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DOI: 10.1055/a-1957-6305
Selective Serotonin Reuptake Inhibitor Use and Risk of Major Bleeding during Treatment with Vitamin K Antagonists: Results of A Cohort Study
Funding/Acknowledgments This study was performed by S.B. within the master's degree program in Pharmacy of Leiden University. J.L.I.B. is funded by a ZonMw grant (848017007). This study was not funded.
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Abstract
Background Selective serotonin reuptake inhibitors (SSRIs) may increase the risk of major bleeding by decreasing platelet function or decreasing vitamin K antagonist (VKA) metabolism via cytochrome P450 (CYP) inhibition.
Aims To determine whether SSRIs are associated with major bleeding during VKA treatment and investigate the possible mechanisms.
Methods In this cohort study, information on SSRI use and bleeding complications was obtained from patient records of VKA initiators between 2006 and 2018 from two anticoagulation clinics. Conditional logistic regression and time-dependent Cox regression were used to estimate the effect of SSRIs on a high international normalized ratio (INR ≥ 5) within 2 months after SSRI initiation and on major bleeding during the entire period of SSRI use, respectively. SSRI use was stratified for (non-)CYP2C9 inhibitors.
Results A total of 58,918 patients were included, of whom 1,504 were SSRI users. SSRI initiation versus nonuse was associated with a 2.41-fold (95% confidence interval [CI]: 2.01–2.89) increased risk for a high INR, which was 3.14-fold (95% CI: 1.33–7.43) among CYP2C9-inhibiting SSRI users. The adjusted hazard ratio of major bleeding was 1.22 (95% CI: 0.99–1.50) in all SSRI users and 1.31 (95% CI: 0.62–2.72) in CYP2C9-inhibiting SSRI users compared with nonusers.
Conclusion SSRI use is associated with an increased risk of high INR and might be associated with major bleeding. The risk of a high INR was slightly more elevated for CYP2C9-inhibiting SSRI users, suggesting there might be a pharmacokinetic interaction (by CYP2C9 inhibition) next to a pharmacodynamic effect of SSRIs on platelet activation.
Keywords
SSRI - serotonin reuptake inhibitors - cohort study - drug interactions - hemorrhages - coumarinsAuthor Contributions
S.B. and J.L.I.B. contributed equally to this article. N.vR., S.B., J.L.I.B., and W.M.L. designed the research. M.J.H.A.K. and F.J.M.vdM. provided data from the anticoagulation clinics. S.B., J.L.I.B., and N.vR. analyzed the data. S.B. and J.L.I.B. wrote the first manuscript draft. J.L.I.B. and N.vR. revised the manuscript. All authors gave final approval of the version to be published.
Data Availability Statement
The deidentified data that support the findings of this study are available from the corresponding author upon reasonable request.
* These authors contributed equally to the manuscript.
Publikationsverlauf
Eingereicht: 01. Juni 2022
Angenommen: 29. September 2022
Accepted Manuscript online:
08. Oktober 2022
Artikel online veröffentlicht:
30. Dezember 2022
© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
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