Objectives The aim of this study was to determine the association between antidepressant (AD) classes, types and duration of use during pregnancy and the risk of gestational diabetes mellitus (GDM).
Design and setting A nested case–control study was conducted within the Quebec Pregnancy Cohort (QPC), a Canadian provincial database which includes data on all pregnancies and children in Quebec from January 1998 to December 2015.
Primary outcome measures Gestational diabetes mellitus.
Participants Cases of GDM were identified after week 20 of pregnancy and randomly matched 1:10 to controls on gestational age at index date (ie, calendar date of GDM) and year of pregnancy. AD exposure was assessed by filled prescriptions between the beginning of pregnancy (first day of last menstrual period) and index date. Conditional logistic regression models were used to estimate crude and adjusted odds ratios (aOR).
Results Among 20 905 cases and 209 050 matched controls, 9741 (4.2%) women were exposed to ADs. When adjusting for potential confounders, AD use was associated with an increased risk of GDM (aOR 1.19, 95% CI 1.08 to 1.30); venlafaxine (aOR 1.27, 95% CI 1.09 to 1.49) and amitriptyline (aOR 1.52, 95% CI 1.25 to 1.84) were also associated with an increased risk of GDM. Moreover, the risk of GDM was increased with longer duration of AD use, specifically for serotonin norepinephrine reuptake inhibitors, tricyclic ADs and combined use of two AD classes. No statistically significant association was observed for selective serotonin reuptake inhibitors.
Conclusion The findings suggest that ADs—and specifically venlafaxine and amitriptyline—were associated with an increased risk of GDM.
- gestational diabetes
- insulin resistance
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Contributors All authors participated in the study conception and design. AB acquired the data. MD and OS performed the analyses. MD wrote the manuscript and all authors participated in the interpretation of the results and critical revision of the manuscript. AB is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Funding This study was funded by the Canadian Institutes of Health Research (CIHR) – CAN-AIM grant; Fonds de la recherche du Québec-Santé (FRQ-S) - Réseau de recherche sur les médicaments RQRM-AbbVie. The funding body had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; or the decision to submit the manuscript for publication.
Competing interests AB has served as a consultant for plaintiffs in litigations involving antidepressants and birth defects. MD and OS report no conflicts of interest; no other financial relationships with any organisations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work.
Patient consent for publication Not required.
Ethics approval The study was approved by the Sainte-Justine’s Hospital Ethics Committee (#1740). The Quebec “Commission d’accès à l’information” authorized database linkages (#2976).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement No data are available. All data relevant to the study are included in the article or uploaded as supplementary information.
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