28 Current Women’s Health Reviews, 2011, 7, 28-34
1573-4048/11 $58.00+.00 © 2011 Bentham Science Publishers Ltd.
Antidepressant Use During Breastfeeding
Jan Øystein Berle1,* and Olav Spigset2,3
1Department of Psychiatry, Haukeland University Hospital, P.O. Box 23 Sandviken, N-5812 Bergen, Norway;
2Department of Clinical Pharmacology, St Olav University Hospital, Trondheim, Norway; 3Department of Laboratory
Medicine, Children’s and Women’s Health, Norwegian University of Science and Technology, Trondheim, Norway
Abstract: Background: The treatment of breastfeeding mothers with depression raises several dilemmas, including the
possible risk of drug exposure through breast milk for the infant. This article provides background information and pre-
sents practical advice and recommendations for the clinician dealing with the treatment of depression and related disorders
in the postpartum period.
Methods: An electronic search for relevant articles was performed. As the use of tricyclic antidepressants has considerably
decreased during the last decade and no new information on breastfeeding has emerged for the tricyclics in this period,
this review exclusively focuses on the newer, non-tricyclic compounds.
Results: Most newer antidepressants produce very low or undetectable plasma concentrations in nursing infants. The
highest infant plasma levels have been reported for fluoxetine, citalopram and venlafaxine. Suspected adverse effects have
been reported in a few infants, particularly for fluoxetine and citalopram.
Conclusions: Infant exposure of antidepressants through breast milk is generally low to very low. We consider that when
antidepressant treatment is indicated in women with postpartum depression, they should not be advised to discontinue
breastfeeding. Paroxetine and sertraline are most likely suitable first-line agents. Although some concern has been ex-
pressed for fluoxetine, citalopram and venlafaxine, we nevertheless consider that if the mother has been treated with one
of these drugs during pregnancy, breast-feeding could also be allowed during continued treatment with these drugs in the
postpartum period. However, an individual risk-benefit assessment should always be performed.
Keywords: Antidepressant, breastfeeding, postpartum, nursing infant, SSRI, depression.
postpartum period; a prevalence of 10 to 15 % is often re-
ported [1-3]. During this period, challenges are related to
caretaking of the newborn infant in addition to the poten-
tially harmful effects of the depression on the mother. De-
pressed mothers may be intrusive or withdrawn and disen-
gaged, and are less sensitively attuned to their infants than
healthy women . In a study of 112 mother-infant pairs,
chronic maternal depression in the first year postpartum was
related to delayed psychomotor development in the infant at
15 months . Moreover, untreated maternal depression may
also affect the cognitive and emotional development of the
infant. Thus, the high prevalence of postpartum depression,
causing functional impairment in the mother and potential
disturbances of the mother-infant relationship, makes it
important to initiate effective, rapid-onset therapies in
women suffering from this disorder [4, 6-8].
Depression is a common illness among women in the
may be even more common than postpartum depression .
The peak age of onset for anxiety disorders in women corre-
sponds with their childbearing years, and particularly the
Postpartum anxiety disorders are underemphasized and
*Address correspondence to this author at the Bergen Mental Health
Research Center, Haukeland University Hospital, Department of Psychiatry,
P.O. Box 23 Sandviken, N-5812 Bergen, Norway; Tel: 0047 55958461;
Fax: 0047 55958436; E-mail: email@example.com
rates of obsessive-convulsive disorder and generalized anxi-
ety disorder are increased in postpartum women. Due to few
studies only very limited data are available to guide clinical
interventions for women with or at risk for having perinatal
anxiety disorders . Medication with antidepressants, in
particular selective serotonin reuptake inhibitors, may be
indicated also in some of these women.
for the infant and the mother . Human milk represents the
ideal primary source of nutrients and provides better immu-
nological and antioxidant protection than do milk substitutes
[7, 10, 11]. Therefore, women are strongly encouraged to
breastfeed when possible . Both the American Academy
of Pediatrics and the World Health Organisation recommend
the exclusive use of breast milk for 6 months, with use
of milk substitutes only for infants who cannot be breastfed
The benefits of breastfeeding are well documented, both
weighing the potential risk to the infant of antidepressant
exposure through breast milk against the disadvantage of not
receiving mother’s milk. A third alternative, to discontinue
or not commence drug treatment, might be even more harm-
ful, taking into account the risk of not receiving adequate
treatment for the mother and thereby indirectly also for the
infant [5, 6]. Specific questions to be answered when decid-
ing how to handle a woman with postpartum depression in-
clude: What are the risks for the mother and the infant if the
The dilemma in the treatment of breastfeeding mothers is
Antidepressant Use During Breastfeeding Current Women’s Health Reviews, 2011, Vol. 7, No. 1 29
maternal depression is not adequately treated? How strong is
the mother’s desire to breastfeed her infant? What are the
disadvantages of not receiving mother’s milk for the infant?
What are the risks for the infant of being exposed to an anti-
depressant through breast milk? Is there any evidence to
suggest that some antidepressants are more favorable than
others to use during breastfeeding, and are there sufficient
data to give conclusive advice for the most recently marketed
antidepressants? Could any practical strategies be used to
reduce the drug exposure to the infant? And finally, given
that there is a (small) risk of adverse effects in the infant due
to drug exposure and breastfeeding nevertheless is allowed,
should the infant be monitored in any way?
option, and women with postpartum depression tend to pre-
fer non-pharmacological treatment instead of using medi-
cines . It has also been shown that women in the postpar-
tum period receive fewer prescriptions of psychotropic drugs
than do non-breastfeeding women, but although psychother-
apy is effective in the treatment of postpartum depression
, it is not widely available. Thus, there is a risk that
women not receiving antidepressant treatment would be in-
adequately treated for their illness. One major study showed
that psychological intervention for post-partum depression
improved maternal mood in the short term, but that this
benefit was not superior to spontaneous remission in the long
In some cases, non-pharmacological treatment may be an
antidepressants in the postpartum period. Recent case re-
ports, case series and open trials suggest efficacy in women
suffering from postpartum depression, although many of
these trials excluded women who were breastfeeding .
Several studies have shown improvements in postpartum
depressive symptoms resulting from treatment with selective
serotonin reuptake inhibitors (SSRIs), such as sertraline ,
fluvoxamine  and fluoxetine , and the SSRIs are
thus considered first-line therapy in postpartum depression
. The SSRI group is also recommended in the treatment
of postpartum dysthymia, panic disorder, and obsessive-
compulsive disorder . In addition, the serotonin-
noradrenaline reuptake inhibitor (SNRI) venlafaxine has
been found to reduce the symptoms of postpartum depres-
A few studies have specifically addressed the effect of
sion comprise a high-risk group for subsequent episodes; a
recurrence risk of about 25% has been reported . The
findings from a small randomised study comparing sertraline
and placebo in asymptomatic women with at least one prior
episode of postpartum depression suggest that postpartum
depression can be prevented , although the result needs
to be replicated in a larger scale. Psychosocial or psycho-
logical interventions have not been shown to significantly
prevent the risk of developing postpartum depression .
Women with a previous episode of postpartum depres-
partum depression from 2005 concluded that it is not possi-
ble to draw any clear conclusions about the effectiveness of
antidepressants in preventing postpartum depression .
The reason was the lack of conclusive evidence, and the
authors stated that larger trials were needed.
A Cochrane review of antidepressant prevention of post-
antidepressant treatment given during pregnancy could be
continued or not when the mother wants to breastfeed. Dis-
continuing essential antidepressant treatment in the postpar-
tum period should be avoided, and switching to another anti-
depressant might also be problematic in this vulnerable pe-
riod. Thus, the issue of infant safety in the postpartum period
should preferably be taken into consideration already when
drug treatment is started in a woman, irrespective of whether
it is before or during pregnancy.
Knowledge about infant effects of antidepressants trans-
ferred via breast milk is mostly based upon case studies and
small case series. A comprehensive review and pooled
analysis of antidepressant levels in breast milk and nursing
infants, including possible adverse effects in the infants, was
published in 2004 . An update of this review, adding
new information from the period 2004 - 2008, was published
in 2009 . The aim of the present article is to take even
newer data into account, providing aggregated background
information and presenting practical advice and recommen-
dations for the clinician dealing with the treatment of depres-
sion in the postpartum period. During the last decade, the use
of tricyclic antidepressants has considerably decreased,
mostly because they are no longer considered first-line ther-
apy due to their adverse effect profile and toxicity. There-
fore, this review focuses on the newer, non-tricyclic antide-
pressants, i.e. the SSRIs citalopram, escitalopram, fluoxetine,
fluvoxamine, paroxetine and
venlafaxine and duloxetine, and reboxetine, bupropion and
mirtazapine. First, we present data on the levels of these
antidepressants in breast milk and in infant plasma; thereafter
we discuss the reported short-term and long-term adverse
effects in infants. Finally, we suggest a number of practical
In some cases, there is a question of whether an effective
sertraline, the SNRIs
ANTIDEPRESSANT LEVELS IN BREAST MILK
antidepressants studied [7, 27-29]. In general, drug concen-
trations in milk parallel those in maternal plasma, but with a
slight delay. Due to the lipophilicity of the drugs, milk levels
are typically somewhat higher than the levels in maternal
plasma. For example for citalopram, the milk/plasma con-
centration ratio, i.e. the ratio between the concentration in
milk and in maternal plasma, is in the interval 1.2–3.0 [10,
30]. Notably, the triglyceride levels in milk have been shown
to influence the drug concentrations. In a study from our
group, higher triglyceride levels were, as expected, found in
post-feed milk than in pre-feed milk, with accordingly higher
drug concentrations in post-feed milk, as shown e.g. for
citalopram, sertraline and fluoxetine . Consequently, for
research purposes and when comparing results from different
studies, it is important to provide information about in which
phase the milk sample has been obtained.
Detectable levels have been found in breast milk for all
daily drug dose ingested by the infant, assuming an average
milk intake of 150 ml per kg body weight per day. The infant
dose per kg body weight can then be expressed as a percent-
age of the maternal dose per kg body weight. When the
relative dose is below 10%, the exposure could generally
be considered negligible, and a notational level of concern of
The milk drug concentration can be used to estimate the
30 Current Women’s Health Reviews, 2011, Vol. 7, No. 1 Berle and Spigset
10% has therefore been suggested . The 10% limit has
subsequently also been accepted by organisations such as the
American Academy of Pediatrics. The relative infant doses
are close to 10% and in some cases even above 10% for cita-
lopram, fluoxetine and venlafaxine, and somewhat lower for
escitalopram, whereas the relative infant doses are low for
fluvoxamine, paroxetine, sertraline, duloxetine, reboxetine,
bupropion and mirtazapine (Table 1).
ANTIDEPRESSANT LEVELS IN THE INFANT
more direct measure of infant exposure than is the milk con-
centration. Among the SSRIs, paroxetine, fluvoxamine and
sertraline basically produce undetectable plasma levels. The
levels of citalopram have been measurable in some infants,
albeit mostly relatively low. Fluoxetine and venlafaxine pro-
duce the highest infant plasma concentrations [10, 27], in
some infants up to more than 80% and 30% of the assumed
Obviously, the drug concentration in infant plasma is a
therapeutic concentrations in adults, respectively. However,
such high concentrations are uncommon; e.g. for fluoxetine,
infant plasma concentrations higher than 10 % of the mater-
nal plasma levels were found in 8 of 36 cases (22 %), only,
in a review . The other antidepressants have either been
undetectable (duloxetine, bupropion) or been detected at
extremely low concentrations (escitalopram, reboxetine, mir-
tazapine) in infant plasma (Table 1).
tions have been found, the infants have generally been below
3-4 months of age . The capacity to metabolize drugs is
generally not fully developed in neonates, but increases
gradually as the hepatic function matures during the first 3-6
months postpartum. After this period, measurable infant
plasma levels would not be expected to occur for any antide-
pressant. On the other hand, in preterm newborns, the meta-
bolic capacity will be even more impaired than in full-term
neonates. As a consequence of the immature hepatic function
in neonates and the gradual development of the metabolic
It should be noted that in the cases where high concentra-
Table 1. Infant Doses and Plasma Concentrations of Newer Antidepressants after Excretion in Breast Milk
Drug Approximate Number of
Mother/Infant Pairs Studied1
Absolute Infant Plasma
Relative Infant Plasma
Selective serotonin reuptake inhibitors
Citalopram 8012 0.14 3-10 Negligible5 Up to 106
Escitalopram 12 0.04 3-6 <5 <4
Fluoxetine7 149 0.14 <12 Up to 1008 Up to 808
Fluvoxamine 12 0.12 <2 Not detected9 -
Paroxetine 119 0.03 0.5-3 Not detected9 -
Sertraline 145 0.04 0.5-3 Not detected9 -
Venlafaxine10 2313 0.50 6-9 Up to 40 Up to 30
Duloxetine 614 <0.03 <1 Not detected 9 -
Reboxetine 4 0.03 1-3 <5 <2
Bupropion11 2015 0.20 2 Not detected9 -
Mirtazapine 1116 0.04 0.5-3 0.2 16 <1 16
1 The numbers given here are the sum of the number of cases included in the review by Weissmann et al. , the number of cases included in the review by Lanza di Scalea et al.
, and the number of cases obtained from literature published after the Lanza di Scalea review was completed. The new references are shown in footnotes 12-16.
2 Calculated for an infant with a body weight of 5 kg, and assuming a daily milk intake of 150 ml/kg body weight.
3 Infant daily dose per kg body weight expressed as a percentage of maternal daily dose per kg body weight. A value below 10 % is generally considered negligible.
4 Infant plasma concentration expressed either as a percentage of the measured maternal plasma concentration or as a percentage of what could be considered a low therapeutic con-
centration in adults .
5 In most cases below the lower limits of detection for the analytical methods employed, which were mostly in the range of 2–5 ng/ml. However, in a few cases, which also have been
associated with suspected adverse effects, concentrations up to 15 ng/ml have been found.
6 In a few cases, which also have been found associated with suspected adverse effects, concentrations up to about 50 % of the therapeutic concentration range have been found.
7 The values represent the sum of fluoxetine and the active metabolite norfluoxetine.
8 In some cases, which also have been associated with suspected adverse effects, as high as about 500 ng/ml, i.e., clearly within the therapeutic concentration range.
9 Below the lower limits of detection for the analytical methods employed, which were mostly in the range of 1–5 ng/ml.
10 The values represent the sum of venlafaxine and the active metabolite O-desmethylvenlafaxine.
11 Including one or several of the active metabolites of bupropion.
12 One new case (cf. footnote 1) is obtained from Werremeyer, 2009 .
13 Thirteen new cases (cf. footnote 1) are obtained from Newport et al., 2009 .
14 One new case (cf. footnote 1) is obtained from Briggs et al., 2009 .
15 Four new cases (cf. footnote 1) are obtained from Davis et al., 2009 .
16 One new case (cf. footnote 1) is obtained from Tonn et al., 2009 . In this case, the infant plasma concentration was 10 ng/ml, corresponding to about 30 % of the maternal
Antidepressant Use During Breastfeeding Current Women’s Health Reviews, 2011, Vol. 7, No. 1 31
capacity of drugs, infant age is a central factor to take into
account when performing an individual risk analysis.
pacity of hepatic enzymes involved in the metabolism of
antidepressants may also affect the infant plasma levels. The
most relevant enzymes with regard to antidepressant metabo-
lism are the polymorphic cytochrome P-450 enzymes
CYP2D6 and CYP2C19. In a study of 24 lactating mothers
treated with SSRIs or venlafaxine and their 25 infants, a
genetically determined impaired capacity to metabolise
drugs via these enzymes (in the mother and/or the infant) did
not significantly increase infant exposure . Notably, a
mother who was a CYP2C19 poor metaboliser and was
treated with the CYP2C19 substrate citalopram had the high-
est plasma concentration of citalopram among all subjects
studied. Nevertheless, her twin infants (who both were het-
erozygous extensive CYP2C19 metabolisers) still had ex-
tremely low plasma concentrations of citalopram .
Genetically determined differences in the metabolic ca-
POSSIBLE ADVERSE EFFECTS IN THE INFANT
most infants are able to exert pharmacological effects re-
mains an open question. For the drugs causing the lowest –
and in many cases even undetectable – levels, such an influ-
ence is unlikely. In two studies attempting to elucidate the
pharmacodynamic potential of antidepressants in breastfed
infants, platelet serotonin levels were measured in the infants
before and during maternal treatment with SSRIs [33, 34].
In the first study, no differences were observed when
the mothers were treated with sertraline . In the second
study, no effects were seen in 10 of 11 infants whose
mothers were treated with fluoxetine .
Whether the low antidepressant concentrations found in
antidepressants through breast milk have been suspected in a
few cases, and more often after exposure to fluoxetine and
citalopram than after exposure to other drugs [7, 27, 35-40].
The effects observed have mostly been subtle and unspecific,
and may even have arisen by coincidence. For example, cry-
ing, irritability, decreased feeding and watery stools have
been described in a few cases for fluoxetine [35-37]. For
citalopram, hypotonia, colic, decreased feeding and sleep
difficulties have been reported in single cases [38, 39]. For
other SSRIs the observations are even scantier . Al-
though single case reports are difficult to interpret with re-
gard to causality it is interesting to note that the number of
reports is higher for the drugs showing the highest infant
plasma levels, i.e. citalopram and fluoxetine. For ven-
lafaxine, which also has a relatively high infant exposure, no
adverse events have been reported [10, 41-43], but the total
number of exposed infants is considerably lower for ven-
lafaxine than for e.g. citalopram and fluoxetine (Table 1).
Adverse events in breastfed infants exposed to newer
old breastfed infant after 4 days of maternal bupropion
treatment . Although seizures are a well-known adverse
effect of bupropion, the relationship remains obscure, par-
ticularly as the infant was relatively old and had a respiratory
tract infection, and as the levels of bupropion and/or active
metabolites were not documented, neither in milk nor in the
A single case of seizures has been reported in a 6-month-
of SSRIs and previously suspected adverse events in breast-
fed infants we developed a questionnaire of infant symptoms
to be filled in by the mothers . The questionnaire was
completed by 20 mothers treated with SSRIs or venlafaxine
and well as by a control group of 68 medication-free breast-
feeding mothers. The questionnaire included signs such as
sneezing, regurgitation or vomiting, loud crying, decreased
sleep, increased sleep, irritability, tremor, decreased muscle
tone, and suckling or feeding problems. There were no
significant differences in any symptoms between the two
Based on known adverse reactions after therapeutic use
adverse events in 31 infants whose mothers were treated
with citalopram, 7 infants whose mothers were treated with
other SSRIs, 5 infants whose mothers were treated with non-
SSRIs and 31 infants of healthy mothers not taking any
medication . There were no significant differences in the
frequency of signs reported in the infants between the groups
(3/31, 0/12 and 1/31, respectively). Nevertheless, the three
infants in the citalopram group presented with decreased
feeding, colic and irritability, respectively, which have been
suspected as adverse effects also in other reports [38, 39].
Another study has compared the frequency of possible
feeding mothers has been proposed . The index is ex-
pressed as the ratio between the reported number of infants
with adverse events after exposure to an antidepressant
through milk and the reported total number of exposed in-
fants for the same antidepressant, multiplied by 100. It is
suggested that a value ?2 indicates that the drug is relatively
safe; a value of 2.1-10 indicates that the drug should be used
with great caution, and a value above 10 indicates that the
drug should be contraindicated in breastfeeding mothers. The
index has some limitations, such as that it is less reliable
when the number of cases in the literature is low, and that it
does not take into consideration the quality of raw data, e.g.
whether the suspected adverse events most likely have arisen
by coincidence or whether the relationship to drug exposure
more likely is causal. Finally, there is a risk that the numbers
found are abnormally high, as one could expect that there are
numerous exposures without any adverse effects that have
not been reported in the literature, whereas the reporting rate
is considerably higher for infants where possible adverse
effects were observed. By applying the safety index on the
cases reported before 2007, the calculated values were 0.68
and 0.95 for sertraline and paroxetine, and 3.5 and 5.3 for
fluoxetine and citalopram, respectively . These differ-
ences in safety index values between the various drugs
are consistent with what would be expected from literature
reviews applying more qualitative investigative approaches
In conclusion, even though antidepressants probably have
been subject to more published data then any other drug
class (cf. Table 1) there is, with a few exceptions, little evi-
dence for causality between exposure through breast milk
and adverse events in the infants .
A specific safety index for antidepressant use in breast-
THE POTENTIAL RISK OF LONG-TERM EFFECTS
SSRI exposure via breast milk and body weight increase
Several studies have investigated the possible effect of
32 Current Women’s Health Reviews, 2011, Vol. 7, No. 1 Berle and Spigset
during the first year of life. In a study of 78 nursing infants
whose mothers were treated with SSRIs (n=75) or ven-
lafaxine (n=3), there were no differences in body weight
compared to values from normative populations . In
a study on 11 infants exposed to citalopram, there were no
differences in body weight after 12 months compared to 10
infants of medication-free mothers . Finally, in a study
on 27 infants exposed to paroxetine, there were no differ-
ences in body weight at 6 and 12 months compared to 27
breastfeed and 19 bottle-feed infants of medication-free
Long-term nevrobehavioural data on infant antidepres-
sant exposure through breast milk is generally lacking. Such
studies are also methodologically challenging, as the longer
follow-up time, the greater influence would other factors,
such as maternal mental health, be expected to have on the
infant, relative to the role of drug exposure through breast
milk. Although there is a lack of data concerning exposure
through breast milk, some long-term information is available
after antidepressant exposure in utero [47-52]. In these stud-
ies, no detrimental long-term effects were revealed for fac-
tors such as global intelligence quotient, language, behav-
ioural development and neurological development. In a re-
cent study in four-year-old children investigated by the Child
Behaviour Check List , maternal mood was found to be
more predictive of internalising behaviours than prenatal
exposure to psychotropic drugs. Moreover, in another study
no differences in externalising behaviours were detected
between four-year-old children exposed to SSRIs during
pregnancy and a non-exposed group . These results are
reassuring, as antidepressant exposure in utero causes serum
concentrations that are at least 5- to 10-fold higher than ex-
posure through breast milk [47, 52, 55].
breast-feeding during treatment with antidepressants have
been made, including some more comprehensive reviews
and overviews [7, 27, 29, 40, 45]. Also scientific organisa-
tions have attempted to develop practical guidelines [56-58],
but two of these guidelines [56, 58] put more focus on drug
treatment during pregnancy than in the postpartum period
and are relatively vague with regard to the choice of specific
drugs in lactating women.
Most of the reviews and guidelines recommend that the
choice of specific treatment should be based upon an indi-
vidual risk-benefit analysis. In such an analysis both the risk
of untreated maternal illness for the mother and the infant,
the risk/benefit of the specific treatment for the mother and
the infant, the risk/benefit of being breastfed or not for the
infant, the possible maternal risks of renouncing breastfeed-
ing, and the mother’s desire to breastfeed should be taken
into consideration. Medication exposure may involve a risk
for the infant, but there are also risks both with an untreated
depression and of not receiving mother’s milk for the infant.
Therefore, no clinical decision in the context of postpartum
depression is completely risk-free .
Several attempts to guide clinical decisions regarding
apy should be considered, particularly for mild to moderate
depression. For women with moderate to severe depression
Non-pharmacological interventions such as psychother-
and in some cases also with anxiety disorder, medications
are generally the most appropriate choice of treatment.
Moreover, for women with previous postpartum depression
or women who have been treated with antidepressants during
pregnancy, antidepressants are the preferred mode of treat-
ment in the prophylaxis or new episodes/relapses.
ally recommended that paroxetine and sertraline should be
preferred over other SSRIs due to the low infant exposure for
these drugs (Table 1) [7, 29, 40, 57]. However, paroxetine
might have some disadvantages related to the treatment of
women in fertile age in general. First, if the mother needs
long-term treatment and subsequently becomes pregnant
once again, paroxetine is probably not the first choice due to
the risk of cardiac defects. Second, the risk of withdrawal
symptoms might be higher than for other SSRIs if one or a
few doses are missed (which possibly might occur more of-
ten among busy, and perhaps even sleep-deprived, post-
partum mothers than among other women).
Regarding the choice of specific antidepressant, it is usu-
and citalopram should be avoided or used with caution due
to the higher infant plasma levels than for other drugs and
the possible risk of adverse effects in the infant [7, 29, 40].
However, if the mother has been treated with fluoxetine or
citalopram previously and the treatment was effective, or if
the mother has used one of these drugs during pregnancy, it
could also be used in the postpartum period [7, 29]. In a
study from our group including various SSRIs and ven-
lafaxine , we concluded that when antidepressant treat-
ment is indicated in the postpartum period, the women
should generally not be advised to discontinue breastfeeding.
It is often recommended that when possible, fluoxetine
drugs, with about 100 cases for fluoxetine, paroxetine, ser-
traline and citalopram, but less than 25 for the other newer
antidepressants (Table 1). Some degree of uncertainty inevi-
tably exists for the drugs with the lowest numbers of exposed
infants, also when no adverse effects have been reported. On
this basis, drugs for which little data exist, such as fluvoxam-
ine, venlafaxine, duloxetine, reboxetine, bupropion and mir-
tazapine, should not be considered as first-line therapies, but
they can be used in special cases [7, 29, 57].
The numbers of exposed cases vary significantly between
monitoring, particularly if the infant is sick, premature or has
a low body weight [7, 27, 57]. However, given the very low
risk of infant effects and the unspecific nature of possible
infant symptoms, we consider there is no general need for
regular and specific follow-up examinations .
Some of the reviews and guidelines recommend infant
drug concentration analysis is generally not recommended
[7, 27, 45]. It can, however, be helpful if the infant has signs
that may be indicative of drug exposure . In addition, it
is our experience that it is often reassuring for a mother who
has a strong desire to continue breastfeeding to know that the
drug is found in negligible concentrations in milk and/or
infant plasma. Thus, arguments exist to perform milk or in-
fant plasma drug analyses more liberally than often recom-
mended, at least when such analyses are easily available.
As antidepressants are lipophilic drugs, their excretion in
breast milk is expected to vary with milk triglyceride content
Routine breast milk and/or infant serum sampling for
Antidepressant Use During Breastfeeding Current Women’s Health Reviews, 2011, Vol. 7, No. 1 33
[10, 60]. Yet, the nutritional value of human milk is also
linked to its triglyceride levels. Therefore, any effort to avoid
the rather minimal additional drug exposure imposed by
breast milk containing high vs. low triglyceride levels cannot
be recommended .
Most antidepressants have long elimination half-lives and
their levels in breast milk generally vary relatively little dur-
ing a dose interval. Consequently, avoiding breastfeeding
during the peak concentration phase, e.g. by taking the daily
drug dose in the evening and avoiding breastfeeding during
the night, will only reduce the infant drug intake to a small
sure is of little value. First, there is no indication that there is
a risk threshold that is crossed if the infant exposure is re-
duced to some extent, e.g. by 30-50%. Second, discarding
breast milk implicitly implies that drug exposure is detrimen-
tal if the infant is feeded by breast milk, only. Third, in our
experience, a procedure of e.g. 50% breast-feeding and 50%
bottle-feeding most often ends with bottle-feeding, only,
after a relatively short period of time.
Pumping and discarding breast milk to reduce the expo-
in need of effective treatment. Several modalities of inter-
vention may be helpful, and both psychotherapy and treat-
ment with antidepressants are recommended.
Data from a large number of studies show that antide-
pressants differ with respect to infant exposure. Available
data are clearly homogenous with this respect, showing that
in the SSRI group, paroxetine and sertraline are excreted in
milk in low amounts that do not produce measurable concen-
trations in infant plasma, and these drugs have neither been
associated with clear-cut adverse effects in the infant. On the
other hand, fluoxetine and citalopram are excreted in milk in
higher amounts, which in a few cases have caused significant
plasma levels in the infant and suspected adverse effects. For
other newer antidepressants, data are scarce, with relatively
few exposed infants reported. Of these drugs, preliminary
data indicate that venlafaxine causes somewhat higher infant
exposure than the other drugs.
Postpartum depression is a potentially serious condition
suggest that when antidepressant treatment is indicated in
women with postpartum depression, they should generally
not be advised to discontinue breastfeeding. With regard to
choice of specific agent, paroxetine and sertraline should be
considered first. Nevertheless, although some concern has
been expressed for fluoxetine, citalopram and venlafaxine,
we consider that if the mother has been treated with one of
these drugs during pregnancy, breast-feeding could generally
also be allowed during continued treatment with these drugs
instead of switching to a “safer” drug. However, these drugs,
in addition to drugs for which very little information exist,
should not be considered first-line agents if there are not
specific reasons for preferring them.
Taking all current knowledge into consideration, we
Berle JØ, Aarre TF, Mykletun A, Dahl AA, Holsten F. Screening
for postnatal depression. Validation of the Norwegian version of
the Edinburgh Postnatal Depression Scale, and assessment of
risk factors for postnatal depression. J Affect Disord 2003; 76:
O´Hara MW, Schwain AM. Rates and risk of postpartum depres-
sion – a meta-analysis. Rev Psychiatry 1996; 8: 37-54.
Gaynes B, Gavin N, Meltzer-Brody S, et al. Perinatal depression:
prevalence, screening accuracy, and screening outcomes. Evid Rep
Technol Assess 2005; 119: 1-8.
Murray L, Fiori-Cowley A, Hooper R, Cooper P. The impact of
postnatal depression and associated adversity on early mother-
infant interactions and later infant outcome. Child Dev 1996; 67:
Cornish AM, McMahon CA, Ungerer JA, Barnett B, Kowalenko N,
Tennant C. Postnatal depression and infant cognitive and motor de-
velopment in the second postnatal year: the impact of depression
chronicity and infant gender. Infant Behav Dev 2005; 28: 407-17.
Brockington IF. Diagnosis and management of post-partum disor-
ders: a review. World Psychiatry 2004; 3: 89-95.
Lanza Di Scalea T, Wisner KL. Antidepressant medication use
during breastfeeding. Clin Obstet Gynecol 2009; 52: 483-97.
Poobalan AS, Aucott LS, Ross L, Smith WCS, Helms PJ. Effects
of treating postnatal depression on mother-infant interaction and
child development. Br J Psychiatry 2007; 191: 378-86.
Ross LE, McLean LM. Anxiety disorders during pregnancy and the
postpartum period: A systematic review. J Clin Psychiatry 2006;
Berle JØ, Steen VM, Aamo TO, Breilid H, Zahlsen K, Spigset O.
Breast-feeding during maternal antidepressant treatment with sero-
tonin reuptake inhibitors: Infant exposure, clinical symptoms and
cytochrome P-450 (CYP) genotypes. J Clin Psychiatry 2004; 65:
Newton ER. Breastmilk: the gold standard. Clin Obstet Gynecol
2004; 47: 632-42.
Gartner LM, Mortan J, Lawrence RA, et al. American Academy of
Pediatrics policy statement: breastfeeding and the use of human
milk. Pediatrics 2005; 115: 496-506.
World Health Organization. Infant and young child feeding.
Geneva, Switzerland: World Health Organization; 2003. Available
at: http//www.who.int/en. [Accessed on: January 31, 2010].
Pearlstein TB, Zlotnick C, Battle CL, et al. Patient choice of treat-
ment for postpartum depression: a pilot study. Arch Womens Ment
Health 2006; 9: 303-8.
O’Hara MW, Stuart S, Gorman LL, Wenzel A. Efficacy of inter-
personal psychotherapy for postpartum depression. Arch Gen Psy-
chiatry 2000; 57: 1039-45.
Cooper PJ, Murray L, Wilson A, Romaniuk H. Controlled trial of
the short- and long-term effect of psychological treatment of post-
partum depression. Impact on maternal mood. Br J Psychiatry
2003; 182: 412-9
Wisner KL, Hanusa BH, Perel JM, et al. Postpartum depression. A
randomized trial of sertraline versus nortriptyline. J Clin Psycho-
pharmacol 2006; 26: 353-60.
Suri R, Burt VK, Altshuler LL, Zuckerbrow-Miller J, Fairbanks L.
Fluvoxamine for postpartum depression. Am J Psychiatry 2001;
Appleby L, Warner R, Whitton A, Faragher B. A controlled study
of fluoxetine and cognitive behavioural counselling in the treatment
of postnatal depression. BMJ 1997; 314: 932-6.
Wisner KL, Parry BL, Piontek CM. Clinical practice: postpartum
depression. N Engl J Med 2002; 347: 194-9.
Boerner RJ, Möller HJ. The importance of the new antidepressants
in the treatment of anxiety/depressive disorders. Pharmacopsychia-
try 1999; 32: 119-26.
Cohen LS, Viguera AC, Bouffard SM, et al. Venlafaxine in the
treatment of postpartum depression. J Clin Psychiatry 2001; 62:
Wisner KL, Perel JM, Peindl KS, Hanusa BH, Findling RL, Rap-
port D. Prevention of recurrent postpartum depression: a random-
ized controlled trial. J Clin Psychiatry 2001; 62: 82-6.
Wisner KL, Perel JM, Peindl KS, Hanusa BH, Piontek CM,
Findling RL. Prevention of recurrent postpartum depression: a ran-
domized clinical trial. Am J Psychiatry 2004; 161: 1290-2.
Dennis CL. Psychosocial and psychological interventions for pre-
vention of postnatal depression: systematic review. BMJ 2005;
34 Current Women’s Health Reviews, 2011, Vol. 7, No. 1 Berle and Spigset Download full-text
Howard LM, Hoffbrand S, Henshaw C, Boath L, Bradley E. Anti-
depressant prevention of postnatal depression. Cochrane Database
Syst Rev 2005: CD004363.
Weissman AM, Levy BT, Hartz AJ, et al. Pooled analysis of
antidepressant levels in lactating mothers, breast milk, and nursing
infants. Am J Psychiatry 2004; 161: 1066-78.
Spigset O, Hägg S. Excretion of psychotropic drugs into breast
milk. CNS Drugs 1998; 9: 111-34.
Berle JØ, Spigset O. Maternal antidepressant use and breast-
feeding. Curr Med Lit – Psychiatry 2008; 19: 33-7.
Spigset O, Carleborg L, Öhman R, Nordstöm A. Excretion of
citalopram in breast milk. Br J Clin Pharmacol 1997; 44: 295-8.
Begg EJ, Atkinson HC, Duffull SB. Prospective evaluation of a
model for the prediction of milk:plasma drug concentrations from
physicochemical characteristics. Br J Clin Pharmacol 1992; 33:
Kearns GL, Abdel-Rahman SM, Alander SW, et al. Developmental
pharmacology – drug disposition, action, and therapy in infants and
children. N Engl J Med 2003; 349: 1157-67.
Epperson N, Czarkowski KA, Ward-O’Brien D, et al. Maternal
sertraline treatment and serotonin transport in breast-feeding
mother–infant pairs. Am J Psychiatry 2001; 158: 1631-7.
Epperson CN, Jatlow PI, Czarkowski KA, Anderson GM. Maternal
fluoxetine treatment in the postpartum period: effects on platelet
serotonin and plasma drug levels in breastfeeding mother–infant
pairs. Pediatrics 2003; 112: e425.
Isenberg KE. Excretion of fluoxetine in human breast milk. J Clin
Psychiatry 1990; 51: 169.
Lester BM, Cucca J, Andreozzi L, Flanagan P, Oh W. Possible
association between fluoxetine hydrochloride and colic in an infant.
J Am Acad Child Adolesc Psychiatry 1993; 32: 1253-5.
Kristensen J, Illett KF, Hackett LP, Yapp P, Paech M, Begg EJ.
Distribution and excretion of fluoxetine and norfluoxetine in hu-
man milk. Br J Clin Pharmacol 1999; 48: 521-7.
Schmidt K, Olesen OV, Jensen PN. Citalopram and breast-feeding:
serum concentration and side-effects in the infant. Biol Psychiatry
2000; 47: 164-5.
Lee A, Woo J, Ito S. Frequency of infant adverse events that
are associated with citalopram during breast-feeding. Am J Obstet
Gynecol 2004; 190: 218-21.
Gentile S. Use of contemporary antidepressants during breast-
feeding: a proposal for specific safety index. Drug Saf 2007; 30:
Hendrick V, Altshuler L, Wertheimer A, Dunn WA. Venlafaxine
and breast-feeding. Am J Psychiatry 2001; 158: 2089-90.
Ilett KF, Kristensen JH, Hackett LP, Paech M, Kohan R, Rampono
J. Distribution of venlafaxine and its O-desmethyl metabolite in
human milk and their effects in breastfed infants. Br J Clin Phar-
macol 2002; 53: 17-22.
Newport DJ, Ritchie JC, Knight BT, Glover BA, Zach EB, Stowe
ZN. Venlafaxine in human breast milk and nursing infant plasma:
determination of exposure. J Clin Psychiatry 2009; 70: 1304-10.
Chaudron LH, Schoenecker CJ. Bupropion and breastfeeding: a
case of a possible infant seizure. J Clin Psychiatry 2004; 65: 881-2.
Ragan K, Stowe ZN, Newport DJ. Use of antidepressants and
mood stabilizers in breast-feeding women. In: Cohen LS, Nonacs
RM, Eds. Mood and anxiety disorders during pregnancy and post-
partum (Review of Psychiatry Series, Volume 24, Number 4; Old-
ham JM and Riba MB, series editors). Washington, DC, American
Psychiatric Publishing, 2005; pp. 105-44.
Hendrick V, Smith LM, Hwang S, Altshuler LL, Haynes D. Weight
gain in breastfed infants of mothers taking antidepressant medica-
tions. J Clin Psychiatry 2003; 64: 410-2.
Heikkinen T, Ekblad U, Kero P, Ekblad S, Laine K. Citalopram in
pregnancy and lactation. Clin Pharmacol Ther 2002; 72: 184-91.
Merlob P, Stahl B, Sulkes J. Paroxetine during breast-feeding:
infant weight gain and maternal adherence to counsel. Eur J Pediatr
2004; 163: 135-39.
Nulman I, Rovet J, Stewart DE, et al. Neurodevelopment of
children exposed in utero to antidepressant drugs. N Engl J Med
1997; 336: 258-62.
Simon GE, Cunningham ML, Davis RL. Outcomes of prenatal
antidepressant exposure. Am J Psychiatry 2002; 159: 2055-61.
Ericson A, Kallén B, Wiholm B-E. Delivery outcome after the use
of antidepressants in early pregnancy. Eur J Clin Pharmacol 1999;
Heikkinen T, Ekblad U, Palo P, Laine K. Pharmacokinetics of
fluoxetine and norfluoxetine in pregnancy and lactation. Clin
Pharmacol Ther 2003; 73: 330-7.
Misri S, Reebye P, Kendrick K, et al. Internalizing behaviors in 4-
year-old children exposed in utero to psychotrophic medications.
Am J Psychiatry 2006; 163: 1026-31.
Oberlander TF, Reebye P, Misri S, Papsdorf M, Kim J, Grunau RE.
Externalizing and attentional behaviors in children of depressed
mothers treated with selective serotonin reuptake inhibitor anti-
depressant during pregnancy. Arch Pediatr Adolesc Med 2007;
Hendrick V, Stowe ZN, Altshuler LL, Hwang S, Lee E, Haynes D.
Placental passage of antidepressant medications. Am J Psychiatry
2003; 160: 993-6.
National Collaborating Centre for Mental Health. NICE guideline
on clinical management and service guidance. Antenatal and post-
natal mental health. No. 45, 2007. Available at: http://www.nice.
org.uk/nicemedia/pdf/CG45fullguideline.pdf. [Accessed on: January
The Academy of Breastfeeding Medicine Protocol Committee.
ABM clinical protocol No. 18. Use of antidepressants in nursing
mothers. Breastfeed Med 2008; 3: 44-52.
ACOG Practice Bulletin Clinical Management Guidelines for
Obstetrician-Gynecologists No. 92, April 2008. Use of psychiatric
medication during pregnancy and lactation. Obstet Gynecol 2008;
Newport DJ, Hostetter A, Arnold A, Stowe ZN. The treatment
of post-partum depression: minimizing infant exposures. J Clin
Psychiatry 2002; 63 (S7): 31-44.
Öhman R, Hägg S, Carleborg L, Spigset O. Excretion of paroxetine
into breast milk. J Clin Psychiatry 1999; 60: 519-23.
Baumann P, Ulrich A, Eckermann G, et al. Arbeitsgemeinschaft für
Neuropsychopharmacologie und Pharmacopsychiatrie – Therapeutic
Drug Monitoring Group. The AGNP-TDM expert consensus
guidelines: focus on therapeutic monitoring of antidepressants.
Dialogues Clin Neurosci 2005; 7: 231-47.
Werremeyer A. Ziprasidone and citalopram use in pregnancy and
lactation in a woman with psychotic depression. Am J Psychiatry
2009; 166: 1298.
Briggs GG, Ambrose PJ, Ilett KF, Heckett LP, Nageotte MP,
Padilla G. Use of duloxetine in pregnancy and lactation. Ann
Pharmacother 2009; 43: 1898-1902.
Davis MF, Miller HS, Nolan PE. Bupropion levels in breast milk
for 4 mother-infant pairs: more answers to lingering questions. J
Clin Psychiatry 2009; 70: 297-8.
Tonn P, Reuter SC, Hiemke C, et al. High mirtazapine plasma
levels in infant after breast feeding: case report and review of the
literature. J Clin Psychopharmacol 2009; 29: 191-2.
Received: February 12, 2010
Revised: April 26, 2010 Accepted: May 31, 2010