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Depression in Medical Settings

Depression in Medical Settings. Revised 2019: Christopher Wilson, DO, Iqbal Ahmed, MD Revised 2013: Sermsak Lolak , MD Revised 2011: Robert C. Joseph, MD, MS

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Depression in Medical Settings

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  1. Depression in Medical Settings Revised 2019: Christopher Wilson, DO, Iqbal Ahmed, MD Revised 2013: SermsakLolak, MD Revised 2011: Robert C. Joseph, MD, MS Original version: 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 Version of March 15, 2019 APM Resident Education Curriculum

  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. Depressive Disorders (DSM-5) Major Depressive Disorder Persistent Depressive Disorder (Dysthymia) Adjustment disorder With depressed mood Depressive Disorder Due to Another Medical Condition Substance/Medication-Induced Depressive Disorder Premenstrual Dysphoric Disorder

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

  6. 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

  7. Depression Criteria Controversy (Bukberg, et. al, 1984) Exclusive criteria Substitutive criteria Inclusive criteria

  8. 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

  9. 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

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

  11. Depression in medical illness • Coexistence • Induced by illness or medications • Causes or exacerbates somatic symptoms

  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. Other Conditions With 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. Medications commonly associated with depressive symptoms Antiepileptics * = studies showing mixed/inconclusive results.Angiotensin-converting enzyme inhibitors* (Boal et al, 2016; Gerstman et al, 1996)Antihypertensives (especially clonidine, methyldopa, thiazides) Antimicrobials (amphotericin, ethionamide, metronidazole) Antineoplastics (procarbazine, vincristine, vinblastine, asparaginase) Benzodiazepines, sedative–hypnotic agentsBeta-blockers* (Boal et al, 2016; Gerstman et al, 1996)Calcium channel blockersCorticosteroidsEndocrine modifiers (especially estrogens, leuprolide)InterferonIsotretinoinMetoclopramideNonsteroidal anti-inflammatory drugs (especially indomethacin) OpiatesStatins * (Parsaik et al, 2013)(Thompson et al, 2016) (Rackley & Bostwick Psych Clin North Am, 2012)

  23. Differential Diagnosis • Uncomplicated bereavement • 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 • Delirium, particularly the hypoactive type • Untreated pain

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

  25. 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

  26. Demoralization • 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)

  27. 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

  28. 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 • Treatment non-adherence • Decision to include family if available

  29. Time Course and Associations

  30. Impact of Depression in 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)

  31. “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)

  32. 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

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

  34. Treatment 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)

  35. Treatment of depression in medical setting Utilize medications, psychotherapies, and psychoeducation Be aware of pharmacokinetic (e.g., binding, CYP 450, clearance) and pharmacodynamic (neurotransmitter receptor and transporter effects) factors Be mindful of additive sedative, anticholinergic effects from several medications ( e.g., pain meds, H2 blockers, antibiotics, antihistamines, steroids, TCAs)

  36. Evidenced Based Treatments for Depression • Biological treatments • Antidepressant medications • Psychostimulants • Psychological interventions • Cognitive behavioral therapy • Interpersonal therapy • Supportive-expressive therapy • Electroconvulsive therapy • Transcranial magnetic stimulation

  37. First Line Medication Treatment (s)= strong inhibitor, (m)= moderate inhibitor, (w) weak inhibitor

  38. Clinical Concerns • 2D6 inhibitors can affect beta-blockers and potentiate fall in blood pressure and pulse (orthostasis) • Cigarette smokers may need higher doses of mirtazapine through CYP 1A2 induction • Users of oral contraceptives may have more antidepressant side effects and need lower doses of many medications • Antidepressants with CYP 2D6 inhibition may decrease effectiveness of Tamoxifen and Codeine (which are pro-drugs) • May want to consider alternatives such as venlafaxine and mirtazapine

  39. Clinical Concerns • Combining serotonergic and/or MAOI medications may cause Serotonin syndrome • E.g., SSRI, TCAs, venlafaxine, mirtazapine, triptans, linezolid, tramadol, meperidine • Citalopram FDA warning (8/23/2011) • Citalopram should not be used in doses >40mg qday due to concerns of QT prolongation • Citalopram should not be used in doses >20mg qday 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, particularly quetiapine and aripiprazole, 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 affected 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 appeared safe on cardiac parameters 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.(Glassman et al, 2002)(Joynt & O’Connor, 2005) • CREATE: Citalopram effective in treating depression in cardiac patients • Interpersonal therapy not superior to placebo. • Not designed to test effects on cardiac outcomes, mortality.(CREATE, 2007) • ENRICHD: CBT reduced depression modestly at 6 months, but did not reduce mortality - No benefit of CBT at 30 months. - (ENRICHD, 2003) • MIND-IT: Mirtazapine safe for post-MI depression, and showed efficacy vs placebo on some primary and secondary outcome measures at 24 weeks.- Tricyclic and heterocyclic anti-depressants are not considered safe post-MI(van den Brink RH, et. al 2002)

  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 Resistance Factors

  47. (Simon,1993; Lin,1995; Sansone, 2012) 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’ symptoms and course, and affect the patient’s health related quality of life • Depression may be successfully treated by addressing medical conditions and medical drugs, and utilizing biological, psychological and educational interventions

  50. References Boal AH, et al. Monotherapy with major antihypertensive drug classes and risk of hospital admissions for mood disorders. Hypertension 2016; 1132-1138. Bukberg J, Penman J, Holland J. Depression in hospitalized cancer patients. J Psychosomatic Medicine 1984; 46(3):199-211. 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 Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). http://medicine.iupui.edu/clinpharm/ddis/" Accessed October 26, 2017. Frasure-Smith N, Lesperance F, Talajic M. Depression following myocardial infarction. Impact on 6-month survival. JAMA 1993;270(15):1819-25. Gerstman BB, et al. The incidence of depression in new users of beta-blockers and selected antihypertensives. Journal of Clinical Epidemiology 1996; 49(7):809-815. 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):701-709. Griffith JL, Gaby L. Brief psychotherapy at the bedside: countering demoralization from medical Illness. Psychosomatics. 2005 Mar-Apr;46(2):109-16.5.

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