NEW YORK — Two antipsychotics, quetiapine (Seroquel, AstraZeneca) and olanzapine (Zyprexa, Lilly), have been linked to an increased risk for gestational diabetes in women who continue to take these drugs during pregnancy, new research shows.
Results of a large study of nondiabetic pregnant women who were enrolled in Medicaid and were taking an antipsychotic medication showed that quetiapine was associated with a 28% increased risk for gestational diabetes and that olanzapine was associated with a 61% increased risk.
“The best advice to clinicians at this point is to use these data as a starting point to initiate a conversation with their patients to let them know that there is a small to moderate increased risk of gestational diabetes with these two atypical antipsychotics and discuss whether it is worth considering a switch to a lower-risk medication at the start of pregnancy or to just continue on a stable regimen,” lead investigator Krista F. Huybrechts, PhD, told Medscape Medical News.
The findings were released at a press briefing here at the American Psychiatric Association (APA) 2018 annual meeting and were simultaneously published online in the American Journal of Psychiatry.
In the United States, an estimated 5% to 9% of women develop gestational diabetes. The disorder can lead to adverse pregnancy outcomes, including preeclampsia, cesarian delivery, neonatal hypoglycemia, and macrosomnia.
In addition, up to 50% of women with gestational diabetes develop type 2 diabetes in the decades following pregnancy. The risk for women with gestational diabetes is more than seven times greater than for those without the disorder.
In the general population, use of atypical antipsychotics is associated with rapid adverse metabolic changes, including altered triglyceride levels, weight gain, and diabetes.
In 2013, the US Food and Drug Administration mandated that manufacturers of atypical antipsychotics add warnings to their labels about the risks for hyperglycemia and diabetes.
Huybrechts said there is little information about antipsychotic drug treatment during pregnancy and that metabolic safety in relation to these medications is not well understood. Nevertheless, the investigators note that in the United States, an increasing number of women of reproductive age are being treated with antipsychotics.
To investigate the drug-specific risk for gestational diabetes in pregnant women, the investigators conducted a large, nationwide, observational study using Medicaid data for 1.5 million women. All of the patients had been undergoing treatment with one of five of the most commonly prescribed antipsychotic medications before the start of pregnancy.
The investigators compared the risk of developing gestational diabetes between those who continued antipsychotic treatment during pregnancy and their counterparts who discontinued treatment before the start of pregnancy.
The study cohort included nondiabetic pregnant women who had a live-born infant, were enrolled in Medicaid between 2000 and 2010, and who had received one or more prescriptions for an antipsychotic drug in the 3 months before pregnancy. The antipsychotics included aripiprazole (Abilify, Otsuka) (n = 1924), ziprasidone (Geodon, Pfizer) (n = 673), quetiapine (n = 4533), risperidone (multiple brands) (n = 1824), and olanzapine (n = 1425).
For each the antipsychotic drugs, women who had received the antipsychotic medication two or more times (“continuers”) were compared with women who had not been dispensed an antipsychotic medication in the first 20 weeks of pregnancy (“discontinuers”).
Results showed that, depending on the antipsychotic, the absolute risk for gestational diabetes among continuers ranged from 4.2% to 12%. Among discontinuers, the range was 3.8% to 4.7%.
However, only two of the five antipsychotics, olanzapine and quetiapine, were associated with an increased risk for gestational diabetes.
The adjusted relative risk was 0.82 (95% confidence interval [CI], 0.50 – 1.33) for aripiprazole, 0.76 (95% CI, 0.29 – 2.00) for ziprasidone, 1.28 (95% CI, 1.01 – 1.62) for quetiapine, 1.09 (95% CI, 0.70 – 1.70) for risperidone, and 1.61 (95% CI, 1.13 – 2.29) for olanzapine.
Huybrechts pointed out that although the “relative risks may sound impressive at 28% and 61%, the absolute risk it is still relatively small.”
The investigators note that their study had several strengths, including the fact that the study population was from a nationwide Medicaid program that finances almost 50% of all pregnancies in the United States, 80% of all antipsychotic prescriptions, and 36% of all costs associated with treatment of gestational diabetes.
However, the researchers acknowledge it also had limitations.
“It is important to consider alternative explanations for these findings,” Huybrechts said in a statement. “The main concern is potential factors not captured fully in the data, particularly obesity. However, we demonstrated that the imbalance in the obesity prevalence between those continuing treatment and those discontinuing would have to be very high to fully explain the increased risk. This seems unlikely, given that all women were treated before the start of pregnancy, and we accounted for a broad range of proxy variables,” she added.
Huybrechts said that after more data accumulate, she and her team will conduct a similar study to determine “how these current findings stand up.” In the meantime, the investigators are investigating the use of antipsychotics in pregnancy and their long-term impact on neurodevelopmental outcomes in offspring.
Commenting on the findings for Medscape Medical News, Michael Roy, executive editor of the American Journal of Psychiatry, said the study identifies an important risk factor for a medical condition that can have potentially serious consequences. It also provides clinicians with valuable guidance as to how to manage this risk.
“If one of your patients is entering a pregnancy period and is on an antipsychotic, this is a discussion that you can have. This study provides very important additive information that informs doctors and their patients,” he said.
Dr Park has served as a consultant for Optum. Dr Huybrechts has disclosed no relevant financial relationships. The disclosures of the remaining investigators are published in the study. Michael Roy has disclosed no relevant financial relationships.
American Psychiatric Association (APA) 2018. Presented May 7, 2018.
Am J Psychiatry. Published online May 7, 2018. Abstract