5-HT per se is

a weak activator, but dose-dependently enhances platelet activation induced by adenosine diphosphate (ADP) and, in particular, thrombin in whole blood.12 It also potentiates aggregation in the presence of epinephrine or collagen,13 and potentiates release reactions through a mechanism of amplification by an increase in free cytoplasmic intracellular calcium ion concentration. This induces a shape-change reaction of platelets, priming platelet surfaces for interactions with coagulation factors.14 5-HT may therefore be directly Inhibitors,research,lifescience,medical involved in increased cardiovascular mortality and morbidity in depressed Inhibitors,research,lifescience,medical patients. A relationship between depressive symptoms and increased platelet activity has been established in physically healthy depressed patients15-17 as well as in postmyocardial infarction (MI)

depressed patients.8,18 The following mechanisms mediating platelet abnormalities observed in major depression have been proposed19: Trichostatin A altered platelet function by increased Inhibitors,research,lifescience,medical plasma concentrations of 5-HT and epinephrine, affected platelet function by increased intraplatelet calcium mobilization, upregulation of 5-HT2A receptors or ot-adrenoreceptors, downregulation of 5-HT transporter number, altered second messenger signal transduction, or altered intraplatelet concentrations of monoamines

and catecholamines.17 Thus, 5-HT probably plays a role in the pathophysiological mechanisms of depression as well as in primary hemostasis platelet activity, and this neurotransmitter might be a key element Inhibitors,research,lifescience,medical in the understanding of the relationship between depression and increased risk Inhibitors,research,lifescience,medical of cardiovascular disease. Amplification of platelet aggregation could be altered by antidepressants that inhibit serotonin reuptake, in particular selective 5-HT reuptake inhibitors (SSRIs), because of depletion or decrease in intraplatelet 5-HT levels. The purpose of this review of the literature is to summarize changes in hemostatic function observed during treatment by antidepressants. We performed a MEDLINE search of the relevant literature, and reviewed prospective and retrospective studies, as well as case reports and reviews of literature related to bleeding side effects and hemostasis crotamiton laboratory findings, associated with antidepressant treatment in the psychiatric population, in post-MI depressed patients, or in healthy volunteers. The prothrombotic effect of typical and atypical antipsychotics, as well as the impaired platelet function and thrombocytopenia caused by the mood stabilizer valproate and the possible procoagulant effect of treatment by lithium, are not examined here.