Effect of antidepressants on death in patients with heart failure: a systematic review and meta-analysis

Abstract

Depression is associated with an increased risk of death in patients with heart failure (HF); however, the association between the use of antidepressants and HF prognoses remains controversial. Therefore, this meta-analysis aimed to evaluate the effect of antidepressants on the risk of death in HF patients. We retrieved data from the PubMed and EMBASE databases until August 2019 for studies reporting the use of antidepressants in HF patients. Data were extracted from the eligible articles, and a random effects model was used to pool the effect estimates (risk ratios (RRs) and 95% confidence intervals (CIs)). A total of 8 studies were included in this meta-analysis. Overall, the use of antidepressants was associated with increased risks of all-cause death (RR = 1.27; 95% CI, 1.21–1.34) and cardiovascular death (RR = 1.14; 95% CI, 1.08–1.20) in HF patients with or without depression. Specifically, HF patients with depression taking antidepressants had increased risks of all-cause death (RR = 1.21; 95% CI, 1.16–1.27) and cardiovascular death (RR = 1.21; 95% CI, 1.13–1.30). Compared with nonusers, the use of selective serotonin reuptake inhibitors (SSRIs), tricyclics (TCAs), and selective serotonin reuptake inhibitors (SNRIs) significantly increased the rate of all-cause death (SSRIs (RR = 1.26; 95% CI, 1.19–1.32), TCAs (RR = 1.30; 95% CI, 1.16–1.46), and SNRIs (RR = 1.17; 95% CI, 1.08–1.26)) but not cardiovascular death (SSRIs (RR = 1.03; 95% CI, 0.84–1.26), TCAs (RR = 1.02; 95% CI, 0.86–1.21), and SNRIs (RR = 0.92; 95% CI, 0.48–1.78)). Based on current publications, the use of antidepressants could increase the risk of all-cause death in HF patients, regardless of whether they have depression or the type of antidepressants they use. Further study is needed to determine the relationship between antidepressant use and cardiovascular death.

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References

  1. 1.

    Celano CM, Villegas AC, Albanese AM, Gaggin HK, Huffman JC (2018) Depression and anxiety in heart failure: a review. Harv Rev Psychiatry 26(4):175–184

    Article  Google Scholar 

  2. 2.

    Lin TK, Hsu BC, Li YD, Chen CH, Lin JW, Chien CY, Weng CY (2019) Prognostic value of anxiety between heart failure with reduced ejection fraction and heart failure with preserved ejection fraction. J Am Heart Assoc 8(12)

  3. 3.

    Rutledge T, Reis VA, Linke SE, Greenberg BH, Mills PJ (2006) Depression in heart failure a meta-analytic review of prevalence, intervention effects, and associations with clinical outcomes. J Am Coll Cardiol 48(8):1527–1537

    Article  Google Scholar 

  4. 4.

    Gathright EC, Goldstein CM, Josephson RA, Hughes JW (2017) Depression increases the risk of mortality in patients with heart failure: a meta-analysis. J Psychosom Res 94:82–89

    Article  Google Scholar 

  5. 5.

    Sokoreli I, de Vries J, Pauws SC, Steyerberg EW (2016) Depression and anxiety as predictors of mortality among heart failure patients: systematic review and meta-analysis. Heart Fail Rev 21(1):49–63

    Article  CAS  Google Scholar 

  6. 6.

    Jha MK, Qamar A, Vaduganathan M, Charney DS, Murrough JW (2019) Screening and management of depression in patients with cardiovascular disease. J Am Coll Cardiol 73(14):1827–1845

    Article  Google Scholar 

  7. 7.

    Tousoulis D, Antoniades C, Drolias A, Stefanadi E, Marinou K, Vasiliadou C, Tsioufis C, Toutouzas K, Latsios G, Stefanadis C (2008) Selective serotonin reuptake inhibitors modify the effect of β-blockers on long-term survival of patients with end-stage heart failure and major depression. J Card Fail 14(6):456–464

    Article  CAS  Google Scholar 

  8. 8.

    Chung ML, Dekker RL, Lennie TA, Moser DK (2013) Antidepressants do not improve event-free survival in patients with heart failure when depressive symptoms remain. Heart Lung 42(2):85–91

    Article  Google Scholar 

  9. 9.

    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 (2016) Effect of escitalopram on all-cause mortality and hospitalization in patients with heart failure and depression. JAMA 315(24):2683–2693

    Article  CAS  Google Scholar 

  10. 10.

    O’Connor CM, Jiang W, Kuchibhatla M, Silva SG, Cuffe MS, Callwood DD, Zakhary B, Stough WG, Arias RM, Rivelli SK, Krishnan R (2010) Safety and efficacy of sertraline for depression in patients with heart failure. J Am Coll Cardiol 56(9):692–699

    Article  CAS  Google Scholar 

  11. 11.

    O’Connor CM, Jiang W, Kuchibhatla M, Mehta RH, Clary GL, Cuffe MS, Christopher EJ, Alexander JD, Califf RM, Krishnan RR (2008) Antidepressant use, depression, and survival in patients with heart failure. Arch Intern Med 168(20):2232

    Article  Google Scholar 

  12. 12.

    Brouwers C, Christensen SB, Damen NL, Denollet J, Torp-Pedersen C, Gislason GH, Pedersen SS (2016) Antidepressant use and risk for mortality in 121,252 heart failure patients with or without a diagnosis of clinical depression. Int J Cardiol 203:867–873

    Article  Google Scholar 

  13. 13.

    EL Fosb L, Gislason GH, Poulsen HE, Hansen ML, Folke F, Schramm TK, Olesen JB, Bretler D, Abildstrøm SZ, Sørensen R, Hvelplund A, Køber L, Torp-Pedersen C (2009) Prognosis in heart failure and the value of β-blockers are altered by the use of antidepressants and depend on the type of antidepressants used. Circ Heart Fail 2(6):582–590

    Article  CAS  Google Scholar 

  14. 14.

    Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6(7):e1000097

    Article  Google Scholar 

  15. 15.

    Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA (2011) The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343:d5928

    Article  Google Scholar 

  16. 16.

    Wells GA, Shea B, O’Connell D, Peterson J, Welch V, Losos M, Tugwell P (2014) The Newcastle Ottawa Scale (NOS) for assessing the quality if nonrandomized studies in meta-analyses. Available at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed 1 August 2019

  17. 17.

    Zhu W, Wan R, Liu F, Hu J, Huang L, Li J, Hong K (2016) Relation of body mass index with adverse outcomes among patients with atrial fibrillation: a meta-analysis and systematic review. J Am Heart Assoc 5(9):e4006

    Article  Google Scholar 

  18. 18.

    Diez-Quevedo C, Lupón J, González B, Urrutia A, Cano L, Cabanes R, Altimir S, Coll R, Pascual T, de Antonio M, Bayes-Genis A (2013) Depression, antidepressants, and long-term mortality in heart failure. Int J Cardiol 167(4):1217–1225

    Article  Google Scholar 

  19. 19.

    Veien KT, Videbæk L, Schou M, Gustafsson F, Hald-Steffensen F, Hildebrandt PR (2011) High mortality among heart failure patients treated with antidepressants. Int J Cardiol 146(1):64–67

    Article  Google Scholar 

  20. 20.

    Sherwood A, Blumenthal JA, Trivedi R, Johnson KS, O’Connor CM, Adams KF, Dupree CS, Waugh RA, Bensimhon DR, Gaulden L, Christenson RH, Koch GG, Hinderliter AL (2007) Relationship of depression to death or hospitalization in patients with heart failure. Arch Intern Med 167(4):367–373

    Article  Google Scholar 

  21. 21.

    Samartzis L, Dimopoulos S, Tziongourou M, Koroboki E, Kyprianou T, Nanas S (2013) SSRIs versus exercise training for depression in chronic heart failure: a meta-analysis of randomized controlled trials. Int J Cardiol 168(5):4956–4958

    Article  Google Scholar 

  22. 22.

    Lekakis J, Ikonomidis I, Papoutsi Z, Moutsatsou P, Nikolaou M, Parissis J, Kremastinos DT (2010) Selective serotonin re-uptake inhibitors decrease the cytokine-induced endothelial adhesion molecule expression, the endothelial adhesiveness to monocytes and the circulating levels of vascular adhesion molecules. Int J Cardiol 139(2):150–158

    Article  Google Scholar 

  23. 23.

    Fraguas R, Da Silva Telles RM, Alves TCTF, Andrei AM, Rays J, Iosifescu DV, Wajngarten M (2009) A double-blind, placebo-controlled treatment trial of citalopram for major depressive disorder in older patients with heart failure: the relevance of the placebo effect and psychological symptoms. Contemp Clin Trials 30(3):205–211

    Article  CAS  Google Scholar 

  24. 24.

    Gottlieb SS, Kop WJ, Thomas SA, Katzen S, Vesely MR, Greenberg N, Marshall J, Cines M, Minshall S (2007) A double-blind placebo-controlled pilot study of controlled-release paroxetine on depression and quality of life in chronic heart failure. Am Heart J 153(5):868–873

    Article  CAS  Google Scholar 

  25. 25.

    Jimenez JA, Redwine LL, Rutledge TR, Dimsdale JE, Pung MA, Ziegler MG, Greenberg BH, Mills PJ (2012) Depression ratings and antidepressant use among outpatient heart failure patients: implications for the screening and treatment of depression. Int J Psychiatry Med 44(4):315–334

    Article  Google Scholar 

  26. 26.

    Fan H, Yu W, Zhang Q, Cao H, Li J, Wang J, Shao Y, Hu X (2014) Depression after heart failure and risk of cardiovascular and all-cause mortality: a meta-analysis. Prev Med 63:36–42

    Article  Google Scholar 

  27. 27.

    Konig F, Hafele M, Hauger B, Loble M, Wossner S, Wolfersdorf M (1996) Bradycardia after beginning therapy with metoprolol and paroxetine. Psychiatr Prax 23(5):244–245

    PubMed  CAS  Google Scholar 

  28. 28.

    Kim C, Duan L, Phan DQ, Lee M (2019) Frequency of utilization of beta blockers in patients with heart failure and depression and their effect on mortality. Am J Cardiol 124(5), 746–750

  29. 29.

    Davidson KW, Kupfer DJ, Bigger JT, Califf RM, Carney RM, Coyne JC, Czajkowski SM, Frank E, Frasure-Smith N, Freedland KE, Froelicher ES, Glassman AH, Katon WJ, Kaufmann PG, Kessler RC, Kraemer HC, Krishnan KR, Lesperance F, Rieckmann N, Sheps DS, Suls JM (2006) Assessment and treatment of depression in patients with cardiovascular disease: National Heart, Lung, and Blood Institute working group report. Ann Behav Med 32(2):121–126

    Article  Google Scholar 

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Contributors

WF-H and YH-F performed the whole meta-analysis, including literature search, data extraction, statistical analysis, and writing the manuscript. Y-Z, B-W, and JY-M offered help in the process of revision.

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Correspondence to Yonghui Fu.

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He, W., Zhou, Y., Ma, J. et al. Effect of antidepressants on death in patients with heart failure: a systematic review and meta-analysis. Heart Fail Rev 25, 919–926 (2020). https://doi.org/10.1007/s10741-019-09850-w

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Keywords

  • Heart failure
  • Depression
  • Antidepressant
  • Death