Reproductive Decisions

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Brief Report

Reproductive Decisions by Women With Bipolar Disorder
After Prepregnancy Psychiatric Consultation
Adele C. Viguera, M.D.
Lee S. Cohen, M.D.
Suzanne Bouffard, B.A.
T. Hatch Whitfield, M.S.
Ross J. Baldessarini, M.D.
Objective: This study ascertained family planning decisions by
women with bipolar disorder after psychiatric consultation.

Method: The authors surveyed 116 women with DSM-IV bipolar disorder after specialized consultation about treatment options and risks regarding pregnancy.
Results: Of 70 respondents, 45% had been advised to avoid
pregnancy by a health care professional before consultation. After consultation, 63% decided to pursue pregnancy.
Conclusions: Women with bipolar disorder often encounter
obstacles from health care professionals regarding pregnancy.
Individualized comprehensive review of risks and benefits of
treatment options during specialized preconception consultation can support thoughtful clinical planning.
(Am J Psychiatry 2002; 159:2102–2104)

B

ipolar disorder presents special challenges to women
of childbearing age as well as to their families and clinicians. Problems include lower fertility rates, strong genetic
loading, and potential fetal teratogenic risks as well as
high risks of illness recurrence if treatment is discontinued
abruptly (1–10). It is noteworthy, however, that family
planning issues for women with bipolar disorder have received scant research consideration (1, 4). Pregnancy
poses several clinical dilemmas, and evidence-based
guidelines for the clinical care of this population remain
very sparse. Extensive clinical experience suggests that
women with bipolar disorder are often counseled to avoid
or terminate pregnancy in order to avoid risks of potential
fetal exposure to psychiatric medications or risk of recurrent illness.
Mood stabilizers, including valproate, carbamazepine,
and lithium, are associated with teratogenic risks (2, 7).
First-trimester exposure to lithium probably increases the
risk of cardiac malformations, notably Ebstein’s anomaly,
by several-fold, from a baseline risk of 0.005% (1 in 20,000
live births) to a risk ranging from 0.05% to 0.1% (1 in 2,000
to 1 in 1,000 live births) (2). Compared with lithium, anticonvulsants such as carbamazepine and valproic acid
may pose even greater risks, including high rates (1%–5%)
of neural-tube defects such as spina bifida as well as
craniofacial anomalies, cardiac anomalies, microcephaly,
and growth retardation (3, 10). Reproductive safety information about other, newer agents used to treat bipolar
disorder remains very limited, leaving lithium as a plausible first-line option, especially during mid-to-late pregnancy (3, 10). Concern about teratogenic risks associated
with the standard mood stabilizers can lead to incomplete
consideration of the major risks associated with recurrences of bipolar disorder illness during pregnancy. These
risks include not only the particularly high risk of early re-

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lapse after interruption of ongoing treatment but also the
higher risk for postpartum recurrence as well as the impact of untreated psychiatric illness on the development
of the fetus (1, 3, 6, 7, 10).
Although there are no empirically based treatment
guidelines for the management of bipolar disorder during
pregnancy, substantial progress has been made with improved information on the reproductive safety of psychotropic drugs used to treat bipolar disorder and a better understanding of the course of the disorder and the risks of
recurrence during pregnancy and the postpartum period.
Increasingly, women with bipolar disorder who wish to
conceive seek preconception consultation to better understand the risks and benefits of treatment options (10).
This report describes the family planning decisions made
by patients with bipolar disorder after preconception consultation by a reproductive psychiatry subspecialty service
in a major medical center.

Method
A questionnaire was sent to women who sought outpatient
consultation at the Perinatal and Reproductive Psychiatry Program at Massachusetts General Hospital during 1997–2000. The
survey was designed to ascertain information regarding reproductive decisions that followed consultation designed to provide
reliable information about the spectrum of risks associated with
the maintenance or discontinuation of pharmacologic treatment,
thus facilitating informed reproductive decisions.
The Perinatal and Reproductive Psychiatry Program was established in 1987 as a consultation service that provides specialized
care to women suffering from reproductive-associated mood disorders, including affective disorders in pregnancy and the postpartum period.
The goal of the preconception consultation is to provide up-todate information regarding the spectrum of risks associated with
either maintenance or discontinuation of treatment with psychiatric medications. The main objective of the consultation is not to
Am J Psychiatry 159:12, December 2002

BRIEF REPORTS
dictate treatment but to provide accurate information that patients may use to make personal decisions regarding treatment
during pregnancy. In our clinical experience, patients with similar
illness histories who are presented with the same risk-benefit information may make different decisions about maintenance or
discontinuation of treatment in pregnancy. Although patients
surveyed in this study were seen by at least four different clinicians in our program, the variability in treatment practices is
minimal since there is general consensus among those who practice within the program regarding the management of bipolar disorder in pregnancy. A review of our program’s proposed tentative
guidelines for the clinical management of bipolar disorder
throughout pregnancy has been published recently (10).
A 13-question instrument addressed 1) demographic information, 2) reproductive history, 3) family planning practices, 4) reasons for seeking the original consultation, and 5) clinical outcome
after consultation. Questions 3–5 were multiple choice, and multiple answers were encouraged. Patients were given a nominal
payment to encourage cooperation. Massachusetts General Hospital’s institutional review board approved all study procedures,
and subjects provided informed consent for use of questionnaire
data for reporting in anonymous aggregate analyses.

Results
Of 116 questionnaires sent, 13 were undeliverable, and
70 of 103 (68%) were completed and analyzed. The mean
current age of the 70 respondents was 35.4 years (SD=5.7,
range=20–49). Most were Caucasian (97%), were married
(87%), and had a college degree (69%). The mean age at
menarche was 13.2 years (SD=1.8, range=10–20). Irregular
menstrual cycles were reported by half of the group, 11%
(N=8) had undertaken infertility treatment, 19% (N=13)
had at least one miscarriage, and 20% (N=14) had at least
one therapeutic abortion. Before consultation, pregnancies per subject averaged 1.6 (SD=1.3, range=0–5), with a
median of one live birth per subject.
Before consultation, 45% of the respondents (29 of 65)
had been advised not to become pregnant by a health professional: 69% (20 of 29) by psychiatrists or other mental
health professionals and 14% (four of 29) by primary care
physicians or obstetricians. A spouse had urged 21% of the
patients (six of 29) to avoid pregnancy, and 45% (13 of 29)
reported that a parent or sibling had advised against
pregnancy.
Respondents cited several reasons for seeking specialized consultation regarding management of their illness
during a potential pregnancy. A majority, 52% (36 of 69),
had been encouraged by a medical professional to seek
such consultation, and 42% (29 of 69) reported seeking “a
second opinion” on their own. Of those in our group, 55%
(38 of 69) had been considering becoming pregnant and
had sought information about the likely course of their illness and about the relative risks of the various treatment
options, and 22% (15 of 69) had been pregnant at the time
of consultation. About 25% of the group (17 of 69) sought
consultation because they had previously experienced recurrences of bipolar disorder during pregnancy or the
postpartum period.
Am J Psychiatry 159:12, December 2002

Most respondents, 85% (55 of 65), reported that they
had followed the treatment options outlined in their consultation. After consultation, 63% of the group (29 of 46)
attempted to conceive on the basis of their personal assessment of the risks and benefits provided at the consultation and after review of these with their treating psychiatrist. Of those who tried to conceive, 69% (20 of 29)
became pregnant within 12 months. The other 37% (17 of
46) chose to avoid pregnancy, including one who sought to
adopt a child. The most commonly reported reasons to
avoid pregnancy were fear of adverse effects of medicines
on fetal development (56%, 10 of 18) and fear of illness recurrence if maintenance treatment were discontinued
(50%, nine of 18). Fewer women expressed concerns about
potential genetic transmission of bipolar disorder to offspring (22%, four of 18), reluctance to repeat previous
pregnancy-associated illness (17%, three of 18), and fear
that recurring mania or depression would adversely affect
a fetus or existing children (17%, three of 18).
Similar proportions of women perceived that pregnancy
had a positive influence on their illness course and overall
well-being (47%, 16 of 34) as those who reported negative
effects (53%, 18 of 34). In addition, one-half reported that
becoming a mother had bolstered their self-esteem.

Discussion
This follow-up survey of women with bipolar disorder
who had been evaluated in consultation within our program has clear limitations, including incomplete surveying and bias toward women who were well educated, economically advantaged, and highly motivated to seek
expert advice. Nevertheless, it yielded interesting preliminary insights into the concerns of women of childbearing
potential who suffer from bipolar disorder. Approximately
one-half of the 70 respondents had been advised against
pregnancy by a psychiatrist, primary care physician, obstetrician, or family members, suggesting widespread bias
against pregnancy for such women.
Our experience indicates that many women with bipolar disorder, regardless of educational and socioeconomic
background, as well as physicians who care for them, are
ill-informed about the relative risks of perinatal exposure
to psychotropics and the high rates of relapse during pregnancy and the postpartum period without treatment (3, 9,
10). An important finding was that 37% of the patients
chose not to pursue pregnancy when presented with very
similar risk-benefit information on 1) the course and risk
of recurrence of illness during pregnancy and the postpartum period and 2) the reproductive safety data of the various mood stabilizers, as compared to the 63% who attempted to conceive. This finding underscores the role of
patient autonomy in clinical decision making and the importance of providing information about competing risks
and potential benefits involved so that patients can make
informed decisions about pregnancy.

2103

BRIEF REPORTS

A majority of respondents cited concerns about teratogenic risks as well as risk of recurrence after discontinuing
maintenance medication as reasons for deciding against
pregnancy. For this study group, both types of risk were
given similar weight, but this outcome may reflect the impact of the consultation process itself and recent emphasis on maternal risk of treatment discontinuation in our
center (10). On the basis of our clinical experience, fears
about potential teratogenic risks of drug treatment during
pregnancy appear still to have a strong restraining effect
on both patients and physicians, despite the serious risks
of treatment discontinuation in bipolar disorder, which
have been appreciated more recently (6, 7, 10).
The study findings support our impression that providing accurate and balanced information about treatment
options and relative risks, including the limits of current
knowledge, can contribute importantly to informed family planning by women with bipolar disorder. We propose,
specifically, that judgments concerning “reasonable risks”
during pregnancy require shared responsibility but ultimately rest with the patient herself. Moreover, clinicians
should resist automatic discontinuation of ongoing psychotropic medication in pregnancy without informing the
patient of the considerable clinical risks involved (6, 7, 10)
and taking her wishes about treatment and pregnancy
into account. Studies in broader samples of women of
childbearing age with bipolar disorder are required to clarify the unique reproductive health needs of this special
and understudied population and to develop sound policies for their care.

requests to Dr. Viguera, Perinatal and Reproductive Psychiatry Program, WACC 812, Massachusetts General Hospital, 15 Parkman St.,
Boston, MA 02114; [email protected] (e-mail).

Presented in part at the 154th annual meeting of the American
Psychiatric Association, New Orleans, May 5–10, 2001. Received Jan.
25, 2002; revision received June 12, 2002; accepted June 26, 2002.
From the Department of Psychiatry, Harvard Medical School, Boston;
the Perinatal and Reproductive Psychiatry Program, Massachusetts
General Hospital; the Department of Biostatistics, Harvard School of
Public Health, Boston; and the International Consortium for Bipolar
Disorder Research, McLean Hospital, Belmont, Mass. Address reprint

9. Freeman MP, Wosnitzer-Smith K, Freeman SA, McElroy SL,
Kmetz GF, Wright R, Keck PE Jr: The impact of reproductive
events on the course of bipolar disorder in women. J Clin Psychiatry 2002; 63:284–287

2104

Supported in part by NIMH grant MH-01609 and a Young Investigators Award from the National Alliance for Research on Schizophrenia
and Depression (to Dr. Viguera), a grant from the Stanley Foundation
(to Dr. Cohen), and an award from the Bruce J. Anderson Foundation
and the McLean Hospital Psychopharmacology Research Fund (to Dr.
Baldessarini).

References
1. Packer S: Family planning for women with bipolar disorder.
Hosp Community Psychiatry 1992; 43:479–482
2. Cohen LS, Friedman JM, Jefferson JW, Johnson EM, Weiner ML:
A re-evaluation of risk of in utero exposure to lithium. JAMA
1994; 271:146–150
3. Altshuler LL, Cohen L, Szuba MP, Burt VK, Gitlin M, Mintz J:
Pharmacologic management of psychiatric illness during pregnancy: dilemmas and guidelines. Am J Psychiatry 1996; 153:
592–606
4. Leibenluft E: Women with bipolar illness: clinical and research
issues. Am J Psychiatry 1996; 153:163–173
5. Blehar MC, DePaulo JR Jr, Gershon ES, Reich T, Simpson SG,
Nurnberger JI Jr: Women with bipolar disorder: findings from
the NIMH Genetics Initiative sample. Psychopharmacol Bull
1998; 34:239–243
6. Baldessarini RJ, Tondo L, Viguera AC: Effects of discontinuing
lithium maintenance treatment. Bipolar Disord 1999; 1:17–24
7. Viguera AC, Nonacs R, Cohen LS, Tondo L, Murray A, Baldessarini RJ: Risk of recurrence of bipolar disorder in pregnant and
nonpregnant women after discontinuing lithium maintenance. Am J Psychiatry 2000; 157:179–184
8. Blackwood DH, Visscher PM, Muir WJ: Genetic studies of bipolar affective disorder in large families. Br J Psychiatry 2001;
178(suppl 41):S134–S136

10. Viguera AC, Cohen LS, Baldessarini RJ, Nonacs R: Managing bipolar disorder during pregnancy: weighing the risks and benefits. Can J Psychiatry 2002; 47:426–436

Am J Psychiatry 159:12, December 2002

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