Apr. 11 2016

Gestational Exposure to SSRIs Associated with Adolescent Offspring Depression

Researchers at Columbia University’s Mailman School of Public Health and Columbia University Medical Center with collaborators from the University of Turku and Helsinki in Finland report that medical use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy was associated with increased rates of offspring depression by early adolescence. This is the first study that followed children beyond childhood for depressive disorders which typically do not emerge until after the onset of puberty. The paper, “Gestational Exposure to Selective Serotonin Reuptake Inhibitors and Offspring Psychiatric Disorders: A National Register-Based Study” is published in the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP).

SSRIs have been prescribed increasingly to pregnant women since their introduction 30 years ago, and today 6% of pregnant women in the U.S. and 4% in Finland are on SSRIs at some stage of pregnancy. Earlier research had suggested an association between mother’s SSRI use and offspring autism spectrum disorders and attention deficit hyperactivity disorder.

To address the question if SSRI use during pregnancy is associated with offspring psychiatric disorders, the team of researchers examined offspring psychiatric diagnoses, including depression, anxiety, ASD and ADHD of nearly 16,000 mothers using SSRIs during pregnancy from 1996-2010, using national register data from Finland. Children in this cohort ranged in age from birth to 15 years. Because maternal psychiatric illness can affect offspring neurodevelopment in the absence of SSRIs, primary comparisons were made between offspring of the SSRI group and offspring of mothers with a diagnosis of psychiatric disorders but no antidepressant use.  

Children exposed to SSRIs during gestation were diagnosed with depression at an increasing rate following age 12, reaching a cumulative incidence of 8.2% by age 15, compared to 1.9% in the group of children exposed to maternal psychiatric illness but no antidepressants. Rates of anxiety, ASD and ADHD diagnoses did not differ significantly between the two groups. Comparing SSRI exposed to offspring of mothers with neither antidepressant use nor psychiatric diagnosis, the rates were significantly elevated for each outcome.

According to the researchers, the results suggest that SSRI use during pregnancy increases the risk of offspring depression. However, the oldest subjects had only just entered the age of risk for depression and mood disorders typically emerge after the onset of puberty.  Further research is therefore urgently needed to follow these children as they get older to substantiate the findings. Also, until confirmed, these findings must be balanced against the adverse consequences of untreated maternal depression.

“While some women with mild to moderate depression may do well coming off antidepressants during pregnancy, severe depression left untreated can lead to serious consequences in the mother and can have direct and indirect adverse effects on the pregnancy, the fetus, and the child,” said Myrna Weissman, PhD, Diane Goldman Kemper Family Professor of Epidemiology at the Mailman School of Public Health and co-director of a NIMH-funded Silvio O. Conte Translational Center, from the Sackler Institute at Columbia.

While results related to offspring risk of ASD and ADHD after prenatal exposure to SSRIs provide some reassurance, SSRI exposure during gestation may have delayed, but significant effects on offspring risk for depression. “Further studies should determine whether the developing fetus is particularly sensitive to the effects of SSRIs in different trimesters, whether some medications may be safer than others for the fetus, and whether evidence based psychotherapies could be better utilized to maximize maternal benefits while minimizing risk to the long-term health of the developing fetus,” noted Alan Brown, MD, MPH, Mailman School professor of Epidemiology and Psychiatry.

The research was supported by National Institutes of Health grant P50MH090966, the Sackler Institute for Developmental Psycho-biology of Columbia University, and grants from the Sigrid Juselius Foundation, the Foundation for Pediatric Research in Finland, and the Finnish Medical Foundation. The authors report no conflicts of interest.