Skip to main content

The Risk of Thromboembolism in Users of Antidepressants and Antipsychotics

  • Chapter
  • First Online:
Thrombosis and Embolism: from Research to Clinical Practice

Abstract

Arterial and venous thromboembolism are common causes of morbidity and mortality in the Western world. Mental disorders are also highly prevalent with a lifetime risk of experiencing any psychiatric disease ranging between 32 % and 37 %. Depression and schizophrenia may increase the risk of thromboembolism through genetic, behavioral, and biological mechanisms. Treatment of psychiatric patients with psychotropic drugs is imperative to improve quality of life and to reduce morbidity and mortality. However, studies have shown that psychotropic drugs themselves may modify the risk of arterial and venous thromboembolism, which should be taken into consideration when using these drugs in clinical practice. This association is, however, multifactorial, complex and susceptible to several confounding factors. Psychotropic drugs are widely prescribed, also among patients with cardiovascular disease. Therefore, understanding the association with thromboembolism and the underlying pathophysiological mechanisms is of major importance and will be reviewed in this chapter.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Bak S, Tsiropoulos I, Kjaersgaard JO, Andersen M, Mellerup E, Hallas J et al (2002) Selective serotonin reuptake inhibitors and the risk of stroke: a population-based case-control study. Stroke 33(6):1465–1473

    Article  CAS  PubMed  Google Scholar 

  • Barbui C, Conti V, Cipriani A (2014) Antipsychotic drug exposure and risk of venous thromboembolism: a systematic review and meta-analysis of observational studies. Drug Saf 37(2):79–90

    Article  CAS  PubMed  Google Scholar 

  • Berger M, Gray JA, Roth BL (2009) The expanded biology of serotonin. Annu Rev Med 60:355–366

    Article  CAS  PubMed  Google Scholar 

  • Blanchette CM, Simoni-Wastila L, Zuckerman IH, Stuart B (2008) A secondary analysis of a duration response association between selective serotonin reuptake inhibitor use and the risk of acute myocardial infarction in the aging population. Ann Epidemiol 18(4):316–321

    Article  PubMed  Google Scholar 

  • Boullin DJ, Woods HF, Grimes RP, Grahame-Smith DG (1975) Increased platelet aggregation responses to 5-hydroxytryptamine in patients taking chlorpromazine. Br J Clin Pharmacol 2(1):29–35

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brauer R, Douglas I, Smeeth L (2011) The association between antipsychotic agents and the risk of myocardial infarction: a systematic review. Br J Clin Pharmacol 72(6):871–878

    Article  PubMed  PubMed Central  Google Scholar 

  • Brauer R, Smeeth L, Anaya-Izquierdo K, Timmis A, Denaxas SC, Farrington CP et al (2014) Antipsychotic drugs and risks of myocardial infarction: a self-controlled case series study. Eur Heart J 21;36(16):984–992

    Google Scholar 

  • Chapelle C, Quenet S, Delavenne X, Lacut K, Mismetti P, Laporte S et al (2013) Antipsychotics: a real or confounding risk factor for venous thromboembolism? Pharmacopsychiatry 46(1):36–37

    CAS  PubMed  Google Scholar 

  • Cohen HW, Gibson G, Alderman MH (2000) Excess risk of myocardial infarction in patients treated with antidepressant medications: association with use of tricyclic agents. Am J Med 108(1):2–8

    Article  CAS  PubMed  Google Scholar 

  • Dall M (2010) Schaffalitzky de Muckadell OB, Lassen AT, Hallas J. There is an association between selective serotonin reuptake inhibitor use and uncomplicated peptic ulcers: a population-based case-control study. Aliment Pharmacol Ther 32(11-12):1383–1391

    Article  CAS  PubMed  Google Scholar 

  • de Abajo FJ (2011) Effects of selective serotonin reuptake inhibitors on platelet function: mechanisms, clinical outcomes and implications for use in elderly patients. Drugs Aging 28(5):345–367

    Article  PubMed  Google Scholar 

  • de Abajo FJ, Garcia-Rodriguez LA (2008) Risk of upper gastrointestinal tract bleeding associated with selective serotonin reuptake inhibitors and venlafaxine therapy: interaction with nonsteroidal anti-inflammatory drugs and effect of acid-suppressing agents. Arch Gen Psychiatry 65(7):795–803

    Article  PubMed  Google Scholar 

  • Dong JY, Zhang YH, Tong J, Qin LQ (2012) Depression and risk of stroke: a meta-analysis of prospective studies. Stroke 43(1):32–37

    Article  PubMed  Google Scholar 

  • Draper B, Berman K (2008) Tolerability of selective serotonin reuptake inhibitors: issues relevant to the elderly. Drugs Aging 25(6):501–519

    Article  CAS  PubMed  Google Scholar 

  • Dworkin RH (1994) Pain insensitivity in schizophrenia: a neglected phenomenon and some implications. Schizophr Bull 20(2):235–248

    Article  CAS  PubMed  Google Scholar 

  • Elderon L, Whooley MA (2013) Depression and cardiovascular disease. Prog Cardiovasc Dis 55(6):511–523

    Article  PubMed  Google Scholar 

  • Goldhaber SZ (2010) Risk factors for venous thromboembolism. J Am Coll Cardiol 56(1):1–7

    Article  PubMed  Google Scholar 

  • Hackam DG, Mrkobrada M (2012) Selective serotonin reuptake inhibitors and brain hemorrhage: a meta-analysis. Neurology 79(18):1862–1865

    Article  CAS  PubMed  Google Scholar 

  • Hagg S, Spigset O (2002) Antipsychotic-induced venous thromboembolism: a review of the evidence. CNS Drug 16(11):765–776

    Article  Google Scholar 

  • Hagg S, Jonsson AK, Spigset O (2009) Risk of venous thromboembolism due to antipsychotic drug therapy. Expert Opin Drug Saf 8(5):537–547

    Article  PubMed  Google Scholar 

  • Halperin D, Reber G (2007) Influence of antidepressants on hemostasis. Dialogues Clin Neurosci 9(1):47–59

    PubMed  PubMed Central  Google Scholar 

  • Hamer M, Batty GD, Seldenrijk A, Kivimaki M (2011) Antidepressant medication use and future risk of cardiovascular disease: the Scottish Health Survey. Eur Heart J 32(4):437–442

    Article  CAS  PubMed  Google Scholar 

  • Harman JS, Edlund MJ, Fortney JC (2009) Trends in antidepressant utilization from 2001 to 2004. Psychiatr Serv 60(5):611–616

    Article  PubMed  Google Scholar 

  • Hippisley-Cox J, Pringle M, Hammersley V, Crown N, Wynn A, Meal A et al (2001) Antidepressants as risk factor for ischaemic heart disease: case-control study in primary care. BMJ 323(7314):666–669

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jacobs BL, Azmitia EC (1992) Structure and function of the brain serotonin system. Physiol Rev 72(1):165–229

    CAS  PubMed  Google Scholar 

  • Jiang HY, Chen HZ, Hu XJ, Yu ZH, Yang W, Deng M et al (2015) Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal bleeding: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 13(1):42–50.e3

    Google Scholar 

  • Jick SS, Li L (2008) Antidepressant drug use and risk of venous thromboembolism. Pharmacotherapy 28(2):144–150

    Article  CAS  PubMed  Google Scholar 

  • Jonsson AK, Horvath-Puho E, Hagg S, Pedersen L, Sorensen HT (2009) Antipsychotics and risk of venous thromboembolism: a population-based case-control study. Clin Epidemiol 1:19–26

    Article  PubMed  PubMed Central  Google Scholar 

  • Kales HC, Maixner DF, Mellow AM (2005) Cerebrovascular disease and late-life depression. Am J Geriatr Psychiatry 13(2):88–98

    Article  PubMed  Google Scholar 

  • Kessler RC, Angermeyer M, Anthony JC, DE Graaf R, Demyttenaere K, Gasquet I et al (2007) Lifetime prevalence and age-of-onset distributions of mental disorders in the World Health Organization’s World Mental Health Survey Initiative. World Psychiatry 6(3):168–176

    PubMed  PubMed Central  Google Scholar 

  • Kimmel SE, Schelleman H, Berlin JA, Oslin DW, Weinstein RB, Kinman JL et al (2011) The effect of selective serotonin re-uptake inhibitors on the risk of myocardial infarction in a cohort of patients with depression. Br J Clin Pharmacol 72(3):514–517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kobberoe SK, Schmidt M, Pedersen L, Horvath-Puho E, Toft SH (2014) 30-year mortality following venous thromboembolism: a population-based cohort study. Circulation 130(10):829–836

    Google Scholar 

  • Kraglund KL, Mortensen JK, Grove EL, Johnsen SP, Andersen G (2015) TALOS: a multicenter, randomized, double-blind, placebo-controlled trial to test the effects of citalopram in patients with acute stroke. Int J Stroke 10(6):985–987

    Google Scholar 

  • Lacut K, Le Gal G, Couturaud F, Cornily G, Leroyer C, Mottier D et al (2007) Association between antipsychotic drugs, antidepressant drugs and venous thromboembolism: results from the EDITH case-control study. Fundam Clin Pharmacol 21(6):643–650

    Article  CAS  PubMed  Google Scholar 

  • Laursen TM, Nordentoft M (2011) Heart disease treatment and mortality in schizophrenia and bipolar disorder - changes in the Danish population between 1994 and 2006. J Psychiatr Res 45(1):29–35

    Article  PubMed  Google Scholar 

  • Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F et al (2013) Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet 382(9896):951–962

    Article  CAS  PubMed  Google Scholar 

  • Lichtman JH, Froelicher ES, Blumenthal JA, Carney RM, Doering LV, Frasure-Smith N 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

    Article  PubMed  Google Scholar 

  • Lin ST, Chen CC, Tsang HY, Lee CS, Yang P, Cheng KD et al (2014) Association between antipsychotic use and risk of acute myocardial infarction: a nationwide case-crossover study. Circulation 130(3):235–243

    Article  CAS  PubMed  Google Scholar 

  • MacDonald TM, McMahon AD, Reid IC, Fenton GW, McDevitt DG (1996) Antidepressant drug use in primary care: a record linkage study in Tayside. Scotland BMJ 313(7061):860–861

    CAS  PubMed  Google Scholar 

  • Maurer-Spurej E (2005) Serotonin reuptake inhibitors and cardiovascular diseases: a platelet connection. Cell Mol Life Sci 62(2):159–170

    Article  CAS  PubMed  Google Scholar 

  • Mazza M, Lotrionte M, Biondi-Zoccai G, Abbate A, Sheiban I, Romagnoli E (2010) Selective serotonin reuptake inhibitors provide significant lower re-hospitalization rates in patients recovering from acute coronary syndromes: evidence from a meta-analysis. J Psychopharmacol 24(12):1785–1792

    Article  CAS  PubMed  Google Scholar 

  • Meier CR, Schlienger RG, Jick H (2001) Use of selective serotonin reuptake inhibitors and risk of developing first-time acute myocardial infarction. Br J Clin Pharmacol 52(2):179–184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Monster TB, Johnsen SP, Olsen ML, McLaughlin JK, Sorensen HT (2004) Antidepressants and risk of first-time hospitalization for myocardial infarction: a population-based case-control study. Am J Med 117(10):732–737

    Article  CAS  PubMed  Google Scholar 

  • Muhonen MG, Robertson SC, Gerdes JS, Loftus CM (1997) Effects of serotonin on cerebral circulation after middle cerebral artery occlusion. J Neurosurg 87(2):301–306

    Article  CAS  PubMed  Google Scholar 

  • Newman SC, Schopflocher D (2008) Trends in antidepressant prescriptions among the elderly in Alberta during 1997 to 2004. Can J Psychiatry 53(10):704–707

    PubMed  Google Scholar 

  • Oger E (2000) Incidence of venous thromboembolism: a community-based study in Western France. EPI-GETBP Study Group. Groupe d’Etude de la Thrombose de Bretagne Occidentale. Thromb Haemost 83(5):657–660

    CAS  PubMed  Google Scholar 

  • Orr MW, Boullin DJ (1976) The ralationship between changes in 5-HT induced platelet aggregation and clinical state in patients treated with fluphenazine. Br J Clin Pharmacol 3(5):925–928

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Osborn DP, Wright CA, Levy G, King MB, Deo R, Nazareth I (2008) Relative risk of diabetes, dyslipidaemia, hypertension and the metabolic syndrome in people with severe mental illnesses: systematic review and metaanalysis. BMC Psychiatry 8:84–244X-8-84

    Google Scholar 

  • Parker C, Coupland C, Hippisley-Cox J (2010) Antipsychotic drugs and risk of venous thromboembolism: nested case-control study. BMJ 341:c4245

    Article  PubMed  Google Scholar 

  • Parkin L, Skegg DC, Herbison GP, Paul C (2003) Psychotropic drugs and fatal pulmonary embolism. Pharmacoepidemiol Drug Saf 12(8):647–652

    Article  CAS  PubMed  Google Scholar 

  • Pedersen CB, Mors O, Bertelsen A, Waltoft BL, Agerbo E, McGrath JJ et al (2014) A comprehensive nationwide study of the incidence rate and lifetime risk for treated mental disorders. JAMA Psychiatry 71(5):573–581

    Article  PubMed  Google Scholar 

  • Potvin S, Marchand S (2008) Hypoalgesia in schizophrenia is independent of antipsychotic drugs: a systematic quantitative review of experimental studies. Pain 138(1):70–78

    Article  CAS  PubMed  Google Scholar 

  • Quinn GR, Singer DE, Chang Y, Go AS, Borowsky LH, Udaltsova N et al (2014) Effect of selective serotonin reuptake inhibitors on bleeding risk in patients with atrial fibrillation taking warfarin. Am J Cardiol 114(4):583–586

    Article  CAS  PubMed  Google Scholar 

  • Ray JG, Mamdani MM, Yeo EL (2002) Antipsychotic and antidepressant drug use in the elderly and the risk of venous thromboembolism. Thromb Haemost 88(2):205–209

    CAS  PubMed  Google Scholar 

  • Rugulies R (2002) Depression as a predictor for coronary heart disease. a review and meta-analysis. Am J Prev Med 23(1):51–61

    Article  PubMed  Google Scholar 

  • Sacchetti E, Turrina C, Valsecchi P (2010a) Cerebrovascular accidents in elderly people treated with antipsychotic drugs: a systematic review. Drug Saf 33(4):273–288

    Article  CAS  PubMed  Google Scholar 

  • Sacchetti E, Turrina C, Cesana B, Mazzaglia G (2010b) Timing of stroke in elderly people exposed to typical and atypical antipsychotics: a replication cohort study after the paper of Kleijer, et al. J Psychopharmacol 24(7):1131–1132

    Article  CAS  PubMed  Google Scholar 

  • Sadock BJ, Sadock VA, Ruiz P (eds) (2009) Kaplan and Sadocks comprehensive textbook of psychiatry. Lippincott Williams & Wilkins, Philadelphia

    Google Scholar 

  • Sauer WH, Berlin JA, Kimmel SE (2001) Selective serotonin reuptake inhibitors and myocardial infarction. Circulation 104(16):1894–1898

    Article  CAS  PubMed  Google Scholar 

  • Sauer WH, Berlin JA, Kimmel SE (2003) Effect of antidepressants and their relative affinity for the serotonin transporter on the risk of myocardial infarction. Circulation 108(1):32–36

    Article  CAS  PubMed  Google Scholar 

  • Schlienger RG, Fischer LM, Jick H, Meier CR (2004) Current use of selective serotonin reuptake inhibitors and risk of acute myocardial infarction. Drug Saf 27(14):1157–1165

    Article  PubMed  Google Scholar 

  • Shi YZ, Xiang YT, Wu SL, Zhang N, Zhou J, Bai Y et al (2014) The relationship between frontal lobe lesions, course of post-stroke depression, and 1-year prognosis in patients with first-ever ischemic stroke. PLoS One 9(7):e100456

    Article  PubMed  PubMed Central  Google Scholar 

  • Shin D, Oh YH, Eom CS, Park SM (2014) Use of selective serotonin reuptake inhibitors and risk of stroke: a systematic review and meta-analysis. J Neurol 261(4):686–695

    Article  CAS  PubMed  Google Scholar 

  • Smoller JW, Allison M, Cochrane BB, Curb JD, Perlis RH, Robinson JG et al (2009) Antidepressant use and risk of incident cardiovascular morbidity and mortality among postmenopausal women in the Women’s Health Initiative study. Arch Intern Med 169(22):2128–2139

    Article  PubMed  Google Scholar 

  • Sohn M, Talbert J, Blumenschein K, Moga DC (2015) Atypical antipsychotic initiation and the risk of type II diabetes in children and adolescents. Pharmacoepidemiol Drug Saf 24(6):583–591

    Google Scholar 

  • Stapelberg NJ, Neumann DL, Shum DH, McConnell H, Hamilton-Craig I (2011) A topographical map of the causal network of mechanisms underlying the relationship between major depressive disorder and coronary heart disease. Aust N Z J Psychiatry 45(5):351–369

    Article  PubMed  Google Scholar 

  • Swenson JR, Doucette S, Fergusson D (2006) Adverse cardiovascular events in antidepressant trials involving high-risk patients: a systematic review of randomized trials. Can J Psychiatry 51(14):923–929

    PubMed  Google Scholar 

  • Takeuchi K, Tanaka A, Nukui K, Kojo A, Gyenge M, Amagase K (2011) Aggravation by paroxetine, a selective serotonin reuptake inhibitor, of antral lesions generated by nonsteroidal anti-inflammatory drugs in rats. J Pharmacol Exp Ther 338(3):850–859

    Article  CAS  PubMed  Google Scholar 

  • Tata LJ, West J, Smith C, Farrington P, Card T, Smeeth L et al (2005) General population based study of the impact of tricyclic and selective serotonin reuptake inhibitor antidepressants on the risk of acute myocardial infarction. Heart 91(4):465–471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Taylor WD, Aizenstein HJ, Alexopoulos GS (2013) The vascular depression hypothesis: mechanisms linking vascular disease with depression. Mol Psychiatry 18(9):963–974

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thomassen R, Vandenbroucke JP, Rosendaal FR (2001) Antipsychotic medication and venous thrombosis. Br J Psychiatry 179:63–66

    Article  CAS  PubMed  Google Scholar 

  • Trifiro G, Dieleman J, Sen EF, Gambassi G, Sturkenboom MC (2010) Risk of ischemic stroke associated with antidepressant drug use in elderly persons. J Clin Psychopharmacol 30(3):252–258

    Article  CAS  PubMed  Google Scholar 

  • Wooltorton E (2002) Risperidone (Risperdal): increased rate of cerebrovascular events in dementia trials. CMAJ 167(11):1269–1270

    PubMed  PubMed Central  Google Scholar 

  • World Health Organisation (2015) The top 10 causes of death. Available at: http://www.who.int/mediacentre/factsheets/fs310/en/. Accessed 1 June 2015

  • Wu CS, Chang CM, Chen CY, Wu EC, Wu KY, Liang HY et al (2013) Association between antidepressants and venous thromboembolism in Taiwan. J Clin Psychopharmacol 33(1):31–37

    Article  CAS  PubMed  Google Scholar 

  • Wu RH, Feng C, Xu Y, Hua T, Liu XY, Fang M (2014) Late-onset depression in the absence of stroke: associated with silent brain infarctions, microbleeds and lesion locations. Int J Med Sci 11(6):587–592

    Article  PubMed  PubMed Central  Google Scholar 

  • Xekardaki A, Santos M, Hof P, Kovari E, Bouras C, Giannakopoulos P (2012) Neuropathological substrates and structural changes in late-life depression: the impact of vascular burden. Acta Neuropathol 124(4):453–464

    Article  PubMed  Google Scholar 

  • Yamaguchi T, Hidaka N, Suemaru K, Araki H (2008) The coadministration of paroxetine and low-dose aspirin synergistically enhances gastric ulcerogenic risk in rats. Biol Pharm Bull 31(7):1371–1375

    Article  CAS  PubMed  Google Scholar 

  • Zhang R, Dong L, Shao F, Tan X, Ying K (2011) Antipsychotics and venous thromboembolism risk: a meta-analysis. Pharmacopsychiatry 44(5):183–188

    Article  CAS  PubMed  Google Scholar 

  • Zornberg GL, Jick H (2000) Antipsychotic drug use and risk of first-time idiopathic venous thromboembolism: a case-control study. Lancet 356(9237):1219–1223

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Erik L. Grove M.D., Ph.D, FESC .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Adelborg, K., Sundbøll, J., Videbech, P., Grove, E.L. (2016). The Risk of Thromboembolism in Users of Antidepressants and Antipsychotics. In: Islam, M. (eds) Thrombosis and Embolism: from Research to Clinical Practice. Advances in Experimental Medicine and Biology(), vol 906. Springer, Cham. https://doi.org/10.1007/5584_2016_125

Download citation

  • DOI: https://doi.org/10.1007/5584_2016_125

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-22107-6

  • Online ISBN: 978-3-319-22108-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics