Depression and the Medically Ill Steven A. Epstein, MD Georgetown University Hospital and School of Medicine

Steven A. Epstein, MD Disclosures

 Research/Grants: None  Speakers Bureau: None  Consultant: None  Stockholder: None  Other Financial Interest: None  Advisory Board: None

Learning Objective List considerations for developing an individualized diagnostic and treatment plan for a medically ill patient with depression

Why Is Depression Important to Diagnose in the Medically Ill?  Adds to burden of medical illness  May lead to discovery of medical

cause of depression

– Hypothyroidism, stroke, medication (e.g., corticosteroids, interferon)

 Important regardless of possible

relationship to medical illness

Why Is Depression Important to Diagnose in the Medically Ill? (cont.)  Decreases functional status, tx adherence1 – Example: DM  May lead to adverse medical outcomes and

increased mortality2 – Example: CVD

 Somatization and/or physical symptoms of

depression are common – Example: fatigue

CVD = cardiovascular disease; DM = diabetes mellitus; Tx = treatment 1. Ciechanowski PS. Arch Intern Med 2000;160:3278-3285. 2. Iosifescu DV. Psychiatr Clin North Am 2007;30:77-90.

Diagnostic Difficulties

Problem 1: Symptom Etiology  MDE symptoms may be due to medical disorder

or hospitalization, not depression

– Examples: weight loss, insomnia, anergia  Cognitive symptoms difficult to assess – Example: anhedonia in immobile patient with prolonged hospitalization  Controversy over whether to consider overlapping

symptoms

– Exclusive approach: under-recognition of depression – Inclusive approach: over-diagnosis of depression MDE = major depressive episode

Diagnostic Difficulties

Symptom Etiology: Suggestions  Note time course of all depressive

symptoms

 Focus attention on symptoms less likely

affected by medical illness – Example: guilt

 Add symptoms to clarify diagnosis – Examples: hopelessness, helplessness

Diagnostic Difficulties

Problem 2: Differential Diagnosis  Patient can appear depressed but have a

different neuropsychiatric condition

– Examples: hypoactive delirium, post-stroke apathy, apathy in dementia

Diagnostic Difficulties

Differential Diagnosis: Suggestions  Pt history to differentiate apathy from mood

disturbance

 Neurologic history, exam – Consider consultation and imaging studies  Differentiate hypoactive delirium from depression – Cognitive exam to assess: – Sustained attention (e.g., every other letter of alphabet) – Constructional praxis (e.g., clock-drawing) – Important in hospitalized patients

Diagnostic Difficulties

Problem 3: Bereavement?  Medical illness often involves major loss,

such as ability to function effectively

– As with bereavement, challenging to differentiate normal reaction from MDE

Diagnostic Difficulties

Bereavement?: Suggestion  Careful history of time course and severity

of symptoms

Diagnostic Difficulties

Problem 4: Suicidal Thoughts  Suicidal thoughts often indicate depression  Thoughts of dying and desire for death in

medically ill patients not necessarily due to depression

Diagnostic Difficulties

Suicidal Thoughts: Suggestions  Carefully explore: – Intensity of thoughts of dying – Accuracy of patient’s self-assessed prognosis (i.e., are there cognitive distortions?) – Whether patient has a plan  Must carefully assess suicide risk in

medically ill patient, even one nearing end of life

Depression in Selected Medical Conditions CAD: Depression leads to increased morbidity and mortality  Dementia: Depression among most common neuropsychiatric conditions  PD: Very high prevalence of depression  Post-stroke 

– Depression very common – May be more common in anterior left-sided strokes; conflicting data



DM: Extensive data showing depression leads to reduced tx adherence

CAD = coronary artery disease; PD = Parkinson’s disease Iosifescu DV. Psychiatr Clin North Am 2007;30:77-90.

Medications that May Cause Depression  Selected medications: corticosteroids,

interferon alfa, beta blockers, isotretinoin, ACE inhibitors, CCBs, varenicline, vinblastine1,2 – Data contradictory for many medications reported to cause depression2,3

ACE = angiotensin-converting enzyme; CCB = calcium channel blocker 1. Patten SB. Psychother Psychosom 1997;66:63-73. 2. Kotlyar M. Am J Geriatr Pharmacother 2005;3:288-300. 3. Patten SB. Compr Psychiatry 2001;42:124-131.

Treatment: Psychotherapy  Cognitive-behavioral psychotherapy1 – Include pleasant activity scheduling  Interpersonal psychotherapy2 – Address new roles related to impairment from medical illness – Family involvement – Support groups  Therapy focused on meaning and dignity for

individuals near end of life3

1. Lustman PJ. Ann Intern Med 1998;129:613-621. 2. Cuijpers P, et al. J Consult Clin Psychol 2008;76:909-922. 3. Chochinov HM, et al. J Clin Oncol 2005 ;23:5520-5525.

Treatment: Antidepressants Antidepressants effective in medical populations even with neurologic cause1  Consider lower dosages in some patients 

– Example: liver disease



Consider medication with minimal drug-drug interactions



Potential side effects especially relevant in medically ill

– Examples: citalopram, escitalopram, sertraline, venlafaxine, mirtazapine2 – Arrhythmias with TCAs3 – SIADH or platelet dysfunction with SSRIs4

SIADH = syndrome of inappropriate antidiuretic hormone; SSRI = selective serotonin reuptake inhibitor; TCA = tricyclic antidepressant

1. Small GW. J Am Geriatr Soc 1996;44:1220-1225. 2. Spina E. Clin Ther 2008;30:1206-1227. 3. Jiang W. Am Heart J 2005;150:871-881. 4. Draper B. Drugs Aging 2008;25:501-519.

Treatment: Antidepressants (cont.) 

Consider agent whose side effects may help medical symptoms

– Example: mirtazapine for patient with cachexia and insomnia due to advanced cancer1



Consider medication that may help medical condition



Consider psychostimulant in patient with fatigue

1. 2. 3. 4.

Croom KF. CNS Drugs 2009;23:427-452. Kroenke K. Gen Hosp Psychiatry 2009;31:206-219. Saarto T. Cochrane Database Syst Rev 2007;(4):CD005454. Hardy SE. Am J Geriatr Pharmacother 2009;7:34-59.

– Example: TCAs, venlafaxine, or duloxetine in patients with pain2,3 – Note: data not strong for many pain conditions – Example: methylphenidate4

Conclusions  Depression highly prevalent among

medically ill

– Causes significant impairment – Increases morbidity and mortality risk

 Conduct structured examination to address

diagnostic challenges  Wide range of effective treatments

– Tailor plan based on individual patient and disease factors

Selected References  Ford DE. Optimizing Outcomes for Patients with

Depression and Chronic Medical Illnesses. Am J Med 2008;121:S38-S44.  Katon W. The association of depression and anxiety with medical symptom burden in patients with chronic medical illness. Gen Hosp Psych 2007;29:147-155.  The Medical Letter on Drugs and Therapeutics. Volume 50, December 2008.  Rodin GM. Depression. In: Levenson JL (ed.), Textbook of Psychosomatic Medicine. American Psychiatric Publishing, 2005.

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Depression and the Medically Ill Steven A. Epstein, MD Chochinov HM, Hack T, Hassard T, et al. Dignity therapy: a novel psychotherapeutic intervention for patients near the end of life. J Clin Oncol 2005;23:5520-5525. Ciechanowski PS, Katon WJ, Russo JE. Depression and diabetes: impact of depressive symptoms on adherence, function, and costs. Arch Intern Med 2000;160:3278-3285. Croom KF, Perry CM, Plosker GL. Mirtazapine: a review of its use in major depression and other psychiatric disorders. CNS Drugs 2009;23:427-452. Cuijpers P, van Straten A, Andersson G, van Oppen P. Psychotherapy for depression in adults: a meta-analysis of comparative outcome studies. J Consult Clin Psychol 2008;76:909-922. Draper B, Berman K. Tolerability of selective serotonin reuptake inhibitors: issues relevant to the elderly. Drugs Aging 2008;25:501519. Hardy SE. Methylphenidate for the treatment of depressive symptoms, including fatigue and apathy in medically ill older adults and terminally ill adults. Am J Geriatr Pharmacother 2009;7:34-59. Iosifescu DV. Treating depression in the medically ill. Psychiatr Clin North Am 2007;30:77-90. Jiang W, Davidson JR. Antidepressant therapy in patients with ischemic heart disease. Am Heart J 2005;150:871-881. Kotlyar M, Dysken M, Adson DE. Update on drug-induced depression in the elderly. Am J Geriatr Pharmacother 2005;3:288-300. Kroenke K, Krebs EE, Bair MJ. Pharmacotherapy of chronic pain: a synthesis of recommendations from systematic reviews. Gen Hosp Psychiatry 2009 ;31:206-219. Lustman PJ, Griffith LS, Freedland KE, Kissel SS, Clouse RE. Cognitive behavior therapy for depression in type 2 diabetes mellitus. A randomized, controlled trial. Ann Intern Med 1998;129:613-621. Patten SB, Lavorato DH. Medication use and major depressive syndrome in a community population. Compr Psychiatry 2001;42:124-131. Patten SB, Love EJ. Drug-induced depression. Psychother Psychosom 1997;66:63-73. Saarto T, Wiffen PF. Antidepressants for neuropathic pain. Cochrane Database Syst Rev 2007;CD005454. Review. Small GW, Birkett M, Meyers BS, Koran LM, Bystritsky A, Nemerof CB. Impact of physical illness on quality of life and antidepressant response in geriatric major depression. Fluoxetine Collaborative Study Group. J Am Geriatr Soc 1996;44:12201225. Spina E, Santoro V, D’Arrigo C. Clinically relevant pharmacokinetic drug interactions with second-generation antidepressants: an update. Clin Ther 2008;30:1206-1227.