Evidence-Based Reviews

Treating bipolar disorder during pregnancy

Current Psychiatry. 2011 September;10(9):59-66

Optimal outcomes require careful preconception planning, medication risk/benefit analysis

References

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Ms. M, age 31, has bipolar I disorder and takes lamotrigine, 200 mg/d, and aripiprazole, 10 mg/d. She was first hospitalized at age 20 for a manic episode and was discharged on lithium, 1,200 mg/d. She was hospitalized again at age 25 for a depressive episode that occurred after she stopped taking lithium because of undesirable side effects. She was switched to lamotrigine, 200 mg/d, which she tolerated well. Aripiprazole, 10 mg/d, was added 1 year later to address emergence of mild mood elevation symptoms.

During a recent follow-up appointment, Ms. M expresses interest in getting pregnant in the next 6 months. Her mood has been stable for 5 years and she asks if she should stop taking her medications in preparation for pregnancy. What would you recommend?

Because the typical age of onset for bipolar disorder (BD) is late adolescence or early adulthood, women are at risk for new onset or recurrence of mood episodes throughout their peak reproductive years. This article updates practitioners on the treatment of BD during pregnancy, including preconception planning and the risks and benefits of medication use during pregnancy. We also cover treatment considerations during the postpartum period, such as prophylaxis of mood episodes and mood stabilizer treatment for women who breast-feed.

Prenatal planning

Ideally, “prenatal planning” should begin long before women with BD prepare to have children. Because one-half of pregnancies in the United States are unplanned¹ and manic episodes may result in impulsivity and increased sexual activity, all women of reproductive age with BD should be counseled about birth control and risks of unplanned pregnancies. Discussions about risks of in utero exposure to psychotropics should occur when medications are first prescribed. Because certain mood stabilizers, (eg, carbamazepine) may decrease efficacy of oral contraceptives by inducing cytochrome P450 (CYP450) enzymes, women taking these medications also should be counseled about additional methods of birth control.²

Oral contraceptives also may affect mood stabilizer levels through similar mechanisms. Because of CYP450 induction, lamotrigine serum levels are lower during the 3 “active” weeks of exposure to exogenous estrogen. During the “pill-free” last week, lamotrigine levels may increase up to 54%.³

Because mood stabilizers such as valproate are associated with teratogenic risks, women with BD should be asked about contraception at every visit.⁴ Valproate also has been associated with an increased risk of menstrual cycle irregularity. Some studies have shown that even before initiating mood stabilizers, women with BD have a higher incidence of menstrual cycle irregularity than women without BD, which suggests the link between polycystic ovarian syndrome (PCOS) and BD may be independent of medications and part of the endophenotype.⁵

Clinical Point

Because mood stabilizers are associated with teratogenic risks, ask women with BD about contraception at every visit

The importance of prenatal vitamins should be discussed. The recommended folate dosage for women planning to become pregnant is 0.4 to 1 mg/d and 0.8 to 5 mg/d for women with either a previous pregnancy with neural tube defects or those taking an antiepileptic medication.⁶

Table 1⁷ summarizes recommendations to improve prenatal planning in women with BD. Goals include:

meeting with the patient at least 3 months before conception to review current menstrual cycle functioning. If your patient exhibits any signs or symptoms of PCOS, consider referral to a gynecologist
meeting with patient and partner/significant supports to discuss treatment decisions
optimizing the patient’s mood before conception, preferably for at least 3 to 6 months
prescribing monotherapy at the lowest therapeutic dose if clinically feasible
assessing the patient’s personal preferences and beliefs regarding medication use during pregnancy and breast-feeding
assessing the patient’s capacity to understand the risks and benefits of medication continuation/discontinuation during pregnancy, including risk for relapse, current literature on teratogenicity, perinatal complications, and neurodevelopmental studies. Document that the patient provides informed consent.

Table 1

Pregnancy and BD: Medication management guidelines

Comprehensive prenatal counseling should begin at least 3 months before pregnancy. Folate supplementation is advised
Medication should be avoided if clinically feasible (particularly during the first trimester). Avoid abrupt discontinuation. Increase psychosocial and clinical supports
If medication is pursued: Use minimum effective dose Monotherapy is preferable Avoid changing effective medications unless there is significant safety or clinical advantage Increase frequency of clinical monitoring as indicated
Comprehensive postpartum counseling should begin before and be reinforced throughout pregnancy, emphasizing: importance of sleep postpartum prophylaxis risks/benefits of breast-feeding importance of social support and identification of support structure, including psychoeducation session with support team
BD: bipolar disorder Source: Adapted from reference 7

CASE CONTINUED: Medication decisions

Ms. M’s first question is, “Should I stop taking my medications?” Ms. M and her psychiatrist review the risks and benefits of medication exposure during pregnancy (Table 2) and decide against discontinuing all medications because of her history of relapse when she stopped lithium. Because Ms. M’s mood has been stable for 5 years, she and her psychiatrist decide to limit her medications to lamotrigine monotherapy at her current dose, and agree to slowly taper aripiprazole. One week later, Ms. M calls and states she has a positive pregnancy test and is wondering if she should stop aripiprazole all at once. Ms. M is advised to continue with the original plan to slowly taper aripiprazole.