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Krissy Reinstatler, PharmD, MBA, BCPP
Clinical Pharmacy Specialist
UC Health University of Cincinnati Medical Center
UC Health UCMC Psychiatric Services
Cincinnati, OH

Ever wondered which QTc correction calculation is most correct? Dr. Chris Celano, MD, FACLP, the Associate Director of the Cardiac Psychiatry Research Program at Massachusetts General Hospital and an Assistant Professor at Harvard Medical School, explored this and other cardiovascular conundrums in his talk Don’t Go Breakin’ My Heart: Managing Depression and Anxiety in Cardiac Patients at CPNP 2022.

Dr. Celano’s discussion of depression and anxiety with comorbid cardiac disease was excellent and extremely relevant to psychiatric pharmacists, since up to 45% of patients with cardiac disease, such as coronary artery disease and heart failure, have clinically significant depressive symptoms, with 15-20% meeting criteria for major depressive disorder. Depression and anxiety increase the risk of developing cardiac disease and contribute to poor outcomes, including increased mortality for cardiac patients with co-morbid depression. This increased risk could be due to biological as well as behavioral mechanisms, including altered platelet function, inflammation, endothelial dysfunction, decreased physical activity, poor diet, and smoking.1

How does one manage these complex patients? Dr. Celano presented evidence supporting psychotherapy, collaborative care, and pharmacotherapy. Cognitive behavioral therapy (CBT) is effective in reducing depression and anxiety in patients with cardiac disease, although this does not seem to translate to decreases in mortality.2,3 Collaborative care models, like those seen in the TEAM Care and COMPASS studies, can improve psychiatric symptoms and cardiac health. A blended model of care that manages both psychiatric and medical symptoms seems to have the greatest impact on overall health.4,5

Multiple clinical trials support pharmacotherapy interventions for depression in patients with cardiac disease. Specifically, the evidence suggests a small but significant reduction in depressive symptoms for citalopram6, escitalopram7, and mirtazapine8 in patients with coronary artery disease (CAD). Sertraline9 shows a trend towards significant reduction in symptoms, with stronger and more significant results in individuals with recurrent depression and with more severe symptoms. In patients with heart failure, however, sertraline10 and escitalopram11 showed similar reductions in depressive symptoms as placebo. This may be due to the severity of heart failure in the trials versus the relatively low depression scores. When considering the impact of antidepressants on mortality, evidence suggests adequately treated depression may lower rates of mortality in patients with cardiac disease.2,12-14

Side effects of antidepressants, such as increased bleeding risk and QTc prolongation, can be a cause for concern in patients with comorbid cardiac disease. In a focused discussion of QTc prolongation, Dr. Celano described the equations used to correct QTc for heart rate and the resulting variation in QTc measurement. Based on available data, the Hodges formula is preferred as it provides a QTc interval that is an independent risk marker for all-cause mortality.15

Overall, antidepressants seem to have little impact on QTc, as demonstrated in the slide below. This meta-analysis by Beach and colleagues found citalopram, escitalopram, and TCAs associated with the most change in QTc, although all were less than the 30ms difference considered to be clinically significant.16 The association between antidepressants and adverse cardiac events is less clear, with studies showing both an association and no difference from placebo.17-19 Dr. Celano suggests monitoring QTc and electrolytes in patients with significant risk factors or on a high-risk medication, such as citalopram or escitalopram. For patients without significant risk factors and on lower-risk medications, no monitoring is needed.

 

Take home points:

  • Depression and anxiety are very common in patients with cardiac disease and are associated with poor health outcomes.
  • Both biological and behavioral mechanisms may mediate the relationships between psychiatric symptoms and cardiac health.
  • There are safe and effective treatments for depression in patients with cardiac disease, but the most effective treatment program will likely require several treatment modalities.
  • Treating psychiatric illness may improve both psychiatric and cardiovascular outcomes in patients with heart disease.

References

  1. Celano CM, Huffman JC. Depression and cardiac disease: a review. Cardiol Rev. 2011 May-Jun;19(3):130-42. doi: 10.1097/CRD.0b013e31820e8106. PMID: 21464641.
  2. Berkman LF, Blumenthal J, Burg M, Carney RM, Catellier D, Cowan MJ, Czajkowski SM, DeBusk R, Hosking J, Jaffe A, Kaufmann PG, Mitchell P, Norman J, Powell LH, Raczynski JM, Schneiderman N. 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;289:3106-16.
  3. Reavell J, Hopkinson M, Clarkesmith D, Lane DA. Effectiveness of cognitive behavioral therapy for depression and anxiety in patients with cardiovascular disease: A systematic review and meta-analysis. Psychosom Med. 2018 Oct;80(8):742-753.
  4. Katon WJ, Lin EH, Von Korff M, Ciechanowski P, Ludman EJ, Young B, Peterson D, Rutter CM, McGregor M, McCulloch D. Collaborative care for patients with depression and chronic illnesses. N Engl J Med. 2010;363:2611-20.
  5. Rosssom RC et al.  Impact of a national collaborative care initiative for patients with depression and diabetes or cardiovascular disease.  Gen Hosp Psychiatry.  2017;44:77-85.
  6. Lesperance F, Frasure-Smith N, Koszycki D, Laliberte MA, van Zyl LT, Baker B, Swenson JR, Ghatavi K, Abramson BL, Dorian P, Guertin MC. 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;297:367-79.
  7. Kim JM, Bae KY, Stewart R, Jung BO, Kang HJ, Kim SW, Shin IS, Hong YJ, Kim JH, Shin HY, Kang G, Ahn Y, Kim JK, Jeong MH, Yoon JS. Escitalopram treatment for depressive disorder following acute coronary syndrome: a 24-week double-blind, placebo-controlled trial. J Clin Psychiatry. 2015; 76(1):62-68.
  8. Honig A, Kuyper AMG, Schene AH, van Melle JP, de Jonge P, Tulner DM, Schins A, Crijns HJGM, Kuijpers PMJC,Vossen H, Lousberg R, Ormel J.  Treatment of post-myocardial infarction depressive disorder: A randomized, placebo-controlled trial with mirtazapine. Psychosom Med. 2007;69:606-613.
  9. 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.
  10. O'Connor CM, Jiang W, Kuchibhatla M, Silva SG, Cuffe MS, Callwood DD, Zakhary B, Stough WG, Arias RM, Rivelli SK, Krishnan R. Safety and efficacy of sertraline for depression in patients with heart failure: results of the SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) trial. J Am Coll Cardiol. 2010;56:692-9.
  11. Angermann CE, Gelbrich G, Störk S, Gunold H, Edelmann F, Wachter R, Schunkert H, Graf T, Kindermann I, Haass M, Blankenberg S, Pankuweit S, Prettin C, Gottwik M, Böhm M, Faller H, Deckert J, Ertl G; MOOD-HF Study Investigators and Committee Members. Effect of Escitalopram on All-Cause Mortality and Hospitalization in Patients With Heart Failure and Depression: The MOOD-HF Randomized Clinical Trial. JAMA. 2016;315(24):2683-93
  12. Scherrer JF, Chrusciel T, Garfield LD, Freedland KE, Carney RM, Hauptman PJ, Bucholz KK, Owen R, Lustman PJ. Treatment-resistant and insufficiently treated depression and all-cause mortality following myocardial infarction. Br J Psychiatry. 2012;200(2):137-42.
  13. Smolderen KG, Buchanan DM, Gosch K, Whooley M, Chan PS, Vaccarino V, Parashar S, Shah AJ, Ho PM, Spertus JA. Depression Treatment and 1-Year Mortality After Acute Myocardial Infarction: Insights From the TRIUMPH Registry (Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients' Health Status). Circulation. 2017;135(18):1681-1689.
  14. Lavoie KL, Paine NJ, Pelletier R, Arsenault A, Diodati JG, Campbell TS, Pilote L, Bacon SL. Relationship between antidepressant therapy and risk for cardiovascular events in patients with and without cardiovascular disease. Health Psychol. 2018;37(11):989-999.
  15. Patel PJ, Borovskiy Y, Killian A, Verdino RJ, Epstein AE, Callans DJ, Marchlinski FE, Deo R.  Optimal QT interval correction formula in sinus tachycardia for identifying cardiovascular and mortality risk: findings from the Penn Atrial Fibrillation Free study.  Heart Rhythm.  2016; 13: 527-535.
  16. Beach SR, Kostis WJ, Celano CM, Januzzi JL, Ruskin JN, Noseworthy PA, Huffman JC. Meta-analysis of selective serotonin reuptake inhibitor-associated QTc prolongation. J Clin Psychiatry.  2014;75(5):e441-449.
  17. Weeke P, Jensen A, Folke F, et al. Antidepressant use and risk of out-of-hospital cardiac arrest: A nationwide case-time-control study. Clin Pharmacol Ther. 2012;92(1):72-79.
  18. Ray WA, Chung CP, Murray KT, Hall K, Stein CM. High-Dose Citalopram and Escitalopram and the Risk of Out-of-Hospital Death. J Clin Psychiatry. 2017 Feb;78(2):190-195.
  19. Thase M, Larsen KG, Reines E, et al. The cardiovascular safety profile of escitalopram. Eur Neuropsychopharmacol. 2013 Nov;23(11):1391-400.
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