Use of serotonin reuptake inhibitor antidepressants and the risk of bleeding complications in patients on anticoagulant or antiplatelet agents: a systematic review and meta-analysis
Bibliographic record
Abstract
Background Serotonin reuptake inhibitor (SRI) antidepressants are implicated in increasing the risk of bleeding among users; however, the comparative increase in bleeding risk with concurrent antithrombotic therapy (anticoagulant or antiplatelet) remains unclear. As such, we performed a systematic review and meta-analysis of all available evidence to evaluate the effects of SRI and the risk of bleeding complications among patients receiving antithrombotic therapy.Methods We searched Medline, Embase, PubMed, PsycINFO, Cochrane Library, Web of Science, Scopus, CINAHL, and grey literature (Google Scholar and preprint reports) up to 26 November, 2020, with no language restrictions (updated on 31 July 2021). The primary outcome of interest was major bleeding. Secondary outcomes included intracranial haemorrhage, gastrointestinal bleeding, and any bleeding events. We used a random-effects model meta-analysis to estimate the odds ratios (ORs) and 95% confidence intervals (CIs).Results We did not identify any randomised studies but found 32 non-randomized studies (cohort or case–control) with 1,848,285 patients that fulfilled the study selection criteria and were included in the meta-analysis. Among individuals receiving anticoagulants (13 studies), SRI users experienced a statistically higher risk of major bleeding compared to non-SRI users: pooled OR was 1.39 (95% CI, 1.23–1.58; p < .001; moderate heterogeneity). Among individuals receiving antiplatelet therapy (2 studies), SRI users were associated with an increased risk of major bleeding: pooled OR was 1.45 (95% CI, 1.17–1.80; p = .001; low heterogeneity). For secondary outcomes, the use of SRI among individuals treated with antithrombotic therapy revealed a higher risk of gastrointestinal bleeding or any bleeding events, whereas only anticoagulant use was illustrated an increased risk of intracranial haemorrhage.Conclusions The use of SRI antidepressants among patients treated with antithrombotic therapy (either anticoagulant or antiplatelet) is associated with a higher risk of bleeding complications, suggesting that caution is warranted in co-prescription.PROSPERO Registration CRD42018083917KEY MESSAGESIn this meta-analysis of 32 non-randomized studies, SRI users were associated with the risk of bleeding complications compared to non-SRI users, with concurrent antithrombotic use (either anticoagulant or antiplatelet).The risk was consistently elevated across types of bleeding events (major bleeding, gastrointestinal bleeding, or any bleeding events), whereas only anticoagulant use was associated with intracranial haemorrhage.To promote the rational use of medicines, our findings suggest that the risk-benefit ratio must account for the clear efficacy of SRI against safety concerns in terms of bleeding risks.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.013 | 0.029 |
| Meta-epidemiology (narrow) | 0.003 | 0.002 |
| Meta-epidemiology (broad) | 0.020 | 0.037 |
| Bibliometrics | 0.008 | 0.009 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".