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A new mouse study investigated the impact of SSRIs on brain development. juanma hache/Getty Images
  • A new mouse study found antidepressant use during pregnancy may influence brain development in utero.
  • Most antidepressants are safe to use during pregnancy, according to experts. Depending on the severity of mental illness, withholding medication can lead to more severe health risks.
  • Other treatments for depression include cognitive behavioral therapy, interpersonal psychotherapy, support groups, mindfulness, yoga, and exercise.

A new mouse study found taking antidepressants during pregnancy may affect brain development in utero and be a risk factor for developing mental health disorders later in life.

The findings were published February 16 inNature Communications.

Researchers examined the impact of a chemical called fluoxetine on mice.

Fluoxetine elevates the amount of serotonin in the brain and is typically used in selective serotonin reuptake inhibitors (SSRI) medications such as Prozac and Sarafem which are used to help treat depression and perinatal depression. The researchers looked at how serotonin influences prefrontal cortex development in a fetus – specifically, the effect of deficiency and surplus of serotonin on brain development in mice.

Results showed that serotonin not only impacts overall brain function but also impacts how individual connections between neurons change and adapt. This, in turn, affects the way the brain learns.

“This is certainly a fascinating scientific study on postnatal development in the mouse brain but how it applies to the human brain still remains a question,” said Dr. Michael Cackovic, maternal-fetal medicine physician at Bridgeport Hospital.

Cackovic wasn’t involved in the study.

Most brain development in humans occurs in the first two years of life and 90% before kindergarten so it would make sense that giving “pups” this medication early in life could potentially cause a problem, Cackovic explained.

Researchers looked at the effects of serotonin on the part of a developing brain called prefrontal cortex when it is exposed to fluoxetine.

Fluoxetine goes into the placenta but also into breast milk.

“All known SSRI medications readily pass through the placenta and enter the fetal circulation,” said Dr. Jay Gingrich, professor of developmental psychology at Columbia University Vagelos College of Physicians and Surgeons. “There are several studies that have examined the health and mental health outcomes of children exposed to SSRIs in utero. Because serotonin receptors and pathways are highly conserved through evolution (across distant species), there has been a presumption that findings in rodents may likely be relevant to human brain development.”

Gingrich continued: “This has been difficult to prove unequivocally, but several studies have found increased rates of depression, anxiety, and adjustment disorders in SSRI-exposed children as they age into adolescence. Other studies have found increased rates of autism, but most of those studies have not controlled for maternal mental health and several studies failed to find a similar linkage.”

The risk of exposure through breast milk is expected to be far lower than through placental passage and should not dissuade mothers from breastfeeding or resuming SSRI use during this period, he added.

These findings do not mean that people who wish to become pregnant should stop taking SSRIs immediately, according to experts.

“There is a tremendous amount of data that supports use of an SSRI during pregnancy when it is taken to help the person achieve remission or maintain remission of their depression and/or anxiety,” said Dr. Katherine Campbell, associate professor of obstetrics, reproductive sciences at Yale School of Medicine.

Campbell, who did not work on the study, did clarify that infants can have symptoms if their parent is on SSRIs while pregnant.

“When babies are born to parents who are on fluoxetine (or other SSRI), the baby can have withdrawal symptoms that can start after birth,” Campbell said. “Withdrawal symptoms can include irritability, jitteriness, and fast breathing. There are newer SSRIs on the market that cross the placenta and cross into breast milk in lower concentrations.”

While there may be risks in taking SSRIs while pregnant, there are also risks of experiencing mental health disorders. Experts point out that untreated mental illness has significant and well-established consequences to maternal and infant health.

For example, untreated depression in pregnancy is associated with preterm birth, low birth weight and stillbirth.

“Antidepressants, and selective serotonin reuptake inhibitors (SSRIs) specifically, are the most studied class of medications in pregnancy and the clinical consensus based on the extensive literature (in human studies), is that they are generally safe to use in pregnancy and in lactation when medically indicated (with the exception of paroxetine, which is usually not prescribed or used in pregnancy due to equivocal evidence on possible minor cardiac malformations),” said Dr. Ariadna Forray, associate professor of psychiatry at Yale School of Medicine and Director at the Center for Wellbeing of Women and Mothers, Psychiatry; Yale Medical Director, ACCESS Mental Health for Moms.

Forray was not involved in the study.

“The irony is that both untreated maternal depression and the use of antidepressants both increase the risk for anxiety and depressive disorders in the offspring in later life,” Gingrich said. “This conundrum is what has made it so difficult to discern whether SSRI use in pregnancy is a net positive to the child or whether we are exacerbating what trends were expected based on maternal history.”

Experts say if you are pregnant and taking SSRIs you can speak with your physician about whether or not it would make sense to stop taking the medication.

In many clinical scenarios, it is problematic to withhold medication treatment during pregnancy because of the severity of the mother’s symptoms.

“We have been working in this area for 20 years in attempt to provide a clearer risk-benefit profile to clinicians and their patients to help inform better decisions. This work is ongoing,” Gingrich added.

There are various non-pharmacological interventions to help treat depression symptoms that people can explore after talking to their psychiatrist and physician if they want to avoid SSRIs.

“Evidence-based interventions include cognitive behavioral therapy and interpersonal psychotherapy,” said Forray. “Things like support groups, mindfulness, yoga and exercise can also be helpful additions to evidence-based treatments.”

In addition, “there are several effective psychotherapies for depression during pregnancy and in the post-partum period (IPT, CBT) and there are new non-SSRI medications specifically indicated for post-partum depression (e.g., Zurzuvae or zuranolone),” Gingrich explained. “The US needs to improve the availability and reimbursement of such non-pharmacologic therapies for patients in need. These are often barriers to obtaining appropriate psychotherapy for the expecting mother.”

According to a new mouse study, antidepressant use during pregnancy may affect brain development in utero. However, further research is needed.

The clinical consensus is that most antidepressants are safe to use during pregnancy, according to experts. It is important to note that withholding medication can pose greater health risks for the pregnant person and child.

Aside from medication, there are other ways to help treat symptoms of depression. These include cognitive behavioral therapy, interpersonal psychotherapy, support groups, mindfulness, yoga, and exercise.