Research explores possible effect of antidepressant use during pregnancy

Researchers have moved a step closer to determining how the antidepressant citalopram, sold under the brand name Celexa, may play a role in contributing to the rare birth defect craniosynostosis. But they say much more work needs to be done and advise women not to jump to conclusions.

James Cray, Ph.D., was principal investigator for the citalopram study at the Medical University of South Carolina. “This specific drug in our hands, our model, seemed to set up a situation where the proper cell cycle regulation was broken.”

The result: Skull joints called sutures turned to bone before their time, forcing the brain to grow in abnormal directions. “Normally, you have cells living and dying. In our research with citalopram, the cells were just maintaining themselves and not dying, so they kept dividing. The disaster for the disease we were looking at, craniosynostosis, is that those cells would make bone, and that seems to be what they’re doing.”

Cray’s research was preclinical, meaning it was not done on humans. That’s important to keep in mind, he said. “A big variable we were not able to incorporate in our model was depression,” Cray said. “We simply looked at the effects of the drug. I would not suggest that anybody stop taking their drug during pregnancy as the result of anything they read. They should talk it over with their health care provider.”

MUSC’s Connie Guille, M.D., was not involved in the citalopram research but echoed Cray’s call for women to keep the results of the study in perspective. She specializes in reproductive psychiatry. “There’s this huge focus right now on the risks of antidepressants in pregnancy. But another important question we need to ask is, what are the risks of this person not being on antidepressants in pregnancy?

“If someone determines their risk of untreated illness is very high, then we’re likely going to take the small risks of birth defects, given that they need to be on those medications. Craniosynostosis is very, very rare.”

Craniosynostosis occurs in one out of every 1,800 to 2,500 births, according to Cray. “It causes problems with not only brain growth but can also affect the development of the eyes,” he said. “You may have increased hypertension in the brain and increased intracranial pressure. There are syndromic cases where you know it at birth.”

Other cases are less apparent. “Some of these kids are crying, they’re not feeding properly, they’re irritable and they’re having projectile vomiting, which are symptoms of increased intracranial pressure.” 

Their parents take them to a doctor to treat those symptoms and find out there’s the larger problem of craniosynostosis, Cray said. “There are very well-prescribed surgeries, but neurosurgery on an infant is nothing to take lightly.”

Cray’s citalopram research is part of his work at MUSC’s pediatric craniofacial lab. He and his team search for ways to prevent disorders such as craniosynostosis, exploring the factors that may lead to skull and facial problems. 

Citalopram isn’t the only possible culprit they’re considering in the case of craniosynostosis. “Thyroid disorders and nicotine are other areas we’re looking at,” Cray said. “Nicotine is a new one, because we’ve studied cigarettes for so long that we kind of lost the forest for the trees.”

He focused on citalopram at the suggestion of collaborators at the Centers for Disease Control and Prevention. “The CDC sees all the surveillance data and all the associations. It cues you that there may be a problem. There’s also plenty of literature that suggests craniosynostosis is popping up in the human population with mothers using SSRIs broadly and citalopram specifically.” 

SSRIs are selective serotonin re-uptake inhibitors, a class of drugs that change the balance of serotonin in the brain, boosting the patient’s mood. Cray is also looking at the possible effect of escitalopram (Lexapro and Cipralex), fluoxetine (Prozac) and sertraline (Zoloft). “There are some basic mechanisms that are similar in how they work,” he said. “They all, with the exception of Prozac, have very similar effects in our model. There’s enough evidence to suggest we need to take a closer look.”

His long-term goal is to give women and their doctors the data they need to make good decisions about antidepressant use during pregnancy. It can be a confusing subject, with studies reaching conflicting conclusions.

Cray said citalopram is well worth further exploration. “If we continue to look at this, we can go to the logical end, which would be dose by time,” Cray said. In other words, are antidepressants safer at certain points during a pregnancy, and is there a safe dose?

“I don’t think we have enough research to have a good answer yet,” Cray said. 

For now, Guille said the benefits of treating clinically depressed women with medication during pregnancy outweigh the potential risk. “Untreated depression in pregnancy increases the risk for things like preterm birth and low birth weight,” she said.

“We also know when women are depressed in pregnancy they have a lot of poor health habits that are associated with birth defects such as using alcohol or nicotine or other drugs. Their health habits are not very good. Those factors are important to weigh.”

Guille directs a reproductive psychiatry clinic at Women's Health Services through the MUSC Health Institute of Psychiatry to help women weigh their options.