While we have data to support the use of antidepressants, including the selective serotonin reuptake inhibitors (SSRIs) and the serotonin norepinephrine reuptake inhibitors (SNRIs), during pregnancy, most studies have focused on risk of congenital malformations, and we have considerably less information on longer term neurodevelopmental outcomes. 

A new study from Galbally and colleagues was designed to determine whether prenatal exposure to antidepressants affects motor development across two domains: sensorimotor development and visuospatial processing. Data were obtained from 195 women and children in three distinct groups: women with untreated depression during pregnancy, women treated with antidepressants, and a control group of women with no depression and no exposure to antidepressants.  The women were followed prospectively across pregnancy and the postpartum period, up until their children were 4 years old. Maternal depression was established at baseline with the Structured Clinical Interview for DSM-IV. Antidepressant exposure was self-reported across pregnancy and the postpartum period . Child sensorimotor and visuospatial processing were assessed at 4 years of age using four subtests from the NEPSY-II, a clinician-administered neuropsychological test validated for 3–16 years old.

Compared to children born to mothers with untreated depression, children with prenatal exposure to antidepressants demonstrated better performance on visuomotor precision completion time.  However, another measure of sensorimotor development, motor manual sequences, was worse in children exposed to antidepressants compared to unexposed children in the control group.  There were no differences between the three groups on tests of Block Construction, Design Copying and Visuomotor Total Errors and Combined subtests.  

One of the strengths of this study is that it attempted to control for confounding by indication. In contrast to previous studies which have used unexposed children born to healthy mothers with no history of psychiatric illness as a comparison group, this study included only women with a history of a mood or anxiety disorder.  While this strategy is likely to decrease potential confounding variables, it cannot completely eliminate confounding as it is likely that the women who elect to remain on antidepressant treatment during pregnancy differ from the women who elect to discontinue medication during pregnancy.  For example, women who decide to maintain treatment may have more chronic or severe depression or may be managing significant life stressors, factors which may ultimately affect the outcomes of their children independent of medication exposure. 

These findings demonstrate an inconsistent pattern of associations with prenatal antidepressant exposure across the neuropsychological subtests of sensorimotor and visuospatial processing. Worse performance on one subtest of visuospatial processing, block construction, was observed in antidepressant-exposed children who had poor neonatal adaptation and children exposed to higher doses of antidepressant. Whether this finding indicates an antidepressant-mediated effect or identifies an underlying neurodevelopmental vulnerability in children with poor neonatal adaptation deserves further exploration.  

Also of note, these findings suggest that untreated depression during pregnancy may influence motor development, in particular visuomotor development, and  that treatment may be protective.  However, these findings are not conclusive and require further exploration.

Putting it All Together

While this study suggests that some children exposed to antidepressants during pregnancy may have worse developmental outcomes, it is important to note that measuring the impact of prenatal antidepressant exposures on neurodevelopmental outcomes presents significant challenges, as outcomes may evolve over the course of many years and are influenced by a myriad of external factors including nutritional status, education level, quality of child care, and adverse childhood experiences.  

Over the last few decades we have seen some studies indicating worse long term outcomes in children; however, a recent study (Rommel et al, 2020) encompassing data from 18 studies revealed no impact of antidepressant exposure on neurodevelopmental outcomes.  When researchers controlled for potential confounding variables, they found no consistent associations between antidepressant exposure and neurodevelopmental outcomes, including cognition, behavior, IQ, motor development, speech, language, and scholastic outcomes.  

Given that we will never be able to conduct large randomized controlled trials in pregnant women, this is as good as it gets.  (There are several excellent articles from Chittaranjan Andrade on this topic, see below.)  While we cannot say (and will never be able to say) that there is zero risk associated with prenatal exposure to SSRI and SNRI antidepressants, we can say that the risk is low, when we take all of the studies into consideration, rather than focusing only on a single or the most recent study.  

Ruta Nonacs, MD PhD

Andrade C.  Genes as Unmeasured and Unknown Confounds in Studies of Neurodevelopmental Outcomes After Antidepressant Prescription During Pregnancy.  J Clin Psychiatry. 2020 May 26;81(3):20f13463. Free Article

Andrade C.  Offspring Outcomes in Studies of Antidepressant-Treated Pregnancies Depend on the Choice of Control Group.  J Clin Psychiatry. 2017 Mar;78(3):e294-e297. Free Article

Galbally M, Watson SJ, Spigset O, Boyce P, Oberlander TF, Lewis AJ.    Antidepressant exposure in pregnancy and child sensorimotor and visuospatial development.  J Psychiatr Res. 2020 Nov 25.

Rommel AS, Bergink V, Liu X, Munk-Olsen T, Molenaar NM.    Long-Term Effects of Intrauterine Exposure to Antidepressants on Physical, Neurodevelopmental, and Psychiatric Outcomes: A Systematic Review.  J Clin Psychiatry. 2020 May 12;81(3):19r12965.

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