de Abajo Francisco J, García-Rodríguez Luis A
Division of Pharmacoepidemiology and Pharmacovigilance, Spanish Agency for Medicines and Healthcare Products, Campezo 1, Madrid 28022, Spain.
Arch Gen Psychiatry. 2008 Jul;65(7):795-803. doi: 10.1001/archpsyc.65.7.795.
Selective serotonin reuptake inhibitors have been reported to increase the risk of upper gastrointestinal tract bleeding. The wide use of these drugs makes such potential risk a public health concern, and identification of factors that may increase or minimize such risk is necessary.
To test the association of selective serotonin reuptake inhibitors and venlafaxine hydrochloride therapy with upper gastrointestinal tract bleeding, to identify subgroups of patients at particularly increased risk, and to explore whether acid-suppressing agents may be effective in minimizing risk.
Nested case-control study.
General practice database from the United Kingdom.
One thousand three hundred twenty-one patients with upper gastrointestinal tract bleeding referred to a consultant or hospital and 10 000 control subjects matched for age, sex, and calendar year of the index date. Main Outcome Measure Risk of bleeding associated with selective serotonin reuptake inhibitors and effect of acid-suppressing agents.
The percentage of current users of selective serotonin reuptake inhibitors (5.3%) or venlafaxine (1.1%) among case subjects was significantly higher than in matched control subjects (3.0% and 0.3%; adjusted odds ratio [OR], 1.6; 95% confidence interval [CI], 1.2-2.1, and OR, 2.9; 95% CI, 1.5-5.6, respectively). An interaction with nonsteroidal anti-inflammatory drugs (OR, 4.8; 95% CI, 2.8-8.3) was observed, in particular among those not using acid-suppressing agents (OR, 9.1; 95% CI, 4.8-17.3) compared with users of these drugs (OR, 1.3; 95% CI, 0.5-3.3). In addition, an interaction with antiplatelet drugs in nonusers of acid-suppressing agents was suggested (OR, 4.7; 95% CI, 2.6-8.3) compared with users of these drugs (OR, 0.8; 95% CI, 0.3-2.5).
Antidepressants with a relevant blockade action on the serotonin reuptake mechanism increase the risk of upper gastrointestinal tract bleeding. The increased risk may be of particular relevance when these drugs are associated with nonsteroidal anti-inflammatory drugs. Our study findings also provide evidence that use of acid-suppressing agents limits such increased risk.
据报道，选择性5-羟色胺再摄取抑制剂会增加上消化道出血的风险。这些药物的广泛使用使这种潜在风险成为一个公共卫生问题，因此有必要确定可能增加或降低这种风险的因素。
检验选择性5-羟色胺再摄取抑制剂和盐酸文拉法辛治疗与上消化道出血之间的关联，确定风险特别增加的患者亚组，并探讨抑酸剂是否可能有效降低风险。
巢式病例对照研究。
来自英国的全科医疗数据库。
1321例因上消化道出血转诊至专科医生或医院的患者以及10000名年龄、性别和索引日期的日历年相匹配的对照者。主要结局指标：与选择性5-羟色胺再摄取抑制剂相关的出血风险以及抑酸剂的作用。
病例组中当前使用选择性5-羟色胺再摄取抑制剂（5.3%）或文拉法辛（1.1%）的比例显著高于匹配的对照组（3.0%和0.3%；校正比值比[OR]分别为1.6；95%置信区间[CI]为1.2 - 2.1，以及OR为2.9；95% CI为1.5 - 5.6）。观察到与非甾体抗炎药存在相互作用（OR为4.8；95% CI为2.8 - 8.3），特别是在未使用抑酸剂的患者中（OR为9.1；95% CI为4.8 - 17.3），而使用这些药物的患者中（OR为1.3；95% CI为0.5 - 3.3）。此外，提示在未使用抑酸剂的患者中与抗血小板药物存在相互作用（OR为4.7；95% CI为2.6 - 8.3），而使用这些药物的患者中（OR为0.8；95% CI为0.3 - 2.5）。
对5-羟色胺再摄取机制具有相关阻断作用的抗抑郁药会增加上消化道出血的风险。当这些药物与非甾体抗炎药联用时，增加的风险可能尤为相关。我们的研究结果还提供了证据表明使用抑酸剂可限制这种增加的风险。
