loss • Poor concentration • Anhedonia and or apathy • Difficult to make the attribution to either the psychological or medical conditions • Medications and interactions can contribute to depressive symptoms

8. Depression Criteria Controversy Exclusive criteria Substitutive criteria Inclusive criteria

9. Exclusive Criteria • Exclusive proponents: The clinician excludes those criteria they can directly attribute to the medical condition • Difficult to weigh and decide • Identifies the most severe forms of depression • May miss milder forms of depression & thus missing opportunities to intervene

10. Substitutive Criteria • More weight is given to the psychological symptoms of depression, not the somatic symptoms of depression • Substitution of symptoms such as irritability, tearfulness, social withdrawal • Unclear which symptoms to include or exclude • Excludes some somatic symptoms • May miss severe forms of depression • Approach not widely adopted

11. Inclusive Criteria Inclusive approach: all symptoms are included without any weight to medical condition Show to be most sensitive and reliable approach

12. Prevalence in Medical Settings

13. Prevalence in Primary Care Clinics 5-15% depends on population, settings

14. Depression and Heart Disease • Major depression: 16-23% • Depressed mood: 37-35% • Depression associated with: • Myocardial infarction • Angioplasty • Congestive heart failure • Coronary bypass graft surgery • Coronary artery disease • Independent risk factor for sudden death and morbidity

15. Depression and Cancer Associated more with pancreatic, lung, brain and oropharyngeal cancers Prevalence 25% (17-32%) in meta-analysis of 24 studies Comorbid with anxiety in half of patients Depression is associated with a decrease in treatment compliance Can also be side effects of chemotherapy/steroids

16. Depression and Diabetes Up to one-third of patients with Type 2 DM has depression Depression can lead to poor compliance and poor medical outcomes Among patients with Type 2 DM, those with comorbid depression appear to be at greater risk for death from non-cardiovascular, non-cancer causes compared to those without depression

17. Depression in Neurological Diseases • Parkinson’s disease: up to 50% • Multiple sclerosis: Up to 50% • Huntington’s disease: Up to 32% • Epilepsy: 10-55% • Post-stroke depression: 9-13% • Alzheimer’s dementia: 10-32%

18. Increased Depression Chronic hepatitis C infection Peptic ulcer disease Inflammatory bowel disorders Fibromyalgia Chronic fatigue syndrome Sleep apnea Systemic lupus erythematosus Rheumatoid arthritis Scleroderma Pain syndromes

19. Evaluation

20. Common Causes of a “Depression” Consult

21. Medical Symptoms Mimicking Depressive Symptoms • Apathy • Weight loss • Change in sleep • Psychomotor retardation • Fatigue • Difficulty concentrating • Thoughts of death but not depressed mood

22. Differential Diagnosis • Normal reaction • Demoralization syndrome • Adjustment disorders • Alcohol and other drugs intoxication or withdrawal • Major depression • Depression secondary to general medical illness or treatment • Psychological Factors Affecting Other Medical Conditions (DSM5) • Delirium • Untreated pain

23. Demoralization Syndrome From Wellen M, Current Psych Report 2010

24. Demoralization • May be the most common reason for psychiatric evaluation of medically-ill patients, though their physicians typically request a “depression” evaluation. • Demoralization is an understandable response, albeit very distressing, to the situation (serious illness, hospitalization, agonizing treatment) • Symptoms include anxiety, guilt, shame, depression, somatic complaints or preoccupation • Can cause extreme frustration, anger, discouragement, non-compliance, and even thoughts of suicide / death wish

25. Perhaps more common than MDD in medical patients (Mangelli et al, J Clin Psych 2005) • Some overlap with but clinically distinct from the diagnosis of major depressive disorder (Mangelli, 2005) • Clues to differentiate between MDD and demoralization (Wellen, 2010) • Major Depression:Anhedonia and nihilistic thinking coming from “within” (i.e., not responding to the external situation), severe neurovegetative symptoms • Demoralization: Mood reactivity (e.g. happy when family is around, or pain is better controlled)

26. Psychiatric Evaluation: Inpatient Challenges • Lack of privacy in shared rooms • Lack of confidentiality if family at bedside • Interruptions: • Patient off to procedures • Other staff coming to see patient • Patient resistant to see psychiatry

27. Psychiatric Interview: Outpatient Challenges • Patient may not show for the appointment • Cognitive impairment • Doesn’t want the evaluation • May not have access to extensive chart • Resistance to seeing psychiatry • “I’m not crazy! You need to help someone who’s really sick” • Stigma • Decision to include family if available

28. Time Course and Associations

29. Depression and Chronic Medical Illness • Increased prevalence of major depression in the medically ill • Depression amplifies ( increased both number and severity of) physical symptoms associated with medical illness • Comorbidity increases impairment in functioning • Depression decreases adherence to prescribed regimens • Depression is associated with increased heath care utilization and cost • Depression is associated with adverse health behaviors (diet, exercise, smoking) • Depression increases mortality associated with certain medical illness (e.g., heart disease) (adapted from Katon and Ciechanowski , 2002)

30. “It is important that somatic symptoms associated with depression should not be confused with somatoform disorders . . . Indeed, results from several surveys suggest that depression, rather than somatoform disorders, may account for most of the somatization symptoms seen in primary care.” (Tylee A, Gandhi P. The importance of somatic symptoms in depression in primary care. Prim Care Companion J Clin Psychiatry, 2005)

31. Factors associated with suicide in medical-surgical patients Rundell and Wise 2000 • Comorbid psychiatric illness, esp. Depression, Substance abuse, Personality disorder • Chronic illness, Debilitating illness • Painful illness, Disfiguring illness • History of recent loss of emotional support • Interpersonal problems with family or staff • Impulsivity

32. Service Utilization and Outcomes for Patients with Depression Rundell and Wise: 2000 • Increased E.R. visits • Lost days from work • Increased suicide attempts • Higher reports of poor physical health Johnson: 1992, Broadhead: 1990

33. Rx of depression in medical setting Identifying possible organic causes, e.g., thyroid, HIV, medications Appropriate management requires first establishing the most likely diagnosis that has caused depression (Rackley and Boswick, 2012)

34. Combine medications, supportive psychotherapy, psychoeducation Aware of pharmacokinetic (e.g., clearance) and pharmacodynamic (e.g., Cyt P 450) issues - although not all are clinically significant Mindful of additive sedative, anticholinergic effects from several meds ( e.g., pain meds, H2 blocker, antibiotics, antihistamine, steroids, TCAs)

35. Evidenced Based Treatments for Depression • Biological treatment • Antidepressant medications • Psychostimulants • Psychological interventions • Cognitive behavioral therapy • Interpersonal therapy • Electroconvulsive therapy

36. First Line Medication Treatment

37. Medications commonly associated with depressive symptoms Rackley & Bostwick Psych Clin North Am, 2012 AntiepilepticsAngiotensin-converting enzyme inhibitorsAntihypertensives (especially clonidine, methyldopa, thiazides) Antimicrobials (amphotericin, ethionamide, metronidazole) Antineoplastics (procarbazine, vincristine, vinblastine, asparaginase) Benzodiazepines, sedative–hypnotic agentsBeta-blockersCalcium channel blockersCorticosteroidsEndocrine modifiers (especially estrogens, leuprolide)InterferonIsotretinoinMetoclopramideNonsteroidal anti-inflammatory drugs (especially indomethacin) OpiatesStatins

38. Clinical Concerns 2D6 inhibitors can effect beta-blockers and potentiate fall in blood pressure and pulse (orthostatic) Cigarette smokers may need higher doses of mirtazapine Users of oral contraceptives may have more antidepressant side effects and need lower doses of many medications Certain SSRIs (paroxetine, fluoxetine) may decrease effectiveness of Tamoxifen (via CYP 2D6) - may want to use venlafaxine instead

39. Combining serotonergic and/or MAOI medications may cause 5HT syndrome • E.g., SSRI, TCAs, venlafaxine, mirtazapine, tryptans, linezolid, tramadol, meperidine • Citalopram FDA warning (8/23/2011) • Citalopram should not be used in doses >40mg qd due to concerns of QT prolongation • Citalopram should not be used in doses >20mg qd in patients with hepatic impairment, >60 years of age, 2C19 or 2D6 poor metabolizers

40. General Principles • Know the drug interactions of the medications you use most often • Look up drug interactions with any and all medicines • Be careful of hidden inhibitors or inducers • Grapefruit juice • Cigarette smoking • Oral contraceptive medications • Herbal medicines

41. Other adjunct agents • Psychostimulants can be helpful in anergic, depressed patients with cancer or organ transplants • Low dose atypical antipsychotic medications may also be helpful • Augmentation • Sleep • Anxiety/Agitation

42. In Transplant and Cancer Populations • Antidepressants can be helpful: be careful of metabolism and the organ effected by the transplant or cancer • Psychostimulants can be safe and effective • Cognitive behavioral therapy can be helpful for depression and anxiety

43. In Chronic Kidney Disease • SSRI: Sertraline considered to have least dependence on renal function • Bupropion: decrease dose – authorities advise caution as increased levels may produce seizure • Mirtazapine: decrease dose - 75% excreted unchanged in urine • SNRI: Venlafaxine may require dose reduction in renal impairment or dialysis • Duloxetine contraindicated in severe renal disease: active metabolite may accumulate and produce confusion

44. In Heart Disease • SADHART: Sertraline cardiac safe and effective in treating depression • Not powered to detect morbidity or mortality • Secondary analysis show some advantage in subgroup with recurrent depression • Subanalysis of SADHART data suggested that onset of depression before ACS, hx of MDD, baseline severity predicted sertraline response • CREATE: Citalopram effective in treating depression in cardiac patients • Interpersonal therapy not superior to placebo • Not designed to test effects on cardiac outcomes, mortality • ENRICHD: CBT reduced depression modestly at 6 months, but did not reduce mortality - No benefit of CBT at 30 months • MIND-IT: Mirtazapine is safe, but not different in both depression and cardiac outcomes at 18 months • Not powered to detect difference in cardiac outcomes • Tricyclic and heterocyclic anti-depressants are not considered safe post-MI

45. In Primary Care Populations • STAR*D: Protocol for treating treatment-refractory patients with medical and psychiatric co-morbidities • Modest effects starting with citalopram and moving to adjunct medications or changing medications • Collaborative Care / Integrated Models • PCP, Depression care manager, consulting psychiatrist working together

46. Treatment ResistanceFactors

47. Schulberg,1995 Simon,1993 Lin,1995 Up to 50% of patients stop antidepressants within three months

48. The Following Messages Improved Medication Compliance in the First Month • Take the medication daily • Antidepressants must be taken for 2 to 4 weeks for a noticeable effect • Continue to take medicine even if feeling better • Do not stop taking antidepressant without checking with the physician • Provide specific instructions regarding what to do to resolve questions regarding antidepressants • In addition: discussions about prior experience with antidepressants and discussions about scheduling pleasant activities also were related to early adherence

49. Take Home Messages • Depression in medically ill can be complex and multifactorial, and needs a thorough evaluation • Check drug-drug interactions for all the patient’s medications • Computer programs, mobile apps widely available • Medical conditions and depression affect each others’ symptomsand course, and affect the patient’s health related quality of life • Depression may be successfully treated by addressing medical conditions and utilizing biological, psychological and educational interventions

50. References • Broadhead WE, Blazer DG, George LK, et al. Depression, disability days, and days lost from work in a prospective epidemiologic survey. JAMA 1990;264(19):2524-8. • Carney RM, Blumenthal JA, Freedland KE, et.al. Depression and late mortality after myocardial infarction in the Enhancing Recovery in Coronary Heart Disease (ENRICHD) study. Psychosom Med 2004;66(4):466-74. • Coleman SM, Katon W, Lin E.Depression and Death in Diabetes; 10-Year Follow-Up of All-Cause and Cause-Specific Mortality in a Diabetic Cohort Psychosomatics 2013 ;54,( 5) :428-436 • Cozza KL, Armstrong SC, Oesterheld JR: Concise Guide to Drug Interaction Principles for Medical Practice: Cytochrome P450s, UGTs, P-Glycoproteins, Second Edition. Washington, DC, American Psychiatric Publishing, 2003 • Frasure-Smith N, Lesperance F, Talajic M. Depression following myocardial infarction. Impact on 6-month survival. JAMA 1993;270(15):1819-25. • Griffith JL, Gaby L. Brief psychotherapy at the bedside: countering demoralization from medical Illness. Psychosomatics. 2005 Mar-Apr;46(2):109-16.5. Glassman AH, O'Connor CM, Califf RM, et.al. Sertraline treatment of major depression in patients with acute MI or unstable angina. JAMA 2002;288(6):701-9. • Horwath E, Johnson J, Klerman GL, et al. Depressive symptoms as relative and attributable risk factors for first-onset major depression. Archives of General Psychiatry 1992;49(10):817-23. • Johnson J, Weissman MM, Klerman GL. Service utilization and social morbidity associated with depressive symptoms in the community. JAMA 1992; 267(11):1478-83.