Current evidence does not support a causal link between the use of almost all antidepressants during pregnancy and an increased risk of neurodevelopmental disorders, including autism and attention-deficit/hyperactivity disorder (ADHD), in children, according to a systematic review and meta-analysis published in The Lancet Psychiatry journal.
Previous meta-analyses looking at the use of antidepressants during pregnancy and risk of neurodevelopmental disorders in children were conducted nearly a decade ago and limited by small study numbers and a lack of controlling for additional factors. This new meta-analysis provides the best evidence to date that the small increase in risk of autism or ADHD in the children of women who used antidepressants when pregnant identified in many studies is not caused by the medication.
"We know many parents-to-be worry about the potential impact of taking medication during pregnancy; our study provides reassuring evidence that commonly used antidepressants do not increase the risk of neurodevelopmental disorders such as autism and ADHD in children. While all medications carry risks, so too does stopping antidepressants during pregnancy due to an increased risk of relapse. Therefore, for women with moderate-severe depression, doctors and patients must carefully weigh the potential risks and benefits of continuing antidepressant treatment during pregnancy against the potential harms of untreated depression," says author Dr Wing-Chung Chang, University of Hong Kong.
He continues, "Although our study found a small increase in the risk of autism and ADHD in the children of women who had used antidepressants during pregnancy, it also found that this risk disappeared when we accounted for other factors. The increased risk was also seen in the children of fathers who took antidepressants and of mothers with antidepressant use before, but not during, pregnancy. Together, this suggests that it is not the antidepressants themselves causing an increased risk in autism and ADHD but it is more likely to be due to other factors, including genetic predisposition to conditions such as ADHD, autism, and mental health conditions."
Authors pooled data from 37 studies which included more than 600,000 pregnant women taking antidepressants and almost 25 million pregnancies with no antidepressant use.
Before controlling for key factors such as mental health conditions, the analysis found that antidepressant use by the mother during pregnancy was associated with a 35% increased risk of ADHD and a 69% increased risk of autism. However, this became greatly reduced or non-significant in analyses that better controlled for confounding factors. Use of antidepressants during pregnancy by the father was associated with a 46% increase in the risk of ADHD and a 28% increase in the risk of autism.
Among studies with analyses restricted to mothers with mental health disorders, all selective serotonin reuptake inhibitors (SSRIs) were found to not be associated, only amitriptyline/nortriptyline remained associated with increased ADHD and autism risk. Amitriptyline/nortriptyline are currently considered second or third options as treatments for depression and are often prescribed for treatment-resistant depression. Therefore, women treated with these may have more severe, chronic, or complex underlying mental health conditions than those receiving more common antidepressants, which could be influencing the association between amitriptyline/nortriptyline and increased ADHD and autism risk.
The study found no difference in risk between high and low doses of antidepressants.
"The evidence suggests a link between either parent having a mental health condition and a slightly higher risk of ADHD or autism. In addition to genetic factors, this link could be explained by the home and social environment as ongoing family stress, changes in how the family functions, and differences in how parents behave and care for their children may influence neurodevelopment. There is a need to ensure both parents have access to support and treatment for mental health conditions; for their own sake and to support neurodevelopment of their child," says Dr. Joe Kwun-Nam Chan, University of Hong Kong.
The researchers note some limitations of their study, including that data on important factors such as socioeconomic status, lifestyle risk factors and low birth weight was lacking in the studies. Additionally, there was only a small number of studies looking at antidepressant use in specific trimesters or exact doses and dose changes, which makes it harder to draw conclusions about these. Finally, women who are prescribed antidepressants tend to have more severe depression than those who are not, so some bias may remain even after controlling for mental health status.
Writing in a linked Comment, Lisa Vitte, Emmanuel Devouche and Gisele Apter from University Rouen Normandy (France), who were not involved in the study, say, "Chang and colleagues' study adds knowledge and confirms some of the pre-existing knowledge on the use of antidepressants during pregnancy: that they should continue to be taken as they protect maternal mental health and do not harm fetal development. This result is of considerable impact after many contradictory and controversial studies."
