Risk of mortality with concomitant use of tamoxifen and selective serotonin reuptake inhibitors: multi-database cohort study
Risk of mortality with concomitant use of tamoxifen and selective serotonin reuptake inhibitors: multi-database cohort study
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DOI：
10.1136/bmj.i5014
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发表时间：
2016-09-30
影响因子：
105.7
通讯作者：
Gagne, Joshua J.
中科院分区：
文献类型：
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作者：
Donneyong, Macarius M.;Bykov, Katsiaryna;Gagne, Joshua J.
目的比较合并使用他莫昔芬和选择性5-羟色胺再摄取抑制剂（SSRI）（细胞色素P450 2D 6酶（CYP 2D 6）的强效抑制剂）的女性之间的死亡率差异与他莫昔芬和其他SSRIs的比较。基于人群的队列研究。设置五个美国数据库，涵盖1995年至2013年参加私人和公共健康保险计划的个人。参与者开始服用他莫昔芬在队列1中，女性在他莫昔芬治疗期间开始服用SSRI。在队列2中，妇女已经服用SSRI时，他们开始服用tamoxifen.Main结局measuresAll原因死亡率在每个队列的妇女服用SSRIs是有效的抑制剂CYP 2D 6（帕罗西汀，氟西汀）与其他SSRIs。倾向评分用于以可变比率方式匹配暴露组。分别测量每个组群的结果，并通过随机效应荟萃分析从两个组群的考克斯回归模型计算组合风险比。在组群1和2中分别有6067和8465名他莫昔芬的新使用者。平均年龄为55岁。队列1和队列2在中位随访2.2（四分位距0.9-4.5）年和2.0（0.8-3.9）年期间分别发生了991例和1014例死亡。队列1和队列2中，强效抑制剂（发生率58.6/1000人年）与其他SSRI（发生率57.9/1000人年）相比的死亡汇总风险比为0.96（95%置信区间0.88 - 1.06）。结果是一致的敏感性analysis. CONCLUSION伴随使用他莫昔芬和有效的CYP 2D 6抑制SSRIs与其他SSRIs与死亡风险增加无关。
OBJECTIVETo compare differences in mortality between women concomitantly treated with tamoxifen and selective serotonin reuptake inhibitors (SSRIs) that are potent inhibitors of the cytochrome-P450 2D6 enzyme (CYP2D6) versus tamoxifen and other SSRIs.DESIGNPopulation based cohort study.SETTINGFive US databases covering individuals enrolled in private and public health insurance programs from 1995 to 2013.PARTICIPANTSTwo cohorts of women who started taking tamoxifen. In cohort 1, women started taking an SSRI during tamoxifen treatment. In cohort 2, women were already taking an SSRI when they started taking tamoxifen.MAIN OUTCOME MEASURESAll cause mortality in each cohort in women taking SSRIs that are potent inhibitors of CYP2D6 (paroxetine, fluoxetine) versus other SSRIs. Propensity scores were used to match exposure groups in a variable ratio fashion. results were measured separately for each cohort and combined hazard ratios calculated from Cox regression models across the two cohorts with random effects meta-analysis.RESULTSThere were 6067 and 8465 new users of tamoxifen in cohorts 1 and 2, respectively. Mean age was 55. A total of 991 and 1014 deaths occurred in cohorts 1 and 2 during a median follow-up of 2.2 (interquartile range 0.9-4.5) and 2.0 (0.8-3.9) years, respectively. The pooled hazard ratio for death for potent inhibitors (rate 58.6/1000 person years) compared with other SSRIs (rate 57.9/1000 person years) across cohorts 1 and 2 was 0.96 (95% confidence interval 0.88 to 1.06). Results were consistent across sensitivity analyses.CONCLUSIONConcomitant use of tamoxifen and potent CYP2D6 inhibiting SSRIs versus other SSRIs was not associated with an increased risk of death.