Platelet Activation in Depression and Effects of Sertraline Treatment: An Open-Label Study

Markovitz, Jerome H.; Shuster, John L.; Chitwood, William S.; May, Roberta S.; Tolbert, Lelland C.

doi:10.1176/appi.ajp.157.6.1006

Cited by 141 publications

(97 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…38 Interestingly, collageninduced platelet secretion, an integral component of the clotting cascade, is significantly reduced after treatment with sertraline. 39 The present data are in agreement with earlier in vitro observations, 14 suggesting that long-term therapy with sertraline is associated with inhibition of platelets and possibly other steps in the clotting cascade. Indeed, at 6 weeks after randomization, patients treated with sertraline exhibited a significant decrease in ␤TG, the well-defined platelet ␣-granule constituent.…”

Section: Discussionsupporting

confidence: 93%

Platelet/Endothelial Biomarkers in Depressed Patients Treated With the Selective Serotonin Reuptake Inhibitor Sertraline After Acute Coronary Events

et al. 2003

View full text Add to dashboard Cite

Background-Depression after acute coronary syndromes (ACSs) has been identified as an independent risk factor for subsequent cardiac death. Enhanced platelet activation has been hypothesized to represent 1 of the mechanisms underlying this association. Selective serotonin reuptake inhibitors (SSRIs) are known to inhibit platelet activity.Whether treatment of depressed post-ACS patients with SSRIs alters platelet function was not known. Accordingly, we serially assessed the release of established platelet/endothelial biomarkers in patients treated with sertraline vs placebo in the Sertraline AntiDepressant Heart Attack Randomized Trial (SADHART). Methods and Results-Plasma samples (baseline, week 6, and week 16) were collected from patients randomized to sertraline (nϭ28) or placebo (nϭ36). Anticoagulants, aspirin, and ADP-receptor inhibitors were permitted in this study. Platelet factor 4, ␤-thromboglobulin (␤TG), platelet/endothelial cell adhesion molecule-1, P-selectin, thromboxane B 2 , 6-ketoprostaglandin F 1a , vascular cell adhesion molecule-1, and E-selectin were measured by ELISA. Treatment with sertraline was associated with substantially less release of platelet/endothelial biomarkers than was treatment with placebo. These differences attained statistical significance for ␤TG (Pϭ0.03) at weeks 6 and 16 and for P-selectin (Pϭ0.04) at week 16. Repeated-measures ANOVA revealed a significant advantage for sertraline vs placebo for diminishing E-selectin and ␤TG concentrations across the entire treatment period. Conclusions-Treatment

show abstract

Section: Discussionsupporting

confidence: 93%

Platelet/Endothelial Biomarkers in Depressed Patients Treated With the Selective Serotonin Reuptake Inhibitor Sertraline After Acute Coronary Events

et al. 2003

View full text Add to dashboard Cite

show abstract

“…4,8,9 This was the a priori hypothesis of our study. SSRIs inhibit serotonin uptake into platelets, 11,26,27 block intracellular calcium mobilization, 28 and are associated with an increase in bleeding time.…”

Section: Depression Ssris and Platelet Functionmentioning

confidence: 82%

“…9,22 This may be attributable to the upregulation of platelet imidazoline 23 and serotonin 24 receptors and enhanced intraplatelet calcium mobilization 25 seen in patients with depression.…”

Section: Depression Ssris and Platelet Functionmentioning

confidence: 99%

Selective serotonin reuptake inhibitors and myocardial infarction

Sauer¹,

Berlin²,

Kimmel³

2002

ACC Current Journal Review

View full text Add to dashboard Cite

Background-Depression is an independent risk factor for myocardial infarction (MI). Selective serotonin reuptake inhibitors (SSRIs) may reduce this risk through attenuation of serotonin-mediated platelet activation in addition to treatment of depression itself. Methods and Results-A case-control study of first MI in smokers 30 to 65 years of age was conducted among all 68 hospitals in an 8-county area during a 28-month period. Cases were patients hospitalized with a first MI. Approximately 4 community control subjects per case were randomly selected from the same geographic area using random digit dialing. Detailed information regarding use of antidepressant medication as well as other clinical and demographic data were obtained by telephone interview. A total of 653 cases of first MI and 2990 control subjects participated. After adjustment, using multivariable logistic regression, for age, sex, race, education, exercise, quantity smoked per day, body mass index, aspirin use, family history of MI, number of physician encounters, and history of coronary disease, diabetes, hypertension, or hypercholesterolemia, the odds ratio for MI among current SSRI users compared with nonusers was 0.35 (95% CI 0.18, 0.68; PϽ0.01). Non-SSRI antidepressant users had a nonsignificant reduction in MI risk with wide confidence intervals (adjusted odds ratio 0.48, CI 0.17, 1.32; Pϭ0.15). However, analysis of this group was limited by the small number of exposed subjects. Conclusions-The use of SSRIs may confer a protective effect against MI. This could be attributable to the inhibitory effect SSRIs have on serotonin-mediated platelet activation or possibly amelioration of other factors associated with increased risk for MI in depression.

show abstract

“…Although in the middle of the nineties Alderman et al (1992) and Berk et al (1995) failed to find a modification in platelet aggregation or haemostasis in patients treated with SSRIs, the application of most modern techniques to measure platelet function led to the confirmation that SSRIs impair both the platelet secretory response (Markovitz et al 2000) and the platelet aggregation induced by ADP, collagen and thrombin (Serebruany et al 2001), and that they cause an inhibition of platelet plug formation as reflected by a significant prolongation of the closure-time measured with a platelet function analyzer (Hergovich et al 2000). Furthermore, in vitro studies have shown that addition of ADP to normal platelets in the presence of SSRIs causes microaggregation and primary aggregation but no or very little dense granule release which leads to the formation of loose and disaggregating clots (Maurer-Spurej 2005).…”

Section: Pharmacology Of Ssris On Platelets and The Biological Plausimentioning

confidence: 99%

Antidepressants and Risk of Upper Gastrointestinal Bleeding

Abajo

Montero

Rodrı́guez

et al. 2006

Basic Clin Pharma Tox

View full text Add to dashboard Cite

show abstract

Platelet Activation in Depression and Effects of Sertraline Treatment: An Open-Label Study

Abstract: Sertraline diminished the increased platelet secretion found among depressed patients, although the findings are limited by a lack of a placebo control group.

Cited by 141 publications

References 11 publications

Platelet/Endothelial Biomarkers in Depressed Patients Treated With the Selective Serotonin Reuptake Inhibitor Sertraline After Acute Coronary Events

Platelet/Endothelial Biomarkers in Depressed Patients Treated With the Selective Serotonin Reuptake Inhibitor Sertraline After Acute Coronary Events

Selective serotonin reuptake inhibitors and myocardial infarction

Antidepressants and Risk of Upper Gastrointestinal Bleeding

Contact Info

Product

Resources

About