Effects of Serotonin Reuptake Inhibitors on Hemostasis

1996 ◽  
Vol 30 (11) ◽  
pp. 1232-1234 ◽  
Author(s):  
Christopher P Alderman ◽  
Prabha Seshadri ◽  
David I Ben-Tovim
Keyword(s):  
Platelet Aggregation ◽  
Serotonin Reuptake ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Serum Bilirubin ◽  
Complete Blood Count ◽  
Clinical Signs ◽  
Serotonin Reuptake Inhibitors ◽  
Bilirubin Concentration ◽  
The Mean ◽  
High Doses

OBJECTIVE: To examine the hematologic safety profile of the selective serotonin reuptake inhibitors (SSRIs), with particular emphasis on the effects of these drugs on platelet aggregation. METHODS: Platelet aggregation studies were undertaken at baseline, and repeated 2 and 4 weeks after the initiation of treatment with an SSRI. Other investigations undertaken included analysis of serum electrolyte and liver enzyme concentrations, complete blood count, and coagulation studies. Patients were also assessed for clinical signs of bleeding. Eight patients (7 treated with fluoxetine, 1 with paroxetine) completed the study protocol. RESULTS: Repeated ANOVA revealed no abnormalities in platelet aggregation, hematopoiesis, or coagulation profile. No patient developed clinical signs of abnormal hemostasis during the study period. A statistically significant elevation in the mean serum bilirubin concentration was detected, but this was not of clinical significance. CONCLUSIONS: Although the SSRIs may cause abnormal hemostasis, this effect is probably rare. Another possibility is that abnormal hemostasis is more likely to occur when high doses of SSRIs are administered.

Selective Serotonin Reuptake Inhibitors Influence Agonist-Induced Platelet Aggregation. Preliminary Results from Comorbidity of Depression and Cardiovascular Disease Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4556-4556
Author(s):  
Omer Iqbal ◽  
Cafer Adiguzel ◽  
Jawed Fareed ◽  
Debra Hoppensteadt ◽  
Evangalos Litinas ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Platelet Aggregation ◽  
Platelet Activation ◽  
Serotonin Reuptake ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Serotonin Reuptake Inhibitors ◽  
Selective Serotonin ◽  
Bleeding Complications ◽  
Bleeding Tendency ◽  
Preliminary Results

Abstract Selective serotonin reuptake inhibitors (SSRI) are a first-line treatment option for depressive illnesses, anxiety and obsessive-compulsive disorders with a favorable risk benefit ratio and side effects. They selectively inhibit neuronal reuptake of serotonin and result in depleted serotonin stores in the dense bodies of platelets. It is hypothesized that depressive illnesses cause platelet activation and endothelial dysfunction, which could be modulated by the use of SSRIs. In order to validate this hypothesis an institutional-based co morbidity of depression and cardiovascular study is undertaken. Patients with depression (n=25) and healthy control (n=25) are recruited in this study. Males and females between the ages of 20 and 65 years meeting the DSM-IV criteria for major depressive disorder served as the inclusion criteria for the study. The exclusion criteria included patients with heart disease, diabetes, lipid disorders, history of smoking, pregnant and lactating women, psychosis, schizoaffective illnesses and presence of other Axis I diagnosis with the exception of generalized anxiety disorder. Blood samples were collected at baseline and then 4 and 8 weeks following treatment with Escitaloprim, an SSRI. Preliminary results from the agonist-induced platelet aggregation showed varying degrees of inhibition of collagen, ADP, arachidonic acid and epinephrine-induced platelet aggregation as shown in the table below. Agonist induced platelet aggregation profile Averaged % aggregation Time Collagen AA ADP Epinephrine Saline Baseline 71.5± 22.4 64.1± 35.1 48.15± 30.9 55.65± 29.2 6.9± 4.5 Week 4 63.4± 19.5 67.1± 25.1 33± 26.7 37.375± 25.8 9.375± 7.8 Week 8 74.7± 21.3 55.71± 36.1 52.4± 31 50.4± 32.3 5± 3.9 While a number of patients showed an inhibition of ADP (2.5μM) and epinephrine (10μg/ml) and collagen (380μg/ml), however, other patients showed an inhibition of collagen-induced platelet aggregation. These results indicate that patients treated with SSRIs may have inhibition of platelet activation and aggregation, which may have an impact in the prevention of atherothrombotic cardiovascular disease. SSRIs might increase the bleeding tendency in some patients by inhibiting platelet aggregation. However, when the SSRIs are given in combination with other drugs patients may have a propensity for bleeding complications due to drug-drug interactions. Further large-scale trials are warranted to validate these results.

The influence of selective serotonin reuptake inhibitors on human platelet serotonin

2004 ◽  
Vol 91 (01) ◽  
pp. 119-128 ◽  
Author(s):  
Cheryl Pittendreigh ◽  
Kevin Solomons ◽  
Elisabeth Maurer-Spurej
Keyword(s):  
Cardiovascular Disease ◽  
Platelet Aggregation ◽  
Normal Control ◽  
Serotonin Reuptake ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Dense Granule ◽  
Serotonin Reuptake Inhibitors ◽  
Selective Serotonin ◽  
Cardiovascular Benefit ◽  
Granule Release

SummaryClinical depression has been proposed to be an independent risk factor for cardiovascular disease. While it is suggested that selective serotonin reuptake inhibitors (SSRIs) reduce the risk of acute cardiovascular problems of depressed patients, the effect of SSRIs on platelets, the only blood cells committed to serotonin (5-HT) transport, remains largely unknown. The goal of this pilot study was to measure the 5-HT levels in platelets of untreated and SSRI-treated depressed patients and normal subjects and to determine whether the interaction of SSRIs with platelets can explain their possible cardiovascular benefit in patients with depression. Platelet 5-HT was determined by an immunocytochemical assay and high-pressure liquid chromatography with electrochemical detection (HPLC-ECD). In normal control subjects without cardiovascular disease, 78 ± 8% of platelets were 5-HT-positive (n = 14). Depression caused a significant reduction in platelet 5-HT to 46 ± 21% in untreated patients (n = 13) and 22 ± 13% in SSRI-treated patients (n = 14). As a class, all selective serotonin reuptake inhibitors significantly reduced the 5-HT concentration in patient platelets. An inverse relationship of 5-HT level and dose of medication might be suggested. These results correlated well with 5-HT data from HPLC (r = 0.8509, p < 0.001). SSRIs did not affect platelet aggregation and dense granule release in response to thrombin, but significantly reduced ADP-induced platelet aggregation and dense granule release in both patient and normal control samples. The active inhibition of platelet aggregation by SSRIs might explain their cardiovascular benefit.

scholarly journals Effect of Low and High Doses of Two Selective Serotonin Reuptake Inhibitors on Pregnancy Outcomes and Neonatal Mortality

Toxics ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 11
Author(s):  
Rafael R. Domingues ◽  
Hannah P. Fricke ◽  
Celeste M. Sheftel ◽  
Autumn M. Bell ◽  
Luma C. Sartori ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Neonatal Mortality ◽  
Pregnancy Outcomes ◽  
Serotonin Reuptake ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Serotonin Reuptake Inhibitors ◽  
Neonatal Outcomes ◽  
Selective Serotonin ◽  
High Dose ◽  
High Doses

Selective serotonin reuptake inhibitors (SSRI) are the most common antidepressant used by pregnant women; however, they have been associated with adverse pregnancy outcomes and perinatal morbidity in pregnant women and animal models. We investigated the effects of two SSRI, fluoxetine and sertraline, on pregnancy and neonatal outcomes in mice. Wild-type mice were treated daily with low and high doses of fluoxetine (2 and 20 mg/kg) and sertraline (10 and 20 mg/kg) from the day of detection of a vaginal plug until the end of lactation (21 days postpartum). Pregnancy rate was decreased only in the high dose of fluoxetine group. Maternal weight gain was reduced in the groups receiving the high dose of each drug. Number of pups born was decreased in the high dose of fluoxetine and low and high doses of sertraline while the number of pups weaned was decreased in all SSRI-treated groups corresponding to increased neonatal mortality in all SSRI-treated groups. In conclusion, there was a dose-dependent effect of SSRI on pregnancy and neonatal outcomes in a non-depressed mouse model. However, the distinct placental transfer of each drug suggests that the effects of SSRI on pup mortality may be mediated by SSRI-induced placental insufficiency rather than a direct toxic effect on neonatal development and mortality.

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