Savvy Psychopharmacology

The heart of depression: Treating patients who have cardiovascular disease

Current Psychiatry. 2011 January;10(1):31-34

References

1. Musselman DL, Evans DL, Nemeroff CB. The relationship of depression to cardiovascular disease: epidemiology, biology, and treatment. Arch Gen Psychiatry. 1998;55:580-592.

2. Carney RM, Freedland KE. Depression in patients with coronary heart disease. Am J Med. 2008;121(11 suppl 2):S20-27.

3. Norpramin [package insert]. Bridgewater, NJ: sanofi-aventis; 2009.

4. American Psychiatric Association. Treatment of patients with major depressive disorder, 3^rd ed. Available at: http://www.psychiatryonline.com/pracGuide/pracGuideChapToc_7.aspx. Accessed December 2, 2010.

5. Bush DE, Ziegelstein RC, Patel UV, et al. Post-myocardial infarction depression. Summary, evidence report/ technology assessment: number 123. Rockville, MD: Agency for Healthcare Research and Quality; May 2005. AHRQ publication 05-E018-1.

6. Roose SP, Miyazaki M. Pharmacologic treatment of depression in patients with heart disease. Psychosom Med. 2005;(67 suppl 1):S54-57.

7. Alvarez W Jr, Pickworth KK. Safety of antidepressant drugs in the patient with cardiac disease: a review of the literature. Pharmacotherapy. 2003;23:754-771.

8. van Melle JP, de Jonge P, Honig A, et al. Effects of antidepressant treatment following myocardial infarction. Br J Psychiatry. 2007;190:460-466.

9. Preskorn SH, Flockhart D. 2006 guide to psychiatric drug interactions. Primary Psychiatry. 2006;13(4):35-64.

10. U.S. Food and Drug Administration. Information for healthcare professionals: update to the labeling of clopidogrel bisulfate (marketed as Plavix) to alert healthcare professionals about a drug interaction with omeprazole (marketed as Prilosec and Prilosec OTC). Available at: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/
DrugSafetyInformationforHeathcareProfessionals/ucm190787.htm. Accessed January 24, 2010.

11. Spina E, Santoro V, D’Arrigo C. Clinically relevant pharmacokinetic drug interactions with second-generation antidepressants: an update. Clin Ther. 2008;30:1206-1227.

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13. Glassman A. Depression and cardiovascular disease. Pharmacopsychiatry. 2008;41(6):221-225.

14. Glassman AH, O’Connor CM, Califf RM, et al. Sertraline treatment of major depression in patients with acute MI or unstable angina. JAMA. 2002;288:701-709.

15. Lespérance F, Frasure-Smith N, Koszycki D, et al. Effects of citalopram and interpersonal psychotherapy on depression in patients with coronary artery disease: the Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy (CREATE) trial. JAMA. 2007;297:367-379.

16. de Jonge P, Honig A, van Melle JP, et al. Nonresponse to treatment for depression following myocardial infarction: association with subsequent cardiac events. Am J Psychiatry. 2007;164:1371-1378.

17. Summers KM, Martin KE, Watson K. Impact and clinical management of depression in patients with coronary artery disease. Pharmacotherapy. 2010;30:304-322.

18. Berkman LF, Blumenthal J, Burg M, et al. Effects of treating depression and low perceived social support on clinical events after myocardial infarction: the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) Randomized Trial. JAMA 2003;289:3106-3116.

Mrs. T, age 59, sustained an ST-elevation myocardial infarction (MI) 6 weeks ago. She has a history of hypertension, hyperlipidemia, and major depressive disorder (MDD). Before her MI, Mrs. T’s MDD was well managed with cognitive-behavioral therapy (CBT). She states that her depressive symptoms have worsened since her MI, and clinicians determine that she is experiencing an acute depressive episode severe enough to require pharmacotherapy. Past medication trials for her depression include sertraline, up to 150 mg/d, and duloxetine, 60 mg/d, but her provider determined they were ineffective after an adequate trial duration. Her hypertension is well controlled on her current regimen, which includes lisinopril, 20 mg/d, metoprolol, 50 mg/d, simvastatin, 40 mg/d, and clopidogrel, 75 mg/d. Her father experienced sudden cardiac death and her mother and younger brother have a history of severe MDD.

Practice Points

Selective serotonin reuptake inhibitors, particularly citalopram and sertraline, are generally well tolerated, effective, and safe to use in patients with cardiovascular disease (CVD), although clinicians must be aware of the risk of drug-drug interactions with these agents.
Tricyclic antidepressants and monoamine oxidase inhibitors are contraindicated in patients with CVD.
The FDA warns against using desipramine in patients with cardiovascular disease; fluoxetine and other CYP2C19 inhibitors may reduce the efficacy of clopidogrel.
Whether pharmacologic or nonpharmacologic treatment of depression improves long-term cardiac outcomes needs to be clarified with sufficiently powered studies.

Depression is more prevalent in patients with cardiovascular disease (CVD) than in the general population, with estimates as high as 23%.¹ Possible mechanisms to help explain the relationship between CVD and depression are summarized in Table 1.² Appropriate antidepressant selection and depression management strategies in patients with CVD, particularly after MI, may reduce the risk for additional cardiac events and reduce mortality.^1,2

Table 1

The link between depression and cardiovascular disease

Depressed patients with CVD often exhibit: Dysregulation of the autonomic nervous system, including decreased heart rate variability and increased heart rate Increase in inflammatory markers, including CRP, TNF-α, and interleukin-6 Increase in platelet activity and coagulation Accelerated atherogenesis via endothelial dysfunction
Other factors that impact cardiovascular risk in patients with depression include: Lifestyle, including activity level and tobacco use Medication adherence
CRP: C-reactive protein; CVD: cardiovascular disease; TNF: tumor necrosis factor Source: Reference 2

Antidepressant choices by class

Many older antidepressants, including tricyclic antidepressants (TCAs), are:

contraindicated during acute recovery from MI
cardiotoxic
lethal in overdose
not recommended for patients with CVD.^1,3

The FDA recently mandated additional labeling for desipramine to alert health care providers to the risk of using this agent in patients with CVD or a family history of sudden death, arrhythmias, or conduction abnormalities.³ Similar to TCAs, monoamine oxidase inhibitors (MAOIs) generally are not recommended for use in this population because of the risk of hypertensive crisis, orthostatic hypotension, tachycardia, and increased QTc interval.² Trazodone, which might help relieve insomnia, is associated with orthostasis and tachycardia. These effects may occur more frequently in patients with cardiac disease.⁴

Clinical Point

In depressed post-MI patients, treatment with mirtazapine or citalopram does not increase the incidence of cardiac events

Selective serotonin reuptake inhibitors (SSRIs) are effective antidepressants post-MI, have antiplatelet activity, and may improve surrogate markers of cardiac risk, although further research is needed.^5,6 Individual SSRIs vary in their effects on the cytochrome P450 (CYP450) system, and therefore carry different risks of drug-drug interactions (see Related Resources).

The cardiovascular impact of serotonin-norepinephrine reuptake inhibitors is unknown. These agents may be associated with hypertension and tachycardia.⁷ Additional research on the use of bupropion and mirtazapine in patients with CVD also is warranted. However, bupropion has been used to help patients with CVD stop smoking and likely is safe, although it may be associated with an increase in blood pressure.^2,7 Bupropion and mirtazapine also can affect appetite and weight, which require monitoring in CVD patients. The Myocardial Infarction and Depression-Intervention Trial (MIND-IT) reveals that antidepressant treatment with mirtazapine or citalopram does not increase the incidence of cardiac events and does not improve long-term depression status compared with treatment as usual in depressed post-MI patients.⁸ Orthostatic hypotension is a possible adverse effect of mirtazapine,⁷ and this antidepressant may reduce the antihypertensive effect of clonidine.

Monitor for interactions

Drug interaction databases—including Micromedex, Lexi-Comp, or Facts and Comparisons—can differ with regard to identifying and classifying drug interactions. Therefore, individual clinicians often carry the burden of recognizing potential drug-drug interactions. Preskorn and Flockhart⁹ suggest developing a “personal formulary” of the medications clinicians regularly prescribe to minimize drug-drug interactions. This formulary includes knowledge of a drug’s:

enzymes responsible for elimination
half-life
relevant clinical trials
receptor affinities
common adverse effects.

Following these recommendations reveals several considerations when selecting an antidepressant for Mrs. T: