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Selective Serotonin Reuptake Inhibitor-Induced Disturbances of Haemostasis

Mechanisms and Therapeutic Implications

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Abstract

Serotonin (5-hydroxytryptamine; 5-HT) has important peripheral functions that include roles in platelet function, primarily in aggregation and modulation of vascular tone. Platelet serotonin is derived predominantly via uptake from the enterochromaffin system. Selective serotonin reuptake inhibitors (SSRIs) substantially reduce platelet serotonin stores via uptake inhibition. SSRIs are associated with infrequent clinical reports of haemostatic dysfunction, primarily easy bruising.

These clinical reports have not, however, been paralleled by prospective studies, which have not found any disturbances in haemostatic function secondary to SSRI therapy. SSRI-associated haemostatic dysfunction appears to be a rare adverse event, and has not been reported to be associated with mortality or substantial morbidity. Nevertheless, a high index of suspicion is warranted in any patient on SSRI therapy who develops unexplained changes in haemostatic function.

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References

  1. Prichard BN, Smith CC. Serotonin: receptors and antagonists — summary of a symposium. Clin Physiol Biochem 1990; 8(3 Suppl.): 120–8

    PubMed  Google Scholar 

  2. Leonard BE. Blood cells as models of neurons: studies in the affective disorders. J Ir Coll Phys Surg 1991; 20: 282–4

    Google Scholar 

  3. Pearse AGE. The diffuse neuroendocrine system: peptides, amines, placodes and the APUD theory. Prog Brain Res 1986; 68: 25–31

    Article  PubMed  CAS  Google Scholar 

  4. Stahl SM. The human platelet. A diagnostic and research tool for the study of biogenic amines in psychiatric and neurologic disorders. Arch Gen Psychiatry 1997; 34: 509–16

    Article  Google Scholar 

  5. Tuomisto J, Tukiainen E. Decreased uptake of 5-hydroxytryptamine in blood platelets from depressed patients. Nature 1976; 262: 596–8

    Article  PubMed  CAS  Google Scholar 

  6. Arora RC, Meltzer HY. Increased serotonin 2 receptor binding as measured by 3H-LSD binding in the blood platelets of depressed patients. Life Sci 1989; 44: 725–34

    Article  PubMed  CAS  Google Scholar 

  7. Berk M, Bodemer W, Van Oudenhove T, et al. The platelet intracellular response to serotonin is augmented in bipolar manic and depressed patients. Hum Psychopharmacol 1995; 10: 189–93

    Article  Google Scholar 

  8. Mikuni M, Kagaya A, Takahashi K, et al. Serotonin but not norepinephrine-induced calcium mobilisation of platelets is enhanced in affective disorders. Psychopharmacology 1992; 106: 311–4

    Article  PubMed  CAS  Google Scholar 

  9. Mikuni M, Kusumi I, Kayaga A, et al. Increased 5-HT2 receptor function as measured by serotonin-stimulated phosphoinositide hydrolysis in platelets of depressed patients. Prog Neuropsychopharmacol Biol Psychiatry 1991; 15: 49–61

    Article  PubMed  CAS  Google Scholar 

  10. Read NW, Gwee KA. The importance of 5-hydroxytryptamine in the gut. Pharmacol Ther 1994; 62: 159–73

    Article  PubMed  CAS  Google Scholar 

  11. Verbeuren TJ, Synthesis, storage and release of 5-hydroxytryptamine in peripheral tissues. In: Fozard JR, editor. The peripheral actions of 5-hydroxytryptamine. New York: Oxford University Press, 1989: 1–25

    Google Scholar 

  12. Blockmans D, Deckmyn H, Vermylen J. Platelet activation. Blood Rev 1993; 9: 143–56

    Article  Google Scholar 

  13. Salzman AG, Morose B, Whitman MM, et al. Cloning of the human serotonin 5-HT2 an 5-HT1C receptor subtypes. Biochem Biophys Res Commun 1991; 181: 1469–78

    Article  Google Scholar 

  14. Skop BP, Brown TM. Potential vascular and bleeding complications of treatment with selective serotonin reuptake inhibitors. Psychosomatics 1996; 37: 12–6

    Article  PubMed  CAS  Google Scholar 

  15. Houston DS, Shepherd JT, Vanhoutte PM. Aggregating human platelets causes direct contraction and endothelium-dependant relaxation of isolated canine coronary arteries: role of serotonin, thromboxane A2 and adenine nucleotide. J Clin Invest 1986; 78: 539–44

    Article  PubMed  CAS  Google Scholar 

  16. George JN, Shattil SJ. The clinical importance of acquired abnormalities in platelet function. N Engl J Med 1991; 324: 27–39

    Article  PubMed  CAS  Google Scholar 

  17. Jain MK, Eskow K, Kunchibhotla J, et al. Correlation of inhibition of platelet aggregation by phenothiazines and local anaesthetics with their effects on a phospholipid bilayer. Thromb Res 1978; 13: 1067–75

    Article  PubMed  CAS  Google Scholar 

  18. 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: 243–9

    Article  PubMed  CAS  Google Scholar 

  19. Wernicke JF. The side effect profile and safety of fluoxetine. J Clin Psychiatry 1985; 46: 59–67

    PubMed  CAS  Google Scholar 

  20. Lemberger L, Bergstrom RF, Wolen RL, et al. Fluoxetine: clinical pharmacology and physiologic disposition. J Clin Psychiatry 1985; 46: 14–9

    PubMed  CAS  Google Scholar 

  21. Alderman CP, Moritz CK, Ben-Tovim DI. Abnormal platelet aggregation associated with fluoxetine therapy. Ann Pharmacother 1992; 26: 1517–9

    PubMed  CAS  Google Scholar 

  22. Yaryura-Tobias JA, Kirschen H, Ninan P, et al. Fluoxetine and bleeding in obsessive compulsive disorder [letter]. Am J Psychiatry 1991; 148: 949

    PubMed  CAS  Google Scholar 

  23. Humphries JE, Wheby MS, VandenBerg SR. Fluoxetine and the bleeding time. Arch Pathol Lab Med 1990; 114: 727–8

    PubMed  CAS  Google Scholar 

  24. Evans TG, Buys SS, Rodgers GM. Acquired abnormalities of platelet function [letter]. N Engl J Med 1991; 324: 1671

    Article  Google Scholar 

  25. Stanford MS, Patton JH. In utero exposure to fluoxetine HCl increases hematoma frequency at birth. Pharmacol Biochem Behav 1993; 45: 959–62

    Article  PubMed  CAS  Google Scholar 

  26. Data on File, Eli Lilly & Co.

  27. Kotsanos JG, Sayler ME, Masica DN, et al. Utilisation of a computerised clinical trial database in epidemiological studies: comparison of bruising events in fluoxetine clinical trials [abstract]. Clin Res 1992; 39: 768a

    Google Scholar 

  28. Aranth J, Lindeburg C. Bleeding, a side effect of fluoxetine [letter]. Am J Psychiatry 1992; 149: 412

    PubMed  CAS  Google Scholar 

  29. Pai VB, Kelly MW. Bruising associated with the use of fluoxetine. Ann Pharmacother 1996; 30: 786–8

    PubMed  CAS  Google Scholar 

  30. Gunzberger DW, Martinez D. Adverse vascular effects associated with fluoxetine [letter]. Am J Psychiatry 1992; 149:1751

    PubMed  CAS  Google Scholar 

  31. Bang NU. Acquired abnormalities of platelet fuction [letter]. N Engl J Med 1991; 324: 1672

    Article  Google Scholar 

  32. Alderman CP, Seshadri P, Ben-Tovim DI. Effects of serotonin reuptake inhibitors on haemostasis. Ann Pharmacother 1996; 30: 1232–4

    PubMed  CAS  Google Scholar 

  33. Berk M, Jacobson BF, Hurly E. Fluoxetine and hemostatic function: a pilot study. J Clin Psychiatry 1995; 56: 14–6

    PubMed  CAS  Google Scholar 

  34. Leung M, Shore R. Fluvoxamine-associated bleeding [letter]. Can J Psychiatry 1996; 41: 604–5

    PubMed  CAS  Google Scholar 

  35. Ottervanger JP, Stricker BHCH, Huls J, et al. Bleeding attributed to the intake of paroxetine. Am J Psychiatry 1994; 151: 781–2

    PubMed  CAS  Google Scholar 

  36. Bannister SJ, Hauser VP, Hulse JD. Evaluation of the potential for interactions of paroxetine with diazepam, cimetidine, warfarin and digoxin. Acta Psychiatr Scand 1989; 80(350 Suppl.): 102–6

    Article  Google Scholar 

  37. Calhoun JW, Calhoun DD. Prolonged bleeding time in a patient treated with sertraline [letter]. Am J Psychiatry 1996; 153:443

    PubMed  CAS  Google Scholar 

  38. Krivy J, Wiener J. Sertraline and platelet counts in idiopathic thrombocytopenia purpura [letter]. Lancet 1995; 345: 132

    Article  PubMed  CAS  Google Scholar 

  39. Data on File, Eli Lilly & Co.

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Authors and Affiliations

  1. Department of Psychiatry, University of the Witwatersrand Medical School, York Road, Parktown, 2193, South Africa

    Michael Berk

  2. Department of Haematology, School of Pathology of the University of the Witwatersrand and the South African Institute for Medical Research, Parktown, South Africa

    Barry Frank Jacobson

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  1. Michael Berk
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  2. Barry Frank Jacobson
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Correspondence to Michael Berk.

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Berk, M., Jacobson, B.F. Selective Serotonin Reuptake Inhibitor-Induced Disturbances of Haemostasis. CNS Drugs 10, 441–446 (1998). https://doi.org/10.2165/00023210-199810060-00005

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  • DOI: https://doi.org/10.2165/00023210-199810060-00005

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