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).
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.
New England healthcare system electronic medical record database.
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.
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.
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.
Previous reports have suggested that antidepressant use may contribute to dysfunction in platelet aggregation and increased risk for bleeding outcomes.
The authors hypothesised that antidepressants with higher affinity for the serotonin transporter would exhibit greater risk for these outcomes than those with lesser affinity.
Use of antidepressants with higher affinity for the serotonin transporter was associated with modest but statistically significant increase in risk for gastrointestinal bleed and stroke.
Electronic medical record-based pharmacovigilance systems provide an opportunity to examine treatment risk in general clinical populations, in a more systematic fashion than traditional postmarketing surveillance.
Strengths and limitations of this study
A strength of this report, in addition to cohort size and generalisability, is the restriction to individuals with major depressive disorder, minimising risk for confounding by indication.
A key limitation is the absence of blood antidepressant levels or data on adherence, which might lead us to underestimate strength of effect.