Incident user cohort study of risk for gastrointestinal bleed and stroke in individuals with major depressive disorder treated with antidepressants.
Incident user cohort study of risk for gastrointestinal bleed and stroke in individuals with major depressive disorder treated with antidepressants.
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DOI：
10.1136/bmjopen-2011-000544
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发表时间：
2012
期刊：
影响因子：
2.9
通讯作者：
Perlis RH
中科院分区：
文献类型：
--
作者：
Castro VM;Gallagher PJ;Clements CC;Murphy SN;Gainer VS;Fava M;Weilburg JB;Churchill SE;Kohane IS;Iosifescu DV;Smoller JW;Perlis RH
研究重度抑郁症（MDD）患者暴露于新型抗抑郁药与胃肠道（GI）和其他出血并发症风险之间的关系。本研究采用事件使用者队列设计，比较每例患者在暴露风险期内血管/出血事件发生率与抗抑郁药对5-羟色胺转运蛋白的相对亲和力（低、中或高）之间的相关性。新英格兰医疗保健系统电子病历数据库。从新英格兰医疗保健系统的310万例患者中确定了36 389例诊断为MDD并接受选择性5-羟色胺再摄取抑制剂、降钙素-去甲肾上腺素再摄取抑制剂或其他新一代抗抑郁药单药治疗的患者。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21，462名受试者中观察到601例胃肠道出血，而低亲和力组的14，927名受试者中观察到333例胃肠道出血（调整后的RR：1.17，95%CI 1.02至1.34）。 同样，高亲和力治疗组中观察到776例卒中，而低亲和力治疗组中观察到434例卒中（校正RR：1.18，95% CI 1.06 - 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）风险的显著相关性。使用对5-羟色胺转运蛋白具有高亲和力的抗抑郁药可能会适度增加胃肠道和其他出血并发症的风险。虽然必须考虑多种方法的局限性，这些结果表明，抗抑郁药与较低的血清素受体亲和力可能是首选患者在更大的风险，这样的并发症。以前的报告表明，抗抑郁药的使用可能会导致血小板聚集功能障碍和出血风险增加。作者假设，与血清素转运蛋白亲和力较高的抗抑郁药比亲和力较低的抗抑郁药对这些结果的风险更大。使用对5-羟色胺转运体有较高亲和力的抗抑郁药与胃肠道出血和中风风险的适度但有统计学意义的增加相关。基于电子病历的药物警戒系统提供了一个机会，以比传统上市后监测更系统的方式检查一般临床人群的治疗风险。除了队列规模和普遍性之外，本报告的优势在于仅限于重度抑郁症患者，最大限度地降低了适应症混淆的风险。一个关键的限制是缺乏血液抗抑郁药水平或依从性数据，这可能导致我们低估效果的强度。
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. 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. 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.
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DOI：
10.1136/bmj.d4551
发表时间：
2011-08-02
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Coupland C;Dhiman P;Morriss R;Arthur A;Barton G;Hippisley-Cox J
通讯作者：
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影响因子：
2.9
作者：
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Mamdani, MM
DOI：
10.1124/jpet.108.142307
发表时间：
2008-12-01
影响因子：
3.5
作者：
Martin, Renee S.;Henningsen, Robert A.;Milla, Marcos E.
通讯作者：
Milla, Marcos E.
DOI：
10.1136/jamia.2009.000893
发表时间：
2010-03-01
影响因子：
6.4
作者：
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通讯作者：
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影响因子：
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作者：
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