Treating bipolar disorder during pregnancy

Evidence about the reproductive safety of other mood stabilizers used in BD is limited. A recent population-based cohort study did not show increased risk of major malformations in children exposed to topiramate, gabapentin, or oxcarbazepine during the first trimester of pregnancy.²¹ Topiramate often is used in combination with other mood stabilizers for weight control, and studies suggest that polypharmacy with topiramate, especially at higher doses and with valproate, increases the risk of major congenital malformations, especially cleft lip and cleft palate.²² Consequently, topiramate is not recommended for women planning to conceive.

Antipsychotics. Although there is increasing information about outcomes of neonates exposed to atypical antipsychotics during pregnancy, the literature still is limited. The greatest number of studies have evaluated olanzapine, risperidone, and quetiapine and show the rate of congenital malformations is 0.9% to 4.1%, which is consistent with general population rates.^23-26 Perinatal complications associated with these atypical antipsychotics include neonatal extrapyramidal syndrome (EPS), possible neonatal adaptation/withdrawal syndrome, and an increased risk of the infant being either large or small for gestational age. Because atypical antipsychotics may increase the risk of metabolic syndrome, women should be counseled about the possible increased risk for gestational diabetes with these medications. None of these drugs have been associated with neurobehavioral sequelae, but long-term follow-up studies of exposed infants are lacking.

For aripiprazole, asenapine, ziprasidone, iloperidone, and lurasidone there is insufficient data about rate of congenital malformations, obstetric complications, and neurobehavioral sequelae. However, perinatal complications associated with these medications include risk of EPS and withdrawal symptoms.^25,26

CASE CONTINUED: Worsening mood symptoms

During pregnancy, Ms. M’s mood is stable on lamotrigine, 200 mg/d, and she participates in individual interpersonally oriented psychotherapy to address anxieties related to becoming a mother. However, late in her third trimester, Ms. M reports worsening symptoms, including depressed mood, insomnia, fatigue, and poor motivation. She also learns her mother had an episode of postpartum depression. Ms. M and her doctor discuss the risks of postpartum relapse, but she declines additional medication for prophylaxis because she is concerned about its impact on breast-feeding.

Two days after delivery, Ms. M complains of increased insomnia and depressed mood, and her husband reports she is not getting out of bed. She describes thoughts and images of throwing her baby out the window, and feels her thoughts are controlled by something outside of herself. Ms. M suspects her husband is having an affair.

Postpartum risks

All women with BD should be counseled regarding prophylaxis with mood stabilizers during the postpartum period. Women with BD are at high risk of mania and psychosis postpartum, particularly those with a personal or family history of postpartum psychosis. Postpartum psychosis frequently presents with an abrupt onset, shortly after delivery (Table 3). Although it may present with the classic symptoms of mania or psychotic depression, it also may have features of delirium.²⁷

Clinicians should immediately implement treatment with mood stabilizers and antipsychotics to manage acute psychotic symptoms, while also ruling out medical causes or comorbidities. Hospitalization should be considered. Aggressive treatment of insomnia will help stabilize mood. Electroconvulsive therapy can be used in treatment-refractory or urgent cases.¹⁰ Lastly, because approximately 4% of women with postpartum psychosis commit infanticide, all mother/child interactions should be closely supervised.²⁷

In small prospective studies, use of lithium within 48 hours of delivery decreased the risk of relapse of postpartum psychosis within the first 3 months.^28,29 In lower-risk patients who have discontinued pharmacotherapy during pregnancy, restarting medication before or immediately after delivery should be considered. At the same time, it is important to minimize sleep disruption, particularly postpartum. Psychoeducation—ideally begun in the preconception counseling visit—is extremely important for emphasizing the need for postpartum sleep.

Table 3

Consequences of postpartum mood relapse

Breast-feeding concerns

Data on risks of infant exposure to medications through breast milk are largely limited to case reports and case series. All mood-stabilizing medications have been found to pass into breast milk at varying concentrations.²⁸ If a patient chooses to breast-feed, she should inform her pediatrician of this decision, and she and her support system should be educated about signs of neonatal toxicity. Ideally, the psychiatrist should liaise with the patient’s pediatrician, especially when infants are premature, because the child’s liver metabolism may be immature, leading to higher serum drug levels and in some cases drug accumulation. Encourage patients to consider bottle feeding, either their own breast milk, pumped and stored, or formula. This will allow others to assist with feedings and the patient to have more consistent sleep, which could stabilize mood.