Fluoxetine, Paroxetine Linked to Increased Birth Defect Risks

Study Didn't Find Similar Risks for Other SSRIs

July 15, 2015 11:30 am Chris Crawford

The use of antidepressants -- especially selective serotonin reuptake inhibitors (SSRIs) -- during pregnancy has previously been linked(www.ncbi.nlm.nih.gov) to an increased risk for birth defects in infants. Now, newly published research further explores that risk, validating some earlier concerns while refuting others.

[Pregnant woman laying on table talking with doctor]

A study(www.bmj.com) published July 8 in BMJ bolstered previous research on paroxetine (Paxil, Pexeva) that identified an increased risk for certain heart defects in infants whose mothers took the drug during the first three months of pregnancy. That earlier finding prompted a 2005 FDA advisory,(www.fda.gov) as well as a reclassification of the drug from Category C to Category D.

The current study confirmed increased risks for five previously reported birth defects associated with paroxetine, including heart defects, anencephaly and abdominal wall defects. Fluoxetine (Prozac, Sarafem) was linked to increased risks for heart wall defects and craniosynostosis. And both drugs were tied to an increased risk of right ventricular outflow tract obstruction cardiac defects.

However, use of the SSRIs citalopram (Celexa), escitalopram (Lexapro) and sertraline (Zoloft) were not found to be linked to any increased risk of birth defects.

Study Breakdown

The BMJ study, which was conducted by the CDC's National Center on Birth Defects and Developmental Disabilities, began with a review of the literature for reports that assessed the relationship between specific SSRIs and one or more of the specific birth defects that are also included in the multicenter U.S. National Birth Defects Prevention Study(www.nbdps.org) (NBDPS).

Story highlights
  • A study published July 8 in BMJ found that both paroxetine and fluoxetine were tied to an increased risk of birth defects.
  • However, use of selective serotonin reuptake inhibitor drugs citalopram, escitalopram and sertraline were not found to be linked to any increased risk of birth defects.
  • This study, conducted by the CDC's National Center on Birth Defects and Developmental Disabilities, analyzed recent meta-analyses and systematic reviews of data from more than 20 epidemiological studies.

To provide a more robust assessment of the link between individual SSRIs and birth defects, the researchers then used Bayesian methods to summarize the independent literature findings and to update those findings using the entire NBDPS data set.

In all, 17,952 mothers of infants with birth defects and 9,857 mothers of infants without birth defects were included in the study; all of the children were born between 1997 and 2009. Of the infants who had birth defects, 659 of their mothers reported having used SSRIs during pregnancy.

Perhaps the best news from this study is that sertraline, which was the most commonly used SSRI (40 percent of the women reporting SSRI use in early pregnancy took the drug), was not linked to the five birth defects previously reported to be associated with the drug. In addition, nine other previously reported associations between maternal SSRI use and birth defects were not supported by the research examined.

However, the study did confirm previously reported associations between right ventricular outflow tract obstruction cardiac defects in infants and maternal use of fluoxetine or paroxetine early in pregnancy, as well as between anencephaly or atrial septal defects in infants and maternal use of paroxetine. (Associations between gastroschisis or omphalocele and paroxetine and between craniosynostosis and fluoxetine that had been seen in an earlier NBDPS data subset analysis also were confirmed by the current analysis, but these findings still require corroboration through an independent data source.)

Even despite the confirmatory results, said the researchers, any increase in absolute risks -- if the associations are causal -- remains small. For example, the absolute risk for anencephaly in children of paroxetine users increased from a baseline of two per 10,000 to seven per 10,000 and for right ventricular outflow tract obstruction cardiac defects from 10 per 10,000 to 24 per 10,000.

Overall, said the researchers, their analysis "confirms the need to assess the association between specific SSRIs and specific birth defects rather than combining an entire drug class or heterogeneous group of birth defects."

Family Physician's Take

Robert Rich, M.D., chair of the Commission on Health of the Public and Science, told AAFP News that he expects pregnant patients using these medications who hear media reports about the study will be asking their family physicians whether they should stop their antidepressant therapy or switch their SSRI. Worst case scenario: Patients will stop the medications themselves.

Rich said family physicians should explain that the two medications in question -- paroxetine and fluoxetine -- have been linked to a small increase in risk of birth defects.

"While the results of the study need further investigation and analysis, I would acknowledge that a possible risk exists and that we would need to discuss the risks versus benefits of continued use of these medications and that we may want to consider an alternative medication for the remainder of the pregnancy if we felt that we need to continue antidepressant therapy," Rich said.

He pointed out that if left untreated, depression increases the risks of complications during pregnancy, including premature birth or low birthweight, and can lead to abuse of alcohol, prescription pain relievers or illegal drugs; poor maternal nutrition; and weight gain, as well as to an increased risk of postpartum depression.

Among limitations of the BMJ analysis, said Rich, was that it didn't address whether the observed birth defects were directly linked to the medications in question or if other factors could explain the observations. Other limitations included the small absolute number of observed birth defects and the study's reliance on patient recall of medication usage.

Rich suggested telling women of childbearing age that all medications and substances taken during pregnancy could potentially affect their unborn children, with the two most important such substances still being tobacco and alcohol.

"This study also serves to remind all providers caring for women of childbearing age that all prescribed medications must be considered from the standpoint of risk to the unborn child if the woman becomes pregnant," Rich said, adding that discussing contraceptive options with patients using medications that could affect an unborn child may be indicated.

Related AAFP News Coverage
CMS Reverses Decision on Medicare Prescription Rules After Outcry From AAFP, Others
(3/19/2014)

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