Role of antidepressant receptor antagonism and the development of gestational diabetes: a nested case-control study

Background How receptor binding profiles of antidepressants (ADs) influence the development of gestational diabetes mellitus (GDM) is infrequently examined. We aimed to investigate which receptor antagonism of antidepressants is associated with GDM development in pregnancy. Methods A nested case-control study (1994–2021) comprising 4014 singleton pregnancies was conducted using the pregnancy subset from the IADB.nl prescription database. GDM cases were pregnant women receiving GDM medication (insulin and or oral hypoglycemic agent) for the first time. Exposure was defined as the recent use of ADs (between six months before and week 16 of pregnancy), stratified by AD antagonistic properties on H1, 5-HT 2C , and M3 receptors. Crude and adjusted odds ratios of GDM were compared between recent users and past users using the logistic regression model. Results Antidepressant use with antagonistic properties on H1 receptors (aOR 2.25(95% CI 1.15–4.10)) and 5-HT 2C receptors (aOR 1.90 (95% CI 1.06–3.23)) were associated with increased odds of GDM. No association was found for AD antagonists on M3 receptors (aOR 1.35(0.82–2.27)). Conclusion The antagonism affinity of antidepressants on H1 receptor and 5-HT 2C receptor antagonism is more associated with the odds of GDM than on M3 receptor. This emphasizes the importance of prescribing antidepressants with weak or non-affinity on these two receptors to minimize the risk for GDM.