Reassuring Data on Atypical Antipsychotic Use in Pregnancy

Megan Brooks

October 07, 2015

Use of a second-generation antipsychotic during the first trimester of pregnancy does not "substantively" raise the risk for major malformations, new research shows.

"A major clinical implication of these findings is that for women with substantial psychiatric morbidity and good response to a second-generation antipsychotic, maintenance treatment with a second-generation antipsychotic during pregnancy may be the most prudent treatment option, similar to recommendations for continued treatment for pregnant women with other serious and chronic medical conditions, such as epilepsy," the authors conclude.

The study was published online October 6 in the American Journal of Psychiatry.

Low Absolute Risk

The findings stem from the National Pregnancy Registry for Atypical Antipsychotics, based at the Center for Women's Mental Health at Massachusetts General Hospital, in Boston. The registry was established to determine the risk for major malformations in infants exposed to second-generation antipsychotics during pregnancy relative to unexposed infants.

As of December 2014, 487 women were enrolled, including 353 who used second-generation antipsychotics and 134 who did not. The most commonly used second-generation antipsychotics in the exposed group were quetiapine (Seroquel, AstraZeneca Pharmaceuticals LP), aripiprazole (Abilify, Otsuka Pharmaceutical Company, Ltd), and olanzapine (multiple brands). Of the exposed group, 8.9% used more than one second-generation antipsychotic during the first trimester.

A total of 214 first-trimester exposed pregnancies and 89 unexposed comparison pregnancies were evaluated for the presence of a major malformation.

The researchers identified three major malformations among the 214 live births to women with first-trimester exposure to second-generation antipsychotics. One infant was exposed to aripiprazole, quetiapine, bupropion (multiple brands), and labetalol (multiple brands) and had a transposition of the great arteries. One infant with a ventricular septal defect had been exposed to ziprasidone (Geodon, Pfizer Inc), sertraline (Zoloft, Pfizer Inc), and lamotrigine (Lamictal, GlaxoSmithKline). The third infant had an imperforate hymen and had been exposed to aripiprazole, bupropion, and trihexyphenidyl (multiple brands).

In the control group of 89 unexposed women, one major malformation ― a midshaft hypospadias ― was confirmed.

The absolute risk for major malformations was 1.4% (95% confidence interval [CI], 0.29 - 4.04) for exposed infants and 1.1% (95% CI, 0.0 - 6.10) for unexposed infants. The odds ratio for major malformations comparing exposed infants with unexposed infants was 1.25 (95% CI, 0.13 - 12.19).

Reassuring, but Not Definitive

"These are some of the first systematically derived data with a control group of nonexposed women," first author Lee Cohen, MD, from Massachusetts General Hospital and Harvard Medical School in Boston, told Medscape Medical News.

"We have very sparse data on this class of medicines which is very widely used by reproductive age women for a spectrum of psychiatric disorders. And that's really been problematic because half of pregnancies in America are still unplanned. The field has really been starved for systematic data from the type of registry that we've done and modeled after, for example, the North American Antiepileptic Drug Pregnancy Registry," he said.

From these current data, Dr Cohen said, "it appears at least at first pass that unlike other psychiatric medications, such as sodium valproate, that as a class, at least second-generation antipsychotics do not appear to be major teratogens. But we need to grow this dataset, and we can only really do that with cooperation from clinicians in the community who refer patients to the registry."

"This study has several strengths that many previous studies did not, most notably, the very careful measurement of the medications that women were taking, as well as the careful measurement of malformations," Simone N. Vigod, MD, Department of Psychiatry, Women's College Research Institute and Women's College Hospital at the University of Toronto, Ontario, Canada, told Medscape Medical News.

"As the authors themselves point out, however, malformations are such a rare outcome that the study size wasn't large enough to make definite conclusions about the relationship between antipsychotic use in pregnancy and malformations. That said, the results ― no significantly increased risk of malformation with antipsychotic exposure in the first trimester of pregnancy ― are very closely aligned with those of our BMJ paper that was conducted with more women, in a different type of sample with a higher malformation rate overall, and using a different study design," said Dr Vigod, who was not involved in the new study.

She said the new data are "reassuring," adding, "but it will be more reassuring once the registry numbers are larger, especially because they are carefully collecting data on all of the information/variables/factors that they need to conduct a rigorous analysis."

The study was supported by AstraZeneca, Bristol-Myers Squibb, Ortho-McNeil-Janssen Pharmaceuticals, Pfizer, and Sunovion Pharmaceuticals. Dr Cohen has received research support for the National Pregnancy Registry for Atypical Antipsychotics from AstraZeneca, Bristol-Myers Squibb/Otsuka, Ortho-McNeil-Janssen Pharmaceuticals, Pfizer, and Sunovion Pharmaceuticals; he has received other research support from Abbott Pharmaceuticals, Bayer HealthCare Pharmaceuticals, Berlex Laboratories, Cephalon, Eli Lilly, Forest Laboratories, GlaxoSmithKline, and Janssen Pharmaceuticals. The original article includes a complete list of author disclosures.

Am J Psychiatry. Published online October 6, 2015. Abstract

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