For decades, clinicians have wrestled with a thorny question: Do antidepressants taken during pregnancy increase the risk of neurodevelopmental disorders in children? Or do those risks stem from the underlying psychiatric illness itself?
A comprehensive new review in The Journal of Clinical Psychiatry suggests the answer is more complicated (and, at the same time, more reassuring) than simply risk estimates might suggest.
The review, led by psychiatrist Chittaranjan Andrade, MD, draws together findings from two separate meta-analyses and three large observational studies. All told, Andrade and his team looked at how gestational exposure to antidepressants relates to later diagnoses of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Together, the studies span millions of pregnancies worldwide.
Two Different Stories
The data paint an ominous portrait. The unadjusted analyses – which compare antidepressant-exposed pregnancies with the general population – kids exposed in utero showed up to a twofold increase in ASD and ADHD risk. These crude estimates, Andrade observed, reflect what clinicians might observe in real-world settings.
But a closer inspection tells a more nuanced story. Those same associations tend to break down once researchers account for confounding factors.
“When analyses are adjusted for maternal psychiatric illness, genetic vulnerability, and shared family environment, the apparent risks often shrink or disappear altogether,” Andrade writes.
In many fully adjusted models, antidepressant exposure no longer shows a statistically significant association with ASD or ADHD.
One of the strongest arguments against a direct drug effect stems from studies designed to address “confounding by indication.” When researchers compared antidepressant-exposed pregnancies with unexposed pregnancies in women who also had psychiatric disorders, the excess risk largely vanished.
Sibling-comparison studies backed this up. In analyses of discordant sibling pairs – where one child was exposed to antidepressants in utero and another wasn’t – neurodevelopmental outcomes followed family history rather than drug exposure. Whether a child developed ASD or ADHD tracked more closely with whether their sibling did.
A Matter of Timing
Timing also mattered in some unexpected ways. Several studies showed that antidepressant exposure outside pregnancy was linked to similar increases in ASD and ADHD risk. Paternal antidepressant use during pregnancy revealed the same pattern. Because neither scenario involves direct fetal exposure, these findings strongly implicate shared genetic, environmental, or health-related factors as opposed to the side effects of any medication.
A large U.S. cohort study of more than 3 million pregnancies illustrated this well. While crude analyses linked antidepressant exposure to a wide range of neurodevelopmental diagnoses, most associations vanished after adjustment or when researchers compared exposed pregnancies with those where antidepressants had been discontinued before conception.
Once again, sibling analyses uncovered no notable connections.
One Exception
The lone major exception came from a massive Taiwanese registry study, the first of its kind in an Asian population. That analysis found elevated ASD and ADHD risks across all exposure windows – even after adjustment.
But Andrade urges caution: the models controlled for very few confounders, and overlapping exposure definitions may have inflated associations.
Taken together, the evidence paints a surprisingly consistent picture. Antidepressant exposure during pregnancy is associated with higher observed rates of ASD and ADHD, but those associations are probably driven largely – if not completely – by maternal illness, parental genetics, and shared family environment.
That distinction matters. Untreated depression during pregnancy carries well-documented risks, including poor prenatal care, substance use, inflammation, and stress-related biological changes that may themselves affect fetal development. Avoiding medication doesn’t eliminate risk. It simply shifts its source.
“The available research cannot rule out a small causal role for antidepressants,” Andrade concludes. “But when risks remain after adjustment, they are modest – and must be weighed against the known harms of untreated maternal depression.”
For clinicians and patients navigating these decisions, context matters. Unadjusted risk estimates can help anticipate real-world outcomes and guide follow-up care. Adjusted analyses help clarify causality. Neither, on its own, should dictate treatment.
As Andrade points out, decisions about antidepressant use during pregnancy should come from shared, individualized discussions that are grounded in evidence, attentive to uncertainty, and mindful that mental health treatment is an important aspect of prenatal care.
