Selective serotonin reuptake inhibitor use is associated with major bleeding during treatment with vitamin K antagonists: results of a cohort study

Aims: To determine whether Selective serotonin reuptake inhibitors (SSRIs) cause major bleeding during vitamin K antagonist (VKA) treatment and investigate the possible mechanisms behind this interaction. Methods: Information on SSRI use and bleeding complications was obtained from patient records at the Anticoagulation Clinics of Leiden and Rotterdam of VKA initiators between 2006 and 2018. Conditional logistic regression and time-dependent Cox regression were used to estimate the effect of SSRIs on a high INR (≥ 5) within 2 months after SSRI initiation and on major bleeding during the entire period of SSRI use, respectively. SSRI use was stratified for (non-)CYP2C9 inhibitors. Results: 58,918 patients were included, of whom 1504 were SSRI users. SSRI initiation versus non-use was associated with a 2.41-fold (95% confidence interval [CI] 2.01-2.89) increased risk for a high INR, which was 3.14-fold (95%CI 1.33-7.43) among CYP2C9 inhibiting SSRIs. SSRI use versus non-use was associated with a 1.22-fold (95%CI 0.99-1.50) increased risk for major bleeding in all SSRI users, which was 1.31-fold (95%CI 0.62-2.72) in CYP2C9 inhibiting SSRIs compared to non-users. Conclusion: SSRIs are associated with an increased risk of high INR and major bleeding. These risks were slightly more elevated for CYP2C9 inhibiting SSRI users, suggesting that this was due to a pharmacokinetic interaction (by CYP2C9 inhibition) as well as a pharmacodynamic effect of SSRIs on platelet activation.

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High Soluble Thrombomodulin Is Associated with an Increased Risk of Major Bleeding during Treatment with Oral Anticoagulants: A Case–Cohort Study

Thrombosis and Haemostasis ◽

10.1055/s-0040-1715459 ◽

2020 ◽

Author(s):

Myrthe M. A. Toorop ◽

Nienke van Rein ◽

Suzanne C. Cannegieter ◽

Felix J. M. van der Meer ◽

Pieter H. Reitsma ◽

...

Keyword(s):

Cohort Study ◽

Vitamin K ◽

Major Bleeding ◽

Cox Regression ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

International Normalized Ratio ◽

Soluble Thrombomodulin ◽

Major Bleed ◽

Increased Risk

Abstract Background Major bleeding occurs in 1 to 3% of patients treated with oral anticoagulants per year. Biomarkers may help to identify high-risk patients. A proposed marker for major bleeding while using anticoagulants is soluble thrombomodulin (sTM). Methods Plasma was available from 16,570 patients of the BLEEDS cohort that consisted of patients who started treatment with vitamin K antagonists between 2012 and 2014. A case–cohort study was performed including all patients with a major bleed (n = 326) during follow-up and a random sample of individuals selected at baseline (n = 652). Plasma sTM levels were measured and stratified by percentiles. Patients were also categorized by international normalized ratio (INR). Adjusted hazard ratios (for age, sex, hypertension, and diabetes) with 95% confidence intervals (CIs) were estimated by means of Cox regression. Results Plasma sTM levels were available for 263 patients with a major bleed and 538 control subjects. sTM levels were dose-dependently associated with risk of major bleeding, with a 1.9-fold increased risk (95% CI: 1.1–3.1) for levels above the 85th percentile versus the <25th percentile. A high INR (≥4) in the presence of high (≥70th percentile) sTM levels was associated with a 7.1-fold (95% CI: 4.1–12.3) increased risk of major bleeding, corresponding with a bleeding rate of 14.1 per 100 patient-years. Conclusion High sTM levels at the start of treatment are associated with major bleeding during vitamin K antagonist treatment, particularly in the presence of a high INR.

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Selective Serotonin Reuptake Inhibitors and the Risk of Osseointegrated Implant Failure

Journal of Dental Research ◽

10.1177/0022034514549378 ◽

2014 ◽

Vol 93 (11) ◽

pp. 1054-1061 ◽

Cited By ~ 47

Author(s):

X. Wu ◽

K. Al-Abedalla ◽

E. Rastikerdar ◽

S. Abi Nader ◽

N.G. Daniel ◽

...

Keyword(s):

Dental Implants ◽

Serotonin Reuptake ◽

Selective Serotonin Reuptake Inhibitors ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Serotonin Reuptake Inhibitors ◽

Implant Failure ◽

Selective Serotonin ◽

Osseointegrated Implants ◽

Increased Risk

Selective serotonin reuptake inhibitors (SSRIs), the most widely used drugs for the treatment of depression, have been reported to reduce bone formation and increase the risk of bone fracture. Since osseointegration is influenced by bone metabolism, this study aimed to investigate the association between SSRIs and the risk of failures in osseointegrated implants. This retrospective cohort study was conducted on patients treated with dental implants from January 2007 to January 2013. A total of 916 dental implants in 490 patients (94 implants on 51 patients using SSRIs) were used to estimate the risk of failure associated with the use of SSRIs. Data analysis involved Cox proportional hazards, generalized estimating equation models, multilevel mixed effects parametric survival analysis, and Kaplan-Meier analysis. After 3 to 67 mo of follow-up, 38 dental implants failed and 784 succeeded in the nonusers group, while 10 failed and 84 succeeded in the SSRI-users group. The main limitation of this retrospective study was that drug compliance dose and treatment period could not be acquired from the files of the patients. The primary outcome was that compared with nonusers of SSRIs, SSRI usage was associated with an increased risk of dental implants failure (hazard ratio, 6.28; 95% confidence interval, 1.25-31.61; p = .03). The failure rates were 4.6% for SSRI nonusers and 10.6% for SSRI users. The secondary outcomes were that small implant diameters (≤4 mm; p = .02) and smoking habits ( p = .01) also seemed to be associated with higher risk of implant failure. Our findings indicate that treatment with SSRIs is associated with an increased failure risk of osseointegrated implants, which might suggest a careful surgical treatment planning for SSRI users.

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New Oral Anticoagulants vs. Vitamin K Antagonists Among Patients With Cardiac Amyloidosis: Prognostic Impact

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.742428 ◽

2021 ◽

Vol 8 ◽

Author(s):

Eve Cariou ◽

Kevin Sanchis ◽

Khailène Rguez ◽

Virginie Blanchard ◽

Stephanie Cazalbou ◽

...

Keyword(s):

Vitamin K ◽

Cardiac Amyloidosis ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Bleeding Complications ◽

Prognostic Impact ◽

Transthyretin Amyloidosis ◽

Increased Risk ◽

All Cause Mortality ◽

History Of

Background: Atrial arrhythmia (AA) is common among patients with cardiac amyloidosis (CA), who have an increased risk of intracardiac thrombus. The aim of this study was to explore the prognostic impact of vitamin K-antagonists (VKA) and direct oral anticoagulants (DOAC) in patients with CA.Methods and Results: 273 patients with CA and history of AA with long term anticoagulation−69 (25%) light chain amyloidosis (AL), 179 (66%) wild-type transthyretin amyloidosis (ATTRwt) and 25 (9%) variant transthyretin amyloidosis (ATTRv)–were retrospectively included between January 2012 and July 2020. 147 (54%) and 126 (46%) patients received VKA and DOAC, respectively. Patient receiving VKA were more likely to have AL with renal dysfunction, higher NT-proBNP and troponin levels. Patients with ATTRwt were more likely to receive DOAC therapy. There were more bleeding complications among patients with VKA (20 versus 10%; P = 0.013) but no difference for stroke events (4 vs. 2%; P = 0.223), as compared to patients with DOAC. A total of 124 (45%) patients met the primary endpoint of all-cause mortality: 96 (65%) and 28 (22%) among patients with VKAs and DOACs, respectively (P < 0.001). After multivariate analysis including age and renal function, VKA was no longer associated with all-cause mortality.Conclusion: Among patients with CA and history of AA receiving oral anticoagulant, DOACs appear to be at least as effective and safe as VKAs.

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HEMATURIA AND OTHER KINDS OF BLEEDINGS ON NON-VITAMIN K ANTAGONIST ORAL ANTICOAGULANTS IN PATIENTS WITH ATRIAL FIBRILLATION: AN UPDATED OVERVIEW ON OCCURRENCE, PATHOMECHANISMS AND MANAGEMENT

Wiadomości Lekarskie ◽

10.36740/wlek202011135 ◽

2020 ◽

Vol 73 (11) ◽

pp. 2528-2534

Author(s):

Dagmara Wojtowicz ◽

Anna Tomaszuk-Kazberuk ◽

Jolanta Małyszko ◽

Marek Koziński

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Anticoagulant Activity ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Vitamin K Antagonist ◽

Bleeding Complications ◽

Reversal Agents ◽

Limited Availability ◽

Increased Risk

Non-vitamin K antagonist oral anticoagulants (NOACs) are currently recommended for oral anticoagulation in patients with non-valvular atrial fibrillation. In the setting, NOACs effectively prevent from stroke and systemic embolic events. In spite of the favorable safety profile of NOACs when compared with vitamin K antagonists, the use of any kind of anticoagulation is associated with an increased risk of bleeding. However, there is still a lack of direct comparisons of effectiveness and safety among NOACs. The results of indirect comparisons and meta-analyses suggest that the risk of various types of hemorrhagic complications differ among the particular NOACs. Management of bleeding in patients under NOAC therapy can be challenging because of limited availability of antidotes and the lack of routine laboratory test monitoring the NOAC anticoagulant effect. In case of life-threatening or critical site bleeding, reversal of NOAC anticoagulant activity is essential together with immediate implementation of causative treatment. Moreover, some patients on chronic NOAC therapy may require urgent surgery or invasive procedures. Specific reversal agents for NOACs have been developed, i.e. more widely available idarucizumab for the factor IIa inhibitor (dabigatran) and andexanet alfa for the factor Xa inhibitors (rivaroxaban, apixaban, edoxaban) with limited availability. This review summarizes the occurrence and management of NOAC-related bleeding complications with a particular emphasis on hematuria.

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Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation and cancer a meta-analysis

Journal of Thrombosis and Thrombolysis ◽

10.1007/s11239-020-02304-3 ◽

2020 ◽

Cited By ~ 2

Author(s):

Marco Valerio Mariani ◽

Michele Magnocavallo ◽

Martina Straito ◽

Agostino Piro ◽

Paolo Severino ◽

...

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Major Bleeding ◽

Meta Analysis ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Significant Risk ◽

Bleeding Complications ◽

Efficacy And Safety

Abstract Background Direct oral anticoagulants (DOACs) are recommended as first-line anticoagulants in patients with atrial fibrillation (AF). However, in patients with cancer and AF the efficacy and safety of DOACs are not well established. Objective We performed a meta-analysis comparing available data regarding the efficacy and safety of DOACs vs vitamin K antagonists (VKAs) in cancer patients with non-valvular AF. Methods An online search of Pubmed and EMBASE libraries (from inception to May, 1 2020) was performed, in addition to manual screening. Nine studies were considered eligible for the meta-analysis involving 46,424 DOACs users and 182,797 VKA users. Results The use of DOACs was associated with reduced risks of systemic embolism or any stroke (RR 0.65; 95% CI 0.52–0.81; p 0.001), ischemic stroke (RR 0.84; 95% CI 0.74–0.95; p 0.007) and hemorrhagic stroke (RR 0.61; 95% CI 0.52–0.71; p 0.00001) as compared to VKA group. DOAC use was associated with significantly reduced risks of major bleeding (RR 0.68; 95% CI 0.50–0.92; p 0.01) and intracranial or gastrointestinal bleeding (RR 0.64; 95% CI 0.47–0.88; p 0.006). Compared to VKA, DOACs provided a non-statistically significant risk reduction of the outcomes major bleeding or non-major clinically relevant bleeding (RR 0.94; 95% CI 0.78–1.13; p 0.50) and any bleeding (RR 0.91; 95% CI 0.78–1.06; p 0.24). Conclusions In comparison to VKA, DOACs were associated with a significant reduction of the rates of thromboembolic events and major bleeding complications in patients with AF and cancer. Further studies are needed to confirm our results.

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Effect of oral antiplatelet agents on major bleeding in users of coumarins

Thrombosis and Haemostasis ◽

10.1160/th08-05-0290 ◽

2008 ◽

Vol 100 (12) ◽

pp. 1076-1083 ◽

Cited By ~ 19

Author(s):

Olaf H. Klungel ◽

Patrick C. Souverein ◽

Anthonius de Boer ◽

Tom Schalekamp

Keyword(s):

Major Bleeding ◽

Conditional Logistic Regression ◽

Vitamin K Antagonists ◽

Antiplatelet Agents ◽

Bleeding Risk ◽

Primary Diagnosis ◽

Antiplatelet Drugs ◽

Antiplatelet Drug ◽

Concurrent Use ◽

Increased Risk

SummaryTreatment with vitamin K antagonists (coumarins) is associated with an increased risk of bleeding. In order to elucidate the bleeding risk of users of antiplatelet drugs among users of coumarins, we assessed the odds ratio of major bleeding associated with use of antiplatelet drugs in users of the coumarins acenocoumarol and phenprocoumon. We used data froma Dutch record linkage system, including pharmacy and linked hospitalization records for approximately two million subjects, to conduct a nested case control study in a cohort of new users of coumarins. Cases were patients who were hospitalized with a primary diagnosis of major bleeding while taking coumarin and were matched with up to four control subjects. Conditional logistic regression analysis was used to determine ORs and 95% confidence intervals (CI).We identified 1848 case patients who were matched to 5818 controls. Users of clopidogrel or aspirin showed a significantly increased risk of hospitalization because of major bleeding (OR 2.9, 95% CI 1.2–6.9 and OR 1.6, 95% CI 1.3–1.9, respectively), whereas users of dipyridamole and combinations of antiplatelet drugs showed a strong trend (OR 1.5, 95% CI 1.0–2.3 and OR 1.8, 95 % CI 1.0–3.3, respectively). In all cases, the risks were greater for upper gastrointestinal bleedings than for other bleedings. In conclusion, the use of any antiplatelet drug increases the risk of hospitalization for major bleeding among users of coumarins. Concurrent use of clopidogrel or dipyridamole and coumarins is probably not safer than concurrent use of aspirin and coumarins.

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Selection, management, and outcome of vitamin K antagonist-treated patients with atrial fibrillation not switched to novel oral anticoagulants

Thrombosis and Haemostasis ◽

10.1160/th15-02-0116 ◽

2015 ◽

Vol 114 (11) ◽

pp. 1076-1084 ◽

Cited By ~ 15

Author(s):

Franziska Michalski ◽

Luise Tittl ◽

Sebastian Werth ◽

Ulrike Hänsel ◽

Sven Pannach ◽

...

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Major Bleeding ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Case Fatality ◽

Bleeding Risk ◽

Vitamin K Antagonist ◽

Bleeding Complications ◽

Treatment Rate

SummaryAtrial fibrillation (AF) patients treated with well-controlled vitamin K antagonists (VKAs) may benefit less from non-vitamin K antagonist oral anticoagulants (NOACs) because they are supposed to be at low risk of thromboembolic and bleeding complications. However, little is known about the selection, management, and outcome of such “stable” VKA patients in current practice. We assessed characteristics, VKA persistence and 12 months' outcome of AF patients selected for VKA continuation. On March 1, 2013, the Dresden NOAC registry opened recruitment of patients continuing on VKA for sites that had been actively recruiting AF patients treated with NOACs in the prior 18 months. Patient characteristics were compared with those of NOAC patients from the same sites. Four hundred twenty-seven VKA patients had a significantly lower bleeding risk profile compared with 706 patients selected for NOAC treatment. For VKA, international normalised ratio time-in-therapeutic range before enrolment was 71% and increased to 75% during a mean follow-up of 15 months. Rates of stroke/transient ischaemic attack/systemic embolism were 1.3/100 patient-years (intention-to-treat) and 0.94/100 patient-years (as-treated). On-treatment rate of ISTH major bleeding was 4.15/100 patient-years (95% CI 2.60–6.29) with a case-fatality rate of 16.3% (all-cause mortality at day 90 after major bleeding). In conclusion, in daily care, AF patients selected for VKA therapy are healthier than those treated with NOAC, demonstrate a high quality of anticoagulant control and very low stroke rates. However, despite adequate patient selection and INR control, the risk of major VKA bleeding is unacceptably high and bleeding outcome is poor.

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Safety of concomitant treatment with Non-Vitamin K Oral Anticoagulants and SSRI/SNRI antidepressants

Current Problems of Psychiatry ◽

10.2478/cpp-2018-0021 ◽

2018 ◽

Vol 19 (4) ◽

pp. 267-278 ◽

Cited By ~ 1

Author(s):

Piotr Boguta ◽

Dariusz Juchnowicz ◽

Paulina Wróbel-Knybel ◽

Agnieszka Biała-Kędra ◽

Hanna Karakuła-Juchnowicz

Keyword(s):

Vitamin K ◽

Serotonin Reuptake ◽

Selective Serotonin Reuptake Inhibitors ◽

Oral Anticoagulants ◽

Critical Role ◽

Selective Serotonin ◽

Concomitant Treatment ◽

Risk Of Bleeding ◽

Noradrenaline Reuptake ◽

Increasing Risk

Abstract Introduction: Warfarin has been considered as a “gold standard” in the prevention and treatment of thromboembolic events since 1954. Since the introduction of direct oral anticoagulants in the last few years (NOAC-Non-Vitamin K antagonist Oral Anticoagulants) prescriptions volume for apixaban, edoxaban, dabigatran and rivaroxaban have been gradually surpassing warfarin. The benefits include: anticoagulation from day one, fixed daily dosing, elimination for the need of international normalised ratio (INR) monitoring, fewer interactions with food and co-administered medicines with reduced risk of bleeding and better overall life quality. Objectives: Assessing evidence for the safe use of Non-vitamin K Oral Anticoagulants (NOAC) with Selective Serotonin Reuptake Inhibitors (SSRI) and Serotonin and Noradrenaline Reuptake Inhibitors (SNRI). Method: Review of literature published between 2014 and 2016 was made using the key words: Selective Serotonin Reuptake Inhibitor, Serotonin and Noradrenaline Reuptake Inhibitors, apixaban, dabigatran, edoxaban, rivaroxaban, bleeding, interaction, depression with time description from 2014 to 2018. Evidence within the literature was then compared with guidelines from the National Institute for Health and Care Excellence (UK), British National Formulary (UK), Clinical Excellence Commission (Australia), Thrombophilia and Anticoagulation Clinic (USA) and Summaries of Product Characteristics (SPC). Results: 1. Serotonin plays a critical role in maintaining homeostasis. Use of SSRI/SNRI compromises its platelet reuptake increasing risk of bleeding. 2. Increased tolerability and safety of NOAC over Warfarin, although caution is advised when NOAC is used with SSRI/SNRI with less evidence suggesting pharmacodynamic interactions. 3. It is not recommended to use NOAC with strong CYP and P-gp inhibitors. Conclusions: With limited literature evidence, caution is advised when co-prescribed NOACs with SSRI/SNRI, especially with other cofactors and interacting medicines further increasing risk of bleeding.

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The impact of selective serotonin reuptake inhibitors on the risk of intracranial haemorrhage: A systematic review and meta-analysis

European Stroke Journal ◽

10.1177/2396987319827211 ◽

2019 ◽

Vol 4 (2) ◽

pp. 144-152 ◽

Cited By ~ 2

Author(s):

Melanie P Jensen ◽

Oliver J Ziff ◽

Gargi Banerjee ◽

Gareth Ambler ◽

David J Werring

Keyword(s):

Serotonin Reuptake ◽

Observational Studies ◽

Intracranial Haemorrhage ◽

Selective Serotonin Reuptake Inhibitors ◽

Meta Analysis ◽

Serotonin Reuptake Inhibitors ◽

Quality Data ◽

Selective Serotonin ◽

Increased Risk ◽

The Impact

Introduction Observational studies have suggested increased risk of intracranial haemorrhage (ICrH) in patients receiving selective serotonin reuptake inhibitors (SSRIs). We sought to clarify the impact of SSRIs on ICrH, accounting for study methodology. Patients and methods A comprehensive search of Medline, Embase and the Cochrane Library from 1960 to December 2017 identified studies comparing SSRIs with control. The outcomes (first-ever and recurrent ICrH) were meta-analysed using a random effects model. Results Twenty-four observational studies and three randomised trials were available for meta-analysis, totalling 4,844,090 patient-years of follow-up. Those receiving SSRIs were more likely to be female ( p = 0.01) and have depression ( p < 0.001). Compared to controls, SSRI users had a significantly increased risk of ICrH (relative risk (RR) 1.26, 95%CI 1.11–1.42). Although SSRI use was associated with increased ICrH risk in those without previous ICrH (RR 1.31, 95%CI 1.15–1.48), this was not the case in those with previous ICrH (RR 0.95, 95%CI 0.83–1.09). Sensitivity analysis according to the bleeding definition reported demonstrated that although ‘haemorrhagic stroke’ was associated with SSRIs (RR 1.40, 95%CI 1.13–1.72), intracerebral haemorrhage was not (RR 1.11, 95%CI 0.86–1.42). Additional sensitivity analyses demonstrated a stronger association between SSRIs and ICrH in studies with a high ( p < 0.001) compared to low risk of bias ( p = 0.09) and with retrospective ( p < 0.001) compared to prospective (p=0.31) study designs. Discussion Although SSRIs are associated with an increased risk of ICrH, the association is partly accounted for by important biases and other methodological limitations in the available observational data. Conclusion Our findings suggest there is insufficient high-quality data to advise restriction of SSRIs because of concern regarding ICrH risk.

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

Blood ◽

10.1182/blood.v112.11.4556.4556 ◽

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.

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