Skip to main content
SpringerLink
Log in

The impact of SSRIs on mortality and cardiovascular events in patients with coronary artery disease and depression: systematic review and meta-analysis

  • Original Paper
  • Published:
Clinical Research in Cardiology Aims and scope Submit manuscript

Abstract

Background

Depression is common in patients after acute coronary syndromes (ACS) and with stable coronary artery disease (CAD) and has been associated with increased mortality and morbidity. However, it is unclear whether selective serotonin receptor inhibitors (SSRIs) reduce mortality or cardiac events in patients with CAD and depression.

Objective

We conducted a systematic review and meta-analysis to assess the effects of SSRIs on cardiovascular events in depressed CAD patients.

Methods

The CENTRAL, MEDLINE, and PsycINFO databases were searched (April 2020) for randomized controlled trials (RCTs) and extended follow-up analyses of RCTs that compared SSRIs with placebo or no intervention in patients with CAD and depression. The primary outcomes were all-cause mortality, cardiovascular mortality, and myocardial infarction incidence. The results were calculated through random-effect meta-analyses and reported in terms of risk ratio (RR) with 95% confidence intervals (CI).

Results

We retrieved 8 RCTs (2 of which with extended follow-up analyses), comprising a total of 1148 patients. 7 studies only included post-ACS patients. SSRIs were associated with a significantly lower risk of myocardial infarction in patients with CAD and depression (RR 0.54, 95% CI 0.34–0.86), and in post-ACS patients with depression (RR 0.56, 95% CI 0.35–0.90). We found no statistically significant difference in all-cause mortality, cardiovascular mortality, hospitalizations, angina, congestive heart failure, or stroke incidence.

Conclusion

The use of SSRIs in post-ACS patients with depression was associated with a 44% relative risk reduction of myocardial infarction. No difference in mortality was found. Given that the quality of the evidence was low, further research is warranted.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Availability of data and material (data transparency)

Any missing dada or material used in this article will be made available to readers upon reasonable request.

Abbreviations

95% CI:

95% Confidence interval

ACS:

Acute coronary syndrome

AD:

Antidepressant

BDI:

Beck's depression inventory

CAD:

Coronary artery disease

CHF:

Congestive heart failure

DSM-III-R:

Diagnostic and Statistical Manual of Mental Disorders III R

DSM-IV:

Diagnostic and Statistical Manual of Mental Disorders IV

F:

Female

FU:

Extended follow-up analysis of an RCT

GRADE:

Grading of recommendations, assessment and evaluation

HAMD-17:

17 Item Hamilton rating scale for depression

HAM-D-24:

24 Item Hamilton rating scale for depression

HDRS:

Hamilton depression rating scale

HF:

Heart failure

HR:

Heart rate

IDD:

Inventory to diagnose depression

IPT:

Interpersonal psychotherapy

LVEF:

Left ventricle ejection fraction

M:

Male

MDD:

Major depressive disorder

mDD:

Minor depressive disorder

MI:

Myocardial infarction

NSTEMI:

Non-ST elevation myocardial infarction

P:

Placebo

PCI:

Percutaneous coronary intervention

RCT:

Randomized controlled trial

RoB2:

Cochrane revised tool for risk of bias in randomized trials

RR:

Risk ratio

RRR:

Risk ratio reduction

SCL-90 DS:

90-Item symptom check list depression scale

SCL-90-R DS:

90-Item symptom check list revised depression subscale

SDS:

Self-rating depression scale

SSRI:

Selective serotonin reuptake inhibitor

STEMI:

ST elevation myocardial infarction

UA:

Unstable angina

References

  1. Thombs BD, Bass EB, Ford DE et al (2006) Prevalence of depression in survivors of acute myocardial infarction. J Gen Intern Med 21(1):30–38. https://doi.org/10.1111/j.1525-1497.2005.00269.x

    Article  PubMed  PubMed Central  Google Scholar 

  2. Kang H-J, Stewart R, Bae K-Y et al (2015) Predictors of depressive disorder following acute coronary syndrome: Results from K-DEPACS and EsDEPACS. J Affect Disord 181:1–8. https://doi.org/10.1016/j.jad.2015.04.004

    Article  PubMed  Google Scholar 

  3. Amin AA, Jones AMH, Nugent K, Rumsfeld JS, Spertus JA (2006) The prevalence of unrecognized depression in patients with acute coronary syndrome. Am Heart J 152(5):928–934. https://doi.org/10.1016/j.ahj.2006.05.006

    Article  PubMed  Google Scholar 

  4. Meijer A, Conradi HJ, Bos EH, Thombs BD, van Melle JP, de Jonge P (2011) Prognostic association of depression following myocardial infarction with mortality and cardiovascular events: a meta-analysis of 25 years of research. Gen Hosp Psychiatry 33(3):203–216. https://doi.org/10.1016/j.genhosppsych.2011.02.007

    Article  PubMed  Google Scholar 

  5. Osler M, Mårtensson S, Wium-Andersen IK et al (2016) Depression after first hospital admission for acute coronary syndrome: a study of time of onset and impact on survival. Am J Epidemiol 183(3):218–226. https://doi.org/10.1093/aje/kwv227

    Article  PubMed  Google Scholar 

  6. Lichtman JH, Froelicher ES, Blumenthal JA et al (2014) Depression as a risk factor for poor prognosis among patients with acute coronary syndrome: systematic review and recommendations: a scientific statement from the American Heart Association. Circulation 129(12):1350–1369. https://doi.org/10.1161/CIR.0000000000000019

    Article  PubMed  Google Scholar 

  7. Vaccarino V, Badimon L, Bremner JD et al (2019) Depression and coronary heart disease: 2018 position paper of the ESC working group on coronary pathophysiology and microcirculation. Eur Heart J. https://doi.org/10.1093/eurheartj/ehy913

    Article  PubMed  PubMed Central  Google Scholar 

  8. Albus C, Waller C, Fritzsche K, Gunold H, Haass M, Hamann B, Kindermann I, Köllner V, Leithäuser B, Marx N, Meesmann M, Michal M, Ronel J, Scherer M, Schrader V, Schwaab B, Weber CS, Herrmann-Lingen C (2019) Significance of psychosocial factors in cardiology: update 2018. Clin Res Cardiol 108(11):1175–1196

    Article  PubMed  Google Scholar 

  9. Bush DE, Ziegelstein RC, Tayback M et al (2001) Even minimal symptoms of depression increase mortality risk after acute myocardial infarction. Am J Cardiol 88(4):337–341. https://doi.org/10.1016/S0002-9149(01)01675-7

    Article  CAS  PubMed  Google Scholar 

  10. Frasure-Smith N, Lespérance F (2008) Depression and anxiety as predictors of 2-year cardiac events in patients with stable coronary artery disease. Arch Gen Psychiatry 65(1):62. https://doi.org/10.1001/archgenpsychiatry.2007.4

    Article  CAS  PubMed  Google Scholar 

  11. Celano CM, Huffman JC (2011) Depression and cardiac disease. Cardiol Rev 19(3):130–142. https://doi.org/10.1097/CRD.0b013e31820e8106

    Article  PubMed  Google Scholar 

  12. Barth J, Schumacher M, Herrmann-Lingen C (2004) Depression as a risk factor for mortality in patients with coronary heart disease: a meta-analysis. Psychosom Med 66(6):802–813. https://doi.org/10.1097/01.psy.0000146332.53619.b2

    Article  PubMed  Google Scholar 

  13. van Melle JP, de Jonge P, Spijkerman TA et al (2004) Prognostic association of depression following myocardial infarction with mortality and cardiovascular events: a meta-analysis. Psychosom Med 66(6):814–822. https://doi.org/10.1097/01.psy.0000146294.82810.9c

    Article  PubMed  Google Scholar 

  14. Kim J-MJ-WH, Stewart R, Lee Y-S et al (2018) Effect of escitalopram vs placebo treatment for depression on long-term cardiac outcomes in patients with acute coronary syndrome. JAMA 320(4):350. https://doi.org/10.1001/jama.2018.9422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Glassman AH, Bigger JT, Gaffney M (2009) Psychiatric characteristics associated with long-term mortality among 361 patients having an acute coronary syndrome and major depression. Arch Gen Psychiatry 66(9):1022. https://doi.org/10.1001/archgenpsychiatry.2009.121

    Article  PubMed  Google Scholar 

  16. Smolderen KG, Buchanan DM, Gosch K et al (2017) Depression treatment and 1-year mortality after acute myocardial infarction. Circulation 135(18):1681–1689. https://doi.org/10.1161/CIRCULATIONAHA.116.025140

    Article  PubMed  PubMed Central  Google Scholar 

  17. National Institute for Health and Clinical Excellence (2009) Depression: the treatment and management of depression in adults (update). (Clinical guideline 90). https://www.nice.org.uk/guidance/CG90. Accessed 21 May 2020

  18. Lichtman JH, Bigger JT, Blumenthal JA et al (2008) Depression and coronary heart disease. Circulation 118(17):1768–1775. https://doi.org/10.1161/CIRCULATIONAHA.108.190769

    Article  PubMed  Google Scholar 

  19. ​Post-Myocardial Infarction Depression Clinical Practice Guideline Panel (2009) AAFP guideline for the detection and management of post-myocardial infarction depression. Ann Fam Med 7(1):71–79. https://doi.org/10.1370/afm.918

    Article  PubMed Central  Google Scholar 

  20. Thombs BD, de Jonge P, Coyne JC et al (2008) Depression screening and patient outcomes in cardiovascular care. JAMA 300(18):2161. https://doi.org/10.1001/jama.2008.667

    Article  CAS  PubMed  Google Scholar 

  21. Pizzi C, Rutjes AWS, Costa GM, Fontana F, Mezzetti A, Manzoli L (2011) Meta-analysis of selective serotonin reuptake inhibitors in patients with depression and coronary heart disease. Am J Cardiol 107(7):972–979. https://doi.org/10.1016/j.amjcard.2010.11.017

    Article  CAS  PubMed  Google Scholar 

  22. Kim Y, Lee YS, Kim MG et al (2018) The effect of selective serotonin reuptake inhibitors on major adverse cardiovascular events. Int Clin Psychopharmacol. https://doi.org/10.1097/YIC.0000000000000238

    Article  PubMed  PubMed Central  Google Scholar 

  23. Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339(1):b2535–b2535. https://doi.org/10.1136/bmj.b2535

    Article  PubMed  PubMed Central  Google Scholar 

  24. Sterne JAC, Savović J, Page MJ et al (2019) RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. https://doi.org/10.1136/bmj.l4898

    Article  PubMed  PubMed Central  Google Scholar 

  25. Wallace BC, Dahabreh IJ, Trikalinos TA, Lau J, Trow P, Schmid CH (2012) Closing the gap between methodologists and end-users: R as a computational back-end. J Stat Softw. https://doi.org/10.18637/jss.v049.i05

    Article  Google Scholar 

  26. Schünemann H, Brożek J, Guyatt G, Oxman A (eds) (2013) GRADE handbook for grading the quality of evidence and strength of recommendations. The GRADE Working Group. https://gdt.gradepro.org/app/handbook/handbook.html. Accessed 21 May 2020

  27. GRADEpro GDT: GRADEpro Guideline Development Tool [Software]. McMaster University, 2015 (developed by Evidence Prime, Inc.). Available from gradepro.org. Accessed 21 May 2020

  28. Strik JJMH, Honig A, Lousberg R et al (2000) 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 62(6):783–789. https://doi.org/10.1097/00006842-200011000-00007

    Article  CAS  PubMed  Google Scholar 

  29. McFarlane A, Kamath MV, Fallen EL, Malcolm V, Cherian F, Norman G (2001) Effect of sertraline on the recovery rate of cardiac autonomic function in depressed patients after acute myocardial infarction. Am Heart J 142(4):617–623. https://doi.org/10.1067/mhj.2001.116766

    Article  CAS  PubMed  Google Scholar 

  30. Glassman AH (2002) Sertraline treatment of major depression in patients with acute MI or unstable angina. JAMA 288(6):701. https://doi.org/10.1001/jama.288.6.701

    Article  CAS  PubMed  Google Scholar 

  31. Mohapatra PK, Kar N, Kar GC, Behera M (2005) Effectiveness of sertraline in treatment of depression in a consecutive sample of patients with acute myocardial infarction: six month prospective study on outcome. Clin Pract Epidemiol Ment Health 1:26. https://doi.org/10.1186/1745-0179-1-26

    Article  PubMed  PubMed Central  Google Scholar 

  32. Kennedy S (University of TOC) (2006) Synopsis-study 10413: a double-blind, multicentre, randomised, parallel-group, placebo-controlled study assessing the efficacy and safety of escitalopram in post-myocardial infarction patients suffering from depressive symptoms. https://www.clinicaltrialsregister.eu/ctr-search/trial/2004-000990-78/results. Accessed 21 May 2020

  33. Lespérance F, Frasure-Smith N, Koszycki D et al (2007) Effects of citalopram and interpersonal psychotherapy on depression in patients with coronary artery disease. JAMA 297(4):367. https://doi.org/10.1001/jama.297.4.367

    Article  PubMed  Google Scholar 

  34. Kim J-M, Bae K-Y, Stewart R et al (2015) Escitalopram treatment for depressive disorder following acute coronary syndrome. J Clin Psychiatry 76(01):62–68. https://doi.org/10.4088/JCP.14m09281

    Article  PubMed  Google Scholar 

  35. Tian X, Wang Q, Guo R, Xu L, Chen QM, Hou Y (2016) Effects of paroxetine-mediated inhibition of GRK2 expression on depression and cardiovascular function in patients with myocardial infarction. Neuropsychiatr Dis Treat 12:2333–2341. https://doi.org/10.2147/NDT.S109880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Chittaranjan A, Chethan KB, Sandarsh S (2013) Cardiovascular mechanisms of SSRI drugs and their benefits and risks in ischemic heart disease and heart failure. Int Clin Psychopharmacol 28(3):145–155. https://doi.org/10.1097/YIC.0b013e32835d735d

    Article  Google Scholar 

  37. Pizzi C, Santarella L, Bugiardini R (2014) Epidemiology and the physiopathological link between depression and cardiovascular disease. IJC Metab Endocr 5:52–55. https://doi.org/10.1016/j.ijcme.2014.10.004

    Article  Google Scholar 

  38. Carvalho AF, Sharma MS, Brunoni AR, Vieta E, Fava GA (2016) The safety, tolerability and risks associated with the use of newer generation antidepressant drugs: a critical review of the literature. Psychother Psychosom 85(5):270–288. https://doi.org/10.1159/000447034

    Article  PubMed  Google Scholar 

  39. Taylor CB (2005) Effects of antidepressant medication on morbidity and mortality in depressed patients after myocardial infarction. Arch Gen Psychiatry 62(7):792. https://doi.org/10.1001/archpsyc.62.7.792

    Article  CAS  PubMed  Google Scholar 

  40. Fang XY, Spieler D, Albarqouni L, Ronel J, Ladwig KH (2018) Impact of generalized anxiety disorder (GAD) on prehospital delay of acute myocardial infarction patients. Findings from the multicenter MEDEA study. Clin Res Cardiol 107(6):471–478. https://doi.org/10.1007/s00392-018-1208-4

    Article  CAS  PubMed  Google Scholar 

  41. Peikert A, Kaier K, Merz J, Manhart L, Schäfer I, Hilgendorf I, Hehn P, Wolf D, Willecke F, Sheng X, Clemens A, Zehender M, von Zur MC, Bode C, Zirlik A, Stachon P (2020) Residual inflammatory risk in coronary heart disease: incidence of elevated high-sensitive CRP in a real-world cohort. Clin Res Cardiol 109(3):315–323. https://doi.org/10.1007/s00392-019-01511-0

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

None.

Author information

Authors and Affiliations

  1. Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028, Lisboa, Portugal

    Nuno Fernandes

  2. Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028, Lisboa, Portugal

    Luísa Prada, Mário Miguel Rosa, Joaquim J. Ferreira, João Costa & Daniel Caldeira

  3. Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028, Lisboa, Portugal

    Mário Miguel Rosa, Joaquim J. Ferreira & João Costa

  4. CNS-Campus Neurológico Sénior, Torres Vedras, Portugal

    Joaquim J. Ferreira

  5. Centro de Estudos de Medicina Baseada na Evidência, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028, Lisboa, Portugal

    João Costa

  6. Centro Cardiovascular da Universidade de Lisboa-CCUL, CAML, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028, Lisboa, Portugal

    Fausto J. Pinto & Daniel Caldeira

  7. Serviço de Cardiologia, Departamento do Coração e Vasos, Hospital Universitário de Santa Maria-CHULN, Avenida Professor Egas Moniz, 1649-028, Lisboa, Portugal

    Fausto J. Pinto & Daniel Caldeira

Authors
  1. Nuno Fernandes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Luísa Prada
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mário Miguel Rosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Joaquim J. Ferreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. João Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fausto J. Pinto
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Daniel Caldeira
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daniel Caldeira.

Ethics declarations

Conflict of interest

JJF had speaker and consultant fees with Grünenthal, Fundação MSD (Portugal), TEVA, MSD, Allergan, Medtronic, GlaxoSmithKline, Novartis, Lundbeck, Solvay, BIAL, Merck-Serono, Merz, Ipsen, Biogen, Acadia, Allergan, Abbvie, Sunovion-Pharmaceuticals. FJP had consultant and speaker fees with Astra Zeneca, Bayer, BMS, Boehringer Ingelheim, and Daiichi Sankyo. DC has participated in educational meetings and/or attended conferences or symposia (including travel, accommodation, and/or hospitality) with Bristol-Myers Squibb, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Merck Serono, Ferrer, Pfizer, Novartis, and Roche. The remaining authors do not have interests to disclose.

Code availability

Not applicable.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 1189 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fernandes, N., Prada, L., Rosa, M.M. et al. The impact of SSRIs on mortality and cardiovascular events in patients with coronary artery disease and depression: systematic review and meta-analysis. Clin Res Cardiol 110, 183–193 (2021). https://doi.org/10.1007/s00392-020-01697-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00392-020-01697-8

Keywords

Search

Navigation