Moderate
Established
Descripción
Ibuprofen combined with SSRIs markedly increases the risk of GI bleeding through synergistic impairment of platelet function and gastric mucosal defense.
Mecanismo
SSRIs deplete serotonin in platelets, reducing aggregation; ibuprofen inhibits COX-1–mediated thromboxane A2 synthesis and damages gastric mucosa. Both effects converge to heighten GI hemorrhage risk.
Relevancia clínica
Epidemiological data show a 15-fold increase in upper GI bleed risk with NSAID + SSRI, compared with a 3-fold increase for each alone.
Manejo clínico
Avoid combination if possible; if co-administration is necessary, add a PPI and use the lowest NSAID dose for the shortest duration.