Key result
Signals for upper gastrointestinal bleeding associated with citalopram (ROR 1.56) and escitalopram (ROR 1.52) disappeared after removing antithrombotic reports, indicating antithrombotics do not mask the bleeding risk of antidepressants in disproportionality analyses.
Why the study?
Disproportionality analysis has struggled to demonstrate increased bleeding risk with antidepressants, possibly because signals are mitigated by strongly haemorrhage-associated agents like antithrombotics.
Does the presence of antithrombotic comedication mask the bleeding risk signals associated with antidepressant drugs in pharmacovigilance databases?
Observational (n=18,409,119)
Does the presence of antithrombotic comedication mask the bleeding risk signals associated with antidepressant drugs in pharmacovigilance databases?
Odds Ratio: 1.56 (95% CI 1.11–2.2)
Antithrombotics do not appear to have a major impact on masking the detection of bleeding risks associated with antidepressant drugs in pharmacovigilance databases.
No evidence of antithrombotic masking in disproportionality data; leaves open independent bleeding risk with these SSRIs.
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.
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Zeiss et al. (2021) conducted an observational in Adverse drug reactions (haemorrhage) (n=18,409,119). Antidepressant drugs vs. Other drugs in the database was evaluated on Upper gastrointestinal haemorrhage (citalopram) (ROR 1.56, 95% CI 1.11-2.20). Signals for upper gastrointestinal bleeding associated with citalopram (ROR 1.56) and escitalopram (ROR 1.52) disappeared after removing antithrombotic reports, indicating antithrombotics do not mask the bleeding risk of antidepressants in disproportionality analyses.
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