Risk of Bleeding Associated with Antidepressant Drugs: The Competitive Impact of Antithrombotics in Quantitative Signal Detection

BACKGROUND: To date, disproportionality analysis has been unable to demonstrate the increased bleeding risk associated with antidepressant drugs, especially selective serotonin reuptake inhibitors. OBJECTIVE: We hypothesised that a potential signal for an increased bleeding risk may be mitigated by the effects of agents other than antidepressant drugs that are strongly associated with haemorrhages, especially antithrombotics. In addition, we investigated if the use of more specific search terms of the Medical Dictionary for Regulatory Activities facilitates the detection of signals. METHODS: Pharmacovigilance data from the Uppsala Monitoring Centre were used to calculate substance-specific reporting odds ratios (RORs) for all types of bleeding and gastrointestinal bleeding. Reporting odds ratios were calculated with and without antithrombotic comedication. RESULTS: Regarding any type of bleeding, no signals were found in association with antidepressant drugs. Concerning upper gastrointestinal bleeding, signals were found related to citalopram (ROR: 1.56 [95% confidence interval 1.11–2.20]) and escitalopram (ROR: 1.52 [95% confidence interval 1.03–2.25]). After removal of reports related to antithrombotics, these signals could no longer be detected, but a new signal related to St. John’s Wort associated with haemorrhages was found (ROR: 1.50 [95% confidence interval 1.21–1.86]). CONCLUSIONS: Antithrombotics seem unlikely to have a major impact on the detection of the bleeding risk of antidepressant drugs. The different categorisation of adverse drug reactions regarding the strength of a causal relationship between a drug and an event in the database may be relevant for this negative finding. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40801-021-00260-9.