Serotonin reuptake inhibitors and cardiovascular diseases: a platelet connection

Abstract

Selective serotonin reuptake inhibitors (SSRIs) are a heterogeneous group of new antidepressants that cause a well documented acquired but reversible serotonin deficiency in blood platelets. Platelets are small, anucleate cells and are the only blood cells specialized in storing peripheral serotonin. Platelets are also an integral part of the hemostatic process that is initiated during pathologic thrombus formation in cardiovascular diseases. Serotonin release from platelets is important for functional hemostasis as indicated by congenital diseases with serotonin-deficient platelets that can lead to life-threatening bleeding problems. The postulate that SSRIs should have an impact on cardiovascular diseases is therefore well founded. Cardiovascular effects of SSRIs have indeed been shown in a number of studies investigating the effect of SSRIs in patients with psychosomatic comorbidity. SSRIs reduce the incidence of recurrent myocardial infarction (MI) in patients suffering from post-MI depression. In addition, SSRIs inhibit tight clot formation of platelets in vitro, which points to a direct anti-thrombotic or pro-fibrinolytic effect of SSRIs.

Antidepressants and Risk of Upper Gastrointestinal Bleeding

“…Furthermore, in vitro studies have shown that addition of ADP to normal platelets in the presence of SSRIs causes microaggregation and primary aggregation but no or very little dense granule release which leads to the formation of loose and disaggregating clots (Maurer-Spurej 2005).…”

Immuno-Thrombotic Effects of Platelet Serotonin

“…The uptake of 5-HT into neurons is very important for the clearance of the synaptic cleft, preventing firing rates and overstimulation of receptors [64]. This uptake and the later release are blocked upon treatment with SSRIs, such as fluvoxamine, fluoxetine, nortryptiline, citopram, and escitalopram [65]. The different SSRIs vary in kinetics being competitive and non-competitive inhibitors.…”

Unplanned Rehospitalizations and Depression

“…7 Patients with depression also have lower rates of medication adherence, increased rates of substance abuse and smoking, and lower levels of physical activity, all of which may contribute to poor cardiac outcomes on top of the physiological effects. 8,9 Differential medical treatment may also be important: Patients with depression and other affective disorders may be less likely to receive cardiac catheterization in the setting of an acute MI, although findings are mixed. 10,11 Interestingly, despite the increased recognition of the relationship between depression and CVD, efforts to intervene thus far have been disappointing.…”