The influence of selective serotonin reuptake inhibitors on human platelet serotonin

Abstract

Clinical depression has been proposed to be an independent risk factor for cardiovascular disease. While it is suggested that selective serotonin reuptake inhibitors (SSRIs) reduce the risk of acute cardiovascular problems of depressed patients, the effect of SSRIs on platelets, the only blood cells committed to serotonin (5-HT) transport, remains largely unknown. The goal of this pilot study was to measure the 5-HT levels in platelets of untreated and SSRI-treated depressed patients and normal subjects and to determine whether the interaction of SSRIs with platelets can explain their possible cardiovascular benefit in patients with depression. Platelet 5-HT was determined by an immunocytochemical assay and high-pressure liquid chromatography with electrochemical detection (HPLC-ECD). In normal control subjects without cardiovascular disease, 78 +/- 8% of platelets were 5-HT-positive (n = 14). Depression caused a significant reduction in platelet 5-HT to 46 +/- 21% in untreated patients (n = 13) and 22 +/- 13% in SSRI-treated patients (n = 14). As a class, all selective serotonin reuptake inhibitors significantly reduced the 5-HT concentration in patient platelets. An inverse relationship of 5-HT level and dose of medication might be suggested. These results correlated well with 5-HT data from HPLC (r = 0.8509, p < 0.001). SSRIs did not affect platelet aggregation and dense granule release in response to thrombin, but significantly reduced ADP-induced platelet aggregation and dense granule release in both patient and normal control samples. The active inhibition of platelet aggregation by SSRIs might explain their cardiovascular benefit.

The role of thrombocyte serotonin system and some thrombocyte characteristics in treatment of depressive patients with cardiovascular diseases

“…The further difference is that a thrombocyte cannot synthetize serotonin itself, because of the lack of tryptophan hydroxylaze [28,29]. Thrombocyte serotonin represents an easily accessible biological index, and numerous studies were designed to investigate its relations with various forms of the depressive disorder, suicidal behaviour and if there was a connection between it and the response to pharmacotherapy [30]. In some of the studies made so far, the results have shown that, in the patients suffering from the major depressive disorder, there is a lower level of thrombocyte serotonin and that the therapy with antidepressants changes some thrombocyte indices.…”

Nonclinical aspects of venous thrombosis in pregnancy

“…Selective serotonin reuptake inhibitors may increase the risk of thrombosis because of the immediate serotonin increase adjacent to specific serotonin receptors, which leads to platelet activation and endothelium-derived contracting factors (Maurer-Spurej et al, 2004;Kurne et al, 2004). Antipsychotics cause an increase in platelet aggregation and vasoconstriction, and hence their use during pregnancy may intensify the risk of venous thrombosis (Hagg and Spigset, 2002).…”

“…Selective serotonin reuptake inhibitors increase serotonin blood levels and cause vasoconstriction resulting in altered blood flow, and may facilitate thrombosis (Kurne et al, 2004;Maurer-Spurej et al, 2004). Although not intended for pregnancy use, ethinyl estradiol carries a greater risk of venous thrombosis because it may increase hematocrit and blood viscosity, which could lead to a decrease in blood flow and lower shear rates (Cushman et al, 2004).…”

Antipsychotics do not affect platelet serotonin in schizophrenic patients

“…repeatedly found after treatment with SSRI [13][14][15][16]. The data on the effects of olanzapine or fluphenazine on 5-HTT in vivo when given to patients in therapeutic doses are still scarce.…”