Studies conducted in non-pregnant subjects have demonstrated an 21%–31% increased risk of type II diabetes (T2DM) in individuals taking antidepressant medications.  Pregnancy predisposes women to insulin resistance, with gestational diabetes emerging in about 2% to 10% of pregnancies in the United States.  Thus, it is important that we have a better understanding of the impact of antidepressants on glucose metabolism during pregnancy.

 A recent study, analyzing data from the Norwegian Mother, Father and Child Cohort Study conducted in 1999-2008 and the national Medical Birth Registry, measured the prevalence of gestational diabetes (GDM) in women taking antidepressants during pregnancy.  Because previous studies in non-pregnant subjects have demonstrated that the risk of T2DM was greater in those using antidepressants with greater affinity for the histamine H1 receptor.  The researchers grouped exposures to antidepressants according to affinity for the H1 receptor.  

Antidepressants with low affinity include selective serotonin reuptake inhibitors (SSRIs: sertraline, fluoxetine, paroxetine, citalopram, escitalopram, fluvoxamine); serotonin-noradrenaline reuptake inhibitors (SNRIs: venlafaxine and duloxetine); and clomipramine.  (Bupropion has low affinity for the H1 receptor, but no women in this cohort were treated with bupropion.)

Antidepressants with low affinity include amitriptyline, trimipramine, maprotiline, nortriptyline, mianserin, mirtazapine, doxepin, and nefazodone.

The study included 6647 pregnancies within women with depressive/anxiety disorders during and/or 6 months prior to pregnancy. Pregnancies exposed in early to mid gestation to antidepressants having low H1 affinity (n = 814) or high H1 affinity (n = 77) were compared to non-medicated women with a history of anxiety or depression (n = 5756). 

Overall, 84 (1.3%) of the pregnancies were affected by GDM. Relative to non-medicated pregnancies, the risk of GDM was slightly lower in pregnancies exposed to antidepressants with low H1 receptor affinity (1.3% vs 1.1%), but was elevated in those exposed to antidepressants with higher H1 receptor affinity (3.9%).

The Bottom Line

This study indicates that exposure to most antidepressants — including SSRIs, SNRIs, and clomipramine — during early to mid-pregnancy is not associated with increased risk for gestational diabetes.  On the other hand, it appears that the use of antidepressants with high H1 receptor affinity may be associated with an elevated risk for GDM.  However, this study could not calculate a relative risk due to the low number of exposures (n=77) to antidepressants with high H1 affinity.  

One of the strengths of this study is that it used a comparator group of women with histories of depression or anxiety in order to decrease risk of confounding by indication. The findings of this study contradict  two prior studies in pregnant women showing a modest association between antidepressant exposure and GDM; however, these studies used unexposed healthy pregnant women as comparators.   Depression during pregnancy, absent any exposure to medication, has also been found to be associated with gestational diabetes, possibly by triggering oxidative stress, chronic inflammation, and insulin resistance.

The information from the current study will be very reassuring to women with concerns regarding the reproductive safety of antidepressants during pregnancy.  Although future studies are needed to better quantify the risk for GDM in women taking tricyclic antidepressants or mirtazapine during pregnancy, the vast majority of women who take antidepressants during pregnancy use SSRIs or SNRIs, which were not associated with an increased risk for GDM.

 

Ruta Nonacs, MD PhD 

 

Lupattelli A, Barone-Adesi F, Nordeng H.  Association between antidepressant use in pregnancy and gestational diabetes mellitus: Results from the Norwegian Mother, Father and Child Cohort Study.  Pharmacoepidemiol Drug Saf. 2021 Nov 24. 

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