Effect of Selective Serotonin Reuptake Inhibitors on Platelet Activation

Abstract

In recent years a large body of evidence from several longitudinal studies has emerged suggesting that depression is an independent risk factor for cardiovascular disease (CVD) and that the association between depression and increased CVD risk is not merely due to negative mood-driven behavior related with depression. Even though the underlying mechanisms are not well understood, several hypotheses and explanations have been proposed such as increased activation of the hypothalamic-pituitary-adrenal axis, abnormalities in the sympathoadrenal system, or abnormalities in platelet function. Platelet function abnormalities, including increased platelet reactivity, may predispose patients with depressive disorders to clotting diatheses and may explain their vulnerability to CVD. Serotonin secreted by platelets induces both platelet aggregation and coronary vasoconstriction. Even though serotonin itself is only a weak platelet agonist, it markedly enhances platelet reactions to a variety of other agonists. Several studies have shown that selective serotonin reuptake inhibitors (SSRIs) reduce platelet and whole blood serotonin concentrations after repeated doses, and could therefore exert an inhibitory effect on platelet activation. For that reason, it was hypothesized that SSRIs could have a protective effect against myocardial infarction (MI). Results from three currently available epidemiological studies assessing the risk of MI in patients treated with antidepressants, including SSRIs, are controversial with respect to a potential beneficial effect of SSRIs on CVD risk in depressed patients. However, there is evidence that exposure to SSRIs does not substantially increase the risk of CVD in patients. A recent randomized, double-blind, placebo-controlled, multicenter trial that evaluated the safety and efficacy of the SSRI sertraline in patients with major depression and acute MI or unstable angina suggested that sertraline is well tolerated and effective. Further epidemiological studies or longer-term clinical trials may shed more light on this issue, and answer the question conclusively, whether the effect of SSRIs on platelets or another mechanism translates into a decreased risk of CVD in depressed patients.

Changes in plasma and platelet BDNF levels induced by S-citalopram in major depression

“…Interestingly, platelets possess different receptors for serotonin (5-HT 2A , 5-HT 3 ) and also the transporter (SERT) in their membranes (Hoyer et al 2002;Stratz et al 2008;Escolar et al 2005;Blakely et al 1991;Hoffman et al 1991;Lesch et al 1993;Ramamoorthy et al 1993). Several studies have shown evidence of a link between increased risk of cardiovascular complications in clinically depressed patients and a possible reduction of this risk after treatment with SSRIs (Schlienger and Meier 2003;Maurer-Spurej et al 2004;Sauer et al 2003). Moreover, our group has recently published an in vitro study in which the effect of serotonin and the SSRI citalopram was evaluated on platelet function (Galan et al 2009).…”

Effects of dipping and psychological traits on morning surge in blood pressure in healthy people

“…There is clinical evidence supporting the use of behavioral 32 and pharmacological interventions targeting depression to improve cardiovascular prognosis. 33,34 Given the well established relationship between depression and cardiovascular disease, 35 there needs to be a greater awareness of the role of depression as a cardiovascular risk factor in a normotensive population. In addition, longitudinal studies are needed to determine whether interventions aimed at decreasing depression have a positive impact on cardiovascular risk in a normotensive population.…”

Fluoxetine and nortriptyline affect NTPDase and 5′-nucleotidase activities in rat blood serum

“…Several studies have found an increased risk of myocardial infarction among depressed patients (Schlienger and Meier, 2003). Tricyclic antidepressants are not recommended in patients with cardiovascular disease owing to their arrhythmic effects (Cohen et al, 2000, Roose andSpatz, 1998;.…”