Escitalopram, but not its major metabolites, exhibits antiplatelet activity in humans.
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.


CONCLUSIONS
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.
Atar
Dan
D
University of Oslo, Aker University Hospital, Oslo, Norway.
Malinin
Alex
A
Takserman
Aviv
A
Pokov
Alex
A
van Zyl
Louis
L
Tanguay
Jean-Francois
JF
Lesperance
Francois
F
Serebruany
Victor
V
D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D000951:Antigens, Neoplasm / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects* / Q000276:immunology; D015283:Citalopram / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010979:Platelet Function Tests; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism; D059666:Lysosomal-Associated Membrane Protein 3
D018687:Antidepressive Agents, Second-Generation; D000951:Antigens, Neoplasm; D015283:Citalopram; D051907:Lysosomal Membrane Proteins; D009363:Neoplasm Proteins; D010975:Platelet Aggregation Inhibitors; D019038:Platelet Glycoprotein GPIb-IX Complex; C114233:LAMP3 protein, human; D059666:Lysosomal-Associated Membrane Protein 3; C049664:glycoprotein GP37