Castro Victor M, Gallagher Patience J, Clements Caitlin C, Murphy Shawn N, Gainer Vivian S, Fava Maurizio, Weilburg Jeffrey B, Churchill Susanne E, Kohane Isaac S, Iosifescu Dan V, Smoller Jordan W, Perlis Roy H
Partners Research Computing, Partners HealthCare System, Boston, MA.
BMJ Open. 2012 Mar 30;2(2):e000544. doi: 10.1136/bmjopen-2011-000544. Print 2012.
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.
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.
研究重度抑郁症（MDD）患者使用新型抗抑郁药与胃肠道（GI）及其他出血并发症风险之间的关联。
本研究采用事件使用者队列设计，比较每位患者在暴露风险期内血管/出血事件的发生率与抗抑郁药对5-羟色胺转运体的相对亲和力（低、中或高）之间的关联。
新英格兰医疗系统电子病历数据库。
从新英格兰医疗系统的310万患者中识别出36389名诊断为MDD且接受选择性5-羟色胺再摄取抑制剂、5-羟色胺-去甲肾上腺素再摄取抑制剂或其他新一代抗抑郁药单一疗法的患者。
出血或其他血管并发症的发生率，包括急性肝衰竭、急性肾衰竭、哮喘、乳腺癌和髋部骨折。
高亲和力组的21462名受试者中观察到601例胃肠道出血，而低亲和力组的14927名受试者中有333例（校正风险比：1.17，95%置信区间1.02至1.34）。同样，高亲和力组观察到776例中风，而低亲和力治疗组为434例（校正风险比：1.18，95%置信区间1.06至1.32）。未发现与先验阴性对照结局（包括急性肝衰竭、急性肾衰竭、哮喘、乳腺癌和髋部骨折）风险有显著关联。
使用对5-羟色胺转运体具有高亲和力的抗抑郁药可能会使胃肠道及其他出血并发症的风险略有升高。虽然必须考虑多种方法学局限性，但这些结果表明，对于此类并发症风险较高的患者，可能更倾向于使用5-羟色胺受体亲和力较低的抗抑郁药。
