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Atypical antipsychotics in first trimester may not increase risk for congenital defects

Analysis of a nationwide sample indicated exposure to atypical antipsychotics in the first trimester of pregnancy did not significantly increase risk for congenital malformations.

“Exposure to antipsychotics during pregnancy is increasingly common. Most newer atypical drugs are less likely to affect fertility than the older typical [antipsychotics]. This unimpaired fecundity combined with deinstitutionalization of patients with psychiatric illness and more widespread off-label use of these drugs have resulted in a doubling in the use of [antipsychotics] during pregnancy in the last decade,” Krista F. Huybrechts, MS, PhD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues wrote. “Since the first systematic review on this topic, clinicians continue to have very little information regarding the safety of these drugs for the developing fetus despite the growing use of atypical [antipsychotics].”

Krista F. Huybrechts

To assess associations between risk for congenital malformations and first-trimester exposure to antipsychotics, researchers evaluated a nationwide sample of 1,341,715 pregnant women enrolled in Medicaid with a live-born infant. Study participants had a mean age of 24.02 years.

Overall, 0.69% (n = 9,258) women filled at least one prescription for an atypical antipsychotic and 0.05% (n = 733) filled at least one prescription for an atypical antipsychotic during the first trimester.

Congenital malformations occurred in 32.7 (95% CI, 32.4-33) per 1,000 births unexposed to atypical antipsychotics, compared with 44.5 (95% CI, 40.5-48.9) births exposed to atypical antipsychotics and 38.2 (95% CI, 26.6-54.7) per 1,000 births exposed to typical antipsychotics.

Unadjusted analyses indicated an increased risk for overall malformations for atypical antipsychotics (RR = 1.36; 95% CI, 1.24-1.5) but not typical antipsychotics (RR = 1.17; 95% CI, 0.81-1.68).

Confounding adjustment reduced relative risk to 1.05 (95% CI, 0.96-1.16) for atypical antipsychotics and 0.9 (95% CI, 0.62-1.31) for typical antipsychotics.

There were similar findings for cardiac malformations.

Analysis of individual agents indicated a small increased risk for overall malformations (RR = 1.26; 95% CI, 1.02-1.56) and cardiac malformations (RR = 1.26; 95% CI, 0.88-1.81) with risperidone, independent of measured confounders.

“This landmark report, with the largest population of women exposed to [antipsychotics] published to date to our knowledge, demonstrates that exposure to [antipsychotics] (other than risperidone) does not significantly increase the risk for birth defects, which has been a major source of concern for women and prescribers,” Katherine L. Wisner, MD, MS, of Northwestern University Feinberg School of Medicine, Chicago, and colleagues wrote in an accompanying editorial. “This publication is timely, given the revision of the FDA Pregnancy and Lactation Labeling Final Rule...Nowhere in medicine is the need for personalization of care so crucial than during pregnancy: personalization of the treatment for serious mental illness with consideration of pregnancy physiology and the mother’s capacity to provide sustenance for the growing fetus and newborn.” – by Amanda Oldt

Disclosure: Huybrechts reports no relevant financial disclosures. Wisner reports that the Department of Psychiatry at Northwestern University received contractual fees for her consultation to Quinn Emanuel Urquhart & Sullivan, LLP (New York City), who represented Pfizer Pharmaceutical Company, in 2015. Please see the full study for a list of all authors’ relevant financial disclosures.