Canadian Team Searches for ‘Safer’ Antidepressants for Pregnant Women

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Without treatment, depression during pregnancy carries risks for both mother and child. Yet antidepressants can affect fetal development. Now, a Canadian team led by Dr. Cathy Vaillancourt at the Institut National de la Recherche Scientifique (INRS) is studying the effects of such drugs to identify the least harmful ones.

Their research targets the enzyme that synthesizes estrogen: aromatase. Estrogen production is essential to the development of the fetus and to the mother’s physiological adaptation during pregnancy.

The results of the study by Professor Vaillancourt, in collaboration with Drs. J. Thomas Sanderson and Nicolas Doucet of the INRS, appear in The Journal of Steroid Biochemistry and Molecular Biology .

Overall, prescribing antidepressants for pregnant women is controversial. Studies show that, when administered to mothers during pregnancy, some of the treatments are associated with a risk of heart and lung malformations in newborns. Others are thought to result in impaired cognitive development, including autism, in children.

The harmful effects of antidepressants are thought to be due to their interaction with certain key hormones. Most antidepressants prescribed to pregnant women target serotonin, a hormone produced both in the brain and in the placenta. These antidepressants, called selective serotonin reuptake inhibitors (SSRIs) include Zoloft, Celexa and Prozac.

But research suggests estrogen would also be targeted by these treatments.

“We wanted to see how the antidepressants that have been developed to block the serotonin transporter also affect aromatase,” said Vaillancourt. “Using molecular models, we found that all the antidepressants we analyzed seemed to be able to bind directly to the enzyme and regulate its activity. This remains to be confirmed and the precise mechanism needs to be further investigated.”

For the study, researchers tested the effect of different types of antidepressants on placenta samples collected after delivery. “The antidepressants we chose to test are those most commonly prescribed in pregnant women, namely sertraline (Zoloft), venlafaxine (Effexor), fluoxetine (Prozac), paroxetine (Paxil), and citalopram (Celexa),” said primary author Dr. Andrée-Anne Hudon Thibeault.

“By comparing different doses and molecules, we were able to uncover some of their specificities.”

Researchers hope that by observing the effects of antidepressants on the placenta’s hormonal system, they can determine in advance if there will be a risk for the fetus. “Fetal development is strongly linked to the placenta. Every healthy fetus has a healthy placenta,” Vaillancourt said.

Experts note that not all types of antidepressants have these harmful effects. Not all pharmacological molecules have the same hormonal affinity.

“Depending on its form, a molecule may not interact the same way with estrogen and may therefore be less harmful to the developing fetus,” said Vaillancourt.

It’s more a matter of the pharmacological molecule being administered and the dosage. “By testing several types of antidepressants at varying doses, our work will contribute to better choices regarding the type of antidepressant and the dose prescribed for pregnant women, while minimizing the side effects on the course of pregnancy and on fetal development,” Thibeault said.

Discontinuing medication isn’t always advisable. Depression can have serious consequences if left untreated. “Depression is one of the leading risk factors for suicide in pregnant women,” said Vaillancourt. “Some studies suggest that depression can also compromise fetal development, due in part to poor lifestyle habits.”

At the same time, Vaillancourt is collaborating with a team of researchers in Vancouver who are studying a cohort of pregnant women and following their children over the long term.

“This will give us a nice map of the various effects in women and the consequences for children’s heart and brain development,” said Vaillancourt. “We’re still in the early stages of the project, but I’m confident that some antidepressants are safer and others can be developed for use during pregnancy.”

Source: Institut National de la Recherche Scientifique (INRS)/EurekAlert

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