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Marlene Busko


January 3, 2008 — In a prospective observational study of 89 pregnant women with bipolar disorder, 71% had at least 1 mood episode recurrence during pregnancy. Compared with the women who continued taking mood stabilizers, those who stopped this treatment had a 2-fold higher risk for mood relapse, a 4-fold shorter time to relapse, and a 5-fold greater amount of time spent ill during pregnancy.

These findings, by Adele C. Viguera, MD, from the Cleveland Clinic Neurological Institute, in Ohio, and colleagues, are published in the December issue of the American Journal of Psychiatry.

"The present findings challenge the evidently common practice of abruptly stopping maintenance treatment for psychiatric disorders during pregnancy," the group writes, adding that given the high morbidity associated with discontinuation of mood-stabilizing treatment and its uncertain impact on fetal development, they recommend a more balanced consideration of risks and benefits in the clinical management of pregnant women with bipolar disorder.

Knowledge Gaps
Women with bipolar disorder who become pregnant encounter several obstacles to care, including "extraordinary knowledge gaps" about the course of the illness during pregnancy, predictors of recurrence, and reproductive safety data for mood stabilizers, the group writes.

They aimed to examine the risk for recurrence of mood episodes among women with a history of bipolar disorder who continued or discontinued taking mood stabilizers when they became pregnant.
They prospectively enrolled 89 pregnant women diagnosed with bipolar disorder (69% bipolar 1 disorder and 31% bipolar 2 disorder) who were seeking psychiatric consultation in a specialized center. The women had a mean age of 32.7 years, and most were white, well-educated, married, and working outside the home. Most women (n=55) were taking lithium, and 32 were taking an anticonvulsant as their primary mood stabilizer; 46 women were also taking an antidepressant, and 24 women were also taking an antipsychotic agent.
A total of 62 of the 89 women discontinued treatment with a mood stabilizer.

High Risk for Maternal Morbidity
During pregnancy, 70.8% of the women experienced at least 1 episode of bipolar disorder. Compared with the women who continued taking a mood stabilizer, those who discontinued this treatment had a 2-fold greater risk for recurrence and a more than 4-fold shorter time to a new episode of bipolar disorder.
Morbidity During Pregnancy: Continuing vs Stopping Mood Stabilizers

MorbidityContinued Treatment, n = 27Discontinued Treatment, n = 62All Subjects, n = 89
At least 1 recurrence of bipolar episode, %37.085.570.8
% of pregnancy weeks spent ill with a mood disorder8.843.332.8
Median time to first recurrence, weeks9.0>40—

Most new mood episodes emerged early in pregnancy; risk in the first, second, and third trimester was 47.2%, 31.9%, and 18.8%, respectively. Most episodes (74%) were depression or a mixed state rather than hypomania or mania.

Women who discontinued their mood stabilizers abruptly (1–14 days, n=35) had a 50% risk for recurrence of mood episodes within 2 weeks; among women who discontinued more gradually, it took 22 weeks to attain this risk level. Rapid discontinuation of medication was more likely with unplanned pregnancy.
The authors note that this study might underrepresent the relapse risk in a broader population.
A major clinical implication is that "for women with severe and frequent recurrences of bipolar disorder, maintenance treatment with a mood stabilizer during pregnancy may be the most prudent strategy, much as maintenance treatment is recommended for pregnant women with other serious and chronic conditions, such as epilepsy," they write.

Fear and Panic Among Psychiatrists, Patients
This is a "groundbreaking" study in that it is the largest known prospective study of the course of bipolar disorder during pregnancy, and it provides a greater understanding of the serious risk for relapse during pregnancy, writes Marlene P. Freeman, MD, from the University of Texas Southwestern Medical Center at Dallas, in an accompanying editorial.

"Psychiatrists and patients alike are frequently overwhelmed with fear and panic when a woman with bipolar disorder discovers she is pregnant," she writes. Known teratogenic risks in the first trimester from treatment with some commonly used mood stabilizers include neural tube defects with valproate and carbamazepine and cardiovascular malformations such as Ebstein's anomaly with lithium, she adds, noting that the time of greatest concern for neural tube defects from anticonvulsants is very early in pregnancy, often before a woman discovers that she is pregnant.

"In the case of an unplanned pregnancy, information from the treating physician about the risks of the medication as well as the risks of untreated bipolar disorder would help avoid the panicked and fear-based decision that often occurs in this situation," she writes.

The authors' postpartum data in a forthcoming report is expected to add valuable insights into this important and understudied area of psychiatry, she concludes.