Meta-analysis: No causal link between antidepressant use in pregnancy and neurodevelopmental disorders

A large-scale systematic review and meta-analysis published in The Lancet Psychiatry has found that common antidepressant use during pregnancy is not causally linked to an increased risk of neurodevelopmental disorders, including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD).¹ The study, which synthesized data from nearly 25 million pregnancies, indicates that the small increase in risk identified in previous research could be driven by underlying parental mental health conditions and genetic factors rather than the medication itself.²

Researchers searched multiple medical databases through May 14, 2025, identifying 37 studies that involved 648,626 antidepressant-exposed and 24,967,806 unexposed pregnancies.¹ This new meta-analysis was designed to provide a more rigorous assessment of confounding by treatment indication, addressing limitations in studies conducted nearly a decade ago that were hindered by small sample sizes.²

Initial findings from the data suggested that prenatal antidepressant use was associated with a 35% increased risk of ADHD (RR 1.35; 95% CI, 1.24–1.47; P < 0.0001) and a 69% increased risk of ASD (RR 1.69; 95% CI, 1.24–2.30; P < 0.0001).¹ However, when the analysis accounted for factors such as maternal mental disorders, familial influences, and genetic predispositions, these associations became non-significant.¹

Evidence for a non-biological link was further supported by the use of paternal antidepressant use as a negative control. Antidepressant use by the father around the time of conception or during the pregnancy was associated with a 46% increase in the risk of ADHD and a 28% increase in the risk of autism.² Because paternal use during pregnancy cannot biologically impact fetal development in the same manner as maternal exposure, researchers concluded that shared environments or genetic influences are the primary drivers.¹

“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.² “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.”²

Specific medications and dosage

The study found no statistically significant difference in ASD risk between high-dose and low-dose antidepressant exposure.¹ When restricting the analysis to mothers with diagnosed mental health disorders, no significant associations were found for specific selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs).¹

Only certain tricyclic antidepressants, specifically amitriptyline and nortriptyline, remained associated with increased risks after minimizing confounding by indication. Amitriptyline was associated with an increased risk of ADHD (RR 1.74; 95% CI, 1.00–3.03) and the combination of amitriptyline and nortriptyline was associated with ASD (RR 2.02; 95% CI, 1.32–3.10).¹ However, the authors noted that these medications are often prescribed for treatment-resistant or more complex mental health conditions, which may influence the remaining association.²

Holistic support for parental mental health

The researchers emphasized that untreated moderate-to-severe depression carries its own significant risks for both the parent and child.

Joe Kwun-Nam Chan of the University of Hong Kong highlighted the impact of the home environment, noting that ongoing family stress and differences in caregiving behaviors may influence neurodevelopment.²

“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 Dr. Chan.² The authors concluded that the current evidence supports continuing antidepressant treatment for pregnant women with moderate-to-severe depression, as optimizing parental mental health is essential for long-term offspring outcomes.¹

Limitations of the study included:

• Data on important factors such as socioeconomic status, lifestyle risk factors, and low birth weight were lacking in the studies.
• A small number of studies looking at antidepressant use in specific trimesters or at exact doses and dose changes.
• Women who are prescribed antidepressants tend to have more severe depression than those who are not, so some bias may remain even after controlling for mental health status.

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. The Lancet Psychiatry. 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. The Lancet. News release. Published May 14, 2026. Accessed May 15, 2026. https://www.eurekalert.org/news-releases/1128154?