Pregnant Women At Risk Of Bipolar Recurrence With Interruption Of Medication

Women with bipolar disorder who stop taking their medication -
such as lithium, antipsychotics and anticonvulsants prescribed as mood stabilizers - before or shortly
after becoming pregnant appear to be much more likely to suffer a recurrence of the disorder,
according to a study reported in the December issue of The American Journal of Psychiatry (AJP), the
official journal of the American Psychiatric Association (APA).


In the prospective study of 89 pregnant women with bipolar disorder, Adele C. Viguera, M.D., and
colleagues at Harvard Medical School and Emory University found that 85 percent of the 62 women
they studied who stopped their mood stabilizer medication-up to six months prior to becoming
pregnant or in the first 12 weeks of pregnancy-experienced a recurrence of the disorder. In
comparison, only 37 percent of the 27 women who continued taking their medication through at least
week 12 of pregnancy experienced a recurrence. In addition, Viguera and her colleagues report in
"Recurrence Risk in Women With Bipolar Disorder During Pregnancy: Prospective Study of Mood-
Stabilizer Discontinuation" that abrupt discontinuation of medication greatly increased and hastened
the recurrence, confirming earlier observations by the same researchers.


The majority of the women studied were taking lithium as a mood stabilizer (55 of the 89, or 62
percent) followed in frequency of use by an anticonvulsant mood stabilizer (32/89; 36 percent) or an
antipsychotic mood stabilizer (24/89; 27 percent). About half of the women in this study were also
taking an antidepressant medication.


Recurrences most often took the form of a depressive or mixed episode (experiencing both symptoms
of depression and mania), and most of the recurrences began within the first trimester of pregnancy.
Of note, in this study it appears that antidepressant treatment did not affect the risk of recurrence.
"Women and their doctors face difficult decisions in pregnancy, because both the illness and the
treatment can potentially harm the fetus," said Robert Freedman, M.D., AJP editor in chief. "Accurate
data on the risk of discontinuing treatment for bipolar disorder during pregnancy is part of the
evidence that is needed to make the best possible decision for each woman and her baby,"
The episodes of recurring illness spanned on average more than 40 percent of the duration of
pregnancy for those women who discontinued mood stabilizer medication, but only 9 percent of the
duration of pregnancy for women who continued to take medication. Those whose mood stabilizer
was discontinued abruptly (over a period of two weeks or less) had a median time to recurrence of two
weeks, compared to 22 weeks for women whose medication was more gradually tapered and stopped.















In designing this study, Dr. Viguera and her colleagues incorporated several improvements over
methods used in earlier studies. Previous studies were limited by small size, restricted subject pools
and/or the use of retrospective assessments. The current findings are consistent with many previous
reports that indicated pregnancy is a period of substantial risk for recurrence of bipolar disorder. The
current findings do not support suggestions in previous studies that pregnancy exerts a favorable effect
on the illness and therefore limits the risk of recurrence during pregnancy.


Recently the public's focus has been on the possible adverse effects mood stabilizing medications may
have on fetal development. As a result, many women (including 70 percent of those in this study) stop
taking mood stabilizers before trying to become pregnant. The authors propose that treatment planning
for pregnant women with bipolar disorder include consideration of the high recurrence risk associated
with discontinuation of mood stabilizer medication.


"These findings have important clinical implications for the overall risk/benefit assessment in
managing bipolar disorder during pregnancy," said lead author Adele Viguera, M.D., now at the
Cleveland Clinic. "Patients should be informed not only that there is a significant risk for recurrence
associated with stopping treatment, but also that this risk appears to be greatest early on in pregnancy
and especially, following abrupt discontinuation. Moreover, stopping treatment is associated with a
longer duration of maternal illness during pregnancy compared to remaining on treatment. Therefore,
it is critical for patients with bipolar disorder who are pregnant or planning pregnancy to be informed
of the magnitude of these risks in order for them to weigh these risks along with risks associated with
fetal exposure to medications."


The study was supported in part by the National Institute of Mental Health, NARSAD, the Stanley
Medical Research Institute, the Bruce J. Anderson Foundation, and the McLean Private Donors
Psychopharmacology Research Fund. Additional financial disclosures appear at the end of the article.


About the American Journal of Psychiatry


The American Journal of Psychiatry, the official journal of the American Psychiatric Association, publishes a monthly
issue with scientific articles submitted by psychiatrists and other scientists worldwide. The peer review and editing
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Association. The Journal's editorial policies conform to the Uniform Requirements of the International Committee of
Medical Journal Editors, of which it is a member. AJP in Advance is a regular online feature within which original
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Advance may be cited by using the date they were posted online and their unique digital object identifier (DOI). For
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About the American Psychiatric Association


The American Psychiatric Association is a national medical specialty society whose more than 38,000 physician
members specialize in diagnosis, treatment, prevention and research of mental illnesses including substance use
disorders. Visit the APA at psych and HealthyMinds.