title: Paroxetine decreases platelet serotonin storage and platelet function in human beings.
abstract: BACKGROUND
  Serotonin is a platelet agonist and potent vasoconstrictor that has recently received attention concerning its potential role in acute coronary artery thrombosis. Selective serotonin-reuptake inhibitors, such as paroxetine, are widely used antidepressant agents. We sought to characterize the potential inhibitory effect of paroxetine on platelet function.
  
  
  METHODS
  Healthy male volunteers received 20 mg/d paroxetine for 2 weeks in a randomized, double-blind, placebo-controlled, two-way cross-over trial.
  
  
  RESULTS
  Paroxetine decreased intraplatelet serotonin concentrations by -83% (P < .01). This inhibited platelet plug formation as reflected by a 31% prolongation of closure time measured with the platelet function analyzer-100 (P < .05). Furthermore, paroxetine lowered expression of the platelet activation marker CD63 in response to two different concentrations of thrombin receptor-activating peptide (P < .01). Plasma concentrations of prothrombin fragment, von Willebrand factor antigen, and circulating P-selectin remained unchanged in either period, indicating that paroxetine does not increase activation of coagulation, endothelium, or platelets in vivo, underlining a favorable safety profile.
  
  
  CONCLUSIONS
  Paroxetine substantially decreases intraplatelet serotonin content and thereby reduces platelet plug formation under shear stress, and responsiveness to thrombin receptor activating peptide-induced platelet activation. Further studies will reveal whether these pharmacodynamic effects can be exploited for treatment of thrombotic artery disease.
authors.affiliation: Department of Clinical Pharmacology, University of Vienna, Austria.
authors.forename: N
authors.initials: N
authors.lastname: Hergovich
authors.forename: M
authors.initials: M
authors.lastname: Aigner
authors.forename: H G
authors.initials: HG
authors.lastname: Eichler
authors.forename: J
authors.initials: J
authors.lastname: Entlicher
authors.forename: C
authors.initials: C
authors.lastname: Drucker
authors.forename: B
authors.initials: B
authors.lastname: Jilma
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D019007:P-Selectin / Q000097:blood; D017374:Paroxetine / Q000494:pharmacology*; D011516:Prothrombin / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D019007:P-Selectin; D017374:Paroxetine; D011516:Prothrombin; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D014841:von Willebrand Factor