Antidepressant Use During Breastfeeding.
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 presents 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 expressed 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.
- SourceAvailable from: aerzteblatt.de[Show abstract] [Hide abstract]
ABSTRACT: ZUSAMMENFASSUNG Hintergrund: Der vorliegende Artikel gibt eine Übersicht über die aktuelle Studienlage zu Prävalenz, Risikofaktoren und Behandlung peripartaler Depression. Methode: Relevante Literatur wurde auf Medline sowie in der Cochrane Library unter "peri/pre/post", "partum/par-tal/natal", "maternal/motherhood/pregnancy" und "de-pression/affective disorder" identifiziert. Ergebnisse: Mit einer Prävalenz von 18,4 % in der Schwangerschaft und 19,2 % in der frühen Mutterschaft sind Depressionen die häufigsten Erkrankungen in der Pe-ripartalzeit. Bereits präpartal sind sie assoziiert mit erhöh-tem Frühgeburtsrisiko, geringerem Geburtsgewicht oder veränderter fötaler Herzaktivität. Langfristig werden bei den Kindern beeinträchtigte kognitive oder emotionale Fä-higkeiten beobachtet. Als Risikofaktoren gelten depressive Vorerkrankung, mangelnde partnerschaftliche wie soziale Unterstützung und belastende Lebensereignisse. Eine pe-ripartale Depression kann psychotherapeutisch wie psy-chopharmakologisch effektiv behandelt werden. Die der-zeitige Datengrundlage ermöglicht den Einsatz ausge-wählter antidepressiver Substanzen in Schwangerschaft wie Stillzeit. Niederschwellige psychosoziale Hilfen bieten vielerorts auch die Schwangerenberatungsstellen. Aller-dings werden wohl nicht mehr als 20 % der betroffenen Frauen erkannt, obwohl mit der Edinburgh Postnatal De-pression Scale (EPDS) und den beiden Whooley-Fragen ein schnelles Screening möglich ist.
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ABSTRACT: Mental disorders are among the most common morbidities of pregnancy and the postnatal period, and can have adverse effects on the mother, her child, and family. This Series paper summarises the evidence about epidemiology, risk factors, identification, and interventions for non-psychotic mental disorders. Although the phenomenology and risk factors for perinatal mental disorders are largely similar to those for the disorders at other times, treatment considerations differ during pregnancy and breastfeeding. Most randomised controlled trials have examined psychosocial and psychological interventions for postnatal depression, with evidence for effectiveness in treating and preventing the disorder. Few high-quality studies exist on the effectiveness or safety of pharmacological treatments in the perinatal period, despite quite high prescription rates. General principles of prescribing of drugs in the perinatal period are provided, but individual risk-benefit analyses are needed for decisions about treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.The Lancet 11/2014; 384(9956):1775-88. · 39.21 Impact Factor
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ABSTRACT: Context-awareness is a central aspect in the design of ubiquitous systems, characterizing their ability to observe the environment's context changes and adapt its structure and behavior according. Since those systems can be able to make autonomous decisions (i.e., without direct user intervention), dependability becomes an important requirement. The exception handling is a well-known error recovery technique employed to improve the software robustness and contributes to the overall software system's reliability and dependability. However, despite its benefits, exception handling still not widely used in the development of ubiquitous systems. In fact, we argue that is consequence of the lack of a proper exception handling mechanism to support it during the development and execution phases. In order to address this problem, we propose a context-aware exception handling mechanism designed specifically for context-aware ubiquitous systems. The proposed mechanism is implemented as a Java-based framework that provides a task-based model for building robust ubiquitous systems. A prototype of a ubiquitous parking control system is implemented to explore and validate the features of the proposed mechanism.2014 28th International Conference on Advanced Information Networking and Applications Workshops (WAINA); 05/2014
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: firstname.lastname@example.org
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.
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Received: February 12, 2010
Revised: April 26, 2010 Accepted: May 31, 2010