Selective serotonin reuptake inhibitors and increased bleeding risk: Are we missing something?

PURPOSE: Selective serotonin reuptake inhibitors (SSRIs) are first line agents to treat clinical depression. Although these medications exhibit a favorable safety profile, there are multiple case reports, registries, and uncontrolled studies suggesting that use of SSRIs might be associated in the increased risk of bleeding events. There is also emerging evidence that these side effects of SSRIs are due to blockade of serotonin reuptake in platelets and subsequent platelet dysfunction. METHODS: The analysis of evidence linking SSRIs with bleeding episodes to define the prevalence, specific clinical characteristics, and estimated risk when SSRIs are used in combination with antiplatelet agents or/and anticoagulants. RESULTS: There are over 120 MEDLINE-cited peer-reviewed research papers and more than 50 000 Web pages devoted to SSRI-related bleeding events. CONCLUSION: Independently of the brand, use of SSRIs is indeed associated with increased bleeding risk. Although such complications are rare, their frequency is growing, and physicians should be aware of SSRI-induced hemorrhages, especially in patients with hereditary platelet defects, and those treated with antiplatelet agents. Prospective studies are urgently needed to determine whether SSRIs will yield additional bleeding risks when used long term concomitantly with aspirin or clopidogrel.