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.

Abstract

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), beta-thromboglobulin (beta-TG), platelet/endothelial cell adhesion molecule 1 (PECAM-1), P-selectin, thromboxane B(2) (TxB(2)), prostacyclin (6-keto-PGF1alpha), 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), beta-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 TxB(2) (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- PGF1alpha 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.

• Authors: Victor L Serebruany, Raymond F Suckow, Thomas B Cooper, Christopher M O'Connor, Alex I Malinin, K Ranga R Krishnan, Louis T van Zyl, Vladimir Lekht, Alexander H Glassman, Sertraline Antidepressant Heart Attack Randomized Trial
• Journal: The American journal of psychiatry (Am J Psychiatry) Vol. 162 Issue 6 Pg. 1165-70 (Jun 2005) ISSN: 0002-953X [Print] United States
• PMID: 15932816 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Serotonin Uptake Inhibitors
• desmethylsertraline
• Sertraline

Topics

• Biomarkers (blood, metabolism)
• Blood Platelets (drug effects, metabolism)
• Coronary Disease (blood, metabolism)
• Coronary Vessels (drug effects, metabolism)
• Endothelium, Vascular (drug effects, metabolism)
• Humans
• Selective Serotonin Reuptake Inhibitors (blood, pharmacology, therapeutic use)
• Sertraline (analogs & derivatives, blood, pharmacology, therapeutic use)