Second-Generation Antipsychotics Do Not Raise Risk of Major Malformations

May 1, 2016

Bret A. Moore, PsyD, ABPP Board-Certified Clinical Psychologist, San Antonio, TX Dr. Moore has disclosed that he has no relevant financial or other interests in any commercial companies pertaining to this educational activity.

Subject: (Cohen L et al, JAMA Psychiatry 2016;173:263–270)

Short Description: Second-generation antipsychotics (SGA) are used for a variety of psychiatric conditions, but even though they’ve been around for 20 years, we know little about what impact they have on the developing fetus. These medications are widely considered to be relatively safe during pregnancy, but this assumption is based on scant evidence. In this paper, researchers tapped into the Massachusetts General Hospital (MGH) National Pregnancy Registry of Atypical Antipsychotics and reported some reassuring results.

Over a six-year period, 214 women between the ages of 18 and 45 who had been exposed to an SGA during their first trimester were enrolled. These women were compared to a control group of 89 women who had a psychiatric illness during pregnancy, and who were treated with psychiatric medications but who were not exposed to an SGA. The women were interviewed at three time points: time of enrollment in the registry, 7 months pregnant, and 3 months post-partum. Medical records were also reviewed. There were a few differences between the two groups: notably 24% of SGA-exposed women smoked, compared to only 10% of women in the control group.

SGA-exposed women were also twice as likely to also be exposed to an anticonvulsant (40% vs 19%). Interestingly, the majority of women (about 60%) in both groups had a primary diagnosis of bipolar disorder, and only a small proportion (about 2%) carried a primary diagnosis of schizophrenia.

In the exposed group, the risk of developing a serious malformation was 1.4% (3 of 214 births); in the unexposed group, the risk was 1.1% (1 of 89 births). The researchers concluded that SGAs are unlikely to be teratogenic, but that the study sample is too small to reach a definite conclusion. They point out that the MGH registry continues to collect data on this issue, and that as the sample size increases, they will likely be able to estimate the risk with more precision.

TCPR’s Take: SGAs probably do not increase the risk of serious fetal malformations, which is reassuring. It’s important to note that the study did not report on less serious effects, such as higher birthweight, neonatal withdrawal, or even gestational diabetes. Prior studies of SGAs have shown possible associations with these outcomes, so counseling pregnant women about these meds remains complicated.

General Psychiatry