Meta-analysis finds no causal association between antidepressant use in pregnancy and neurodevelopmental disorders

A systematic review and meta-analysis published in The Lancet Psychiatry found no evidence of a causal association between antidepressant use during pregnancy and neurodevelopmental disorders such as autism spectrum disorder (ASD) or attention-deficit/hyperactivity disorder (ADHD) in children. The investigators reported that previously observed increases in risk appeared to be largely explained by parental mental health conditions, shared familial factors, and genetic predisposition rather than medication exposure itself.^1,2

The analysis included data from 37 studies comprising 648,626 antidepressant-exposed pregnancies and 24,967,806 unexposed pregnancies. Researchers searched multiple medical databases through May 14, 2025, to evaluate the relationship between prenatal antidepressant exposure and offspring neurodevelopmental outcomes while more rigorously accounting for confounding by indication.

Initial pooled analyses demonstrated associations between prenatal antidepressant exposure and increased risks of ADHD (RR, 1.35; 95% CI, 1.24-1.47) and ASD (RR, 1.69; 95% CI, 1.24-2.30). However, after adjustment for maternal psychiatric illness, familial influences, and genetic liability, the associations were no longer statistically significant.

Researchers also used paternal antidepressant exposure as a negative control analysis. Antidepressant use by fathers around conception or during pregnancy was associated with a 46% increased risk of ADHD and a 28% increased risk of ASD in offspring. Because paternal antidepressant exposure during pregnancy would not directly affect fetal neurodevelopment biologically, the findings supported the role of shared environmental and genetic factors in explaining the observed associations.

“We know many parents-to-be worry about the potential impact of taking medication during pregnancy; our study provides reassuring evidence that commonly used antidepressants do not increase the risk of neurodevelopmental disorders such as autism and ADHD in children," said study author Wing-Chung Chang of the University of Hong Kong. “While all medications carry risks, so too does stopping antidepressants during pregnancy due to an increased risk of relapse. Therefore, for women with moderate-severe depression, doctors and patients must carefully weigh the potential risks and benefits of continuing antidepressant treatment during pregnancy against the potential harms of untreated depression.”

"Although our study found a small increase in the risk of autism and ADHD in the children of women who had used antidepressants during pregnancy, it also found that this risk disappeared when we accounted for other factors,” Chang continued. “The increased risk was also seen in the children of fathers who took antidepressants and of mothers with antidepressant use before, but not during, pregnancy. Together, this suggests that it is not the antidepressants themselves causing an increased risk in autism and ADHD but it is more likely to be due to other factors, including genetic predisposition to conditions such as ADHD, autism, and mental health conditions.”

Did specific antidepressants affect autism or ADHD risk?

The investigators reported no statistically significant differences in ASD risk between high-dose and low-dose antidepressant exposure. Additionally, analyses restricted to mothers with diagnosed mental health disorders found no significant associations between specific selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) and ASD or ADHD risk.

Only certain tricyclic antidepressants remained associated with elevated risks after efforts to minimize confounding. Amitriptyline exposure was associated with increased ADHD risk (RR, 1.74; 95% CI, 1.00-3.03), while combined exposure to amitriptyline and nortriptyline was associated with ASD risk (RR, 2.02; 95% CI, 1.32-3.10). Investigators noted these medications are often prescribed for more treatment-resistant or complex psychiatric conditions, which may contribute to residual confounding.

Why does parental mental health remain important during pregnancy?

The authors emphasized that untreated moderate-to-severe depression during pregnancy also carries clinically important risks for both the pregnant patient and child.

Joe Kwun-Nam Chan of the University of Hong Kong highlighted the potential contribution of family stressors and caregiving differences to child neurodevelopment.

“There is a need to ensure both parents have access to support and treatment for mental health conditions; for their own sake and to support neurodevelopment of their child," said Chan.

The authors concluded that the findings support continuation of antidepressant treatment during pregnancy for patients with moderate-to-severe depression when clinically indicated, emphasizing that optimizing parental mental health remains important for long-term offspring outcomes.

Investigators noted several study limitations, including incomplete data on socioeconomic status, lifestyle factors, and low birth weight across included studies. They also cited limited data regarding trimester-specific exposure and antidepressant dose changes during pregnancy. Residual confounding related to depression severity may also remain despite adjustment for psychiatric diagnoses.

References

1. Chan J, Zhong A, Lam J, et al. Maternal and paternal antidepressant use before and during pregnancy and offspring risk of neurodevelopmental disorders: a systematic review and meta-analysis. Lancet Psychiatry. Published online May 14, 2026. doi:10.1016/S2215-0366(26)00089-1

2. The Lancet Psychiatry: No clear link between common antidepressant use in pregnancy and autism or ADHD in children, finds most comprehensive study to date. News release. The Lancet. Published May 14, 2026. Accessed May 15, 2026. https://www.eurekalert.org/news-releases/1128154?