Exploring psychotherapeutic issues and agents in clinical practice
Robert H. Howland, MD, Section Editor
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Psychopharmacology
Prescribing Psychotropic Medications
During Pregnancy and Lactation
Principles and Guidelines
Abstract
Treating mental disorders in pregnant
or breastfeeding women is an impor-
tant clinical issue. Antidepressant and
antipsychotic drugs are generally
considered to be relatively safe when
used during pregnancy or breast-
feeding. Benzodiazepine drugs, used
for anxiety or insomnia, have a small
but significant risk of birth defects.
Antidepressant drugs could be used
Journal of Psychosocial Nursing • Vol. 47, No. 5, 2009
as an alternative for treating anxiety
and insomnia. Lithium and anticon-
vulsant drugs (with the exception
of lamotrigine) should generally be
avoided during pregnancy. Antipsy-
chotic drugs can be substituted for
mood stabilizers. Use of anticonvul-
sant drugs is compatible with breast-
feeding. Psychotherapy is a poten-
tial alternative to medication for the
Robert H. Howland, MD
treatment of depression, anxiety dis-
orders, and insomnia. Untreated ma-
ternal psychiatric illness can have ad-
verse effects on pregnancy outcome
and infant well-being. Available treat-
ments and their potential risks when
used during pregnancy or lactation
should be discussed in the context
of the risks of not treating maternal
psychiatric illness effectively.
19
Psychopharmacology
T
reating mental disorders
in pregnant or breast-
feeding women is an
important clinical issue (Ameri-
can College of Obstetricians
and Gynecologists Committee
on Practice Bulletins—Obstet-
rics [ACOG], 2008). In the first
article of this series (Howland,
2009b), I described the kinds of
studies conducted to evaluate
the safety of medications dur-
ing pregnancy and lactation. In
the second article (Howland,
2009a), I described the current
and proposed U.S. Food and Drug
Administration (FDA) classifica-
tion system for medication label-
ing in these situations. In this ar-
ticle, I discuss general principles
and guidelines for prescribing
psychotropic medications during
pregnancy and lactation.
Medication safety
concerns during
pregnancy and
lactation
The ways in which psycho-
tropic medications might affect
pregnancy depend on the tim-
ing of exposure (Altshuler et al.,
1996). Fetal physical malforma-
tions are most likely to arise from
drug exposures during the first
trimester when organ and limb
development occurs. This is an
especially important potential
problem for unplanned pregnan-
cies, because the patient might
not know she is pregnant until
well into the first trimester. Drugs
might affect intra-uterine fetal
growth, contributing to growth
retardation (resulting in low
birth weight neonates) or weight
gain (resulting in large for gesta-
tional age neonates).
Perinatal drug effects might
adversely affect labor and deliv-
ery. Drugs can have immediate
20
postnatal effects, including drug
withdrawal effects or toxicity in
the neonate (e.g., respiratory,
feeding, or neuromuscular distur-
bances). Some drugs might also
affect the fetus in ways that are
apparent only during early child-
hood development or even into
adulthood. Finally, infants could
be adversely affected by drug ex-
posure during breastfeeding, but
this will depend on understand-
ing the extent of drug transfer
into breast milk, as well as the
consequent effects of breast milk
drug exposure in infants.
Antidepressant Medications
Since the initial introduction
of tricyclic antidepressant (TCA)
drugs, antidepressant medica-
tions have been widely used in
clinical practice for nearly 50
years. The serotonin reuptake in-
hibitor (SRI) drugs are the most
commonly used class of antide-
pressant agents, and they are one
of the most commonly prescribed
drugs among all prescription
medications. Hence, clinical ex-
perience with and research data
on antidepressant drug use during
pregnancy and lactation is more
extensive than for other psycho-
tropic drugs. By and large, there
is limited evidence that TCA
and SRI drugs are significantly
harmful when used during preg-
nancy or breastfeeding (ACOG,
2008; Freeman, 2009). The best
available information pertains
to the use of fluoxetine (Pro-
zac®), paroxetine (Paxil®), and
sertraline (Zoloft®). Concerns
about possible adverse cardio-
vascular effects with paroxetine
in particular have been raised,
prompting a change in its FDA
pregnancy classification to D.
The methodology of the studies
identifying a specific cardiovas-
cular risk for paroxetine has been
strongly criticized, however, and
the totality of information about
paroxetine does not consistently
support an association (ACOG,
2008; Einarson et al., 2008; Gen-
tile & Bellantuono, 2009).
Newer generation non-SRI
atypical antidepressant drugs
also have limited evidence of
safety concerns, although it
should be noted that these drugs
have been less well studied and
have been used clinically for a
much shorter time compared
with TCA and SRI drugs (Way,
2007). With the exception of
paroxetine (FDA D rating) and
bupropion (Wellbutrin®) (FDA
B rating), the TCA, SRI, and
atypical antidepressant drugs
have FDA C ratings.
During the postpartum period,
neonatal SRI-discontinuation
syndromes have been described
but without significant sequelae.
Long-term follow up of infants
born to mothers taking antide-
pressant drugs during pregnancy
have not consistently revealed
significant adverse developmen-
tal effects, whereas the long-term
effects of antidepressant exposure
during lactation have not been
well studied. Various psychother-
apies are effective for treating
depression, and they could be an
appropriate alternative to medi-
cation (Raudzus & Misri, 2009).
Anti-Anxiety and Sedative-
Hypnotic Medications
Benzodiazepine drugs had
been associated with a small risk
of birth defects in early studies,
although more recent case con-
trol studies have not confirmed
this association (ACOG, 2008).
Those benzodiazepine drugs used
for anxiety, such as alprazolam
(Xanax®), lorazepam (Ativan®),
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and clonazepam (Klonopin®),
all have FDA D ratings, whereas
those used for insomnia, such as
estazolam (ProSom®), flurazepam
(Dalmane®), quazepam (Doral®),
temazepam (Restoril®), and tri-
azolam (Halcion®), all have X
ratings. By contrast, the non-
benzodiazepine drugs buspirone
(Buspar®), used for anxiety, and
zolpidem (Ambien®), zaleplon
(Sonata®), and eszopiclone
(Lunesta®), all marketed for in-
somnia, have not been associated
with significant adverse pregnan-
cy outcomes. These drugs all have
FDA C ratings. A concern with
the use of benzodiazepine drugs
during late pregnancy is the risk
of postpartum neonatal toxicity
(“floppy infant syndrome”) and
withdrawal syndromes. Sedation
in infants is possible with benzodi-
azepine use during breastfeeding,
but these drugs are less concen-
trated in breast milk compared
with other psychotropic drugs.
The long-term effects on infants
whose mothers took anti-anxiety
or sedative-hypnotic drugs have
not been clearly established.
Because SRI drugs are effec-
tive for various anxiety disorders,
these drugs and buspirone might
be preferred over benzodiazepine
drugs for the prenatal and post-
partum treatment of anxiety
disorders. Likewise, low dosages
of antidepressant drugs, such as
trazodone (Desyrel®), mirtazap-
ine (Remeron®), or sedating
TCA drugs, could be considered
for the treatment of insomnia in
such women. Variations of cog-
nitive-behavioral psychotherapy
are effective for treating anxi-
ety disorders and insomnia, and
these would be considered clini-
cally appropriate to use as an al-
ternative to medication (Ross &
McLean, 2006).
Journal of Psychosocial Nursing • Vol. 47, No. 5, 2009
Antipsychotic Medications
Antipsychotic medications
are prescribed less frequently
than antidepressant drugs, but
they have been used clinically
for more than 50 years. Overall,
there is limited evidence that an-
tipsychotic drugs pose a signifi-
cant hazard when they are used
during pregnancy or breastfeed-
ing (ACOG, 2008), although
much more data are available
for first generation (typical) an-
tipsychotic (FGA) drugs com-
pared with second generation
(atypical) antipsychotic (SGA)
drugs. Because maternal obesity
is associated with a small but
significantly increased risk of
congenital anomalies (Stothard,
Tennant, Bell, & Rankin, 2009),
The selection and use of psychotropic medication
during pregnancy or lactation should be based on
a careful analysis and discussion of various risks
and benefits.
there are potential concerns
about weight gain and use of an-
tipsychotic medications.
A recent study found that in-
fants exposed to SGA drugs had
a significantly higher incidence
of being large for gestational age
and having a heavier birth weight
compared with infants exposed
to FGA drugs (Newham, Thom-
as, MacRitchie, McElhatton, &
McAllister-Williams, 2008). Se-
dation and parkinsonian effects
are possible in breastfed infants
whose mothers are taking antipsy-
chotic drugs. With the exception
of clozapine (Clozaril®), FGA
and SGA drugs have FDA C rat-
ings. Clozapine has a B rating but
has been associated with several
Psychopharmacology
reports of serious adverse effects
in breastfed infants (Gentile,
2008). No form of psychotherapy
would be considered appropriate
to use alone as an alternative to
medication for the treatment of
schizophrenia.
Mood-Stabilizing
Medications
Lithium (Eskalith®, Litho-
bid®) is associated with an in-
creased risk of congenital cardiac
malformations and has an FDA D
rating (ACOG, 2008). The use
of lithium during breastfeeding
also is associated with significant
adverse effects in infants. The
anticonvulsant drugs valproic
acid (Depakene®), valproate so-
dium (Depacon®), divalproex
sodium (Depakote®), and carba-
mazepine (Tegretol®, Equetrol®)
are each associated with birth
defects, although the relative
risk is greater with valproic acid
(Harden & Sethi, 2008; Meador,
2008; Meador et al., 2008). Both
drugs have FDA D ratings, but
they do not pose a significant risk
to infants during breastfeeding.
Unlike the other anticonvulsant
drugs, lamotrigine (Lamictal®)
has not been associated with a
significant risk of birth defects
(FDA C rating), but its clinical
effects in breastfed infants are
not well established (Newport,
Pennell, et al., 2008).
Because women with bipo-
lar disorder have a high risk of
21
Psychopharmacology
relapse, especially during the
postpartum period, pharma-
cological treatment is manda-
tory, and psychotherapy alone is
not appropriate (Yonkers et al.,
2004). Lithium and anticonvul-
sant drugs (with the exception of
lamotrigine) should be avoided
during pregnancy. Antipsychotic
drugs, having anti-manic efficacy,
are an appropriate alternative if
lamotrigine monotherapy is not
sufficient (Newport, Stowe, et
al., 2008). Lithium can be started
immediately postpartum in non-
breastfeeding women. Valproic
acid or carbamazepine could
be initiated postpartum even if
breastfeeding is planned.
Medication
management during
pregnancy and
lactation
Considerations for the use
of medication during and after
pregnancy should begin before
pregnancy ever occurs. Is the
patient sexually active, using
birth control, capable of be-
coming pregnant, or planning
a pregnancy? Would the patient
expect to breast-feed? Patients
should be advised that pregnan-
cy should be planned but also
told what to do if they become
pregnant unexpectedly. Discus-
sions should include the patient
and partner, primary care pro-
vider, obstetrician, pediatrician,
and mental health clinician.
Untreated maternal psychiat-
ric illness can have adverse ef-
fects on pregnancy outcome and
infant well-being. Therefore,
available treatments and their
potential risks when used during
pregnancy or lactation should be
discussed in the context of the
risks of not treating maternal
psychiatric illness effectively.
22
The selection and use of psy-
chotropic medication during
pregnancy or lactation should
be based on a careful analysis
and discussion of various risks
and benefits. What is the risk of
not using medication? What is
known about the relative risks
of different psychotropic medica-
tions for the condition? Are any
nonpharmacological alternative
therapies available? Are there
other current medical conditions
that might affect pregnancy out-
come? Is the patient taking other
nonpsychotropic medications?
Does she use nicotine, alcohol,
or any illicit drugs?
If the patient is treatment
naïve, selecting a medication
with the best-known reproduc-
tive and breastfeeding safety
profile is the best approach. For
patients with a known treat-
ment history, medication that
has been previously or is cur-
rently effective should be used
or continued. Unless the patient
has a strong preference, trying or
switching to a different medica-
tion that does not have a clear
safety advantage over previously
or currently effective medication
is not advisable. The risk of not
effectively treating the patient
during pregnancy or lactation by
trying a new medication is prob-
ably greater than any potential
safety advantage.
Regardless of what medica-
tion is used, mother and fetus
should be closely monitored
during pregnancy. Because the
pharmacokinetics of many drugs
are affected during pregnancy,
dosage adjustments might be
needed to maintain optimal ef-
fectiveness (Fotopoulou et al.,
2009; Sit, Perel, Helsel, & Wis-
ner, 2008). Using the lowest ef-
fective drug dosage is appropri-
ate. However, targeting a lower
subtherapeutic dosage to further
minimize fetal exposure, result-
ing in mild or residual symp-
toms, should be discouraged.
This practice may not only ex-
pose the fetus to any potential
adverse effects of drug exposure
but also to the effects of the in-
adequately treated illness.
Clinical monitoring of moth-
er and infant during breastfeed-
ing is also obviously important.
The pharmacokinetics of many
drugs may change again in
mothers during the postpartum
period. Laboratory studies in
infants (e.g., monitoring drug
concentrations) are not routine-
ly necessary during breastfeed-
ing. Breastfed infants should be
closely observed for any behav-
ioral changes that might be as-
sociated with the drug.
Conclusion
Physicians and nurses have a
responsibility to provide patients
with information about the rela-
tive risks and benefits of using
medication during pregnancy,
the availability of nonpharmaco-
logical alternatives, and the po-
tential harm of not treating men-
tal disorders during pregnancy.
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