Reproductive Safety of Second-Generation Antipsychotics


Do atypical antipsychotics increase the risk of major malformations among exposed infants?



Second-generation antipsychotics are used as primary or adjunctive therapy in many major psychiatric disorders, including psychotic, mood, and anxiety disorders. Available reproductive safety data suggest that these agents are not major teratogens.1 In 2008 the National Pregnancy Registry for Atypical Antipsychotics, based at Massachusetts General Hospital in Boston, was established to obtain reproductive safety data regarding fetal exposure to these agents.

Cohen and colleagues2 recently reported on current results from this registry. As of December 2014, 487 women aged 18 to 45 years were enrolled, including 353 who used second-generation antipsychotics and 134 women with significant psychiatric histories who were not exposed to these agents. Women were followed up prospectively during pregnancy and the postpartum period, and obstetric and pediatric records were obtained for 82% of participants.

Thus far, 303 women have completed the study and were included in the analyses. The mean age of participants was 32; 64% were college educated, 78% were married, and 91% were Caucasian. Among the 303 women, there were 214 live births with first-trimester exposure to second-generation antipsychotics and 89 live births in the control (unexposed) groups.

In the exposed group, major malformations were confirmed in 1.4% of live births (n = 3), versus 1.1% in the control group (n = 1), resulting in a non-significant odds ratio of 1.25 (95% confidence interval, 0.13 - 12.19). In sensitivity analyses, adjustment for a number of potential confounding or moderating factors results in an adjusted odds ratio closer to 1.00 (ie, closer to the null hypothesis that second-generation antipsychotic exposure is not associated with an increased odds of major malformations). First-trimester cigarette smoking and anticonvulsant use were notable exceptions.

The bottom line
The authors concluded that it would be unlikely for first-trimester second-generation antipsychotic exposure to raise the risk of major malformations more than 10-fold above what has been observed in control groups using other psychotropic medications or in the general population. At present, it is reasonable to conclude that these agents are not major teratogens. Future results will inform (and hopefully provide reassurance for) both clinicians and women regarding decisions about second-generation antipsychotic use during pregnancy.


Dr Miller is Associate Professor in the Department of Psychiatry at Georgia Regents University in Augusta, GA, and Schizophrenia Section Editor for Psychiatric Times. He reports no conflicts of interest concerning the subject matter of this article.


1. Ennis ZN, Damkier P. Pregnancy exposure to olanzapine, quetiapine, risperidone, aripiprazole and risk of congenital malformations. A systematic review. Basic Clin Pharmacol Toxicol. 2015;116:315-320.
2. Cohen LS, Viguera AC, McInerney KA, et al. Reproductive safety of second-generation antipsychotics: current data from the Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics. Am J Psychiatry. 2016;173:263-270.

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