Large Study Finds Antipsychotic Use During First Trimester Does Not Increase Risk of Malformations
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Review of: Huybrechts KF, Hernández-Díaz S, Patorno E, et al. Antipsychotic use in pregnancy and the risk for congenital malformations. JAMA Psychiatry 2016;73(9):938–946.
Study Type: Retrospective cohort study
The use of antipsychotics during pregnancy has doubled over the past decade, and there have been ongoing concerns about the risk of congenital malformations. In the May issue of TCPR, we reviewed a pregnancy registry study showing no significant association between atypical antipsychotic use and major malformation (Cohen L et al, JAMA Psychiatry 2016;173:263–270). Another study was just published reinforcing those results by looking at a larger population.
Using national Medicaid data, researchers identified pregnant women who filled at least one antipsychotic prescription during their first trimester, the most critical time for fetal development. Out of over 1.3 million women between 12 and 55 years of age, 9,258 (0.69%) filled an atypical antipsychotic (eg, olanzapine) and 733 (0.05%) filled a typical antipsychotic (eg, haloperidol). The study outcomes were straightforward: risk of overall congenital and cardiac malformations identified within 90 days after delivery.
Prior to adjusting for potential study confounders (eg, psychiatric and physical comorbidities), the risk of congenital malformations was higher in women treated with atypicals (44.5 per 1,000 births) and typicals (38.2 per 1,000 live births) compared to those not treated (32.7 per 1,000 live births). However, the women prescribed antipsychotics were older, had higher rates of psychiatric and medical comorbidities, and took more psychiatric and teratogenic medications. Once the researchers controlled for these factors, there were no significant differences between the groups in the rates of overall congenital nor cardiac malformations.
One outlier, however, was risperidone. Risperidone had a 26% increased risk for causing both overall or cardiac malformations than no antipsychotic, but this increased risk was only statistically significant for overall malformations, not cardiac malformations.
A major strength of the article is the sample size, which is about 17 times the size of any previous study on the topic. It’s not clear what to make of the finding that risperidone may be the only teratogenic antipsychotic. More data should help clarify this issue.
Explain to patients that the baseline rate of malformations in all women (even those who are not taking any medication) is around 2%–4%, and that large studies have shown that antipsychotics are unlikely to increase the risk. For the time being, risperidone should be at the bottom of your list if an antipsychotic must be prescribed during pregnancy.