Psychiatric Drugs, Pregnancy and Lactation: Limitations of Pregnancy Risk Categories
March 1, 2001 from
ObGynNews
By Lee S. Cohen, M.D.
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 citalopram, prompting the clinician to incorrectly
assume that the absence of adverse data implies safety.
In this scenario, not only is the patient put at risk of not responding to
the new antidepressant and having a relapse, but she is unnecessarily taken off
a medicine for which there is a relatively abundant amount of safety data.
Category labeling also fails us when we consider the SSRIs as a class. This
is a particularly important issue because it is incorrect to assume that all
drugs within the same class have equal reproductive safety. All the available
SSRIs are labeled category C, but there's nowhere near the amount of information
on first-trimester exposure to paroxetine (Paxil) and sertraline (Zoloft) as
there is for fluoxetine and citalopram.
Lithium is another dramatic example of the complexity of risk assessment of
psychiatric medications when considering category label assignment. Other
factors come into play when considering whether an agent should be used during
pregnancy.
For example, lithium is a category D drug because of clear evidence of an
increased risk of a cardiovascular malformation (Ebstein's anomaly) associated
with first-trimester exposure. Many women with bipolar disorder who become
pregnant or want to become pregnant are counseled by their physicians to
discontinue lithium, even abruptly, solely based on the category D label.
However, the absolute risk of Ebstein's anomaly is estimated at 0.05%-0.1%.
Since the risk of relapse within the first 6 months of lithium discontinuation
is so high-over 60%-women with bipolar disease may choose to assume the
relatively small absolute risk for teratogenesis associated with first-trimester
exposure, regardless of the drug's category.
These examples underscore the limitations of the category-labeling system and
the need to complement this information with other data from the medical
literature and elsewhere. By not relying exclusively on the labeling system,
physicians and their patients can make more informed decisions when selecting
psychiatric drugs.
References on this topic are also available on the Massachusetts General
Hospital Web site at www.mgh.harvard.edu/depts/ womens/index.htm.
Dr. Lee Cohen is a psychiatrist and director of the
perinatal psychiatry program at Massachusetts General Hospital, Boston. He is a
consultant for and has received research support from manufacturers of several
SSRIs. He is also a consultant to Astra Zeneca, Lilly and Jannsen -
manufacturers of atypical antipsychotics.
continue: Antipsychotics in
Pregnancy . drugs during pregnancy index
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Reviewed: 03/2006
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