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) alter 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 of these types of 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 Clinformatics Data Mart. An initial cohort of 16,124 patients with blood clotting disorders 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 follow up 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 period. The use of antidepressant medications was determined by prescription drug dispensings three months prior to the follow up period. Both univariate and multivariate logistic regression models were built to enhance a final multivariate predictive model. Results: The use of SSRI and SNRI antidepressant medications was not associated with an increased risk of bleeding events (p=0.93). Risk factors for having a major bleeding event included older age (P=\u3c0.0001), male gender (P=0.0001), diabetes (P=0.0001), nonsteroidal anti-inflammatory drug (NSAID) use (p=0.0040), anticoagulant use (P=0.0001), and Hemophilia A (p=0.0001). 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 (95% CI: 1.31-2.61). The risk increases to 3.47 times for those between the ages of 66-90 (95% CI: 2.36-5.11). Males were 1.84 times more likely to have a major bleeding event in comparison to females (95% CI: 1.42-2.38). Patients who had diabetes are at 1.84 times the risk of a major bleeding even than those with diabetes (95% CI: 1.35-2.52). Patients with Hemophilia A had approximately twice the risk of experiencing a bleeding event as compared with patients having other blood clotting disorders (OR 2.13; 95% CI: 1.54-2.93). Conclusion: SSRI and SNRI antidepressant medications were not associated with an increased risk of bleeding events in this study. Factors associated with major bleeding events included male gender, older age, the use of NSAIDs or anticoagulants, and a diagnosis of Hemophilia A