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Relationship Between Release of Platelet/Endothelial Biomarkers and Plasma Levels of Sertraline and N -Desmethylsertraline in Acute Coronary Syndrome Patients Receiving SSRI Treatment for Depression

2005; American Psychiatric Association; Volume: 162; Issue: 6 Linguagem: Inglês

10.1176/appi.ajp.162.6.1165

1535-7228

Victor L. Serebruany, Raymond F. Suckow, Thomas B. Cooper, Christopher M. O’Connor, Alex I. Malinin, Kousik Krishnan, Louis T. van Zyl, Vladimir Lekht, Alexander H. Glassman,

Heart Rate Variability and Autonomic Control

OBJECTIVE: In a platelet/endothelial biomarker substudy of the Sertraline AntiDepressant Heart Attack Randomized Trial (SADHART), the authors sought to determine whether plasma levels of sertraline and its primary metabolite N-desmethylsertraline affect the release of platelet/endothelial biomarkers. METHOD: Fifty-five acute coronary syndrome patients with depression were randomly assigned to receive sertraline (N=23) or placebo (N=32). Twenty-six serial plasma samples collected at week 6 (N=12) and week 16 (N=14) were analyzed. Platelet factor 4 (PF4), β-thromboglobulin (β-TG), platelet/endothelial cell adhesion molecule 1 (PECAM-1), P-selectin, thromboxane B2 (TxB2), prostacyclin (6-keto-PGF1α), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin were measured by enzyme-linked immunosorbent assay. Concentrations of sertraline and N-desmethylsertraline were determined by liquid chromatography with fluorescence detection in autologous samples. RESULTS: Strong, mostly time-dependent negative correlations were found for the plasma levels of sertraline and N-desmethylsertraline with PF4 (week 6: r=–0.69 and –0.33, respectively; week 16: r=–0.63 for both), β-TG (week 6: r=–0.43 and –0.29; week 16: r=–0.66 and –0.57), PECAM-1 (week 6: r=–0.82 and –0.49; week 16: r=–0.60 for both), P-selectin (week 6: r=–0.82 and –0.49; week 16: r=–0.73 and –0.43), and TxB2 (week 6: r=–0.66 and –0.59; and week 16: r=–0.64 and –0.41). Regression analysis revealed some borderline correlations for endothelial markers such as 6-keto- PGF1α and E-selectin and a positive correlation for VCAM-1. CONCLUSIONS: This is the first documented evidence that plasma release of platelet/endothelial biomarkers is directly related to the levels of sertraline and N-desmethylsertraline in acute coronary syndrome patients receiving SSRI treatment for depression. The clinical significance of these findings should be assessed in the setting of a randomized clinical trial.