Clinician Article

Concomitant Use of Selective Serotonin Reuptake Inhibitors and Oral Anticoagulants and Risk of Major Bleeding: A Systematic Review and Meta-analysis.

  • Rahman AA
  • He N
  • Rej S
  • Platt RW
  • Renoux C
Thromb Haemost. 2023 Jan;123(1):54-63. doi: 10.1055/a-1932-8976. Epub 2022 Aug 29. (Review)
PMID: 36037829
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  • Psychiatry
    Relevance - 6/7
    Newsworthiness - 6/7
  • Family Medicine (FM)/General Practice (GP)
    Relevance - 6/7
    Newsworthiness - 5/7
  • General Internal Medicine-Primary Care(US)
    Relevance - 6/7
    Newsworthiness - 5/7
  • Internal Medicine
    Relevance - 6/7
    Newsworthiness - 5/7
  • Hemostasis and Thrombosis
    Relevance - 5/7
    Newsworthiness - 6/7


BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs), the most prescribed antidepressants, are associated with a modestly increased risk of major bleeding. However, in patients treated with both SSRIs and oral anticoagulants (OACs), the risk of major bleeding may be substantial.

OBJECTIVE: To assess the risk of major bleeding associated with concomitant use of SSRIs and OACs, compared with OAC use alone.

METHODS: We searched MEDLINE, Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials (from inception to December 1, 2021) for clinical trials and observational studies assessing the association between concomitant use of SSRIs and OACs and the risk of major bleeding. Given sufficient homogeneity of studies, we conducted a random-effects meta-analysis to estimate a pooled hazard ratio (HR) of major bleeding associated with concomitant use of SSRIs and OACs, compared with OAC use alone.

RESULTS: The review comprised 14 studies, including 7 cohort and 7 nested case-control studies. Following assessment of clinical and methodological heterogeneity, eight studies with a total of 98,070 patients were eligible for the meta-analysis. The pooled HR of major bleeding associated with concomitant use of SSRIs and OACs was 1.35 (95% confidence interval [CI]: 1.14-1.58). In secondary analyses, the pooled HR for concomitant use of SSRIs and direct OACs was 1.47 (95% CI: 1.03-2.10).

CONCLUSIONS: Concomitant use of SSRIs and OACs was associated with an increased risk of major bleeding. Overall, our findings suggest that physicians may need to tailor treatment according to individual patient risk factors for bleeding when prescribing SSRIs to patients using OACs.

Clinical Comments

Internal Medicine

A well-conducted systematic review and meta-analysis. The statistics are robust, and the sensitivity analysis as well as the leave-one-out analysis are well appreciated in this kind of study. Bear in mind, however, that a hazard ratio is a relative measure, and that the 35% increased risk for major bleeding associated with the concomitant use of SSRIs and OACs is, hence, relative, not absolute. Relative indicators, such as HRs, should always be accompanied by absolute measures to guarantee a better interpretation of treatment or the exposition risk, in this case a better interpretation of the absolute increase (in numbers) of bleeding in patients exposed to both SSRIs and OAC. It is troublesome if such numbers are not provided because we have to read the individual studies in the meta-analysis to get an appreciation for the absolute numbers.

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