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Drugs for Bipolar Disorder in Pregnancy

Following are some drugs commonly used to treat the symptoms of bipolar disorder during pregnancy:

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Lithium. Although effective in only a limited number of patients, lithium is a popular treatment for bipolar disorder. Recent studies have shown the teratogenicity rates are much lower than reported. The most common effects of fetal exposure are high birth weight and "floppy-baby" syndrome.

Valproate and carbamazepine. These anticonvulsants are associated with major congenital malformations and carry a greater risk of birth defects than lithium. Valproate and carbamazepine have been linked to neural tube defects, craniofacial anomalies, urogenital problems, growth retardation, microcephaly, and heart defects.

Late last year, the American Epilepsy Society's pregnancy outcomes forum panel recommended that valproate should not be prescribed as first line therapy for any indication in women of childbearing age because it significantly increases the risk of major malformations in infants who were exposed in utero.

Lamotrigine. This anticonvulsant is associated with a low overall rate of fetal malformations, but it carries a higher rate of miscarriages and stillbirths than seen in unmedicated women. The agent also has been linked to a skin rash in infants who have different antigen characteristics than their mothers.

Chlorpromazine. This first-generation antipsychotic often is used to treat mania during pregnancy. It is among the best-studied of the antipsychotics in pregnancy, and the data support its relative safety in this population. Related compounds, such as trifluoperazine and perphenazine, also may have low teratogenic risk, although they are not as well studied as phenothiazine chlorpromazine.

Lorazepam and clonazepam. These benzodiazepines often are used to treat the anxiety, agitation, and sleep disturbances that accompany bipolar disorder. They have not been linked to significant increases in malformation rates, although chronic use of benzodiazepines during pregnancy has been linked to withdrawal symptoms in babies.

Olanzapine. One of the newer atypical antipsychotics, olanzapine, is used for acute mania and for prophylaxis against recurrent mania; however, data on this and the other atypical antipsychotics in pregnancy are still too sparse to make conclusions regarding their reproductive safety, according to Dr. Viguera.

Strategies for minimizing the risks associated with all of these drugs include using monotherapy rather than a combination of drugs, and relying on the lowest possible effective dose, Dr. Viguera said. Folic acid supplementation--in addition to a daily prenatal vitamin--may help reduce the increased risk of neural-tube defects. She recommended that women taking anticonvulsants, in particular, take 4 mg of supplemental folic acid per day during the preconception period through the first trimester.

"All women taking these medications during the first trimester should obtain a high-resolution ultrasound at 16-18 weeks to detect the presence of fetal malformations," Dr. Viguera noted.

In addition, because drug metabolism changes during pregnancy, both maternal and fetal serum drug levels should be monitored regularly.

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next: Effects of Atypical Antipsychotics During Pregnancy

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Reviewed: 03/2006



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