10/19/12. Depression in the Medically Ill. Ondria C. Gleason, MD Disclosures. Dr. Gleason has no disclosures to report

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1 Depression in the Medically Ill Ondria C. Gleason, MD University of Oklahoma School of Community Medicine Tulsa, OK Ondria C. Gleason, MD Disclosures Dr. Gleason has no disclosures to report 1

2 Learning Objective Accurately identify and treat patients whose depressive symptoms are secondary to a medical illness or to agents used to treat medical illness Overview Differential diagnosis of patient with depressive symptoms Specific medical conditions and depression Management of depression in the medically ill Differential Diagnosis for Depression in Medically Ill Patients 2

3 10/19/12 Differential Diagnosis Rule out depression due to general medical condition Rule out depression due to medications or substances Major depressive disorder Other psychiatric conditions Anxiety disorders Medical Conditions With Depressive Symptoms Cardiovascular diseases Congestive heart failure Myocardial infarction Hereditary disorders Acute intermittent porphyria Wilson disease Infectious diseases Hepatitis C HIV Endocrinopathies Hyperthyroidism Hypothyroidism Hyperparathyroidism Hypoparathyroidism Syndrome of inappropriate anti-diuretic hormone secretion Cushing syndrome Adrenocortical insufficiency (Addison disease) Insulinoma Sadock BJ, et al. Kaplan and Sadock s Comprehensive Textbook of Psychiatry, 7th ed Medical Conditions With Depressive Symptoms (cont d) Malignancies Pancreatic carcinoma Carcinoid syndrome Neurologic conditions Multiple sclerosis Huntington disease Systemic lupus erythematosus Vitamin deficiencies Thiamine (B1) Nicotinamide (B3) Pyridoxine (B6) Sadock BJ, et al. Kaplan and Sadock s Comprehensive Textbook of Psychiatry 7th ed

4 10/19/12 Medications Associated With Depression Medication Classes and Agents That Can Cause Depressive Symptoms ACE inhibitors Acetazolamide Acyclovir Amantadine Amphetamines Anabolic steroids Antiepileptics Asparaginase Baclofen Barbiturates Benzodiazepines Beta blockers Bromocriptine Calcium channel blockers Clonidine Corticosteroids Cycloserine Dapsone Digoxin Disopyramide Disulfiram Dopamine receptor antagonists Efavirenz Estrogens Fluoroquinolone [No author listed]. Med Lett Drugs Ther. 2002;1134(44): PMID: None. Medications Associated With Depression (cont d) Medication Classes and Agents that Can Cause Depressive Symptoms (cont d) Mefloquine NSAIDs Steroids Methyldopa Opioids Methysergide Metoclopramide Metronidazole Pergolide Phenylpropanolamine Statins Thiazide diuretics Trimethoprimsulfamethoxazole Vinblastine Zaleplon [No author listed]. Med Lett Drugs Ther. 2002;1134(44): PMID: None. Psychoactive Substances Associated With Depressive Symptoms Alcohol Benzodiazepines Marijuana Opioids Methamphetamine/amphetamine Withdrawal Cocaine Withdrawal Rackley S, Bostwick JM. Psychiatr Clin North Am. 2012;35(1): PMID:

5 The 8 Ds: Conditions That Can Make Medically Ill Patients Appear Depressed Percentage of conditions seen in 100 patients referred for inpatient psychiatric consultation for depression Category % Interventions Depressed 29 Psychotherapy ± antidepressants Demoralized 23 Compassion, normalization, support, PT/OT Disaffiliated 3 Encouragement of increased support, grief counseling Difficult 29 Multidisciplinary care conference, consistent communication Delusional 2 Collateral information, resumption of antipsychotic therapy Dulled 2 Collateral information, safety assessment of home Drugged 12 Safety, withdrawal support and monitoring, reassessment Delirious 11 Identification and correction of underlying medical condition Bostwick JM, Rackley S. Curr Psychiatry. 2012;11(6): PMID: None. Rackley S, Bostwick JM. Psychiatr Clin North Am. 2012;35(1): PMID: Heart Disease Cardiovascular Disease Depression is a risk factor for cardiovascular disease (CVD) RR of > 1.6 for developing CVD in depression Dose-related Increased prevalence of depression in patients with coronary artery disease (CAD) 30% 50% with depressive symptoms 15% 20% with major depression Increased mortality post-mi RR is for depressed patients RR = relative risk; MI = myocardial infarction Frasure-Smith N, Lesperance F. Can J Psychiatry. 2006;51(12): PMID: Frasure-Smith N, Lesperance F. Can J Psychiatry. 2006;51(12): PMID:

6 10/19/12 Mortality After Myocardial Infarction Peveler R, et al. BMJ. 2002;325(7356): PMID: Relationship Between Ischemic Heart Disease (IHD) 2,832 participants in National Health Examination Follow-Up Study Ages with no IHD Baseline assessment with the depression subscale of the General Well-Being Schedule Depressed affect 11.5% Moderate hopelessness 10.8% Severe hopelessness 2.9% Follow-up Mean 12.4 years 189 cases of fatal IHD Depressed affect and hopelessness may have causal role in occurrence of both fatal and non-fatal IHD Anda R, et al. Epidemiology. 1993;4: PMID: SADHART Design Sertraline Antidepressant Heart Attack Randomized Trial Multicenter study: USA, Canada, Australia, Denmark, Sweden, Italy, Germany Primary safety and clinical endpoints were obtained at week 164 Patient identification ~2 weeks Hospitalization (MI or unstable angina) 0 RANDOMIZATION Sertraline (flexible dosing, 50 mg 200 mg) Placebo Single-blind placebo washout Double-blind treatment period Glassman AH, et al. JAMA. 2002;288(6): PMID:

7 10/19/12 SADHART Subjects Male or female, aged 21 years or older In past 30 days, patient meets criteria for a dual cardiac/psychiatric diagnosis: Either acute MI (74%) or unstable angina (26%) and Major depression (using DSM-IV criteria based on a structured interview) Mean HAM-D score = 19.6 DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition HAM-D =Hamilton Rating Scale for Depression Glassman AH, et al. JAMA. 2002;288(6): PMID: SADHART Relative Risk for Cardiovascular Events Event Relative risk (95% CI) Death 0.39 ( ) Myocardial 0.70 ( ) infarction Relative risk for sertraline vs. placebo Stroke 0.98 ( ) Worsened 0.85 ( ) angina Congestive 0.70 ( ) heart failure Composite* 0.77 ( ) * Composite consists of combination of five individual events Glassman AH, et al. JAMA. 2002;288(6): PMID: SADHART Week 16 HAM-D Change Scores HAM-D Change Score Total Intent-to-Treat (ITT) Sample Prior Depression Subgroup p = p =.009 Sertraline (mean dose 68.8 mg/day) Placebo (mean dose 70.5 mg/day equivalent) More Severe Depression Subgroup p =.012 Glassman AH, et al. JAMA. 2002;288(6): PMID:

8 10/19/12 ENRICHD Enhancing Recovery in Coronary Heart Disease randomized trial 2,500 patients post-mi with depression or low social support Cognitive Behavioral Therapy (CBT) versus Usual Care Severely depressed could receive sertraline Depression improved more in CBT group Four-year survival was not statistically different, although those with sertraline did better (but not random assignment) No drug n = 1,481 SSRI n = 353 p-value All-cause mortality 15.3% 7.4%.0004 CVD mortality 9.8% 4.5%.0003 Berkman LF, et al. JAMA. 2003;289(23): PMID: CREATE Canadian Randomized Evaluation of Antidepressant and Psychotherapy Efficacy Trial Patients with coronary artery disease Citalopram (up to 40 mg) superior to placebo for depression symptoms Interpersonal psychotherapy (IPT) no difference from usual care Lesperance F, et al. JAMA. 2007;297(4): PMID: Depression s Impact on Self-Management of Chronic Medical Illness Depressed post-mi patients more likely to drop out of exercise programs 1 Depressed smokers 40% less likely to quit smoking over a nine-year period 2 Depressed patients with CAD less likely to adhere to low-dose aspirin therapy 3 CAD = coronary artery disease 1. Blumenthal JA, et al. Psychosom Med. 1982;44: PMID: Anda RF, et al. JAMA. 1990;264: PMID: Carney RM, et al. Health Psychol. 1995;14: PMID:

9 Stroke Stroke Depression increases risk of stroke 4x (< 65 y/o) Nearly 50% of patients develop post-stroke major or minor depression Natural course duration over two years for some patients, with average of 9-10 months for major depression Left frontal lobe relationship Resolution of depression higher in patients with subcortical and cerebellar lesions than with cortical lesions Responsive to antidepressants and psychostimulants Robinson RG, et al. Stroke. 1983;14(5): PMID: Association of Depression With 10-Year Post-Stroke Mortality Not depressed 40% Minor and major depression 70% Morris PL, et al. Am J Psychiatry. 1993;150(1): PMID:

10 Hepatitis C Increased Prevalence of Depression Among Patients With Hepatitis C: Theories High-risk population Intravenous substance use is most common route of transmission Psychological impact of hepatitis C diagnosis Biological effects of virus HCV+ patients show cognitive impairment, especially in attention and executive function HCV has been found in CSF; brain-specific variants identified New evidence of alterations in gene expression in HCV+ patients, related to brain oxidative and energy metabolism Decreased N-acetyl-aspartate/creatine ratio in magnetic resonance spectroscopy and EEG, especially in patients with excessive fatigue Rifai MA, et al. Prim Care Companion J Clin Psychiatry. 2010;12(6):e1-e13. PMID: Diabetes 10

11 Diabetes Depression is an independent risk factor for type 2 diabetes mellitus1 Depression in diabetes if associated with Non-adherence to oral hypoglycemics2 Poor glycemic control3 Earlier onset of microvascular and macrovascular complications, disability, and death3,4 Diabetes also is a risk factor for depression Kawakami N, et al. Diabetes Care. 1999;22(7): PMID: Ciechanowski PS, et al. Arch Intern Med. 2000;160(21): PMID: de Groot M, et al. Psychosom Med. 2001;63(4): PMID: Black SA, et al. Diabetes Care. 2003;26(10): PMID: Cancer Cancer Associated with poor prognosis and increased morbidity Due to: Psychological impact of receiving cancer diagnosis and experiencing declining physical status and pain Direct consequence of antineoplastic therapy Raison CL, Miller AH. Biol Psychiatry. 2003;54(3): PMID:

12 Treating Depression in the Medically Ill It s Still Depression In patients with medical illness, the depression treatment goals are still the same as with treatment goals in patients without medical illness Evans DL, et al. Biol Psychiatry. 2005;58(3): PMID: Antidepressants Selective serotonin reuptake inhibitors: fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, escitalopram GI side effects, sexual dysfunction, insomnia Cytochrome P-450 inhibition Highly protein-bound Bupropion Avoid in seizure-prone patients, eating disorders Studies show safety in cardiac patients, low sexual dysfunction Rothschild AJ. The Evidence-Based Guide to Antidepressant Medications

13 10/19/12 Antidepressants Venlafaxine Dose-related blood pressure elevations Low protein-binding Mirtazapine Sedation and increased appetite at lower doses Duloxetine Cases of hepatic failure and cholestatic jaundice Constipation and urinary retention Rothschild AJ. The Evidence-Based Guide to Antidepressant Medications Antidepressants Tricyclic antidepressant agents Anticholinergic (dry mouth, blurred vision, constipation, urinary retention, ileus, delirium) Orthostatic hypotension, sedation, slowed cardiac conduction (avoid in patients with QTc interval >440msec) Monoamine oxidase inhibitors: phenelzine, tranylcypromine Potentially fatal drug interactions Dietary restrictions Orthostasis, hypotension Rothschild AJ. The Evidence-Based Guide to Antidepressant Medications Psychostimulants Fast onset of action, well-tolerated, and generally safe in both older and medically ill persons Useful early in treatment while waiting for standard antidepressant to take effect not recommended as a long-term treatment Rothschild AJ. The Evidence-Based Guide to Antidepressant Medications

14 Electroconvulsive Therapy Effective 83% response rate No absolute contraindications Increased morbidity associated with: Conditions causing increased intracranial pressure Conditions with increased risk of hemorrhage Acute myocardial infarction, arrhythmias Avery D, Lubrano. Am J Psychiatry Apr;136(4B): PubMed PMID: Clinical Connections medical conditions often coexist, yet depression is underrecognized and undertreated in patients with medical illness Identifying depression in the medically ill population is difficult; often, the symptoms that are used to identify depression are confused with the underlying symptoms of the medical illness Still very little is known about the biological mechanisms at work in depressed medically ill patients that would account for their increased morbidity and mortality Evidence suggests that depression in patients with other major medical illnesses can be successfully treated with pharmacological agents Co-sponsored by 14

15 10/19/12 Save the Date! 6th Annual Chair Summit September 26-28, 2013 Westin Tampa Harbour Island Tampa, Florida 15