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J Clin Pharmacol ; 46(4): 468-75, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16554456

ABSTRACT

Depression is associated with an increased incidence of vascular events and develops after stroke and myocardial infarction. Beside potential clinical outcome benefits of selective serotonin reuptake inhibitors for vascular diseases, bleeding events were reported. We investigated whether paroxetine and aspirin synergistically inhibit platelet function. Paroxetine (20 mg/d) was administered over 18 days to 20 men in a randomized, placebo-controlled, crossover design. Aspirin (100 mg/d) was coadministered within the last 4 study days. Platelet function was assessed by the platelet function analyzer and by flow cytometry. Paroxetine prolonged epinephrine-dependent predictive index within 14 days (P<.02). Aspirin enhanced the predictive index (P<.004 vs baseline and P>.05 between periods). A trend toward decreased thrombin receptor-activating peptide-induced CD62P expression after paroxetine was further enhanced by aspirin treatment (P>.05 between periods). The combination of paroxetine and aspirin did not further inhibit platelet plug formation under high shear stress in male smokers.


Subject(s)
Aspirin/pharmacology , Paroxetine/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation/drug effects , Selective Serotonin Reuptake Inhibitors/pharmacology , Smoking/physiopathology , Adult , Aspirin/adverse effects , Collagen/pharmacology , Cross-Over Studies , Double-Blind Method , Drug Synergism , Epinephrine/pharmacology , Flow Cytometry , Humans , In Vitro Techniques , Male , P-Selectin/biosynthesis , Paroxetine/adverse effects , Peptide Fragments/pharmacology , Platelet Aggregation Inhibitors/adverse effects , Platelet Function Tests , Selective Serotonin Reuptake Inhibitors/adverse effects , Smoking/adverse effects
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