Pregnant women with bipolar disorder and their physicians face a
dilemma: stay on mood-stabilizing medications, which carry risks of causing
birth defects, or discontinue the medications and brace for the possibility of
The possibility of relapse due to interrupted pharmacotherapy has been
quantified in a study published in the December 2007 American Journal of
Psychiatry, which warns that pregnant women with bipolar disorder who
discontinue mood stabilizers are much more likely to suffer the return of
their illness than those who continue taking the medications.
Adele Viguera, M.D., and colleagues at Harvard Medical School and Emory
University conducted this observational study in which they prospectively
followed 89 women, all of whom had a diagnosis of bipolar disorder, from
pregnancy or the planning of pregnancy to one year after the childbirth to
trace the course of the disease.
More than two-thirds of the enrolled women discontinued their drug therapy
for bipolar disorder in the period between six months before and 12 weeks
after conception, while 27 remained on the medications through at least 12
weeks after conception. Those who discontinued their bipolar medications
within six months before through 12 weeks after conception were compared with
women who continued taking mood stabilizers at least through 12 weeks after
conception (see chart).
The women who discontinued their bipolar medications more than doubled
their likelihood of suffering a recurrence of at least one episode of the
illness (85.5 percent versus 37.0 percent) and spent over 40 percent of the
time during pregnancy suffering bipolar symptoms, compared with only 8.8
percent of the time during pregnancy for those who maintained
In addition, the women who abruptly stopped their mood stabilizers (within
one to 14 days) had a 50 percent risk of recurrence within just two weeks. In
contrast, a more gradual discontinuation (more than 15 days) reached the same
risk in 22 weeks. This observation further emphasizes the danger of
interruption to medication treatment.
The researchers also observed a "striking excess" of depressive
or dysphoric mixed episodes, even among those with bipolar I disorder, while"
mania and hypomania were relatively infrequent." They also noted
in their report that the study results call into question previous suggestions
that pregnancy may have some protective effect against new or worsening
The women in this study who maintained mood stabilizers during pregnancy
were not necessarily more severely ill than those who discontinued the
treatment, but they did skew toward having bipolar I disorder, taking lithium
rather than an anticonvulsant, and having a history of psychotic features."
Nearly 70 percent of women in the present study sample elected to
discontinue mood-stabilizing treatment at the start of pregnancy, regardless
of illness severity," Viguera told Psychiatric News."
Moreover, we found that most patients with an unplanned pregnancy
stopped their mood stabilizer abruptly, which exacerbated their risk of
recurrence with respect to becoming ill faster than women who tapered off
treatment more slowly."
Mood stabilizing medications do pose risks of birth defects. Lithium and
divalproex are both pregnancy category D drugs according to the FDA's
classification, as both carry risks of causing congenital abnormalities such
as neural tube and cardiovascular defects.
The authors pointed out, however, that untreated relapses of bipolar
episodes are also dangerous for the health of both the mother and the fetus."
Maternal psychiatric illness, if inadequately treated or untreated, may
be associated with poor compliance with prenatal care, inadequate nutrition,
increased alcohol and tobacco use, disruption in maternalinfant attachment,
and family stress. Data also suggest that children of depressed parents are at
greater risk for behavioral and emotional difficulties," Viguera
She urged clinicians to provide the best information on the spectrum of
risks associated with both pursuing and deferring treatment during pregnancy,
including the risk of relapsed illness. Effective communication between the
physician and the patient "affords clinicians the opportunity to make
collaborative treatment decisions consistent with individual needs and
wishes." Like epilepsy and other illnesses with serious complications,
bipolar disorder may require continued drug therapy during pregnancy for
In an accompanying editorial, Marlene Freeman, M.D., an associate professor
of psychiatry at the University of Texas South-western Medical Center, called
this study "groundbreaking." She urged clinicians to anticipate
the complications of pregnancy in treating bipolar disorders and proactively
discuss the risks and benefits with patients, since most female patients
become ill before or during their reproductive years.
"Especially in the case of neural tube defects with the use of
anticonvulsants, the window of greatest concern is very early in
pregnancy," said Freeman. "By the time a woman discovers she is
pregnant, the most serious period of risk for the fetus has frequently already
passed." Rapid disruption of medication at this time therefore can pose
more risks than protection.
The study was funded by the National Institute of Mental Health, NARSAD,
the Bruce J. Anderson Foundation, McLean Private Donors Psychopharmacology
Research Fund, and Stanley Research Institute.
"Risk of Recurrence in Women With Bipolar Disorder During
Pregnancy: Prospective Study of Mood Stabilizer Discontinuation" is
the editorial "Bipolar Disorder and Pregnancy: Risks Revealed" is