Practice Guidelines: ACOG Guidelines on Psychiatric Medication Use During Pregnancy and Lactation - American Family Physician

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Practice Guidelines (http://www.aafp.org/afp/viewRelatedDepartmentsByDepartment.htm?departmentId=99&page=0)

ACOG Guidelines on Psychiatric Medication Use During

Pregnancy and Lactation
CARRIE ARMSTRONG
Am Fam Physician. 2008 Sep 15;78(6):772-778.

Guideline source: American College of Obstetricians and Gynecologists

Literature search described? Yes
Evidence rating system used? Yes
Published source: Obstetrics & Gynecology, November 2007
Available at: http://www.greenjournal.org/content/vol110/issue5 (http://www.greenjournal.org/content/vol110/issue5)

An estimated 500,000 pregnancies in the United States each year involve women who have or who will develop psychiatric illness during the pregnancy. The use of
psychotropic medications in these women is a concern because of the risks of adverse perinatal and postnatal outcomes. However, advising these women to
discontinue medication presents new risks associated with untreated or inadequately treated mental illness, such as poor adherence to prenatal care, inadequate
nutrition, and increased alcohol and tobacco use.
Ideally, decisions about psychiatric medication use during and after pregnancy should be made before conception. The use of a single medication at a higher dosage is
preferred over multiple medications, and those with fewer metabolites, higher protein binding, and fewer interactions with other medications are also preferred. All
psychotropic medications cross the placenta, are present in amniotic fluid, and can enter breast milk. The U.S. Food and Drug Administration has categorized
medications according to risk during pregnancy (Table 1).
View/Print Table

Table 1
Safety of Psychiatric Medications During Pregnancy and Lactation
DRUG

FDA PREGNANCY CATEGORY*

AAP RATING

LACTATION RISK CATEGORY

Anxiolytics and hypnotics

Benzodiazepines
Alprazolam (Xanax)

Unknown, of concern

L3

Chlordiazepoxide (Librium)

NA

L3

Clonazepam (Klonopin)

NA

L3

Clorazepate (Tranxene)

NA

L3

Diazepam (Valium)

Unknown, of concern

L3; L4 if used chronically

Estazolam (Prosom)

NA

L3

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Practice Guidelines: ACOG Guidelines on Psychiatric Medication Use During Pregnancy and Lactation - American Family Physician

Flurazepam (Dalmane)

NA

L3

Lorazepam (Ativan)

Unknown, of concern

L3

Oxazepam (Serax)

NA

L3

Quazepam (Doral)

Unknown, of concern

L2

Unknown, of concern

L3

Temazepam (Restoril)
Major Depression

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Ten to 16 percent
of(Halcion)
pregnant women meet diagnostic
criteria for depression, and up to 70NA
percent of pregnant women have
Triazolam
X
L3 symptoms of depression. Studies have
shown a relapse rate of 68 percent in women who discontinue antidepressant therapy during pregnancy. Untreated maternal depression is associated with increased
rates
of adverse outcomes
(e.g.,
Nonbenzodiazepine
anxiolytics
and premature
hypnotics birth, low birth weight, fetal growth restriction, postnatal complications), especially when depression occurs in the late
second to early third trimesters.
Buspirone (Buspar)

NA

L3

There is limited evidence of teratogenic effects from the use of antidepressants in pregnancy and adverse effects from exposure during breastfeeding. Exposure to
selective serotonin
reuptake inhibitors (SSRIs) late
transient neonatal complications;
Chloral hydrate
C in pregnancy has been associated withCompatible
L3 however, the potential risks associated
with SSRI use must be weighed against the risk of relapse if treatment is discontinued. Treatment with SSRIs or selective norepinephrine reuptake inhibitors during
(Lunesta)
C
NA
NA
pregnancy Eszopiclone
should be individualized.
Paroxetine Zaleplon
(Paxil) should
(Sonata)be avoided by pregnantCwomen and women who plan to becomeUnknown,
pregnant,
of concern
and fetal echocardiography
L2
should be considered for women
exposed to paroxetine during early pregnancy. Because abrupt discontinuation of this drug is associated with withdrawal symptoms and a high rate of relapse,
(Ambien)
B
NA
L3
prescribingZolpidem
information
about discontinuation of therapy
should be followed carefully.
Antiepileptics
and
stabilizersand SSRI use has not been studied extensively; however, medication exposure from breastfeeding is less than the exposure that
The
combination
of mood
breastfeeding
occurs transplacentally. Isolated adverse effects have been reported, the most notable of which was an infant who had transient apnea after being exposed to
Carbamazepine
(Tegretol)
D
Compatible
citalopram
(Celexa).
Generally, no long-term neurobehavioral
studies have been done in infants
exposed to SSRIs throughL2breast milk. Most tricyclic antidepressants
seem to be safe during lactation except for doxepin (Sinequan), which reportedly led to an incident of infant respiratory depression.
Lamotrigine (Lamictal)

Bipolar Disorder
Lithium

Unknown

L3

Contraindicated

L4

Rates of postpartum relapse in women with bipolar disorder range from 32 to 67 percent. Perinatal episodes of the disorder tend to be depressive and are more likely
to Valproic
recur inacid
subsequent
psychosis is increased by as much
as 46 percent in women with
(Depakene)pregnancies. The risk of postpartum
D
Compatible
L2 this disorder.

LITHIUM
THERAPY
Antidepressants
The use of lithium during pregnancy has been associated with congenital cardiac malformations, fetal and neonatal cardiac arrhythmias, hypoglycemia, premature
Tricyclics
andother
heterocyclics
delivery,
and
adverse outcomes. However, neurobehavioral sequelae were not found in a five-year follow-up of 60 school-age children exposed to lithium during
gestation. The decision to discontinue lithium therapy during pregnancy because of fetal risks should be weighed against the maternal risks of illness exacerbation.
Amitriptyline

Unknown, of concern

L2

The physiologic changes of pregnancy may affect the absorption, distribution, metabolism, and elimination of lithium, and close monitoring of lithium levels during
(Asendin) period is recommended.
C
Unknown,
of concern
L2 disorder who are taking lithium and plan
pregnancy Amoxapine
and the postpartum
The following guidelines have been
suggested
for women with bipolar
to conceive:
Clomipramine (Anafranil)

Unknown, of concern

L2

Lithium therapy should be gradually tapered before conception in women who have mild, infrequent episodes.
Desipramine (Norpramin)

Unknown, of concern

L2

Lithium therapy should be tapered before conception, but gradually restarted after organogenesis in women who have more severe episodes and are at
moderate
risk
of short-term relapse.
Doxepin
(Sinequan)
C
Unknown, of concern
L5
Lithium therapy should be continued throughout the pregnancy in women who have severe, frequent episodes, and these patients should be counseled about
Imipramine (Tofranil)
C
Unknown, of concern
L2
the reproductive
risks associated with therapy.
Fetal echocardiography should be considered in women exposed to lithium in the first trimester.
Maprotiline (Ludiomil)

NA

L3

The use of lithium during breastfeeding has been associated with a number of adverse effects; however, only 10 maternal-infant dyads have been studied. Effects
Nortriptyline (Pamelor)
C
Unknown, of concern
L2
included lethargy, hypotonia, hypothermia, cyanosis, and electrocardiography changes. No long-term studies have examined the neurobehavioral consequences of
lithium therapy during breastfeeding.
Protriptyline (Vivactil)

NA

NA

ANTIEPILEPTIC THERAPY FOR BIPOLAR DISORDER

Selective serotonin reuptake inhibitors

Several antiepileptic drugs are used in the treatment of bipolar disorder, including valproic acid (Depakene), carbamazepine (Tegretol), and lamotrigine (Lamictal).
However, data
on the(Celexa)
fetal effects of these drugs come
primarily from studies of women with
Citalopram
C
NA seizures. It is not clear whether
L3 the underlying pathology of epilepsy
contributes to the teratogenic effect of these drugs on the fetus.
Escitalopram (Lexapro)

NA

L3 in older infants

Exposure to valproic acid during pregnancy is associated with an increased risk of neural tube defects, craniofacial and cardiovascular anomalies, fetal growth
restriction, Fluoxetine
and cognitive
impairment. Carbamazepine
exposure during pregnancy is associated
withoffacial
dysmorphism and
fingernail
hypoplasia.
It is unclear whether
(Prozac)
C
Unknown,
concern
L2 in
older infants;
L3 in neonates
carbamazepine use increases the risk of neural tube defects or developmental delay. Although these drugs are superior to lithium in the treatment of patients with
mixed episodes or rapid cycling, they should be avoided during pregnancy.
Fluvoxamine (Luvox)

http://www.aafp.org/afp/2008/0915/p772.html#

Unknown, of concern

L2

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Practice Guidelines: ACOG Guidelines on Psychiatric Medication Use During Pregnancy and Lactation - American Family Physician

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The use of lamotrigine during pregnancy has not been associated with any major fetal anomalies and is an option for maintenance therapy in women with bipolar
disorder.
Valproic acid use during lactation has been studied in 41 maternal-infant dyads; only one infant was adversely affected with thrombocytopenia and anemia. The
American Academy of Pediatrics and the World Health Organization consider valproic acid safe in breastfeeding women. Carbamazepine is ruled probably safe; rare
side effects include transient cholestatic hepatitis and hyperbilirubinemia.

Anxiety Disorders
Anxiety disorders are the most common psychiatric disorders, and some (e.g., panic disorder, generalized anxiety disorder, posttraumatic stress disorder, agoraphobia)
are twice as likely to be diagnosed in women than in men. Anxiety and stress during pregnancy are associated with spontaneous abortion, preterm delivery, and
delivery complications, although a direct causal relationship has not been established.
The use of benzodiazepines in women with anxiety disorders does not carry a significant teratogenic risk. Prenatal exposure to diazepam (Valium) increases the risk of
oral cleft, but the absolute risk increases by only 0.01 percent (from six to seven in 10,000 infants). Maternal use of benzodiazepines shortly before delivery is
associated with floppy infant syndrome (i.e., hypothermia, lethargy, poor respiratory effort, and feeding difficulties), and withdrawal syndromes may persist for several
months after delivery in infants whose mothers took alprazolam (Xanax), chlordiazepoxide (Librium), or diazepam.
In general, use of benzodiazepines during breastfeeding affects the infant only if he or she has an impaired ability to metabolize the drug. In this situation, the infant
may demonstrate sedation and poor feeding.

Schizophrenia
Adverse outcomes have been reported in women with schizophrenia, including preterm delivery, low birth weight, placental abnormalities, increased rates of congenital
malformation, and a higher incidence of postnatal death. If left untreated during pregnancy, schizophrenia can have devastating effects on the mother and child.
Atypical antipsychotics have replaced typical agents as first-line therapy for psychotic disorders because these drugs are better tolerated and may be more effective in
managing the negative symptoms of schizophrenia. The reproductive safety data on atypical antipsychotics are limited, but the use of olanzapine (Zyprexa),
risperidone (Risperdal), quetiapine (Seroquel), and clozapine (Clozaril) has been associated with increased rates of low birth weight and therapeutic abortion. No longterm studies of children exposed to atypical antipsychotics during gestation have been conducted. Therefore, the routine use of these drugs during pregnancy and
lactation is not recommended.
Typical antipsychotics have a larger reproductive safety profile; no significant teratogenic effect has been documented with chlorpromazine (Thorazine), haloperidol
(Haldol), or perphenazine (Trilafon). Doses of typical antipsychotics should be minimized during the peri-partum period to limit the necessity of using additional
medications to manage extrapyramidal side effects.
Data on antipsychotic use in breastfeeding women are limited. A small study of chlorpromazine use during breastfeeding showed no developmental deficits in children
up to five years of age; however, a study of both chlorpromazine and haloperidol revealed developmental deficits in children 12 to 18 months of age.
Coverage of guidelines from other organizations does not imply endorsement by AFP or the AAFP

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