Limitations of Pregnancy Risk Categories.

Clinicians are frequently caught between a teratologic rock and a clinical hard place when it comes to the use of psychiatric medications during pregnancy Unfortunately the Food and Drug Administration's current classification system, which assigns ratings with respect to the safety of drugs during pregnancy, does not necessarily help and can be misleading.

Recognizing such limitations, the FDA is in the process of revamping the system, but for now it's incumbent on physicians to go beyond the package insert and refer to the available literature and other resources to get a better picture of the full amount of reproductive safety data available on a certain drug.

The use of certain antidepressants during pregnancy is a striking example of how category labeling does not necessarily help guide clinical care--and how it can make certain compounds with relatively less safety data appear to be "safer" than medicines for which we have far more safety data.

For example, bupropion, marketed as Wellbutrin for depression and Zyban for smoking cessation, has been classified as a category B compound based on anecdotal human data from a very small sample of women and limited animal data, which do not support adverse effects associated with prenatal exposure.

Although the manufacturer has established a bupropion pregnancy registry, the data on this drug are sparse when compared with the amount of safety data on fluoxetine (Prozac) and citalopram (Celexa). Yet both these selective serotonin reuptake inhibitors (SSRIs) are labeled category C, presumably based on adverse effects seen in studies of rats that ingested 10-18 times the maximum human recommended daily doses of these drugs. Under the current system, these types of data justify a C category almost regardless of the amount of human data available.

The category C label does not reflect human data on more than 2,300 cases of first-trimester exposure to fluoxetine or the nearly 400 cases of first-trimester exposure to citalopram; these data do not support an increased risk for major congenital malformations. But we have seen cases of women who are stabilized on citalopram or fluoxetine and then switched during pregnancy to medicines such as bupropion, because clinicians assume a category B drug is "safer" than fluoxetine or ...