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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5238_Библиотеки_им_академика_М_И_Перельмана.pdf
Antidepressants During Lactation
PierreDesaunay, CamilleBlouet, MélanieAlexandre,
andFabianGuénolé
7.1 Introduction
Breastfeeding, especially when sustained, has signicant benets for both infants
and mothers, such as reduced infant morbidity and mortality, development of intelligence, and lower maternal risk of breast cancer (Victora etal. 2016). In light of
these benets, the World Health Organization (WHO) and the American Academy
of Pediatrics (AAP) recommend exclusive breastfeeding for the rst 6 months, then
children should begin eating safe and adequate complementary foods while continuing to breastfeed for up to 2 years of age (Eidelman etal. 2012; WHO, UNICEF,
USAID, and AED 2008). Antidepressant drugs (ADs), with an international prevalence estimated at 4.1% during pregnancy and rising to 5.8% postpartum (Molenaar
etal. 2020), have been associated with potential adverse reactions in both mother
and newborn.
Perinatal anxiety and depression disorders, as well as AD use, may limit breastfeeding initiation, duration, and exclusivity (Butler etal. 2021; Hoff etal. 2019). In
nursing mothers, serotonin is the main local (i.e., intramammary) regulator of lactation (while prolactin is the main systemic regulator). Homeostatic control of milk
volume within the alveolar spaces of the mammary gland involves a feedback
7
P. Desaunay
Centre Hospitalier Universitaire de Caen Normandie, Service de psychiatrie de l’enfant et de
l’adolescent, Caen, France
C. Blouet · F. Guénolé (
Centre Hospitalier Universitaire de Caen Normandie, Service de psychiatrie de l’enfant et de
l’adolescent, Caen, France
Pôle de formation et recherche en santé, Faculté de médecine, Université de Caen Normandie,
Caen, France
M. Alexandre
Centre Hospitalier Universitaire de Caen Normandie, Service de pédiatrie, Caen, France
© The Author(s), under exclusive license to Springer Nature
Switzerland AG 2025
F. Uguz, L. Orsolini (eds.), Perinatal Psychopharmacology,
https://doi.org/10.1007/978-3-031-99720-4_7
*)
139
140
P. Desaunay et al.
system mediated by serotonin signaling (Stull etal. 2007). Additionally, serotonin
induces the release of parathyroid hormone-related protein, which induces mobilizing calcium through bone resorption for milk synthesis (Marshall et al. 2014).
Consequently, evidence suggests that ADs, which modulate serotonin activity, may
delay alveolar secretory activation, thereby delaying the onset of lactation (Marshall
etal. 2010).
Nursing infants exposed to ADs via breast milk face potential risks of various
adverse reactions, including drowsiness, restlessness, irritability, and, in some
cases, poor feeding and insufcient weight gain. Pathophysiology may include central nervous excitation and autonomic dysfunction (Arbitman et al. 2024). The
safety of ADs use during breastfeeding depends to a large extent on their excretion
into breast milk, which is commonly estimated using the milk/plasma (M/P) ratio
(i.e., the ratio of milk drug concentration to maternal plasma drug concentration).
An M/P ratio below 1.0 indicates low transfer into breast milk. The relative infant
dose (RID, i.e., the percentage of the weight- and time-adjusted infant dose relative
to the weight- and time-adjusted maternal dose) is considered a more accurate indicator of safety (Begg etal. 2002; Gentile etal. 2007). Psychotropic drugs with an
RID below 10% are generally deemed safe for breastfeeding (Sachs etal. 2013),
though some authors advocate for a more stringent threshold of 5% (Larsen etal.
2015). The reported maximum RID, along with infant plasma AD levels, prevalence
of reported adverse reactions, and reported serious ones, constitute safety parameters, all of which are incorporated into an evidence-based “safety scoring system”
for the use of psychotropic drugs during lactation (Uguz 2021).
The objective of this chapter is to review recent safety data on the use of ADs
during breastfeeding, considering outcomes for both nursing mothers and their
infants. For mothers, the focus includes breastfeeding initiation and duration associated with AD use. For infants, the review evaluates safety data for individual ADs
and provides updated safety scores.
7.2 Safety ofAntidepressants forNursing Mothers
7.2.1 Studies onBreastfeeding Initiation andDuration
Three large studies have assessed breastfeeding initiation and duration associated
with AD use started during pregnancy or postpartum. All adjusted for several risk
factors known to reduce breastfeeding (including maternal age, parity, smoking,
socioeconomic status).
The largest study was conducted in Norway and involved a total of 80,882
mother-infant dyads (Grzeskowiak etal. 2022). The rate of breastfeeding initiation
was particularly high (i.e., 99.2%) in mothers without psychiatric disorders or ADs
use. Mothers with AD use from late pregnancy, compared with mothers with anxiety or depression disorders without AD use, showed a slight decrease in breastfeeding initiation (i.e., 92.3% vs. 98.6%, aRR=0.93 [0.90–0.97]). However, there were
no more likely to discontinue breastfeeding abruptly or to experience
7 Antidepressants During Lactation
141
breastfeeding-related complications (including sore nipples and mastitis) during the
rst month postpartum, nor to stop breastfeeding within 6 months. By contrast,
mothers who started ADs postnatal were at greater risk of abrupt breastfeeding discontinuation (aRR= 2.64 [2.07–3.73]) and breastfeeding problems (aRR= 1.37
[1.14–1.64]) during the rst month postpartum. There were also at greater risk of
breastfeeding cessation until 6months postpartum (aRR=0.49 [0.42–0.56]), mainly
for predominant breastfeeding (aRR=0.37 [0.22–0.61]).
The second larger study was conducted in Wales and involved 38,725 motherinfant dyads (Jordan etal. 2019). The breastfeeding rate among mothers without
depression or AD use was low, estimated at 34.31% at 6–8 weeks postpartum.
Results adjusted for risk factors including depression showed a reduction in breastfeeding initiation associated with SSRI use during the second or third trimester
(aOR=0.66 [0.56–0.77]), particularly with SSRIs used at high dose (aOR=0.59
[0.44–0.78]). Mothers were at higher risk of discontinuing breastfeeding 6–8weeks
postpartum, whether they had used ADs during the rst trimester of pregnancy only
(any AD: aOR=0.70 [0.57–0.85]; any SSRI: aOR=0.64 [0.54–0.74]), or during
the second or third trimesters (any AD: aOR = 0.81 [0.67–0.98]; any SSRI:
aOR = 0.77 [0.62–0.95]), particularly at high dose (any SSRI: aOR = 0.45
[0.23–0.86]).
The third larger study was conducted in Australia and involved 32,662 motherinfant dyads (Leggett et al. 2017). The rate of breastfeeding at discharge from
maternity hospital was particularly high (i.e., 88.9%) in mothers without psychiatric
disorders or ADs use. When neonates were born at term, mothers with AD use until
the second and third trimesters of pregnancy were less likely to be breastfeeding
their infants at discharge compared with mothers with psychiatric disorders not
using ADs (aOR= 0.73 [0.55–0.98]). With preterm newborns or admitted to the
neonatal intensive care unit (NICU), no signicant differences in breastfeeding
rates at discharge were observed between mothers with AD use, mothers with psychiatric disorders not using ADs, and mothers without psychiatric disorders or AD
use. A smallest study also conducted in Australia reported no signicant difference
on breastfeeding duration across depressed mothers with AD use, depressed mothers without AD use, and undepressed mothers (Galbally etal. 2019).
7.2.2 Discussion
A consistent decrease in breastfeeding initiation was shown in mothers using ADs
during at least the third trimester of pregnancy, compared to control mothers, after
adjusting for various risk factors including psychiatric ones (Grzeskowiak et al.
2022; Jordan etal. 2019; Leggett etal. 2017). An increased risk of abrupt breast-
feeding discontinuation was also shown in mothers starting ADs postnatally
(Grzeskowiak etal. 2022). These results may involve biological, psychological, or
environmental factors. First, serotonin acts as a homeostatic regulator of lactation
(Stull etal. 2007), and serotonergic ADs may delay alveolar secretary activation,
thereby interfering with the establishment of breastfeeding (Marshall etal. 2010).
142
P. Desaunay et al.
Second, depressed mothers, compared with undepressed ones, are more likely to
experience difculties in initiating breastfeeding, including high physical difculties and signicant pain (Brown etal. 2016). In addition, breastfeeding mothers
with AD use have more severe depressive symptoms and functional impairment
compared with those not receiving ADs (Battle etal. 2008; Molenaar etal. 2018),
and they also demonstrate less efcient coping strategies for initiating and continuing breastfeeding (Da Silva Tanganhito etal. 2020). Third, AD use during late pregnancy is associated with poor neonatal adaptation symptoms including poor sucking
and feeding, irritability, motor and tone symptoms, which may also hinder initiation
of breastfeeding (Gastaldon etal. 2023). Finally, variable and sometimes conicting
safety advices regarding AD use during breastfeeding, difculties in apprehending
the potential risks, societal pressures on breastfeeding mothers, and inconsistent
knowledge among healthcare professionals about the safety of AD use while breastfeeding may inuence mother’s decisions to breastfeed negatively (Battle et al.
2013; McClatchey etal. 2018; Uguz etal. 2020). However, the fact that no signi-
cant differences in breastfeeding rates at discharge were observed after premature
birth or NICU admission across mothers with late pregnancy AD use, mothers without psychiatric disorders or AD use, and mothers without psychiatric disorders or
AD use, suggest that under circumstances in which mothers with AD use can benet
from further breastfeeding support from healthcare providers, their breastfeeding
initiation rates may become similar to those of mothers without psychiatric disorders or AD use (Leggett etal. 2017).
There was a variable reduction in breastfeeding duration. Studies conducted in
Australia and Norway—countries with notably high breastfeeding rates among
high-income nations (Vaz etal. 2021)—reported no increased risk of breastfeeding
discontinuation during the rst and 6months postpartum, nor reduced breastfeeding
mean duration, associated with AD use from pregnancy (Galbally et al. 2019;
Grzeskowiak etal. 2022). In contrast, a study from Wales—a country with one of
the lowest breastfeeding rates among high-income nations (Vaz etal. 2021)—identied an increased risk of breastfeeding discontinuation at 6–8weeks postpartum
associated with AD use initiated during pregnancy (Jordan et al. 2019). As for
breastfeeding initiation, these results suggest that in environments supportive of
breastfeeding, AD use may not signicantly impact breastfeeding duration.
7.3 Safety ofAntidepressants forBreastfed Infants
7.3.1 The Safety Scoring System
The safety scoring system (Uguz 2021) evaluated six safety parameters for AD use
during breastfeeding: (1) reported total sample size (i.e., the total number of breastfed infants exposed to ADs, scored 0 to 2); (2) reported maximum relative infant
dose RID (i.e., reported maximum weight- and time- adjusted infant dose relative to
the weight- and time- adjusted maternal dose; scored 0 to 2); (3) reported sample
size for relative infant dose (i.e., number of breastfed infants with reported RID
7 Antidepressants During Lactation
143
values; scored 0 to 1); (4) infant plasma drug levels (i.e., proportion of breastfed
infants with undetectable AD in plasma; scored 0 to 1); (5) prevalence of reported
any adverse reaction (i.e., prevalence in the total sample size; scored 0 to 2); and (6)
reported serious adverse reactions (i.e., report or no report of severe adverse drug
reaction; scored 0 to 1). The total score ranged from 0 to 10 (≤ 3, very low safety
prole; 3.1 to 5, low safety prole; 5.1 to 7.0, moderate safety prole; 7.1 to 8.5,
good safety prole; 8.6 to 10.0, very good safety prole).
7.3.2 Methods
For each AD assessed, the data were drawn from two primary sources: (1) all studies referenced in LactMed®, specically those detailing “drug levels” and “effects in
breastfeeding infants”, and (2) all studies included in the most recent and comprehensive review of AD use during breastfeeding (Eleftheriou etal. 2024). Included
studies were case reports, case series, cohort studies, case-control studies, letters to
editors, reviews, and meta-analyses published up to November 20th, 2024, and
reporting pharmacological or clinical safety data on infants exposed to ADs through
breastmilk.
Antidepressants evaluated covered the 21 ADs most routinely prescribed worldwide from the N06A category of the Anatomical Therapeutic Chemical classication system (Cipriani etal. 2018; Furukawa etal. 2016; Nahler 2009), as well as
recently developed neurosteroid drugs for postpartum depression (Patterson etal.
2024). These included (1) all second-generation ADs approved by the regulatory
agencies in the USA, Europe, or Japan (i.e., agomelatine, bupropion, citalopram,
desvenlafaxine, duloxetine, escitalopram, uoxetine, uvoxamine, levomilnacipran, milnacipran, mirtazapine, nefazodone, paroxetine, reboxetine, sertraline, trazodone, venlafaxine, vilazodone, and vortioxetine); (2) tricyclic antidepressants
(TCAs) from the WHO Model List of Essential Medicines (i.e., amitriptyline, clomipramine); (3) brexanolone and zuranolone.
Screening, data extraction, and scoring were conducted independently by two
investigators (CB and PD). Any discrepancies were resolved by discussion and
consensus.
7.3.3 Safety Scores
7.3.3.1 Selective Serotonin Reuptake Inhibitors (SSRIs)
Citalopram Its safety prole was moderate, due to a high reported maximum
reported RID >10% (Pogliani etal. 2019) and detected drug in more than half of
infant plasma. Adverse reactions were rare, and all minor. The total score was lower
than in the initial version, due to recent data showing a high transfer of citalopram
into milk in breastfed newborns (Pogliani etal. 2019), and detectable citalopram in
most of infant’s plasma in the largest study that assessed this AD during breastfeed-
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P. Desaunay et al.
ing (Den Besten-Bertholee etal. 2024). In addition, a recent combined analysis
identied a high M/P ratio (mean 2.05, range 0.78–7.23) (Schoretsanitis etal. 2021).
Escitalopram This AD is the stereoisomer of citalopram. Its safety prole was low.
Although the maximum reported RID was <10% (Weisskopf etal. 2017) and the
reported total sample was larger than the initial version, there was a higher proportion of reported adverse reactions - mostly minor ones - resulting in a lower total
score. A case of necrotizing enterocolitis, a serious reaction, was reported in a newborn (Potts etal. 2007). In addition, escitalopram had the highest M/P ratio among
SSRIs in a recent combined analysis (mean 2.19, range 1.68–3.00) (Schoretsanitis
etal. 2021).
Fluoxetine This AD has long half-life compared with other SSRIs. Its safety pro-
le was moderate, similarly to the initial version. This result was due to a high
reported RID >10% (Pogliani etal. 2019), and detected uoxetine and noruoxetine
(its active metabolite) in the serum of most breastfed infants. Adverse events were
all minor.
Fluvoxamine The safety prole was moderate, similarly to the initial version. The
safety of prescribing this AD during breastfeeding has been poorly documented.
Available data indicate a low maximum RID (Kristensen etal. 2002), and limited
adverse events in breastfed infants. A recent combined analysis identied a moderate M/P ratio (mean 0.98, range 0.29–1.57) (Schoretsanitis etal. 2021).
Paroxetine The safety prole was good, thanks to numerous data, a low maximum
RID (Pogliani etal. 2019), and low detectable drug in the infant’s plasma. The total
score was lower than in the initial version, due to higher rate of reported adverse
events in breastfed infants. However, as neonatal adaptation symptoms may be serious following in utero exposure to paroxetine (Desaunay etal. 2022), a misinterpretation of neonatal symptoms related to transplacental transfer and transfer via breast
milk of paroxetine can be discussed in neonates (Costei etal. 2002). A case of
severe hyponatremia in an 18-month-old breastfeed infant was reported (Abdul
Aziz etal. 2004). A recent combined analysis identied a low M/P ratio (mean 0.63,
range 0.05–2.37) (Schoretsanitis etal. 2021).
Sertraline
The safety prole was good, thanks to numerous data, a low RID
(Pogliani et al. 2019), and low detectable drug in most of the infant’s plasma.
Another study with meta-analysis showed that levels of sertraline and its active
metabolite, desmethylsertraline, were below the limit of detection in most of the
infant serums (87.4% and 70%, respectively) (Pinheiro etal. 2015). However, a
recent combined analysis found a M/P ratio > 1 (mean 1.62, range 0.22–3.00)
(Schoretsanitis etal. 2021). There was no report of severe adverse reaction in breast-
7 Antidepressants During Lactation
145
fed infants. The total score was lower than in the initial version, due to a slightly
higher rate of reported adverse reactions. Indeed, a recent prospective study conducted in a pharmacy specialized in breastfeeding reported minor adverse reactions
in 13 of 28 breastfed infants; a selection bias was discussed (Morze etal. 2024).
7.3.3.2 Serotonin andNorepinephrine Reuptake Inhibitors (SNRIs)
Desvenlafaxine This AD is an active metabolite of venlafaxine. Its safety prole
was very low, due to a high maximum reported RID >10% (Rampono etal. 2011)
and insufcient data, although no adverse reaction was reported in any of the infants
described. The total drug exposure of breastfed infants has been estimated approximately half that of breastfed infants exposed to venlafaxine via breastmilk transfer
(Rampono etal. 2011), and a combined analysis found a high M/P ratio (mean 1.86,
range 1.40–2.47) (Schoretsanitis etal. 2021).
Duloxetine The safety prole was low. Although the maximum RID was low
(Briggs etal. 2009), there were limited data regarding potential adverse reactions. A
recent combined analysis identied a low M/P ratio (0.40, range 0.12–1.29)
(Schoretsanitis etal. 2021).
Milnacipran The safety prole was very low, mainly due to a lack of safety data.
However, the maximum RID was low (Forest Pharmaceuticals 2012 n.d.).
Venlafaxine The safety prole was low, due to a high maximum reported RID
>10% (Newport etal. 2009), detectable drug in the plasma of most breastfed infants.
The total score was lower than in the initial version, due to a higher rate of reported
adverse reactions, and the description of two severe adverse reactions, i.e., poor
weight gain and feeding interrupted by distress and easy fatigability (Tran etal.
2016), and apparent toxicity (Eleftheriou etal. 2022). In addition, a recent com-
bined analysis identied a high M/P ratio (mean 2.59, range 0.85–4.85)
(Schoretsanitis etal. 2021).
7.3.3.3 Tricyclic Antidepressants (TCAs)
Amitriptyline The safety prole was low, mainly due to a lack of safety data.
However, the maximum RID was low (Bader and Newman 1980). A case of severe
sedation and poor feeding was reported (Uguz 2017). The mean M/P ratio in a
recent combined analysis was moderate (mean 0.95, range 0.56–1.42) (Schoretsanitis
etal. 2021).
Clomipramine The safety prole was moderate, with a low maximum RID
(Schimmell etal. 1991), and no adverse reaction was reported in breastfed infant.
The mean M/P ratio in a recent combined analysis was moderate (mean 1.08, range
0.89–1.26) (Schoretsanitis etal. 2021).
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P. Desaunay et al.
7.3.3.4 Other Antidepressant Drugs
Agomelatine The safety prole was very low, due to scarcity of safety information,
and no available data on RID.No short- or long-term adverse reactions were noted
in all but one breastfed infants exposed through breastmilk in a small cohort; one
baby showed drowsiness, then developmental concerns of speech and low muscle
tone at 9months of age during follow-up (Kwok etal. 2023).
Bupropion The safety prole was low, similar to the initial version. Although
safety data are numerous, the reported maximum RID was high >10% (Davis etal.
2009), and a high proportion of adverse reactions is reported in breastfeeding
infants. Two cases of seizure were described in 6-month-old breastfed infants
(Chaudron and Schoenecker 2004; Neuman etal. 2014). In addition, a combined
analysis found a high M/P ratio (mean 1.95, range 0.63–5.79) (Schoretsanitis
etal. 2021).
Milnacipran The safety prole was low, due to scarcity of safety information.
However, the maximum reported RID was low.
Mirtazapine The safety prole was good, thanks to numerous safety data, a low
maximum reported RID (Kristensen etal. 2007), and no adverse reactions—including severe ones—reported in breastfed infants. The total score was higher than in
the initial version, due to new data showing a favorable safety prole during breastfeeding. A combined analysis found a moderate M/P ratio (mean 1.08, range
0.56–1.51) (Schoretsanitis etal. 2021).
Nefazodone The safety prole was very low, due to a lack of safety data, and a
severe adverse reaction reported in a 9-week-old breastfed infant, with drowsiness,
lethargy, poor feeding, and low temperature (Yapp etal. 2000). However, the maximum reported RID was low (Dodd etal. 1999).
Reboxetine
The safety prole was very low, due to a lack of safety data. However,
the maximum reported RID was low (Hackett etal. 2006), and there was no severe
adverse reaction reported. In addition, a combined analysis found a low M/P ratio
(mean 0.06, range 0.05–0.08) (Schoretsanitis etal. 2021).
Trazodone The safety prole was low due to a lack of safety data. However, the
maximum reported RID was low (Verbeeck etal. 1986), and there was no severe
adverse reaction reported. In addition, a combined analysis found a low M/P ratio
(mean 0.14±0.04) (Schoretsanitis etal. 2021).
Vortioxetine The safety prole was low due to a lack of safety data. However, the
maximum reported RID was low (Marshall etal. 2021).
7 Antidepressants During Lactation
147
7.3.3.5 Neurosteroids Antidepressants
Brexanolone and zuranolone. These ADs had low safety prole, due to a lack of
safety data. However, the maximum reported RID was low (Deligiannidis etal.
2024; Wald etal. 2022).
7.3.4 Discussion
SSRIs are the most commonly prescribed ADs during pregnancy and postpartum
(Molenaar et al. 2020), and showed the best safety prole during breastfeeding
among all ADs assessed. Among SSRIs, sertraline and paroxetine showed good
safety proles, with sertraline obtaining the highest safety score of all ADs evaluated. Sertraline and paroxetine are preferred ADs in breastfeeding women in most
international guidelines (Larsen et al. 2015; MacQueen etal. 2016; McAllisterWilliams etal. 2017; Portet et al. 2024; Sie et al. 2012; Sriraman etal. 2015).
Considering that sertraline is also a preferred AD during pregnancy in many international guidelines (Molenaar etal. 2018), it should be preferred in pregnant women
planning to breastfeed. In contrast, paroxetine has been associated with higher risks
of birth defects and poor neonatal adaptation symptoms compared to other SSRIs
(Brumbaugh etal. 2023; Desaunay etal. 2023; Gastaldon etal. 2023; Haddad etal.
2005), and is non-preferred AD during pregnancy in most international guidelines
(Molenaar etal. 2018). Therefore, it should preferably be initiated in the postnatal
period in breastfeeding mothers.
Citalopram, uoxetine, and uvoxamine had moderate safety proles. Citalopram
is a preferred AD during pregnancy according to some international guidelines
(Molenaar etal. 2018). However, high reported RID (Pogliani etal. 2019) and M/P
ratio (Schoretsanitis etal. 2021) suggest it could pass signicantly into breastmilk.
Long half-life of uoxetine and its active metabolite suggest a risk of drug accumulation in breastfed infants, although adverse reactions reported were rare and minor.
Some authors and guidelines advise caution in the use of citalopram and uoxetine
during breastfeeding (McDonagh etal. 2014; Orsolini and Bellantuono 2015; Sachs
etal. 2013; VA/DoD 2010), while other guideline identify citalopram as a preferred
AD during breastfeeding (MacQueen etal. 2016).
Escitalopram was the only SSRI with a low safety prole during breastfeeding.
Escitalopram showed the highest rate of adverse reactions in breastfed infants
among SSRIs, though most were minor. Guidelines are conicting regarding escitalopram, with some discouraging its use during breastfeeding (Larsen etal. 2015),
while others classify it as a preferred AD (Eleftheriou etal. 2024; MacQueen etal.
2016). Despite its frequent prescription during pregnancy (Petersen etal. 2021), its
safety prole has been poorly examined in the context of breastfeeding.
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P. Desaunay et al.
Among SNRIs, venlafaxine has been the most widely evaluated during breastfeeding. Newborns exposed in utero to venlafaxine may be at higher risk of birth
defects and poor neonatal adaptation symptoms compared to those exposed to other
ADs (Anderson etal. 2020; Desaunay etal. 2022; Gastaldon etal. 2023; Holland
and Brown 2017), which is to consider if initiating this AD in a pregnant woman
planning to breastfeed. One guideline suggests that venlafaxine should be used with
caution in breastfeeding mothers (Sachs etal. 2013). Both venlafaxine and desvenlafaxine have high RIDs and are detectable in most of breastfed infant’s serum;
however, reported adverse reactions remain low. Duloxetine and milnacipran had
low and very low safety proles, respectively, mainly due to insufcient data despite
low reported RIDs.
Tricyclic ADs are generally not prescribed as rst-line treatments for major
depressive disorders due to their unfavorable safety proles. Newborns exposed in
utero to TCAs may be at higher risk of poor neonatal adaptation symptoms compared to those exposed to other ADs (Desaunay etal. 2022; Gastaldon etal. 2023;
Misri and Sivertz 1991). However, available data suggest that the maximum RID of
TCAs is low, and these drugs are rarely detected in the plasma of breastfed infants.
Among other ADs from the N06A category, mirtazapine was the only one to
achieve a high safety score. Mirtazapine excretion into milk would be very low, and
no adverse reactions have been reported in breastfed infants. Bupropion, while
widely used as a smoking cessation aid during pregnancy (Robijn etal. 2024), has
been associated with a high rate of adverse reactions in breastfed infants, including
severe. Other ADs in this category scored low or very low, despite RIDs below 10%,
due to limited safety data.
For neurosteroid ADs, there is insufcient data on breastfeeding, which is a concern (Rosen-Carole and Ito 2021). Brexanolone and zuranolone all have RIDs
below 10% (ranging from 0.74% to 1.3%). Lactmed reports suggest that brexanolone and zuranolone are unlikely to cause adverse reactions in breastfed infants.
7.4 General Discussion
First, studies in breastfeeding mothers show that under circumstances where mothers benet from a supportive environment toward breastfeeding, initiation and duration of breastfeeding may improve. Mothers using ADs from pregnancy did not
show reduced breastfeeding rates at hospital discharge after preterm birth or NICU
admission, where healthcare providers could offer additional breastfeeding support
(Leggett etal. 2017). Furthermore, studies conducted in high-income countries with
known high breastfeeding rates reported no reduction in breastfeeding duration
among mothers using ADs from pregnancy (Galbally etal. 2019; Grzeskowiak etal.