Key result
Concurrent SSRI and low-dose ASA linked to ~37% higher bleeding risk versus ASA alone.
Why the study?
It was uncertain whether concurrent treatment with an SSRI and low-dose ASA increases bleeding risk compared with an SSRI alone or ASA alone.
Does concurrent treatment with an SSRI and low-dose ASA increase the risk of bleeding in patients compared with SSRI or low-dose ASA alone?
Meta-Analysis
Does concurrent treatment with an SSRI and low-dose ASA increase the risk of bleeding in patients compared with SSRI or low-dose ASA alone?
Hazard Ratio: 1.37 (95% CI 1.1–1.7)
Current evidence is too uncertain to confirm a synergistic interaction increasing bleeding risk when an SSRI is added to low-dose ASA, though adding ASA to an SSRI increases bleeding risk due to the ASA itself.
Aims The aim of this study was to systematically review whether concurrent treatment with an SSRI and low‐dose ASA increases the risk of bleeding compared with treatment with an SSRI alone or ASA alone. Methods Medline, Embase, the Cochrane Library, PsycINFO and Web of Science (from database inception to January 2023) were searched according to PICO: P = patients on treatment with an SSRI and/or low‐dose ASA; I = intervention: SSRI + ASA; C = comparison: ASA or SSRI alone; O = outcomes: bleeding/major bleeding. The included articles were assessed using checklists. Studies without major risk of bias formed the basis for the conclusions. Extracted data were pooled using random‐effects meta‐analyses. Certainty of evidence was assessed according to GRADE. Results Twenty‐four studies met the PICO and were included. One randomized and six nonrandomized studies were assessed not to have major risk of bias. Regarding SSRI + ASA vs . ASA only, the pooled hazard ratio of three nonrandomized studies ( n = 38 467) was 1.37 (95% confidence interval: 1.10; 1.70; I 2 = 0%), and the pooled odds ratio of two nonrandomized studies ( n = 28 296) was 0.95 (0.77; 1.19; I 2 = 0%). Regarding SSRI + ASA vs . SSRI only, the randomized controlled trial ( n = 1048) reported a hazard ratio of 1.82 (0.66; 5.02), the hazard ratio being 1.60 (1.24; 2.06) for ASA vs . placebo in patients without SSRI treatment; and one nonrandomized controlled study ( n = 18 920) reported an incidence rate ratio of 1.03 (0.96; 1.12). Conclusions The compiled evidence was too uncertain to support an interaction when an SSRI is added to low‐dose ASA. Low‐dose ASA added to an SSRI may imply an increased risk of bleeding primarily attributable to the initiation of ASA.
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Axelsson et al. (2024) conducted a meta-analysis in Patients on treatment with an SSRI and/or low-dose ASA. SSRI and low-dose ASA vs. ASA or SSRI alone was evaluated on bleeding/major bleeding (HR 1.37, 95% CI 1.10-1.70). Concurrent treatment with an SSRI and low-dose ASA yielded uncertain evidence of an interaction increasing bleeding risk compared to ASA alone (pooled HR 1.37; 95% CI 1.10-1.70).
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