Duloxetine for Depression and the Incidence of Hepatic Events in Adults
Duloxetine for Depression and the Incidence of Hepatic Events in Adults
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DOI：
10.1097/jcp.0b013e31822347d9
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发表时间：
2011-08
影响因子：
2.9
通讯作者：
F. Xue;I. Strombom;B. Turnbull;Shao Zhu;J. Seeger
中科院分区：
文献类型：
--
作者：
F. Xue;I. Strombom;B. Turnbull;Shao Zhu;J. Seeger
在临床试验和自发报告中，肝酶水平升高和肝损伤与度洛西汀的使用有关，但度洛西汀与广泛的肝脏结果的关联尚未经过观察评估。这项基于 Ingenix 研究数据集市的 2004 年至 2006 年间成人度洛西汀起始药物队列研究涉及 6 个匹配的比较队列，包括 4 个抗抑郁起始药物组（文拉法辛、奈法唑酮、选择性血清素再摄取抑制剂和三环类抗抑郁药）、抑郁但未经治疗的患者和没有抑郁症的个体。对队列进行肝脏事件随访，比例风险回归将度洛西汀起始剂与对照队列进行比较，而泊松回归则比较度洛西汀使用类别以解释随访期间治疗的变化。 21,457 名度洛西汀起始者和对照队列中约 64,000 人年产生了 51 项肝脏结局事件。文拉法辛起始剂（发生率比 [IRR] = 0.34；95% 置信区间 [CI]，0.12-0.95）和无抑郁队列（IRR = 0.30；95% CI，0.10-0.93）的合并肝脏事件发生率低于度洛西汀起始剂，而度洛西汀组在肝脏事件方面没有观察到其他差异与选择性血清素再摄取抑制剂、三环类抗抑郁药和未经治疗的抑郁症患者相关的引发剂。在治疗分析中，相对于不使用，当前（IRR = 4.30；95% CI，1.45-12.81）和近期（IRR = 5.93；95% CI，1.63-21.55）使用度洛西汀与不太严重的肝脏结果发生率较高相关，但与肝脏相关的死亡和潜在的急性肝衰竭无关。尽管度洛西汀似乎不会增加肝脏相关死亡或急性肝衰竭的风险，但它可能与某些不太严重的肝脏事件的风险增加有关。
Elevated hepatic enzyme levels and hepatic injuries have been associated with duloxetine use in clinical trials and spontaneous reports, but the association of duloxetine with a broad spectrum of hepatic outcomes has not been assessed observationally. This cohort study of adult duloxetine initiators between 2004 and 2006 based on the Ingenix Research Data Mart involved 6 matched comparator cohorts, including 4 antidepressant initiator groups (venlafaxine, nefazodone, selective serotonin reuptake inhibitors, and tricyclic antidepressants), depressed but untreated patients, and individuals without depression. The cohorts were followed up for hepatic events, and proportional hazards regression compared duloxetine initiators with comparator cohorts, whereas Poisson regression compared duloxetine usage categories to account for changed therapy during follow-up. Approximately 64,000 person-years among 21,457 duloxetine initiators and comparator cohorts yielded 51 hepatic outcome events. Venlafaxine initiators (incidence rate ratio [IRR] = 0.34; 95% confidence interval [CI], 0.12-0.95) and the cohort without depression (IRR = 0.30; 95% CI, 0.10-0.93) had lower incidences of combined hepatic events than duloxetine initiators, whereas no other differences in hepatic events were observed for duloxetine initiators relative to selective serotonin reuptake inhibitors, tricyclic antidepressants, and untreated depressed patients. In as-treated analyses, relative to nonuse, current (IRR = 4.30; 95% CI, 1.45-12.81) and recent (IRR = 5.93; 95% CI, 1.63-21.55) duloxetine use was associated with greater incidence of less severe hepatic outcomes but not hepatic-related death and potential acute hepatic failure. Although duloxetine does not seem to increase the risk of hepatic-related death or acute hepatic failure, it may be associated with an increased risk of certain less severe hepatic events.