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

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

Research output: Contribution to journalArticle

Abstract

Objective: In a platelet/endothelial biomarker substudy of the Sertraline Anti-Depressant 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.

Original languageEnglish (US)
Pages (from-to)1165-1170
Number of pages6
JournalAmerican Journal of Psychiatry
Volume162
Issue number6
DOIs
StatePublished - Jun 2005

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Sertraline
Acute Coronary Syndrome
Blood Platelets
Biomarkers
CD31 Antigens
Platelet Factor 4
Thromboxane B2
P-Selectin
E-Selectin
Vascular Cell Adhesion Molecule-1
Therapeutics
Epoprostenol
Liquid Chromatography
desmethylsertraline
Randomized Controlled Trials
Fluorescence
Enzyme-Linked Immunosorbent Assay
Myocardial Infarction
Placebos
Regression Analysis

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

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. / Serebruany, Victor L.; Suckow, Raymond F.; Cooper, Thomas B.; O'Connor, Christopher M.; Malinin, Alex I.; Krishnan, K. Ranga R; Van Zyl, Louis T.; Lekht, Vladimir; Glassman, Alexander H.

In: American Journal of Psychiatry, Vol. 162, No. 6, 06.2005, p. 1165-1170.

Research output: Contribution to journalArticle

Serebruany, Victor L. ; Suckow, Raymond F. ; Cooper, Thomas B. ; O'Connor, Christopher M. ; Malinin, Alex I. ; Krishnan, K. Ranga R ; Van Zyl, Louis T. ; Lekht, Vladimir ; Glassman, Alexander H. / 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. In: American Journal of Psychiatry. 2005 ; Vol. 162, No. 6. pp. 1165-1170.
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title = "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 Anti-Depressant 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.",
author = "Serebruany, {Victor L.} and Suckow, {Raymond F.} and Cooper, {Thomas B.} and O'Connor, {Christopher M.} and Malinin, {Alex I.} and Krishnan, {K. Ranga R} and {Van Zyl}, {Louis T.} and Vladimir Lekht and Glassman, {Alexander H.}",
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T1 - 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

AU - Serebruany, Victor L.

AU - Suckow, Raymond F.

AU - Cooper, Thomas B.

AU - O'Connor, Christopher M.

AU - Malinin, Alex I.

AU - Krishnan, K. Ranga R

AU - Van Zyl, Louis T.

AU - Lekht, Vladimir

AU - Glassman, Alexander H.

PY - 2005/6

Y1 - 2005/6

N2 - Objective: In a platelet/endothelial biomarker substudy of the Sertraline Anti-Depressant 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.

AB - Objective: In a platelet/endothelial biomarker substudy of the Sertraline Anti-Depressant 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.

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