A study of the increased risk of bleeding events in patients with blood clotting disorders, associated with antidepressant medication use

Background: Patients with blood clotting disorders have severely depleted levels of blood clotting factor (BCF) proteins in their blood, which results in a significantly higher risk of bleeding events than a typically healthy patient. Serotonin based antidepressant medications, such as selective serotonin reuptake inhibitors (SSRI) or serotonin norepinephrine reuptake inhibitors (SNRI) alters the levels of serotonin in the blood as a mechanism to treat depression. Serotonin is used for many different chemical processes within the body including blood aggregation. We sought to quantify the potential risk associated with the use antidepressant medications to patients with blood clotting disorders. Objective: To determine if patients with BCF disorders who are prescribed SSRI or SNRI medications are at an increased risk of having a major bleeding event. Methods: A retrospective cohort study was conducted using data from the Optum informatics database (name). An initial cohort of 16,124 patients was formed; patients were excluded based upon enrollment eligibility, drug prescription date outside the study timeframe, and age under 12 years. A final study sample of 7,998 patients was formed. A study period of six months was selected to analyze major bleeding events; these events were identified using ICD-9 codes for hemorrhages. Patients were classified as to whether a bleeding event occurred during the study period. The use of antidepressant medications was determined by prescription drug claims three months prior to the start of the outcome assessment period. Results: The use of SSRI and SNRI antidepressant medications was not associated with an increased risk of bleeding events. (p=0.31). However, analyses by individual drug type revealed that patients using Citalopram were at an increased risk of experiencing a bleeding event as compared with patients not on antidepressant medications (OR 1.81; CI: 1.02-3.21, P=0.042). Upon expanding our antidepressant type to include serotonin modulators we found that patients using Trazodone had an increased risk of a major bleeding event compared to those not on antidepressant medications, OR 2.065 (CI 1.04 – 4.10, P=0.038). We also found that other risk factors for having a major bleeding event included older age (P=\u3c0.0001), male gender (P=\u3c0.0001), diabetes (P=0.0001), and Nonsteroidal anti-inflammatory drug (NSAID)/ anticoagulant use (P=\u3c0.0001). Patients who were between 46-65 years old were 1.85 times more likely to have a major bleeding event than those between the ages of 26-45 (CI: 1.31-2.61). This risk increases to 3.47 times for those between the ages of 66-90 (CI: 2.36-5.11). In an analysis of gender, we found that males were 1.84 times more likely to have a major bleed event in comparison to females (CI: 1.42-2.38). Lastly, patients who had diabetes are at 1.84 times the risk of a major bleeding event than those with diabetes (CI: 1.35-2.52). Conclusion: Based on our findings serotonin based antidepressant medications were not associated with an increased risk of bleeding events, with the exception of the SSRI Citalopram and the serotonin modulator Trazodone. Other risk factors that contributed a significant risk to patients include male gender, older age, and the use of NSAIDs or anticoagulants