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
They summarized their findings in the following 15 recommendations and
conclusions stratified according to the strength of the evidence supporting
* Level A evidence (from good and consistent scientific evidence):
* Lithium exposure in pregnancy may be associated with a small
increase in congenital cardiac malformations, with a risk ratio of 1.2 to
* Valproate exposure in pregnancy is associated with an increased risk
for fetal abnormalities and should be avoided if possible, especially during
the first trimester.
* Carbamazepine exposure during pregnancy is associated with fetal
carbamazepine syndrome and should be avoided if possible, especially during
the first trimester.
* Maternal benzodiazepine use shortly before delivery is associated
with floppy infant syndrome.
* Level B evidence (from limited or inconsistent scientific evidence):
* 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
* Prenatal benzodiazepine exposure increased the risk for oral cleft
(absolute risk increased by 0.01%).
* 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.
* Untreated or inadequately treated maternal psychiatric illness may
have various negative consequences.
* Level C evidence (primarily from consensus and expert opinion):
* Multidisciplinary care management involving the patient's
obstetrician, mental health clinician, primary health care provider, and
pediatrician is recommended whenever possible.
* Use of a single medication at a higher dose is favored vs the use of
multiple medications to treat psychiatric illness during pregnancy.
* Close monitoring of lithium during pregnancy and postpartum is
* Measuring serum drug levels in breast-fed neonates is not
* Treatment with selective serotonin-reuptake inhibitors, selective
norepinephrine reuptake inhibitors, or both during pregnancy should be
* 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.
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
* 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
* 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
* The safest medication for the treatment of bipolar disorder during
pregnancy appears to be lamotrigine.
According to the current ACOG Practice Bulletin, which of the following
antidepressants should be avoided during pregnancy?
Which of the following medications has the best safety profile for the
treatment of bipolar disorder during pregnancy?
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