What's the best strategy for bipolar disorder during pregnancy?

Journal of Family Practice, August, 2007 by Genevieve Minick, Michel Atlas, Heather Paladine

Evidence-based answer

Lithium is the first-line treatment for pregnant patients requiring medication (SOR: C, based on expert opinion).

Monotherapy is preferred for women of childbearing age who have bipolar disorder (strength of recommendation [SOR]: C, based on expert opinion).

When prescribing lithium or anticonvulsant drugs (eg, valproic acid and carbamazepine), draw blood levels monthly during the first and second trimesters, and then weekly in the third trimester (SOR: C, based on expert opinion).

Give all pregnant women taking medications for the prevention of mania a detailed fetal anatomy ultrasound at 18 to 20 weeks (SOR: C, based on expert opinion).

Behavior therapy has a role as an adjunct to pharmacologic therapy, but no studies show its benefit alone in preventing mania (SOR: C, based on expert opinion).

Electroconvulsive therapy may be beneficial for patients with refractory depressive symptoms, and may be used in pregnancy (SOR: C, based on expert opinion).

Clinical commentary

Psychiatric consultation is essential

Unfortunately, the medications used to treat this serious health problem can also have important negative effects on a patient's health. Although the principles outlined here are helpful guidelines, in practice I rarely treat patients with bipolar disorder without psychiatric consultation.

As family physicians, it's critical that we address reliable contraception and the importance of preconception planning with women early in the course of this psychiatric illness.

Heather Paladine, MD

University of Southern California, San Gabriel

* Evidence summary

Data on the treatment of bipolar disease among fertile women are limited to case-control studies and drug registries because of a lack of RCTs in this population. (1) Onset of bipolar illness often occurs in the teens and twenties, which puts women with bipolar disorder at risk for having episodes requiring treatment during their childbearing years. Treatment might be initiated for a nonpregnant patient, but you must consider potential pregnancy when choosing a medication.

The TABLE shows common medications used in bipolar illness, their risk categories for pregnancy and lactation, and monitoring recommendations. (1-5)

Lithium is first-line treatment Monotherapy for bipolar illness is preferred; it generally minimizes the risk of congenital anomalies. The use of lithium for long-term management of bipolar disorder is associated with decreased rates of suicide and all-cause mortality. (6)

Is risk of Ebstein's anomaly a factor?. Lithium is associated with 10- to 20-fold higher risk of Ebstein's anomaly, a congenital anomaly affecting the tricuspid valve and right ventricle, with varying clinical effects. However, the absolute risk is small: Ebstein's anomaly occurs in 1:20,000 unexposed pregnancies. (2,7,8) Because concerns about this anomaly are less of a problem than once thought, lithium is the first-line treatment for bipolar disorder in pregnancy. (7)

Discontinue with care. The risk of recurrence of mania is 3 times higher with rapid discontinuation of lithium over less than 2 weeks. (2,7) Taper lithium over 2 to 4 weeks when discontinuing the medication. (7)

Women taking lithium may already be pregnant when you see them, and even a slow lithium taper may not minimize exposure to the developing fetus. (2,8)

Thoroughly discuss the risks and benefits of continued treatment and close monitoring compared with discontinuation.

Anticonvulsants and antipsychotics pose their share of risks

Antiseizure medications, including carbamazepine and valproic acid, are considered human teratogens in the first trimester. (9) If a woman has an unplanned pregnancy and presents late in the first trimester or in the second trimester, discontinuation of these medication in stable patients is not recommended. Valproate and carbamazepine are both compatible with breastfeeding.

Although lamotrigine was thought to have fewer risks than other drugs, the FDA issued an alert in September 2006 suggesting a possible increased risk of cleft palate for infants exposed to lamotrigine in the first trimester. (10)

Typical antipsychotics appear to be safe in pregnancy, but they can have side effects for the mother. These side effects include extrapyramidal symptoms, such as tardive dyskinesia and hyperprolactinemia.

Atypical antipsychotics have not been well studied, but there is no conclusive evidence that they cause fetal malformations. (1)

100-fold higher risk of postpartum psychosis

Women with bipolar disorder have a 100-fold higher risk of developing postpartum psychosis. (2)

For this reason, treatment beyond delivery is recommended, along with close monitoring of the infant.

Drug monitoring and dosing

Second and third trimesters. Monitor the levels of lithium and anticonvulsants monthly through the second trimester, then weekly during the third trimester because of blood volume changes. (2)

Medication doses may also need to be increased up to 50% during the second and third trimesters, when creatinine clearance doubles and the plasma volume increases. (8)