Antidepressants with high serotonin transporter affinity were associated with an increased risk of gastrointestinal bleeding compared to lower affinity agents (adjusted RR 1.17; 95% CI 1.02-1.34).
Cohort (n=36,389)
Does the use of antidepressants with high affinity for the serotonin transporter increase the risk of gastrointestinal bleed and stroke in individuals with major depressive disorder compared to lower affinity antidepressants?
Antidepressants with high affinity for the serotonin transporter are associated with a modestly elevated risk of gastrointestinal bleeding and stroke in patients with major depressive disorder.
Effect estimate: adjusted RR 1.17 (95% CI 1.02 to 1.34)
Absolute Event Rate: 2.8% vs 2.2%
OBJECTIVE: To examine the association between exposure to newer antidepressants and risk of gastrointestinal (GI) and other bleeding complications among individuals with major depressive disorder (MDD). DESIGN: This study uses an incident user cohort design to compare associations between incidence of vascular/bleeding events and the relative affinity (low, moderate or high) of the antidepressant for the serotonin transporter during an exposure risk period for each patient. SETTING: New England healthcare system electronic medical record database. PARTICIPANTS: 36 389 individuals with a diagnosis of MDD and monotherapy with a selective serotonin reuptake inhibitor, serotonin-norepinephrine reuptake inhibitor or other new-generation antidepressant were identified from among 3.1 million patients in a New England healthcare system. PRIMARY AND SECONDARY OUTCOME MEASURES: Rates of bleeding or other vascular complications, including acute liver failure, acute renal failure, asthma, breast cancer and hip fractures. RESULTS: 601 GI bleeds were observed in the 21 462 subjects in the high-affinity group versus 333 among the 14 927 subjects in the lower affinity group (adjusted RR: 1.17, 95% CI 1.02 to 1.34). Similarly, 776 strokes were observed in the high-affinity group versus 434 in the lower affinity treatment group (adjusted RR: 1.18, 95% CI 1.06 to 1.32). No significant association with risk for a priori negative control outcomes, including acute liver failure, acute renal failure, asthma, breast cancer and hip fractures, was identified. CONCLUSIONS: Use of antidepressants with high affinity for the serotonin transporter may confer modestly elevated risk for GI and other bleeding complications. While multiple methodologic limitations must be considered, these results suggest that antidepressants with lower serotonin receptor affinity may be preferred in patients at greater risk for such complications.
Castro et al. (Sun,) conducted a cohort in Major depressive disorder (n=36,389). Antidepressants with high affinity for the serotonin transporter vs. Antidepressants with lower affinity for the serotonin transporter was evaluated on Gastrointestinal bleeding (adjusted RR 1.17, 95% CI 1.02 to 1.34). Antidepressants with high serotonin transporter affinity were associated with an increased risk of gastrointestinal bleeding compared to lower affinity agents (adjusted RR 1.17; 95% CI 1.02-1.34).