New Guidelines Shed Light on Use of Psychiatric Medications During Pregnancy
http://www.medscape.com/viewarticle/572803

April 10, 2008 — The American College of Obstetricians and Gynecologists (ACOG) has issued updated guidelines for the treatment of certain psychiatric illnesses during pregnancy and breast-feeding. The April 2008 Practice Bulletin updates the previous November 2007 bulletin and is based on current evidence of risks and benefits of treatment of psychiatric illnesses during pregnancy. The guidelines are designed to aid clinicians in providing appropriate care.

"The bulletin acknowledges that there's good evidence that untreated or inadequately treated mental illness is unhealthy, which is probably one of the first times it's ever been pointed out so definitively," Zachary N. Stowe, MD, from Emory University in Atlanta, Georgia, who contributed to the development of these guidelines, told Medscape Psychiatry.

The committee that developed the practice bulletin sought to evaluate all available information and provide a critical appraisal of whether particular studies should influence treatment paths, he added.

The study is published in the April issue of Obstetrics & Gynecology.

Risks of Fetal Exposure vs Untreated Maternal Illness

It is estimated that each year in the United States, more than 500,000 women have psychiatric illnesses before or during pregnancy, and one third of all pregnant women are exposed to psychiatric medication during their pregnancy, the bulletin authors write.

"Advising a pregnant or breastfeeding woman to discontinue medication exchanges the fetal or neonatal risks of medication exposure for the risk of untreated mental illness," they note. Untreated or inadequately treated maternal mental illness "may result in poor compliance with prenatal care, inadequate nutrition, exposure to additional medications or herbal medicines, increased alcohol and tobacco use, deficits in mother-infant bonding, and disruptions within the family environment," they add.

"All psychotropic medications studied to date cross the placenta, are present in amniotic fluid and can also enter human breast milk," the authors write.

They summarized their findings in the following 15 recommendations and conclusions stratified according to the strength of the evidence supporting them:

* Level A evidence (from good and consistent scientific evidence):
o Lithium exposure in pregnancy may be associated with a small increase in congenital cardiac malformations, with a risk ratio of 1.2 to 7.7.
o Valproate exposure in pregnancy is associated with an increased risk for fetal abnormalities and should be avoided if possible, especially during the first trimester.
o Carbamazepine exposure during pregnancy is associated with fetal carbamazepine syndrome and should be avoided if possible, especially during the first trimester.
o Maternal benzodiazepine use shortly before delivery is associated with floppy infant syndrome.
* Level B evidence (from limited or inconsistent scientific evidence):
o Paroxetine use in pregnant women and women who are planning to become pregnant should be avoided, if possible, and fetal echocardiography should be considered when fetuses are exposed to paroxetine in early pregnancy.
o Prenatal benzodiazepine exposure increased the risk for oral cleft (absolute risk increased by 0.01%).
o Lamotrigine is a potential maintenance therapy option for pregnant women with bipolar disorder and has a growing reproductive safety profile relative to alternative mood stabilizers.
o Untreated or inadequately treated maternal psychiatric illness may have various negative consequences.
* Level C evidence (primarily from consensus and expert opinion):
o Multidisciplinary care management involving the patient's obstetrician, mental health clinician, primary health care provider, and pediatrician is recommended whenever possible.
o Use of a single medication at a higher dose is favored vs the use of multiple medications to treat psychiatric illness during pregnancy.
o Close monitoring of lithium during pregnancy and postpartum is recommended.
o Measuring serum drug levels in breast-fed neonates is not recommended.
o Treatment with selective serotonin-reuptake inhibitors, selective norepinephrine reuptake inhibitors, or both during pregnancy should be individualized.
o A fetal echocardiogram examination should be considered when the fetus is exposed to lithium during the first trimester of pregnancy.

The Practice Bulletin was developed by the ACOG committee on Practice Bulletins with the assistance of Dr. Stowe and Kimberly Ragan, MSW, at the Life Enrichment Counseling Center, in Gainesville, Virginia.

Obstet Gynecol. 2008;111:1001-1020.
Clinical Context

Psychiatric illness can promote multiple negative effects on pregnancy outcomes. Anxiety disorders are associated with an increased risk for forceps deliveries, prolonged labor, fetal distress, and preterm delivery. Maternal depression increases the risk for low birth weight delivery, as does schizophrenia. Schizophrenia is also associated with placental abnormalities and antenatal hemorrhage.

Despite these negative effects of psychiatric illnesses on pregnancy, there are also significant concerns with the safety of psychotropic medications during gestation. All psychotropic medications cross the placenta and are present in amniotic fluid. The current review examines the safety of these medications.
Study Highlights

* Psychiatric illness during pregnancy is best managed with a multidisciplinary approach involving the obstetrician, mental health clinician, and primary care provider.
* A single medication at a higher dose is preferred vs multidrug therapy for psychiatric illness during pregnancy.
* Of women receiving medications for depression at conception, more than 60% will have symptoms of depression during pregnancy. The risks for negative pregnancy outcomes are higher when depression occurs in the late second to early third trimester.
* Women with depression may be considered for medical therapy during pregnancy on an individual basis, depending primarily on the severity of the illness. However, paroxetine should be avoided because of evidence of congenital cardiac malformations, anencephaly, and omphalocele with the use of this medication during pregnancy.
* Other selective serotonin-reuptake inhibitors are not considered major teratogens. Limited data from studies of antidepressants other than selective serotonin-reuptake inhibitors have failed to demonstrate any significant fetal anomalies associated with their use.
* Prenatal use of benzodiazepines increases the risk for oral cleft by 0.01%, and maternal benzodiazepine use immediately before delivery can result in floppy infant syndrome. It remains unclear whether there are any long-term neurobehavioral consequences of maternal benzodiazepine use on children.
* Lithium can increase the risk for cardiac malformations by a factor of 1.2 to 7.7 and the risk for overall congenital malformations by a factor of 1.5 to 3. Neonatal lithium toxicity can result in flaccidity, lethargy, and poor suck reflexes.
* Echocardiogram examination of the fetus should be considered for women exposed to lithium during the first trimester.
* Women using lithium for mild bipolar disorder should be considered for tapering of the medication before conception, whereas women at moderate risk for relapse of bipolar disorder may stop lithium until organogenesis is complete. Women at a high risk for relapse of bipolar disorder may continue lithium throughout gestation.
* Valproate and carbamazepine should be avoided in pregnancy, if possible, because each is associated with a higher risk for fetal anomalies. Lamotrigine appears to be a safer choice as a treatment of bipolar disorder.
* Typical antipsychotic drugs have a more extensive reproductive safety profile vs second-generation antipsychotic medications. No significant teratogenic effects have been documented with the use of chlorpromazine, haloperidol, and perphenazine. Nonetheless, second-generation antipsychotic drugs have not been associated with a significant risk for neonatal toxicity or somatic teratogenesis.
* Exposure to selective serotonin-reuptake inhibitors in breast milk is lower than during fetal growth, and tricyclic antidepressants (except doxepin) are also generally safe during breast-feeding. The use of lithium during breast-feeding is discouraged, but valproate and carbamazepine are most likely safe.

Pearls for Practice

* Among all antidepressants, paroxetine should be avoided in pregnancy.
* The safest medication for the treatment of bipolar disorder during pregnancy appears to be lamotrigine.
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