Prenatal exposure to selective serotonin reuptake inhibitors (SSRIs) is associated with a higher incidence of depression in early adolescence, according to a population-based observational study from Finland.

Using national register data between 1996 and 2010, researchers studied the diagnosis of depression in offspring (up to age 14) of women exposed to SSRIs during pregnancy. Researchers divided the study participants (pregnant women) into four categories: exposed to SSRIs (n=15,729); exposed to psychiatric disorders but not to antidepressants (n=9,651); exposed to SSRIs only prior to pregnancy (n=7,980); and not exposed to psychiatric disorders or antidepressants (n=31,394). The cumulative offspring neurodevelopment effects investigated were depression, anxiety, autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD) from birth to age 14 years. SSRIs included fluoxetine, citalopram, paroxetine, sertraline, fluvoxamine, and escitalopram. [J Am Acad Child Adolesc Psychiatry 2016;55:359-366]

By age 14.9 years, there was a significantly higher incidence of depression in offspring whose mothers had been exposed to SSRIs during pregnancy compared to those whose mothers had psychiatric disorders but no exposure to SSRIs (8.2 vs 1.9 percent; adjusted hazard ratio [aHR], 1.78, 95 percent confidence interval [CI], 1.12-2.82; p=0.02) and those whose mothers were exposed to SSRIs only prior to pregnancy (2.8 percent; aHR, 1.84, 95 percent CI, 1.14-2.97; p=0.01).

The incidence of anxiety, ASD, and ADHD were comparable between infants with prenatal SSRI exposure, those whose mothers had psychiatric disorders but no antidepressant exposure, and those whose mothers were exposed to SSRIs only before pregnancy.

Limiting the exposure to SSRI monotherapy (n=12,121) during pregnancy maintained the increased risk of adolescent depression compared to the psychiatric disorder but no medication group (HR, 1.85, 95 percent, 1.15-2.98; p=0.01) and the SSRI before pregnancy group (HR, 2.12, 95 percent CI, 1.29-3.48; p=0.003).

“The results indicated that children exposed to SSRIs during gestation were diagnosed with depression at an increasing rate after age 12,” said study author Dr. Heli Malm, an obstetrics and gynaecology specialist at the Teratology Information Service, Helsinki University and Helsinki University Hospital, Helsinki, and Department of Child Psychiatry, University of Turku, Turku, Finland.

However, Malm highlighted the importance of balancing the findings of this study against the negative consequences of untreated maternal depression.

“While some women with mild to moderate depression may do well coming off antidepressants during pregnancy, severe depression when left untreated can lead to serious consequences in the mother and can have direct and indirect adverse effects on the pregnancy, foetus, and child. Therefore, if the mother clearly benefits from treatment, it should not be discontinued. On the other hand, there should always be a proper indication for using these drugs. Until the findings are confirmed or refuted, evidence-based psychotherapies could be better utilized to maximize maternal benefits while minimizing risk to the long-term health of the developing foetus,” she said.

In order to confirm the study findings, Malm recommended follow-up studies involving these children. “The oldest subjects had only just entered the age of risk for depression, which typically emerges after the onset of puberty. Further research is therefore needed to follow these children as they get older to substantiate our findings. Further studies should also determine whether the developing foetus is particularly sensitive to the effects of SSRIs in different trimesters, and whether some antidepressants may be safer than others for the foetus,” said Malm.