The consequences of depression and coronary artery disease (CAD) were reviewed in the literature. The comorbidity of depression and CAD results in an increased cardiovascular mortality. We reviewed possible explanations for this increased morbidity, which include: toxicity of tricyclic antidepressants that can cause cardiac arrhythmias, abnormalities in platelet function leading to increased platelet aggregation due to abnormalities in serotonin in the platelet (an abnormality that possibly causes depression in the central nervous system), diffuse atherosclerosis causing central nervous system abnormalities including depression (vascular depression), as well as the possibility that depressed patients are less compliant with their medications and physician-directed health recommendations. Recent reports of selective serotonin reuptake inhibitors (SSRIs) causing a reduced cardiovascular mortality may be related to serotonin platelet abnormalities in depressed patients that are effectively treated by SSRIs (SADHART and ENRICHD trial). It is possible that these trials reveal a mechanism of depression that also effects platelet function and can be improved with SSRI therapy, suggesting a preferential therapeutic pathway for the treatment of depressed patients with CAD.

1.
McGovern PG, Pankow JS, Shahar E, et al: Minnesota Heart Survey Investigators. Recent trends in acute coronary heart disease: mortality, morbidity, medical care, and risk factors. N Engl J Med 1996;334:884–890.
2.
Forrester AW, Lipsey JR, Teitelbaum ML, et al: Depression following myocardial infarction. Int J Psychiatry Med 1992;22:33–46.
3.
Frasure-Smith N, Lesperance F, Talajic M: Depression following myocardial infarction: impact on 6-month survival. JAMA 1993;270:1819–1825.
4.
Eaton WW, Fogel J, Armenian HK: The Consequences of Psychopathology in the Baltimore Epidemiologic Catchment Area Follow-Up. Medical and Psychiatric Comorbidity over the Lifespan. Washington, American Psychiatric Publishing, 2006, pp 21–38.
5.
Bush DE, Ziegelstein RC, Tayback M, et al: Even minimal symptoms of depression increase mortality risk after acute myocardial infarction. Am J Cardiol 2001;88:337–341.
6.
Jiang W, Davidson J: Antidepressant therapy in patients with ischemic heart disease. Am Heart J 2005;150:871–881.
7.
Parashar S, Rumsfeld JS, Spertus JA, et al: Time course of depression and outcome of myocardial infarction. Arch Intern Med 2006;166:2035–2043.
8.
Dickens CM, McGowan L, Percival C, et al: Contribution of depression and anxiety to impaired health-related quality of life following first myocardial infarction. Br J Psychiatry 2006;189:367–372.
9.
Pedersen SS, Denollet J, Daemen J, et al: Fatigue, depressive symptoms, and hopelessness as predictors of adverse clinical events following percutaneous coronary intervention with paclitaxel-eluting stents. J Psychosom Res 2007;62:455–461.
10.
Rutledge T, Reis SE, Olson MB, et al: Depression symptom severity and reported treatment history in the prediction of cardiac risk in women with suspected myocardial ischemia: the NHLBI-sponsored WISE study. Arch Gen Psychiatry 2006;63:874–880.
11.
Jaffe AS, Krumholz HZ, Catellier DJ, et al: Prediction of medical morbidity and mortality after acute myocardial infarction in patients at increased psychosocial risk in the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) study. Am Heart J 2006;152:126–135.
12.
Kamphuis MH, Kalmijn S, Tijhuis MA, et al: Depressive symptoms as risk factor of cardiovascular mortality in older European men: the Finland, Italy and Netherlands Elderly (FINE) study. Eur J Cardiovasc Prev Rehabil 2006;13:199–206.
13.
Rumsfeld JS, Jones PG, Whooley MA, et al: Depression predicts mortality and hospitalization in patients with myocardial infarction complicated by heart failure. Am Heart J 2005;150:961–967.
14.
Dias C, Mateus PS, Mateus C, et al: Acute coronary syndrome and depression. Rev Port Cardiol 2005;24:507–516.
15.
Dickens C, McGowan L, Percival C, Tomenson B, Cotter L, Heagerty A, Creed F: Depression is a risk factor for mortality after myocardial infarction. J Am Coll Cardiol 2007;49:1834–1840.
16.
Abramson J, Berger A, Krumholz HM, Vaccarino V: Depression and risk of heart failure among older persons with isolated systolic hypertension. Arch Intern Med 2001;161:1725–1730.
17.
Rozzini R, Sabatini T, Frisoni GB, Trabucchi M: Depression and major outcomes in older patients with heart failure. Arch Intern Med 2002;162:362–364.
18.
Sherwood A, Blumenthal JA, Trivedi R, et al: Relationship of depression to death or hospitalization in patients with heart failure. Arch Intern Med 2007;167:367–373.
19.
Sullivan MD, Levy WC, Crane BA, et al: Usefulness of depression to predict time to combined end point of transplant or death for outpatients with advanced heart failure. Am J Cardiol 2004;94:1577–1580.
20.
Murberg TA, Furze G: Depressive symptoms and mortality in patients with congestive heart failure: a six-year follow-up study. Med Sci Monit 2004;10:CR643–CR648.
21.
de Denus S, Spinler SA, Jessup M, et al: History of depression as a predictor of adverse outcomes in patients hospitalized for decompensated heart failure. Pharmacotherapy 2004;24:1306–1310.
22.
Junger J, Schellberg D, Muller-Tasch T: Depression increasingly predicts mortality in the course of congestive heart failure. Eur J Heart Fail 2005;7:261–267.
23.
Friedmann E, Thomas SA, Liu F: Relationship of depression, anxiety, and social isolation to chronic heart failure outpatient mortality. Am Heart J 2006;152:940.e1–e8.
24.
Glassman AH, Roose SP, Bigger JT Jr: The safety of tricyclic antidepressants in cardiac patients: risk-benefit reconsidered. JAMA 1993;269:2673–2675.
25.
Cardiac Arrhythmia Suppression Trial (CAST) Investigators. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med 1989;321:406–412.
26.
Nemeroff CB, Musselman DL: Are platelets the link between depression and ischemic heart disease? Am Heart J 2000;140:S57–S62.
27.
Chrapko WE, Juracz P, Radomski MW, et al: Decreased plasma nitric oxide metabolites and platelet nitric oxide synthase activity in patients with major depression. Biol Psychiatry 2004;56:129–134.
28.
Jarvisalo MJ, Harmoinen A, Hakanen M, et al: Elevated serum C-reactive protein levels and early arterial changes in healthy children. Arterioscler Thromb Vasc Biol 2002;22:1323–1328.
29.
Iosifescu DV, Clementi-Craven N, Fraguas R, et al: Cardiovascular risk factors may moderate pharmacological treatment effects in major depressive disorder. Am Psychosom Soc 2005;67:703–706.
30.
Krishnan KR, Hays JC, Blazer DG: MRI-defined vascular depression. Am J Psychiatry 1997;154:497–501.
31.
Rush AJ, Trivedi MH, Wisniewski SR, et al: Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry 2006;163:1905–1917.
32.
Wilkin LD, Cunningham CL, Fitzgerald RD: Pavlovian conditioning with ethanol and lithium: effects on heart rate and taste aversion in rats. J Comp Physiol Psychol 1982;96:781–790.
33.
Belmaker RH, Lehrer R, Ebstein RP, et al: A possible cardiovascular effect of lithium. Am J Psychiatry 1979;136:577–579.
34.
Berigan TR, Adams DW: Therapeutic lithium-related cardiac conduction disturbance in a previously healthy patient: a case report. Mil Med 1994;159:717.
35.
Tilkian AG, Schroeder JS, Kao J, Hultgren H: Effect of lithium on cardiovascular performance: report on extended ambulatory monitoring and exercise testing before and during lithium therapy. Am J Cardiol 1976;38:701–708.
36.
Cohen HW, Gibson G, Alderman MH: Excess risk of myocardial infarction in patients treated with antidepressant medications: association with use of tricyclic agents. Am J Med 2000;108:2–8.
37.
Glassman AH, Roose SP: Risk of antidepressants in the elderly: tricyclic antidepressants and arrhythmia-revising risks. Gerontology 1994;40(suppl 1):15–39.
38.
Roose SP, Glassman AH: Cardiovascular effects of tricyclic antidepressants in depressed patients with and without heart disease. J Clin Psychiatry 1989;50(suppl):1–18.
39.
Kantor SJ, Glassman AH, Bigger JT, et al: The cardiac effects of therapeutic plasma concentrations of imipramine. Am J Psychiatry 1978;135:534–538.
40.
Roose SP, Dalack GW, Glassman AH, et al: Is doxepin a safer tricyclic for the heart? J Clin Psychiatry 1991;52:338–341.
41.
Glassman AH, Johnson LL, Giardina EGV, et al: The use of imipramine in depressed patients with congestive heart failure. JAMA 1983;250:1997–2001.
42.
Roose SP, Glassman AH, Attia E, et al: Cardiovascular effects of fluoxetine in depressed patients with heart disease. Am J Psychiatry 1998;155:660–665.
43.
Cooper GL: The safety of fluoxetine: an update. Br J Psychiatry 1988;153:77–86.
44.
Fisch C: Effect of fluoxetine on the electrocardiogram. J Clin Psychiatry 1985;46(suppl 2):42–44.
45.
Sauer WH, Berlin JA, Kimmel SE: Selective serotonin reuptake inhibitors and myocardial infarction. Circulation 2001;104:1894–1898.
46.
Musselman DL, Evans DL, Nemeroff CB: The relationship of depression to cardiovascular disease: epidemiology, biology, and treatment. Arch Gen Psychiatry 1998;55:580–592.
47.
Pollock BG, Laghrissi-Thode F, Wagner WR: Evaluation of platelet activation in depressed patients with ischemic heart disease after paroxetine or nortriptyline treatment. J Clin Psychopharmacol 2000;20:137–140.
48.
Serebruany VL, Suckow RF, Cooper TB: Relationship between release of platelet/endothelial biomarkers and plasma levels of sertraline and N-desmethylsertraline in acute coronary syndrome patients receiving SSRI treatment for depression. Am J Psychiatry 2005;162:1165–1170.
49.
Glassman AH, O’Conner CM, Califf RM, et al: Sertraline Antidepressant Heart Attack Randomized Trial (SADHART) Group. Sertraline treatment of major depression in patients with acute MI or unstable angina. JAMA 2002;288:701–709.
50.
Shapiro PA, Lesperance F, Frasure-Smith N, et al: An open-label preliminary trial of myocardial infarction (SADHART). Am Heart J 1999;137:1100–1106.
51.
Lara N, Archer SL, Baker GB, et al: Paroxetine-induced increase in metabolic end products of nitric oxide. J Clin Psychopharmacol 2003;23:641–645.
52.
Strik JJ, Honig A, Lousberg R, et al: Efficacy and safety of fluoxetine in the treatment of patients with major depression after first myocardial infarction: findings from a double-blind, placebo-controlled trial. Psychosom Med 2000;62:783–789.
53.
Feighner JP: Cardiovascular safety in depressed patients: focus on venlafaxine. J Clin Psychiatry 1995;56:574–579.
54.
Amsterdam JD, Garcia-Espana F, Fawcett J, et al: Blood pressure changes during short-term fluoxetine treatment. J Clin Psychopharmacol 1999;19:9–14.
55.
Taylor CB, Youngblood MR, Catellier D, et al: Effects of antidepressant medication on morbidity and mortality in depressed patients after myocardial infarction. Gen Psychiatry 2005;62:792–798.
56.
Lesperance 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.
57.
Hilton S, Jaber B, Ruch R: Moclobemide safety: monitoring a newly developed product in the 1990s. J Clin Psychopharmacol 1995;15 (suppl 2):76s–83s.
58.
Roose SP, Miyazaki M: Pharmacologic treatment of depression in patients with heart disease. Psychosom Med 2005;67(suppl 1): 54s–57s.
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