Ankarfeldt Mikkel Zöllner, Petersen Janne, Andersen Jon Trærup, Fernandes Maria Fernanda Scantamburlo, Li Hu, Motsko Stephen Paul, Fast Thomas, Jimenez-Solem Espen
Copenhagen Phase IV Unit (Phase4CPH), Department of Clinical Pharmacology and Center for Clinical Research and Prevention, Copenhagen University Hospital Bispebjerg and Frederiksberg, Copenhagen, Denmark.
Center for Clinical Research and Prevention, Frederiksberg Hospital, Hovedvejen Indgang 5, Nordre Fasanvej 57, 2000, Frederiksberg, Denmark.
Drugs Real World Outcomes. 2021 Sep;8(3):289-299. doi: 10.1007/s40801-021-00252-9. Epub 2021 May 18.
Depression and antidepressant treatment are widespread among women of childbearing age.
This study evaluates the association between duloxetine exposure during pregnancy and spontaneous and elective abortions.
The nationwide, observational study based on register data from Denmark included women with a recorded pregnancy in the birth register or an abortion in the patient register between 2004 and 2016. Duloxetine-exposed women were compared with (1) duloxetine non-exposed, (2) selective serotonin reuptake inhibitor (SSRI)-exposed, (3) venlafaxine-exposed, and (4) women discontinuing duloxetine before pregnancy. Exposure status was based on records of redeemed prescriptions. Cox regression with adjustments and propensity score matching was applied.
The data from 1,019,957 pregnancies were used, including 1,212 pregnancies exposed to duloxetine. Duloxetine-exposed women had an increased hazard ratio (HR) for spontaneous abortions compared with SSRI-exposed women: propensity score matched HR 1.25 [95% confidence interval (CI), 1.00-1.57]. No increased hazard was observed for duloxetine-exposed women compared with duloxetine non-exposed: 1.08 (95% CI 0.89-1.31); venlafaxine-exposed: 1.08 (95% CI 0.82-1.41); and duloxetine discontinuers: 0.99 (95% CI 0.76-1.30). An increased HR of elective abortions was observed in duloxetine-exposed women compared to duloxetine non-exposed: 1.41 (95% CI 1.25-1.59); SSRI-exposed: 1.32 (95% CI 1.15-1.51); and duloxetine discontinuers: 1.46 (95% CI 1.23-1.75), but not to venlafaxine-exposed women: 1.09 (95% CI 0.93-1.27).
There was no increased risk of spontaneous or elective abortion associated with exposure to duloxetine. The increase risk observed for women exposed to duloxetine in comparison with SSRI-exposed for spontaneous and in comparison with all groups (except venlafaxine-exposed) for elective abortion suggested confounding.
抑郁症及抗抑郁药治疗在育龄女性中广泛存在。
本研究评估孕期暴露于度洛西汀与自然流产和人工流产之间的关联。
这项基于丹麦登记数据的全国性观察性研究纳入了2004年至2016年间在出生登记册中有妊娠记录或在患者登记册中有流产记录的女性。将暴露于度洛西汀的女性与（1）未暴露于度洛西汀的女性、（2）暴露于选择性5-羟色胺再摄取抑制剂（SSRI）的女性、（3）暴露于文拉法辛的女性以及（4）妊娠前停用度洛西汀的女性进行比较。暴露状态基于已兑现处方的记录。应用了经过调整的Cox回归和倾向得分匹配法。
使用了来自1,019,957例妊娠的数据，其中包括1,212例暴露于度洛西汀的妊娠。与暴露于SSRI的女性相比，暴露于度洛西汀的女性自然流产的风险比（HR）升高：倾向得分匹配后的HR为1.25 [95%置信区间（CI），1.00 - 1.57]。与未暴露于度洛西汀的女性相比，暴露于度洛西汀的女性未观察到风险增加：HR为1.08（95% CI 0.89 - 1.31）；与暴露于文拉法辛的女性相比：HR为1.08（95% CI 0.82 - 1.41）；与妊娠前停用度洛西汀的女性相比：HR为0.99（95% CI 0.76 - 1.30）。与未暴露于度洛西汀的女性相比，暴露于度洛西汀的女性人工流产的HR升高：HR为1.41（95% CI 1.25 - 1.59）；与暴露于SSRI的女性相比：HR为1.32（95% CI 1.15 - 1.51）；与妊娠前停用度洛西汀的女性相比：HR为1.46（95% CI 1.23 - 1.75），但与暴露于文拉法辛的女性相比未升高：HR为1.09（95% CI 0.93 - 1.27）。
暴露于度洛西汀与自然流产或人工流产风险增加无关。与暴露于SSRI的女性相比，暴露于度洛西汀的女性自然流产风险增加，与所有组（文拉法辛暴露组除外）相比人工流产风险增加，提示存在混杂因素。
