In the current issue of the Journal of Clinical Psychiatry, Rommel and colleagues present a systematic review examining the long-term effects of prenatal exposure to antidepressants on physical, neurodevelopmental, and psychiatric outcomes in children 4 years of age or older. 

The researchers identified original research articles in the medical literature which included information on the long-term outcomes of prenatal antidepressant exposure. After screening and removal of duplicate studies, a total of 34 studies were included in the analysis.  Methodologies varied considerably across the studies.  About 40% of the studies were prospective; the remainder were retrospective studies relying on large medical databases. Sample sizes ranged from 36 to over 1.5 million.  Because of the significant heterogeneity of the studies, the authors were not able to perform a formal meta-analysis of the data.  The quality of the evidence for the examined outcomes was rated as low to very low (per GRADE guidelines).

PHYSICAL OUTCOMES:  Five studies investigated physical outcomes: asthma, cancer, body mass index (BMI), and epilepsy.  There was no association between exposure and outcomes, except for conflicting results for BMI. 

NEURODEVELOPMENTAL OUTCOMES:  Eighteen studies examined an array of neurodevelopmental outcomes, including cognition, behavior, IQ, motor development, speech, language, and scholastic outcomes.   Although some studies observed worse outcomes in children with prenatal exposure to antidepressants, they found no consistent associations with antidepressant exposure after taking potential confounders into account. 

PSYCHIATRIC OUTCOMES: Eleven studies investigated psychiatric outcomes. After adjusting for confounders, prenatal antidepressant exposure was associated with affective disorders but not with childhood psychiatric outcomes, including autism spectrum disorders or attention-deficit/hyperactivity disorder.

Although previous studies have reported associations between in utero exposure to antidepressants and physical, neurodevelopmental, and psychiatric outcomes, this analysis indicates that these associations seem to reflect the underlying maternal psychiatric disorder, as opposed to prenatal exposure to a particular medication.   When analysis controlled for confounding by indication, prenatal exposure to antidepressants was associated only with offspring BMI (conflicting results) and affective disorders.

When we look at outcomes in children with prenatal exposure to antidepressants, it is difficult to account for all of  the many factors that may impact outcomes, including adherence to the treatment regimen, medication dosage and duration, quality of prenatal care, symptom burden during pregnancy, and exposure to tobacco and other substances.  Most importantly, it is very difficult to factor in the genetic and environmental factors associated with maternal psychiatric illness.

Thus, the most we can conclude from this sort of study is that prenatal antidepressant exposure may be associated with a particular outcome; we cannot draw a causative line between antidepressant exposure and a particular outcome.

You can find the full (and free) text of our commentary on this study HERE

Ruta Nonacs, MD PhD

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.

Nonacs RM, Cohen LS. Challenges in Determining Outcomes of Prenatal Exposure to Antidepressants.  J Clin Psychiatry. 2020 May 12.  Free Article 

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