New study shows link between antidepressant use and gestational diabetes mellitus

By Dr. Liji Thomas, MDOct 2 2019

A new study compared pregnant women who were on antidepressants with those who were not, looking for cases of gestational diabetes mellitus (GDM), or pregnancy-associated diabetes mellitus. The researchers found that the use of antidepressants, specifically venlafaxine and amitryptiline, was associated with a higher risk of developing GDM. When used for longer periods, several drug categories were linked to an increased risk of GDM. This is the first study to look at categories as well as individual antidepressant usage during pregnancy and their association with GDM. The long 17-year follow-up period rules out recall bias and allowed a prospective design. However, some factors that could have contributed to the risk of GDM such as body mass and smoking could not be accounted for.

Jaengpeng | Shutterstock

About GDM and antidepressants

GDM is a condition arising during pregnancy when the woman’s body is not able to metabolize carbohydrates normally. It is diagnosed between 24-28 weeks of pregnancy and affects both maternal and infant health. GDM incidence is seen in 1-20% of women in various parts of the world and is going up as mothers in many countries become overweight. The problems incurred with GDM include a too-large baby size, difficult labor, increased Cesarean deliveries, and a higher rate of obesity and diabetes in the child later on in life. These women are also at a higher risk of cardiovascular disease and type 2 diabetes over time.

Antidepressants (AD) are used in pregnancy to suppress neurotransmitters like serotonin, norepinephrine and dopamine that carry signals between different parts of the brain. Some of these drugs also produce unwanted effects such as weight gain. Probably different AD categories act differently to cause metabolic disruptions such as resistance to the physiological action of insulin, and the resulting block in the normal regulation of glucose in the body.

However, women in the reproductive age group are prone to both depression and overweight. These have even been reported to be associated in some studies, though the direction of association remains unclear. For instance, depressed women may eat more, leading to them becoming overweight. On the other hand, low physical activity could cause other hormonal and nervous system dysfunctions leading to a higher tendency to develop depression. However, women with depression before pregnancy do not show any significant difference in weight gain during pregnancy. Nonetheless, the presence of depression and GDM may complicate any efforts to find the relationship between AD use and GDM as depression by itself can cause weight gain.

The study

The failure to adjust for this factor can mean the study becomes worthless as a means of assessing the presence or strength of such a link. The current study, covering pregnancies under the Quebec Public Prescription Drug Insurance Plan, from 1998 to 2015, looked for GDM in women carrying single babies only. Women with a previous history of GDM, or type 1/type 2 diabetes mellitus, and those with a high body mass index (BMI) were not included in the study as their risk is already different.

All women who had GDM after 24 weeks up to 31 weeks were identified, as were all who had filled at least one AD prescription after the start of pregnancy. There were ten controls for each identified case of GDM. AD exposure by class led to the formation of six groups, namely:

1. Selective serotonin reuptake inhibitors (SSRIs)
2. Serotonin norepinephrine reuptake inhibitors (SNRIs)
3. Tricyclic ADs (TCAs)
4. Others (this category includes all the other ADs used)
5. Exposure to at least two classes of AD
6. No AD exposure during the relevant period

The period of use was classified as:

• Short (≤ 90 days) exposure to AD
• Medium (91-179 days)
• Long duration (≥180 days)

The findings

The incidence of GDM was 8.8%, among which 5.5% had been exposed to ADs during pregnancy. The incidence of GDM increased with age at pregnancy as well. This risk was unchanged despite accounting for differences in age, social and economic age, and underlying conditions.

The risk associated with AD use overall was small, about 19% higher than in those without a history of AD use. However, SNRIs, TCAs and the use of more than two ADs from different categories was associated with an increased risk of 27%, 47%, and 38% respectively. No significant link was found for SSRIs, however.

Among the individual drugs, amitriptyline was associated with a 52% higher risk, compared to 27% and 31% for venlafaxine and the use of two or more different-category drugs.

The risk also increased with the duration of use, from 15% higher with the shortest duration to almost double this risk, at 29% increased risk, for the longest duration.

The theory

The researchers postulate that the association between AD use and GDM could be due to the high blood glucose levels linked to several ADs, especially since many of them act on serotonin which is involved in glucose homeostasis. AD use causes insulin resistance which could lead to GDM. However, SSRIs could cause lowering of the blood glucose whereas the others can increase it by their action on different types of receptors. Moreover, weight gain is associated with depression and the development of GDM.

Adverse outcomes associated with AD use during pregnancy including GDM should be weighed against the consequences of non-medicated depression, especially for women with severe depression. Further studies are needed to replicate our findings [which] raise awareness of the risk of GDM with the use of specific ADs during pregnancy.”