Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used type of antidepressant medications. While these drugs have fewer side effects than other antidepressants, they can cause major bleeding in some people, which requires hospitalization and could be fatal. Patients with atrial fibrillation, the most common heart rhythm disorder, are often treated with oral anticoagulants (i.e. blood thinners), which can also cause major bleeding. SSRIs may interact with oral anticoagulants and further increase their potential to cause major bleeding. Around 20-30% of people living with cardiovascular disease may be diagnosed with depression and may need to be treated with both SSRIs and oral anticoagulants. To date, we have not accurately measured the risk of major bleeding in patients taking both these drugs together. Therefore, the main objective of this research is to determine the risk of bleeding in patients using SSRIs and anticoagulants together and assess if SSRIs may be interacting with oral anticoagulants.
We will assemble a cohort of all patients with a first diagnosis of atrial fibrillation and determine how many patients had a bleeding episode during follow-up. We will compare patients with and without bleeding episodes according to the medications they were using (SSRIs, oral anticoagulants, both, or neither drug). Findings of this study will improve our understanding of the interaction between SSRIs and oral anticoagulants and provide important safety information to physicians prescribing antidepressants to patients with atrial fibrillation.
Selective serotonin reuptake inhibitors (SSRIs) are the most widely used antidepressant medications. Several observational studies have reported an association between SSRI use and major bleeding, including gastrointestinal bleeding, intracranial haemorrhage, perioperative bleeding, and postpartum haemorrhage. Oral anticoagulants (OACs) are prescribed to prevent ischemic stroke in patients with atrial fibrillation (AF), however they also increase the risk of major bleeding. Given that depression is prevalent among patients using oral anticoagulants, concomitant use of SSRIs and OACs is common and may confer an additional risk of major bleeding compared with either of these drugs alone. Moreover, SSRIs may interfere with the metabolism of OACs and prolong their effect, further increasing the risk of major bleeding. Thus, we will conduct a nested case-control study to assess interaction between SSRIs and OACs with respect to the risk of major bleeding. We will form a cohort of all patients newly diagnosed with AF between 2000 and 2022. Within this cohort, we will select all incident cases of major bleeding and up to 30 matched controls. Conditional logistic regression will be used to estimate the interaction between SSRIs and OACs and the risk of bleeding, adjusted for more than 35 covariates, including demographic, socioeconomic, and lifestyle characteristics as well as relevant comorbidities and comedications.
The primary outcome will be the first episode of major bleeding defined as a hospitalization with a first diagnosis of bleeding (defined using ICD codes listed in Appendix 2) any time after cohort entry. Previously, bleeding-related outcomes have shown good validity in the CPRD.1,2 We will also assess any bleeding (defined using Read codes and SNOMED-CT concept IDs listed in Appendix 1) as a secondary outcome.
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Christel Renoux - Corresponding Applicant - McGill University
Alvi Rahman - Collaborator - McGill University
Jean-François Boivin - Collaborator - McGill University
Robert Platt - Collaborator - McGill University
Sarah Beradid - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Soham Rej - Collaborator - McGill University
HES Admitted Patient Care;ONS Death Registration Data;Practice Level Index of Multiple Deprivation