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NSAIDs and Selective Serotonin Reuptake Inhibitors (SSRIs) increase the risk of bleeding. For NSAIDs, the risk is related to the inhibition of COX-1, which has a protective effect on the gastric mucosa, as well as to the inhibition of platelet aggregation for non-COX-selective NSAIDs. For SSRIs, the risk is related to the inhibition of serotonin reuptake by platelets.
Combining an SSRI with agents that promote bleeding, such as NSAIDs, but also acetylsalicylic acid and antithrombotic agents, increases the risk of bleeding (see also Directory 10.3.1.1.). A recent article in La Revue Prescrire1 is devoted to a recently published systematic review with meta-analysis2: this analysis confirms the increased risk of gastrointestinal bleeding when SSRIs and NSAIDs are combined.
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11 observational studies compared simultaneous intake of an SSRI + an NSAID compared to an SSRI alone. A meta-analysis of these studies shows an increase in bleeding risk with the combination compared to the SSRI alone, with an odds ratio of 2.1 (95% CI of 1.5 to 3).
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10 observational studies compared simultaneous intake of an SSRI + an NSAID compared to an NSAID alone. A meta-analysis of these studies shows an increase in bleeding risk with the combination compared to the NSAID alone, with an odds ratio of 1.5 (95% CI of 1.2 to 1.8).
It was not possible to differentiate the risk of bleeding depending on the NSAID or SSRI used. The authors of the meta-analysis state that further studies are needed to determine whether the risk of bleeding differs between different NSAIDs and SSRIs.
In practice: If possible, NSAIDs are avoided during treatment with an SSRI, especially in patients at high risk of gastrointestinal bleeding. If the combination is necessary, caution is advised (duration of the combination as short as possible and dosage as low as possible) and it is important to inform the patient about this risk, especially because some NSAIDs are available without a medical prescription. Depending on the elimination half-life of the SSRI (which may be several days, as in the case of fluoxetine), NSAIDs are also best avoided for some time after the SSRI has been stopped.
Specialities
NSAIDs: see Directory 9.1.1.
SSRIs: see Directory 10.3.1.1.
Specific sources
1 Antidépresseurs IRS + AINS : saignements. La Revue Prescrire 2023 ; 43:747
2 Hossein Haghbin et al. Risk of Gastrointestinal Bleeding with Concurrent Use of NSAID and SSRI: A Systematic Review and Network Meta‑Analysis. Digestive Diseases and Sciences I2023 ; 68:1975–1982 https://doi.org/10.1007/s10620-022-07788-y
