Antiplatelet Properties of Escitalopram in Patients with the Metabolic Syndrome: A Dose-Ranging In Vitro Study

Abstract

There is an increasing body of evidence suggesting that selective serotonin reuptake inhibitors exhibit clinical benefit beyond treating depression, by simultaneously inhibiting platelet activity. We recently demonstrated that escitalopram (ESC), but not its major metabolites, inhibits multiple platelet biomarkers in healthy volunteers. Considering that the metabolic syndrome represents one of the major risk factors for vascular disease, we here determined how ESC affects platelet activity in such patients. We assessed the in vitro effects of preincubation with escalating (50-200 nM/l) concentrations of ESC on platelet aggregation, expression of major surface receptors by flow cytometry, and quantitatively by platelet function analyzers. Blood samples were obtained from 20 aspirin-naïve patients with documented metabolic syndrome. Pretreatment of blood samples with medium (150 nM/l), or high (200 nM/l) doses of ESC resulted in a significant inhibition of platelet aggregation induced by ADP (p ¼ 0.007) and by collagen (p ¼ 0.004). Surface platelet expression of GPIb (CD42, p ¼ 0.03), LAMP-3 (CD63, p ¼ 0.04), and GP37 (CD165, p ¼ 0.03) was decreased in the ESC-pretreated samples. Closure time by the PFA-100 analyzer was prolonged after the 200 nM/l dose (p ¼ 0.02), indicating platelet inhibition under high shear conditions. On the other hand, the lowest tested concentration of ESC (50 nM/l) did not affect platelet activity in these patients. The in vitro antiplatelet characteristics of ESC in patients with the metabolic syndrome are similar to those in healthy volunteers. However, higher ESC doses are required to induce equally potent platelet inhibition. These data justify prospective ex vivo studies with the highest therapeutic dose to determine the potential clinical advantage of ESC in high-risk patients with vascular disease.

Mean Platelet Volume in Patients With Major Depression

“…In the first study, Atar et al 11 has evaluated 20 healthy subjects who had more than 2 risk factors for coronary artery disease and found that escitalopram had inhibited platelet activity. In the second study, the same authors 28 have shown that higher doses of escitalopram were required to induce platelet inhibition in patients with metabolic syndrome. Our findings are consistent with the results of these 2 studies documenting the antiplatelet effect of escitalopram.…”

Selective Serotonin Reuptake Inhibitors and Operative Bleeding Risk

“…Selective serotonin reuptake inhibitors block the serotonin transporter resulting in the inhibition of serotonin uptake into platelets (22,23). Studies of SSRI treatment show that after weeks of SSRI administration there is a consistent and significant reduction in platelet serotonin content, which is in the range of 65–90% compared to controls (24,25).…”

Platelet function in patients with major depression

“…Several recent studies have investigated the effect of SSRI treatment on platelet activity 46–49 . The SSRI escitalopram has been shown to inhibit multiple platelet biomarkers in healthy volunteers 48 and has also been found to inhibit ADP‐induced and collagen‐induced platelet aggregation in individuals with the metabolic syndrome 49 . In general, however, the effects of SSRI on platelet function in patients with depression who are not medically ill or who are not taking traditional antiplatelet agents appear to be fairly mild.…”