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Journal of Clinical Psychopharmacology:
doi: 10.1097/01.jcp.0000204047.76286.6e
Brief Reports

Escitalopram, but Not Its Major Metabolites, Exhibits Antiplatelet Activity in Humans

Atar, Dan MD*; Malinin, Alex MD†; Takserman, Aviv MD*; Pokov, Alex MD†; van Zyl, Louis MD‡; Tanguay, Jean-Francois§; Lesperance, Francois MD§; Serebruany, Victor MD, PhD†

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Abstract

Background: Clinical depression has been identified as an independent risk factor for increased mortality during follow-up in patients suffered from acute coronary events, whereas increased platelet activity has been proposed as one of the mechanisms for this association. Some evidence suggests that selective serotonin reuptake inhibitors and/or their metabolites exhibit potent antiplatelet properties.

Methods: We assessed the in vitro effects of preincubation with escalating (50-200 nmol/L) concentrations of escitalopram (ESC) S-desmethyl-citalopram (S-DCT), and S-di-desmethyl-citalopram, (S-DCT) on platelet aggregation through the expression of major surface receptors using flow cytometry and quantitatively using platelet function analyzers in 20 healthy volunteers.

Results: Pretreatment of blood samples with ESC with ESC resulted in a significant inhibition of platelet aggregation induced by ADP (P = 0.0001) and by collagen with the highest dose (P = 0.001). Surface platelet expressions of glycoprotein Ib (CD42) (P = 0.04), lysosome associated membrane protein-3 (CD63) (P = 0.02), and GP37 (CD165) (P = 0.03) was decreased in the ESC-pretreated samples. Closure time by the Platelet Function Analyzer-100 analyzer was prolonged for the 200 nmol/L dose (P = 0.02), indicating platelet inhibition under high shear conditions. Two major metabolites of ESC, namely S-DCT and S-DDCT, did not affect platelet activity.

Conclusion: Escitalopram, but not its metabolites, exhibited selective inhibition of human platelet properties. The direct antiplatelet effect of ESC requires further prospective or ex vivo testing to determine the possible clinical advantage of this finding.

© 2006 Lippincott Williams & Wilkins, Inc.

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