Second, from the pharmacological point of view, common coadministration, such as with clopidogrel, should be taken into consideration. SSRIs elevated the risk of abnormal upper gastrointestinal bleeding through two mechanisms: antiplatelet activity and increased gastric acidity. But the interaction of SSRI and cytochrome P450 enzyme should also be considered. Clopidogrel is commonly prescribed with aspirin for cardioprotection, and it needs bioactivation mediated by CYP2C19 to achieve the antiplatelet efficacy. Coadministration of CYP2C19-inhibiting drugs reduces the efficacy of clopidogrel. CYP2C is inhibited by fluoxetine, sertraline, and fluvoxamine. With concomitant clopidogrel, aspirin, and CYP2C19-inhibiting SSRI use, the interpretation that aspirin is associated with less upper gastrointestinal bleeding than NSAIDs becomes unclear. Large doses of aspirin inhibit platelet aggregation and vascular synthesis of the prostaglandin I2 (PGI2). PGI2 inhibits platelet aggregation and thus low-dose aspirin is more known for increasing upper gastrointestinal bleeding than large-dose aspirin (4). When considering NSAID- and aspirin-related gastrointestinal bleeding, clinicians should take aspirin dosage and other combined medication into account.