Drug Safety

, Volume 27, Issue 14, pp 1157–1165

Current Use of Selective Serotonin Reuptake Inhibitors and Risk of Acute Myocardial Infarction

  • Raymond G. Schlienger
  • Lorenz M. Fischer
  • Hershel Jick
  • Christoph R. Meier
Original Research Article

Abstract

Background: It has been suggested that increased platelet activation increases the risk of acute myocardial infarction (AMI) in patients with depression. Selective serotonin reuptake inhibitors (SSRIs) may attenuate platelet activation by serotonin depletion in platelets. Observational studies have shown discrepant results of AMI risk associated with the use of SSRIs.

Objective: The aim of this study was to evaluate the association of exposure to different groups of antidepressants, including SSRIs, and the risk of AMI. The study also assessed in more detail the influence of timing of the exposure to antidepressants in a general adult population (<90 years of age), with or without diagnosed risk factors for AMI.

Study design/methods: We conducted a population-based case-control analysis on the UK General Practice Research Database (GPRD). The study included 8688 patients (<90 years of age), with a first-time AMI between 1995 and 2001, and 33 923 controls, who were matched by age, sex, calendar time, and general practice. Conditional logistic regression was used to estimate odds ratios (ORs).

Results: Current use of an antidepressant was defined as a supply of the last prescription for an antidepressant that lasted up to the index date or beyond. Recent past use was defined as a supply of the last prescription for an antidepressant that ended 1–29 days before the index date. SSRIs investigated were citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline and venlafaxine. Non-SSRIs investigated were amitriptyline, clomipramine, dosulepin, doxepin, imipramine, lofepramine, nefazodone, trazodone and trimipramine. Other antidepressants included were amoxapine, desipramine, lithium, maprotiline, mianserin, moclobemide, nortriptyline and protriptyline. Adjusted ORs (with 95% CI) for the current use of SSRIs, non-SSRIs, or other antidepressants, compared with non-use of antidepressants, were 0.63 (95% CI 0.43, 0.91; p = 0.02), 0.92 (95% CI 0.77, 1.09; p = 0.32) and 0.59 (95% CI 0.29, 1.20; p = 0.14), respectively. The adjusted OR of recent past use of SSRIs compared with non-use of SSRIs was 1.42 (95% CI 1.02, 1.97; p = 0.04).

Conclusion: The present analysis provides further evidence that the current use of SSRIs is associated with a slightly decreased risk for AMI.

References

  1. 1.
    Penninx BW, Beekman AT, Honig A, et al. Depression and cardiac mortality: results from a community-based longitudinal study. Arch Gen Psychiatry 2001; 58(3): 221–7PubMedCrossRefGoogle Scholar
  2. 2.
    Ford DE, Mead LA, Chang PP, et al. Depression is a risk factor for coronary artery disease in men. Arch Intern Med 1998; 158(13): 1422–6PubMedCrossRefGoogle Scholar
  3. 3.
    Barefoot JC, Schroll M. Symptoms of depression, acute myocardial infarction, and total mortality in a community sample. Circulation 1996; 93(11): 1976–80PubMedCrossRefGoogle Scholar
  4. 4.
    Pratt LA, Ford DE, Crum RM, et al. Depression, psychotropic medication, and risk of myocardial infarction: prospective data from the Baltimore ECA follow-up. Circulation 1996; 94(12): 3123–9PubMedCrossRefGoogle Scholar
  5. 5.
    Frasure-Smith N, Lesperance F, Talajic M. Depression and 18-month prognosis after myocardial infarction. Circulation 1995; 91(4): 999–1005PubMedCrossRefGoogle Scholar
  6. 6.
    Stewart RA, North FM, West TM, et al. Depression and cardiovascular morbidity and mortality: cause or consequence? Eur Heart J 2003; 24(22): 2027–37PubMedCrossRefGoogle Scholar
  7. 7.
    Musselman DL, Evans DL, Nemeroff CB. The relationship of depression to cardiovascular disease: epidemiology, biology, and treatment. Arch Gen Psychiatry 1998; 55(7): 580–92PubMedCrossRefGoogle Scholar
  8. 8.
    Nemeroff CB, Musselman DL. Are platelets the link between depression and ischemic heart disease? Am Heart J 2000; 140Suppl. 4: 57–62PubMedCrossRefGoogle Scholar
  9. 9.
    Markovitz JH, Matthews KA. Platelets and coronary heart disease: potential psychophysiologic mechanisms. Psychosom Med 1991; 53(6): 643–68PubMedGoogle Scholar
  10. 10.
    Musselman DL, Tomer A, Manatunga AK, et al. Exaggerated platelet reactivity in major depression. Am J Psychiatry 1996; 153(10): 1313–7PubMedGoogle Scholar
  11. 11.
    Lederbogen F, Gilles M, Maras A, et al. Increased platelet aggregability in major depression? Psychiatry Res 2001; 102(3): 255–61PubMedCrossRefGoogle Scholar
  12. 12.
    Zellweger MJ, Osterwalder RH, Langewitz W, et al. Coronary artery disease and depression. Eur Heart J 2004; 25(13): 3–9PubMedCrossRefGoogle Scholar
  13. 13.
    Celada P, Dolera M, Alvarez E, et al. Effects of acute and chronic treatment with fluvoxamine on extracellular and platelet serotonin in the blood of major depressive patients: relationship to clinical improvement. J Affect Disord 1992; 25(4): 243–50PubMedCrossRefGoogle Scholar
  14. 14.
    Hergovich N, Aigner M, Eichler HG, et al. Paroxetine decreases platelet serotonin storage and platelet function in human beings. Clin Pharmacol Ther 2000; 68(4): 435–42PubMedCrossRefGoogle Scholar
  15. 15.
    Musselman DL, Marzec UM, Manatunga A, et al. Platelet reactivity in depressed patients treated with paroxetine: preliminary findings. Arch Gen Psychiatry 2000; 57(9): 875–82PubMedCrossRefGoogle Scholar
  16. 16.
    Serebruany VL, Gurbel PA, O’Connor CM. Platelet inhibition by sertraline and N-desmethylsertraline: a possible missing link between depression, coronary events, and mortality benefits of selective serotonin reuptake inhibitors. Pharmacol Res 2001; 43(5): 453–62PubMedCrossRefGoogle Scholar
  17. 17.
    Maurer-Spurej E, Pittendreigh C, Solomons K. The influence of selective serotonin reuptake inhibitors on human platelet serotonin. Thromb Haemost 2004; 91(1): 119–28PubMedGoogle Scholar
  18. 18.
    Schlienger RG, Meier CR. Effect of selective serotonin reuptake inhibitors on platelet activation: can they prevent acute myocardial infarction? Am J Cardiovasc Drugs 2003; 3(3): 149–62PubMedCrossRefGoogle Scholar
  19. 19.
    Nair GV, Gurbel PA, O’Connor CM, et al. Depression, coronary events, platelet inhibition, and serotonin reuptake inhibitors. Am J Cardiol 1999; 84(3): 321–3PubMedCrossRefGoogle Scholar
  20. 20.
    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(1): 2–8PubMedCrossRefGoogle Scholar
  21. 21.
    Sauer WH, Berlin JA, Kimmel SE. Selective serotonin reuptake inhibitors and myocardial infarction. Circulation 2001; 104(16): 1894–8PubMedCrossRefGoogle Scholar
  22. 22.
    Sauer WH, Berlin JA, Kimmel SE. Effect of antidepressants and their relative affinity for the serotonin transporter on the risk of myocardial infarction. Circulation 2003; 108(1): 32–6PubMedCrossRefGoogle Scholar
  23. 23.
    Meier CR, Schlienger RG, Jick H. Use of selective serotonin reuptake inhibitors and risk of developing first-time acute myocardial infarction. Br J Clin Pharmacol 2001; 52(2): 179–84PubMedCrossRefGoogle Scholar
  24. 24.
    Jick H. A database worth saving. Lancet 1997; 350(9084): 1045–6PubMedCrossRefGoogle Scholar
  25. 25.
    Garcia Rodriguez LA, Perez Gutthann S. Use of the UK General Practice Research Database for pharmacoepidemiology. Br J Clin Pharmacol 1998; 45(5): 419–25PubMedCrossRefGoogle Scholar
  26. 26.
    Walley T, Mantgani A. The UK general practice research database. Lancet 1997; 350(9084): 1097–9PubMedCrossRefGoogle Scholar
  27. 27.
    Jick H, Jick SS, Derby LE. Validation of information recorded on general practitioner based computerized data resource in the United Kingdom. BMJ 1991; 302(6779): 766–8PubMedCrossRefGoogle Scholar
  28. 28.
    Jick H, Terris BZ, Derby LE, et al. Further validation of information recorded on a general practitioner based computerized data resource in the United Kingdom. Pharmacoepidemiol Drug Saf 1992; 1(6): 347–9CrossRefGoogle Scholar
  29. 29.
    Jick SS, Kaye JA, Vasilakis-Scaramozza C, et al. Validity of the general practice research database. Pharmacotherapy 2003; 23(5): 686–9PubMedCrossRefGoogle Scholar
  30. 30.
    Meier CR, Jick SS, Derby LE, et al. Acute respiratory tract infections and risk of first-time acute myocardial infarction. Lancet 1998; 351(9114): 1467–71PubMedCrossRefGoogle Scholar
  31. 31.
    Meier CR, Derby LE, Jick SS, et al. Antibiotics and risk of subsequent first-time acute myocardial infarction. JAMA 1999; 281(5): 427–31PubMedCrossRefGoogle Scholar
  32. 32.
    Schlienger RG, Jick H, Meier CR. Use of nonsteroidal antiinflammatory drugs and the risk of first-time acute myocardial infarction. Br J Clin Pharmacol 2002; 54(3): 327–32PubMedCrossRefGoogle Scholar
  33. 33.
    Jick H, Vasilakis C, Derby LE. Antihypertensive drugs and fatal myocardial infarction in persons with uncomplicated hypertension. Epidemiology 1997; 8(4): 446–8PubMedCrossRefGoogle Scholar
  34. 34.
    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(14): 701–9PubMedCrossRefGoogle Scholar
  35. 35.
    Kimmel SE, Berlin JA, Miles C, et al. Risk of acute first myocardial infarction and use of nicotine patches in a general population. J Am Coll Cardiol 2001; 37(5): 1297–302PubMedCrossRefGoogle Scholar
  36. 36.
    Black K, Shea C, Dursun S, et al. Selective serotonin reuptake inhibitor discontinuation syndrome: proposed diagnostic criteria. J Psychiatry Neurosci 2000; 25(3): 255–61PubMedGoogle Scholar
  37. 37.
    Haddad P. The SSRI discontinuation syndrome. J Psychopharmacol 1998; 12(3): 305–13PubMedCrossRefGoogle Scholar
  38. 38.
    Ditto KE. SSRI discontinuation syndrome: awareness as an approach to prevention. Postgrad Med 2003; 114(2): 79–84PubMedCrossRefGoogle Scholar
  39. 39.
    Hemeryck A, Belpaire FM. Selective serotonin reuptake inhibitors and cytochrome P-450 mediated drug-drug interactions: an update. Curr Drug Metab 2002; 3 (1): 13–37CrossRefGoogle Scholar
  40. 40.
    Mitchell PB. Drug interactions of clinical significance with selective serotonin reuptake inhibitors. Drug Saf 1997; 17(6): 390–406PubMedCrossRefGoogle Scholar
  41. 41.
    Aranth J, Lindberg C. Bleeding, a side effect of fluoxetine. Am J Psychiatry [letter] 1992; 149(3): 412Google Scholar
  42. 42.
    Berg C, Couturier F, Grass F, et al. Saignements sous inhibiteurs de la recapture de la sérotonine: à propos d’un cas clinique. Therapie 2001; 56(1): 65–7PubMedCrossRefGoogle Scholar
  43. 43.
    Cooper TA, Valcour VG, Gibbons RB, et al. Spontaneous ecchymoses due to paroxetine administration. Am J Med 1998; 104(2): 197–8PubMedCrossRefGoogle Scholar
  44. 44.
    Lake MB, Birmaher B, Wassick S, et al. Bleeding and selective serotonin reuptake inhibitors in childhood and adolescence. J Child Adolesc Psychopharmacol 2000; 10(1): 35–8PubMedCrossRefGoogle Scholar
  45. 45.
    Wilmshurst PT, Kumar AV. Subhyaloid haemorrhage with fluoxetine [letter]. Eye 1996; 10(Pt 1): 141PubMedCrossRefGoogle Scholar
  46. 46.
    de Abajo F, Jick H, Derby L, et al. Intracranial haemorrhage and use of selective serotonin reuptake inhibitors. Br J Clin Pharmacol 2000; 50(1): 43–7PubMedCrossRefGoogle Scholar
  47. 47.
    Dalton SO, Johansen C, Mellemkjaer L, et al. Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal tract bleeding: a population-based cohort study. Arch Intern Med 2003; 163(1): 59–64PubMedCrossRefGoogle Scholar
  48. 48.
    Layton D, Clark DW, Pearce GL, et al. Is there an association between selective serotonin reuptake inhibitors and risk of abnormal bleeding? Results from a cohort study based on prescription event monitoring in England. Eur J Clin Pharmacol 2001; 57(2): 167–76PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  • Raymond G. Schlienger
    • 1
    • 2
  • Lorenz M. Fischer
    • 1
  • Hershel Jick
    • 3
  • Christoph R. Meier
    • 1
    • 2
    • 3
  1. 1.Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacology & ToxicologyUniversity Hospital BaselBaselSwitzerland
  2. 2.Department of Pharmaceutical Sciences, Institute of Clinical PharmacyUniversity BaselBaselSwitzerland
  3. 3.Boston Collaborative Drug Surveillance Program, Boston University Medical CenterLexingtonUSA

Personalised recommendations