Is Prenatal Antidepressant Exposure a Risk Factor for ADHD?

A systematic review of the literature found seven studies examining this question. Significantly, six were large cohort studies with a combined total of almost three million individuals. The other was a large case-control study with 7,874 participants.

The largest cohort study, with more than a million and a half children, found that prenatal antidepressant exposure increased the risk for ADHD. The adjusted odds ratio was 1.6 for any antidepressant and for selective serotonin reuptake inhibitors (SSRI). But in sibling comparison models, which better adjust for confounds shared by siblings (e.g., poverty, stress in the home), this study found no increased risk of ADHD.

The second largest cohort study, with over 875 thousand children, found a small adjusted risk of 1.2 for all antidepressants, with little variation by class of antidepressant. The fourth largest study, with over 140 thousand children, likewise found a small adjusted risk of 1.2, which barely achieved statistical significance (95% CI 1.0-1.4).

The third largest study, with over 190 thousand children, obtained an adjusted risk of 1.4 for all antidepressants. But it also pointed to a possible explanation for the small association found in this and other studies suggesting that the apparent association with antidepressant use was due to ADHD’s known genetic association with psychiatric conditions treated by antidepressants.

The fifth largest study, with more than 55 thousand children, similarly found an adjusted risk of 1.7 for SSRIs and an adjusted risk of 1.7 for unmedicated maternal psychiatric disorder. Again, the underlying psychiatric disorder appears to be confounding the effect of antidepressants.

The sixth largest study, with over 38 thousand children, found no evidence of any effect from SSRIs. Yet it found evidence of a large effect from bupropion, with an odds ratio of 3.6, and only one in 50 odds of obtaining such a result by chance (p = 0.02). However, it offered no comparison with untreated depression, and made no adjustments for potential confounders.

The case control study found an odds ratio of 2.3 for maternal use of any antidepressant, which dropped to a statistically nonsignificant 1.6 when adjusted for maternal psychiatric disorder (95% CI 0.66-3.71).

The review concludes, “The evidence available is inadequate to indicate any negative effects of a specific class of antidepressant on the risk of ADHD.”

REFERENCES
Faruk Uguz, “Maternal Antidepressant Use During Pregnancy and the Risk of Attention-Deficit/Hyperactivity Disorder in Children: A Systematic Review of the Current Literature,” Journal of Clinical Psychopharmacology, vol. 38, no. 3 (2018).