Duloxetine Exposure During Pregnancy and the Risk of Spontaneous and Elective Abortion: A Danish Nationwide Observational Study

Mikkel Zöllner Ankarfeldt; Janne Petersen; Jon Trærup Andersen; Maria Fernanda Scantamburlo Fernandes; Hu Li; Stephen Paul Motsko; Thomas Fast; Espen Jimenez-Solem

doi:10.1007/s40801-021-00252-9

Duloxetine Exposure During Pregnancy and the Risk of Spontaneous and Elective Abortion: A Danish Nationwide Observational Study

Drugs Real World Outcomes. 2021 Sep;8(3):289-299. doi: 10.1007/s40801-021-00252-9. Epub 2021 May 18.

Authors

Mikkel Zöllner Ankarfeldt^{1

2}, Janne Petersen^{3

4}, Jon Trærup Andersen^{5

6}, Maria Fernanda Scantamburlo Fernandes⁷, Hu Li⁷, Stephen Paul Motsko⁷, Thomas Fast⁸, Espen Jimenez-Solem^{3

5

6}

Affiliations

¹ Copenhagen Phase IV Unit (Phase4CPH), Department of Clinical Pharmacology and Center for Clinical Research and Prevention, Copenhagen University Hospital Bispebjerg and Frederiksberg, Copenhagen, Denmark. [email protected].
² Center for Clinical Research and Prevention, Frederiksberg Hospital, Hovedvejen Indgang 5, Nordre Fasanvej 57, 2000, Frederiksberg, Denmark. [email protected].
³ Copenhagen Phase IV Unit (Phase4CPH), Department of Clinical Pharmacology and Center for Clinical Research and Prevention, Copenhagen University Hospital Bispebjerg and Frederiksberg, Copenhagen, Denmark.
⁴ Section for Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
⁵ Department of Clinical Pharmacology, Copenhagen University Hospital Bispebjerg and Frederiksberg, Copenhagen, Denmark.
⁶ Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁷ Eli Lilly and Company, Indianapolis, IN, USA.
⁸ Institute of Applied Economics and Health Research, Copenhagen, Denmark.

Abstract

Background: Depression and antidepressant treatment are widespread among women of childbearing age.

Objective: This study evaluates the association between duloxetine exposure during pregnancy and spontaneous and elective abortions.

Patients and methods: 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.

Results: 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).

Conclusion: 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.