Given the number of younger women using atypical or second-generation antipsychotic medications, there is an urgent need for more accurate data regarding the reproductive safety of these medications. One important question is whether these newer antipsychotic medications, which have been associated with an increased risk of metabolic syndrome and diabetes, may increase the risk of gestational diabetes when used during pregnancy.  The findings have been somewhat mixed, with some, but not all, studies suggesting an increased risk of gestational diabetes in women taking antipsychotics during pregnancy.  

Adding to this body of literature is a Swedish national register-based cohort study utilizing data from the Medical Birth Register and the Prescribed Drug Register encompassing 1,307,487 singleton births between July 2006 and December 2017. 

The cohort included pregnancies with exposures to first-generation antipsychotics (n = 728), high-risk metabolic second-generation antipsychotics (SGA) including olanzapine, clozapine and quetiapine (n = 1710), and other SGA (n = 541).  Outcomes in women treated with antipsychotics during pregnancy were compared to women who were not treated with antipsychotics and to women who used antipsychotics before and/or after but not during pregnancy.

Good News, Bad News

The crude risk ratio for gestational diabetes in women treated with high-risk metabolic SGAs during pregnancy was 2.2 (95% confidence interval [CI] 1.6-2.9) when compared to untreated pregnant women and 1.8 (95% CI 1.4-2.5) when compared to women treated before/after pregnancy. After adjustment for maternal factors including body mass index (BMI), the risk ratios were 1.8 (95% CI 1.3-2.4) and 1.6 (95% CI 1.2-2.1). 

Exposed infants had an increased risk of being large for gestational age; the adjusted risk ratios were 1.6 (95% CI 1.3-1.9) and 1.3 (95% CI 1.1-1.6), compared to no maternal antipsychotic use during pregnancy and maternal use before/after the pregnancy. Other antipsychotics were not associated with metabolic risks

Women treated with the other SGAs did not experience an increased risk of gestational diabetes or having a large for gestational age baby.  Most of the women taking other SGAs used aripiprazole (n = 334), risperidone (n = 191).

Clinical Guidelines

The findings of this study are consistent with previous studies.  Based on the findings we have, we can tell patients that there may be a small but statistically significant increase in risk of gestational diabetes associated with use of some second generation antipsychotic medications, specifically quetiapine, olanzapine, and clozapine.  However, we must also inform our patients that discontinuing treatment may place them at increased risk of illness relapse during pregnancy.  Furthermore, discontinuation of treatment may not diminish their risk of gestational diabetes, as other factors, including BMI may increase risk. 

In addition to reviewing the risks associated with taking antipsychotic medications during pregnancy, we must also focus on factors that may reduce the risk for gestational diabetes in women taking these medications, including adhering to a healthy diet, increasing exercise, and maintaining a healthy weight.  Ideally these interventions should be initiated prior to conception.

The National Pregnancy Registry for Atypical Antipsychotic Medications

Because the data available regarding the use of atypical antipsychotic medications in pregnancy is sparse, there is a great need to study these medications and their use in pregnancy.  The National Pregnancy Registry for Atypical Antipsychotics is currently enrolling pregnant patients taking atypical antipsychotic medications to learn more about reproductive safety of these medications.

Interested patients and clinicians may contact the registry by phone at 1-866-961-2388 or by email at for more information.

Ruta Nonacs, MD PhD

Heinonen E, Forsberg L, Nörby U, Wide K, Källén K.    Antipsychotic Use During Pregnancy and Risk for Gestational Diabetes: A National Register-Based Cohort Study in Sweden.  CNS Drugs. 2022 May;36(5):529-539.





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