Antidepressant continuation in pregnancy and risk of gestational diabetes

Abstract

Purpose Previous studies observed modestly higher risk of gestational diabetes (GDM) associated with antidepressant use in pregnancy, potentially due to confounding by indication. We assessed the association of antidepressant continuation in pregnancy with GDM, as well as blood glucose levels, after accounting for confounding. Methods We conducted a retrospective cohort study of singleton live births from 2001 to 2014 to women enrolled in Kaiser Permanente Washington, an integrated health care delivery system, utilizing electronic health data and linked Washington State birth records. We required that women have ≥1 antidepressant prescription fills ≤6 months before pregnancy. Women with an antidepressant fill during pregnancy were categorized as “continuers” (n = 1634); those without a fill were “discontinuers” (n = 1211). We calculated relative risks (RRs) for GDM and mean differences in screening blood glucose levels using generalized estimating equations with inverse probability of treatment weighting to account for baseline characteristics, including mental health conditions and indicators of mental health severity. Results Compared with discontinuers, antidepressant continuers had comparable risk of GDM (RR: 1.10; 95% confidence interval [CI], 0.84‐1.44) and blood glucose levels (mean difference: 2.3 mg/dL; 95% CI, −1.5 to 6.1 mg/dL). We observed generally similar results for specific antidepressants, with the potential exceptions of risk of GDM associated with sertraline (RR: 1.30; 95% CI, 0.90‐1.88) and venlafaxine (RR: 1.52; 95% CI, 0.87‐2.68), but neither association was statistically significant. Conclusions Our study suggests that overall, women who continue antidepressants in pregnancy are not at increased risk for GDM or higher blood glucose, although further study may be warranted for sertraline and venlafaxine.

Association between antidepressant use in pregnancy and gestational diabetes mellitus: Results from the Norwegian Mother, Father and Child Cohort Study

“…Our findings are generally in line with those by Wartko et al, 17 where antidepressant-exposed women were compared to unexposed having an underlying indication for treatment with antidepressants in pregnancy, limiting the risk of indication bias. 15 Maternal depression in pregnancy has also been found to be associated with gestational diabetes, 16 for instance by triggering oxidative stress, chronic inflammation, and insulin resistance, 42 and thus disentangling the effect of medication exposure from that of the underlying maternal disease is crucial.…”

“…This comparison raises however concerns of confounding by indication. 15,16 Two additional studies 17,18 could not replicate these findings for the whole antidepressant group when using as comparator women with depression, albeit the GDM risk was elevated after use of venlafaxine, amitriptyline, or sertraline. 17,18 Although studies in non-pregnant subjects have shown that the risk of T2DM increases following the use of antidepressants with greater affinity to the H 1 receptor, 7,12 this research question has not been systematically studied in the context of GDM.…”

Antidepressant use during pregnancy and gestational diabetes: a systematic review

“…The characteristics and findings of the reviewed studies are summarized in Table 1. Three records were eligible for inclusion in the systematic review, consisting of 1 case-control (Dandjinou et al, 2019), 1 prospective cohort (Lupattelli et al, 2021), and 1 retrospective cohort study (Wartko et al, 2019). They were published from 2011 to 2020, with 1 from Canada, 2 from the United States of America, and 1 from Norway.…”

“…In total, 241,845 women were included in the studies of which 12,583 were exposed to antidepressants during pregnancy. None of the studies reported the antidepressant exposure trimester (Dandjinou et al, 2019;Lupattelli et al, 2021;Wartko et al, 2019).…”

“…The most common antidepressant drugs evaluated by the included studies were: selective serotonin reuptake inhibitors (SSRI), such as citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline (Dandjinou et al, 2019;Lupattelli et al, 2021;Wartko et al, 2019); venlafaxine (Dandjinou et al, 2019;Lupattelli et al, 2021;Wartko et al, 2019); and amitriptyline (Dandjinou et al, 2019;Lupattelli et al, 2021). Research, Society and Development, v. 11, n. 2, e53911226278, 2022 (CC BY 4. The definition of GDM was different between the studies: one study used the diagnosis codes of the 9th or 10th editions of the International Classification of Diseases (ICD) related to GDM or at least one filled prescription for an antidiabetic drug allowed during pregnancy, both after the 20 th week of pregnancy (Dandjinou et al, 2019); another one required at least two codes of ICD-9 648.8 from 16 weeks gestation to delivery or one code at the delivery hospitalization, and also assessed blood glucose levels (mg/dL) for GDM screening (Wartko et al, 2019); and one study adopted fasting plasma glucose level ≥7.0 mmoL/L or 2 hours after glucose challenge test glucose level ≥11.1 mmoL/L at gestational weeks 24-28 as diagnostic criteria of GDM (Lupattelli et al, 2021).…”