European Neuropsychopharmacology (]]]]) ], ]]]–]]]

www.elsevier.com/locate/euroneuro

REVIEW

Mood stabilizers and antipsychotics during

breastfeeding: Focus on bipolar disorder
Isabella Pacchiarottia, Jordi León-Caballeroa,b, Andrea Murrua,
Norma Verdolinia,c, Maria Antonietta Furioa,d,
Corinna Pancheria,e, Marc Valentía, Ludovic Samalina,f,
Eva Solé Roigéa, Ana González-Pintog, Jose Manuel Montesh,
Antonio Benabarrea, Jose Manuel Crespoi,
Consuelo de Dios Perrinoj, Jose Manuel Goikoleaa,
Luis Gutiérrez-Rojask, André F. Carvalhol, Eduard Vietaa,n

a
Hospital Clinic, Institute of Neuroscience, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona,
Catalonia, Spain
b
Institut de Neuropsiquiatria i Addiccions, Parc de Salut Mar, CIBERSAM, Barcelona, Catalonia, Spain
c
Division of Psychiatry, Clinical Psychology and Rehabilitation, Department of Medicine, Santa Maria della
Misericordia Hospital, University of Perugia, Italy
d
UOC di Psichiatria Universitaria, Dipartimento di Medicina di base, Neuroscienze e Organi di senso,
University ‘Aldo Moro’, Bari, Italy
e
Policlinico Umberto I, “Clinica delle Malattie nervose e Mentali, La sapienza Universitá di Roma, Roma, Italy
f
CHU Clermont-Ferrand, Department of Psychiatry, EA7280, University of Auvergne, Clermont-Ferrand,
France
g
BIOARABA Health Research Institute. OSI Araba. University Hospital. University of the Basque Country,
CIBERSAM, Vitoria, Spain
h
Psychiatry Service, University Hospital Ramón y Cajal, University of Alcalá, CIBERSAM, IRYCIS, Carretera
Colmenar km. 9.1, 28034 Madrid, Spain
i
Department of Psychiatry, University Hospital of Bellvitge, Bellvitge Biomedical Research Institute
(IDIBELL), CIBERSAM, Barcelona, Spain
j
University Hospital La Paz, IdiPAZ, CIBERSAM, Madrid, Spain
k
Psychiatry Service, San Cecilio University Hospital, Granada, Spain
l
Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of Medicine,
Federal University of Ceara, Fortaleza, CE, Brazil

Received 30 May 2016; received in revised form 27 July 2016; accepted 5 August 2016

n
Correspondence to: Hospital Clinic, Institute of Neuroscience, University of Barcelona, IDIBAPS, CIBERSAM, 170 Villarroel st., Barcelona,
Catalonia, Spain.
E-mail address: evieta@clinic.ub.es (E. Vieta).

http://dx.doi.org/10.1016/j.euroneuro.2016.08.008
0924-977X/& 2016 Published by Elsevier B.V.

Please cite this article as: Pacchiarotti, I., et al., Mood stabilizers and antipsychotics during breastfeeding: Focus on bipolar disorder.
European Neuropsychopharmacology (2016), http://dx.doi.org/10.1016/j.euroneuro.2016.08.008
2 I. Pacchiarotti et al.

KEYWORDS Abstract
Lactation; Breast milk is considered the best source of nutrients and provides much better protection
Bipolar disorder; than immune modified milk. However, the postpartum period is a phase of increased risk for
Mood stabilizers; all women to experience psychiatric symptoms and recurrences or new episodes of bipolar
Antipsychotics; disorder (BD), especially in those who have discontinued treatment. This is a systematic
Breastfeeding
review of the risks and benefits of mood stabilizers and antipsychotics during breastfeeding
as they relate to the health and well-being of mothers and their infants. Evidence-based
treatment advice for women with BD during lactation is also provided. This systematic
review has been conducted according to the PRISMA (Preferred Reporting Items for
Systematic Reviews and Meta-Analyses) statement. We included studies examining the
exposure and the effects of antipsychotics and mood stabilizers used to treat BD on infants
during breastfeeding clearly reporting the estimated amount of drug or effects on infants.
The final selection included 56 studies. The available data supports the use of lithium as a
possible treatment option during breastfeeding. Carbamazepine and valproic acid are also
considered relatively safe. Lamotrigine can be used but at the lowest doses and considered
for individual cases. Among the antipsychotics, quetiapine and olanzapine should be
considered as first-line treatment options. Risperidone may be compatible with breastfeed-
ing under medical supervision. Clozapine and amisulpiride are currently contraindicated.
Long-term outcome studies evaluating the infant's health and psychosocial and cognitive
functioning are needed.
& 2016 Published by Elsevier B.V.

1. Introduction
Breastfeeding is currently considered the primary and ideal
form of nutrition for infants throughout the postpartum
period by most professional medical groups (American
College of Obstetricians and Gynecologists, 2007; Stowe,
2007; American Academy of Pediatrics, 2012).
However, the postpartum period is considered a time of
heightened vulnerability for bipolar disorder (BD), since it is
a high-risk period for affective recurrences, especially in
bipolar women who have discontinued treatment (Viguera
et al., 2000, 2007, 2011; Pope et al., 2014a, 2014b; Maina
et al., 2014; Larsen et al., 2015). Patients with BD have an
increased risk of developing a post-partum psychosis, espe-
cially during the first 4 weeks after the birth of the child
(Harlow et al., 2007). Moreover, several recent studies have
suggested that the presentation of any mental illness in the
early postpartum period, including a first episode of post-
partum depression or most cases of puerperal psychosis,
could hide a first episode of BD (Pope et al., 2014b;
Chaudron and Pies, 2003; Azorin et al., 2012).
Almost all drugs commonly used for treating BD are
excreted into breast milk and the risk of toxicity for
breast-fed infants from certain psychotropic drugs used in
BD is significant. Nonetheless, these risks should be care-
fully balanced against the increased risk of a breakthrough
episode of bipolar illness or affective recurrences if a
patient's medication is changed or discontinued (Viguera
et al., 2000, 2007, 2011).
Actually, there is a strong consensus on the fact that
mood stabilizers and antipsychotics should be considered as
first line treatments for BD, both in acute and long-term
management of the illness (Samalin et al., 2016).
In this review, the evidence indicating the toxicity for the
breastfed infant of mood stabilizers and antipsychotics, the
drugs most commonly used in BD, is discussed, and
evidence-based treatment recommendations for women
with BD during lactation are provided.
2. Experimental procedures
This review has been conducted according to the PRISMA (Preferred
Reporting Items for Systematic Reviews and Meta-Analyses) state-
ment (Moher et al., 2009).
2.1. Literature search
We systematically searched the MEDLINE/PubMed/Index Medicus,
EMBASE, and Cochrane Library databases from any time to 20
February, 2016, cross-checking the obtained references. The sys-
tematic search was performed by two blind independent research
teams (leaded by IP and JL), who searched as follows:
 MEDLINE/Pubmed/Index Medicus: authors used the keywords
((lactation OR breast feeding OR postpartum)) AND (antipsychotic
agents OR lithium OR valproic acid OR carbamazepine OR lamotrigine
OR oxcarbamazepine OR anticonvulsants OR antiepileptic drugs OR
valproate OR atypical antipsychotic drugs OR typical antipsychotic
drugs OR haloperidol OR chlorpromazine OR clozapine OR risperidone
OR olanzapine OR quetiapine OR ziprasidone OR aripiprazole OR
paliperidone OR lurasidone OR asenapine OR iloperidone),
 Cochrane library: keywords were (lactation OR breast feeding)
AND (mood stabilizer OR antipsychotic).
 EMBASE: lactation, bipolar disorder and treatment.
 clinicaltrials.gov: keywords were lactation, bipolar disorder and
treatment.

Please cite this article as: Pacchiarotti, I., et al., Mood stabilizers and antipsychotics during breastfeeding: Focus on bipolar disorder.
European Neuropsychopharmacology (2016), http://dx.doi.org/10.1016/j.euroneuro.2016.08.008
Mood stabilizers and antipsychotics during breastfeeding
2.2. Study selection
We included studies examining the exposure and the effects of
antipsychotics and mood stabilizers used to treat BD on infants during
breastfeeding clearly reporting the estimated amount of drug or
effects on infants. We included experimental studies (randomized
clinical trials (RCT), quasi-RCTs, non-RCTs), quasi-experimental stu-
dies (controlled before and after studies, interrupted time series),
and observational studies (cohort, case-control, registry studies) of
breastfeeding women and their infants/children. We only included
papers in English and limited to human studies. Studies not aimed at
determining the risk of the treatments used for BD on infants exposed
during breastfeeding were also excluded. Meta-analyses and reviews
were used as evidence to support information that could not be
drawn from individual studies. Data were grouped as: 1. Of interest,
2. Duplicates, and 3. Of no interest, according to the above-described
criteria. After selection, full papers were retrieved and studied.
3. Results
3.1. Systematic search results
The search yielded 1137 studies, 100 studies were deemed
eligible for further assessment. Among them, 12 were
inaccessible and 32 unrelated to the aim of this review.
The final selection included 56 studies. Figure 1 is a flow-
chart of considered and finally selected studies, following
the PRISMA statements.
3.2. General considerations
The amount of drug that passes into the mother's milk
depends on several factors related to the characteristics of
a single drug, including the route of administration, the
absorption rate, the size of the molecule, the pH of the
IDENTIFICATION
1137 papers returned by database search:
- Clinicaltrials.gov: 0
- Cochrane library: 15
- EMBASE: 10
- Pubmed/Medline/Index Medicus: 1112
SCREENING
1116 papers after duplicates removal
ELEGIBILITY
100 Full studies examined and assessed for inclusion:
INCLUDED
56 Included in the present review
Figure 1 Flowchart of considered and finally selected studies, according to the PRISMA statements.
Please cite this article as: Pacchiarotti, I., et al., Mood stabilizers and antipsychotics during breastfeeding: Focus on bipolar disorder.
European Neuropsychopharmacology (2016), http://dx.doi.org/10.1016/j.euroneuro.2016.08.008
3
substrate, the solubility in water and lipids, the protein
binding, the bioavailability and the volume of distribution
(Marks and Spatz, 2003). The foremost parameter that
determines the degree of drug penetration into breast milk
is plasma protein-binding: the higher the percentage of
protein-binding, the less likely the drug is to enter maternal
milk. Regarding the volume of distribution, drugs with a large
volume of distribution are poorly excreted into breast milk
when compared to those with a small volume of distribution.
With regard to the solubility of medication, lipid-soluble
drugs readily diffuse across cell membranes by dissolving in
the lipid bilayer. Another important parameter to determine
the ability of a drug to be excreted in the breast milk is the
milk/plasma (M/P) ratio, which is the ratio of the concentra-
tion of drug in the milk to that in the plasma. The higher the
milk/plasma (M/P) ratio, the greater the amount of the drug
found in breast milk. An M/P ratio greater than 1.0 suggests
that the drug may be sequestered in breast milk in high
concentrations. However, the M/P ratio does not provide all
of the information about the absolute amount of a drug that
can be transferred to the infant from breast milk. Thus, a
high M/P ratio does not necessarily contraindicate the use of
a particular medication. Even if the medication has a high M/
P ratio, if the maternal plasma concentration of the drug is
low, then the absolute amount (i.e., dose) of a drug entering
breast milk will likely be small enough to be considered
subclinical for the infant. Thus, higher M/P ratios can be
misleading because they can provide the impression that
large amounts of a medication are transferred into breast
milk, and this may not be the case if the maternal dosage is
low. In fact, drugs transfer into human milk is a function of
the maternal plasma level. The higher the plasma level, the
higher the transfer into human milk (Rowe et al., 2015).
Another important parameter to evaluate the safety of a
drug while breastfeeding is the relative infant dose which is
21 duplicated results:
- Clinicaltrials.gov: 0
- Cochrane library: 15
- EMBASE: 6
- Pubmed/Medline/Index Medicus: 0
Excluded on the basis of title or abstract: 1016
Full studies excluded: 44
Causes for exclusion:
- No data access: 12
- Of no interest with the aim of the review 32
 4
European Neuropsychopharmacology (2016), http://dx.doi.org/10.1016/j.euroneuro.2016.08.008
Please cite this article as: Pacchiarotti, I., et al., Mood stabilizers and antipsychotics during breastfeeding: Focus on bipolar disorder.

Table 1 Lithium and antiepileptic drugs during breast-feeding.

Drug First author, Study design Sample and drug dosage Main outcomes
year

Lithium Bogen et al., Case series 3 women, 4 infants (600–  Infants' lithium levels at 1 month postpartum ranged from 10% to 17% of maternal levels.
2012 900 mg/day)  Two infants had early feeding problems, which were overcome with breastfeeding education.
 No adverse events reported
Tanaka Case report 2 mother-infant pairs (900–  Spurious toxic levels were found (sampling device containing lithium heparin) Once sampling
et al., 2008 1200 mg/day) was removed, lithium levels undetectable or o0.11 mmol/L
 No adverse events reported
Viguera Case series 10 mother-infant pairs (600–  Serum lithium levels on average 0.16 mEq/L, ranging from 0.09 to 0.25 mEq/L
et al., 2007 1200 mg/day)  No significant adverse effects
Moretti Case series 11 mother-infant pairs (600–  Wide inter-patient variability in lithium concentrations in breast-milk (from 0% to 30% of maternal
et al., 2003 1500 mg/day) weight-adjusted dose).
 No clinically overt adverse effects
Sykes et al., Case report 1 mother-infant pair (800 mg/  Plasma lithium levels in the infant o0.2 mmol/L
1976 day)  No adverse effects
Schou et al., Case series 8 mother-infant pairs (Lithium  Serum lithium concentrations about one-half of the mothers' in the first week of life, one-
1973 daily dose not available) third (ranging from undetectable to 0.6 mmol/L) during the following weeks
 No adverse events reported
Valproate Meador Open label study 11 Children  No adverse effects of VPA exposure via breast milk were observed at age 6 years
et al., 2014  Breastfed children exhibited higher IQs compared to children of mothers under VPA
treatment who did not breastfed
Veiby et al., Open label study 18 Children  Breastfeeding in women using VPA was not associated with any harmful effects on child
2013 development at 6 to 36 months of age
 Breastfeeding protected against low weight during the postnatal period
Meador Open label study 11 Children  No deleterious effects of breastfeeding during VPA therapy on cognitive outcomes in children
et al., 2010 previously exposed in utero (at 36–45 months old)
Piontek Case series 6 mother-infant pairs (750 and  Infants’ serum levels from 0.7 to 1.5 μg/ml (0.9 to 2.3% of maternal serum levels)
et al., 2000 1000 mg/day)  No adverse clinical effects were observed in the infants
Wisner and Case report 2 mother-infant pairs (250–  Infants' serum levels at 1 month of age were 4 mcg/ml (maternal level was 65 mcg/ml).
Perel, 1998 750 mg/day) Infant development was normal at 18 months of age
 Infants' serum levels at 3 month of age were 1 mcg/ml (maternal level was 67 mcg/ml).
Development at 12 months was normal
 No adverse events reported
Stahl et al., Case report 1 mother-infant pair (1200 mg/  A 3-month-old, development of trombocitopenic purpura and anemia.
1997 day)  Infant's serum VPA: 6.6 μg/ml
 Normalization of hemoglobin and the reticulocytes two weeks after stopping breastfeeding,

I. Pacchiarotti et al.
platelet count normalization 3 months after discontinuing breastfeeding.
Philbert Case series 4 mother-infant pairs  VPA in breast milk 5–10% of the maternal serum concentration.
et al., 1985  All children were healthy without any signs of intoxication.
 The amount of VPA excreted into the breast milk was negligible
Von Unruh Case series 11 mother, 12 infants (9.5–  VPA levels in mother's milk were only 3% of maternal serum samples.
et al., 1984 31 mg/kg)  During the first 12 months, four children with a slight retardation in psychomotor
development
 1 mother-infant pair (1600 mg/  VPA level in infant's serum not significant 5 days after delivery and undetectable at 29 days

Mood stabilizers and antipsychotics during breastfeeding

Alexander, Case report
European Neuropsychopharmacology (2016), http://dx.doi.org/10.1016/j.euroneuro.2016.08.008
Please cite this article as: Pacchiarotti, I., et al., Mood stabilizers and antipsychotics during breastfeeding: Focus on bipolar disorder.

1979 day) after delivery.

 VPA in breast milk between 5–10% of that in the mother's serum.
 No evidence of any abnormality in the infant.
Carbamazepine Meador Open label study 23 Children  No adverse effects of CBZ exposure via breast milk were observed at age 6 years
et al., 2014  Breastfed children exhibited higher IQs compared to children of mothers under CBZ
treatment who did not breastfed
Veiby et al., Open label study 40 Children  Breastfeeding in women using CBZ was not associated with any harmful effect on child
2013 development at 6 to 36 months of age
 Breastfeeding protected against low weight during the postnatal period
Meador Open label study 26 Children  No deleterious effects of breastfeeding during CBZ therapy on cognitive outcomes in children
et al., 2010 previously exposed in utero.
Frey et al., Case report 1 mother-infant pair (400 mg/  Between the third and seventh week of life the infant presented transient cholestasis
2002 day)  Simultaneous CBZ blood concentrations in the infant and mother (while nursing) were 0.5 and
12.4 mg/L
Shimoyama Case series 7 Lactating women (250–  Mean levels for CBZ in milk and plasma samples were 3.50 and 6.18 mg/L
et al., 2000 800 mg/day)  Mean milk/plasma ratio of CBZ was 0.64
 No adverse events reported
Wisner and Case report 1 Mother-infant pair (500 mg/  Infant serum level at 3 month of age was 0.7 mcg/ml (maternal level was 4.7 mcg/ml).
Perel, 1998 day)  Infant had normal liver function. Serial blood counts revealed a normal physiologic decrease
in hemoglobin at 3 months with later rebound
 No adverse events reported
Merlob Case report 1 Mother-infant pair (400 mg/  Infants presented transient hepatic dysfunction with spontaneous resolution
et al., 1992 day)  At 2–4 and 6 months of age infants had normal development and were in good general
condition.
Frey et al., Case report 1 Mother-infant pair (600 mg/  A 3-week-old infant developed cholestatic hepatitis most likely due to CBZ exposure during
1990 day) pregnancy and breast-feeding.
 Cholestasis remitted after cessation of nursing.
 Liver function test results and histological findings were compatible with a drug-induced
hepatitis and other causes were excluded.
Lamotrigine Meador Open label study 27 Children  No adverse effects of LTG exposure via breast milk were observed at age 6 years
et al., 2014  Breastfed children exhibited higher IQs compared to children of mothers under LTG
treatment who did not breastfed
Veiby et al., Open label study 46 Children  Breastfeeding in women using LTG was not associated with any harmful effects on children
2013 development at 6 to 36 months of age
 Breastfeeding protected against low weight during the postnatal period
Meador Open label study 30 Children  No deleterious effects of breastfeeding during LTG therapy on cognitive outcomes in children
et al., 2010 previously exposed in utero.
Fotopoulou Case series 4 mother-infant pairs (250–900  Median ratio of breast milk to maternal serum of 0.59 (IQR 0.38–0.7)
et al., 2009 mg/day)  No adverse effects in any of the infants
Nordmo Case report 1 mother-infant pair (850 mg/  Sixteen days after birth several apnea episodes appeared during sleeping.
et al., 2009 day)  Three hours later the infant became cyanotic while nursing, requiring heart compressions.
 At the admission, infant's LTG serum concentration was 4.87 μg/ml
 Apnea episodes disappeared after stopping breastfeeding
 Normal development and no further episodes of apnea up to 7.5 months of age.

5
 6
Table 1 (continued )
European Neuropsychopharmacology (2016), http://dx.doi.org/10.1016/j.euroneuro.2016.08.008
Please cite this article as: Pacchiarotti, I., et al., Mood stabilizers and antipsychotics during breastfeeding: Focus on bipolar disorder.

Drug First author, Study design Sample and drug dosage Main outcomes
year

Wakil et al., Case series 3 mother-infant pair (50–  Intermittently occurring skin rash of scarce clinical significance
2009 250 mg/day)  The children all developed normally at the age of 15 and 18 months
Newport Prospective 30 mother-infant pairs (50–  LTG milk/plasma ratio demonstrated wide variability, ranging from 5.7% to 147%
et al., 2008 observational 800 mg/day)  Elevated platelet counts were observed in 7 of 8 children (no clinical consequences were
study observed)
 No other adverse events were noted
Page-Sharp Case series 6 mother-infant pairs (175–  Mean absolute infant doses, relative infant doses and infant/maternal plasma LTG values
et al., 2006 800 mg/day) were 0.45 mg/kg/day, 7.6% and 18%, respectively
 No adverse effects were reported
Gentile, Case report 1 mother-infant pair (300 mg/  Infant's development showed a normal progress during the first 4 months of life
2005 day)  No detrimental events were recorded
Liporace Case series 4 mother-infant pairs (200–  Serum LTG levels in nursing newborns ranged from o1.0 to 2.0 μg/ml on day 10 of life
et al., 2004 800 mg/day)  LTG levels in newborns were on average 30% of the maternal drug level (range 20–43%)
 While levels of LTG were higher than expected, no short-term adverse effect were observed
in the exposed children
Ohman Case series 9 mothers and 10 infants (100–  Median milk/ maternal plasma concentration ratio was 0.61 (range, 0.47–0.77)
et al., 2000 800 mg/day)  Nursed infants maintained LTG plasma concentrations of 30% (median, range 23–50%) of the
mother's plasma levels.
 No adverse effects were reported in the infants.
Rambeck Case report 1 mother-infant pair (200–  Concentration ratio milk/serum of LTG of the mother was about 0.6
et al., 1997 300 mg/day)  Infant's serum LTG concentration ranged from 0.75 to 2.79 μg/ml during the first three
months of breast-feeding
 The infant showed normal development with no signs of mental retardation or neurological
deficit.
 No adverse events reported
Tomson Case report 1 mother-infant pair (300 mg/  The ratio of milk to plasma concentration was 0.6 two weeks after delivery.
et al., 1997 day)  The plasma concentration in the breast-fed child was 25% of the mother's plasma levels
 No adverse effects were observed in the newborn.
Oxcarbazepine Lutz et al., Case report 1 mother infant pair (600 mg/  Relative and absolute infant dose assessed in this case appears to be low
2007 day)  No delayed development of the child has been noticed in a 5-year follow-up period
 No adverse events reported

IQR=Inter Quartile Range.

IQs=Intelligence quotients.

I. Pacchiarotti et al.
VPA=Valproate.
CBZ=carbamazepine.
LTG=Lamotrigine.
Mood stabilizers and antipsychotics during breastfeeding
a calculation that divides the dose offered to the infant via
milk (mg/kg/d) by the mother's weight-adjusted dose (mg/
kg/d). An infant dose via breast milk of less than 10% of the
maternal weight-adjusted dose is generally considered safe
in breastfeeding (Chad et al., 2013). The frequency of
feedings and the volume of breast milk that the infant
ingests must be considered. The infant who is exclusively
breastfed for long periods of time (e.g., eight or more times
a day) is more likely to be exposed to maternal medications
than is a child who is breastfed only once or twice a day and
takes supplemental nutrition such as solids and juices. The
evaluation of the infant includes taking into consideration
the age of the infant. Premature and newborn infants are at
greater risk than older infants for developing high plasma
drug concentrations because of their immature hepatic and
renal systems. Older infants may tolerate maternally
ingested medications better than the previously mentioned
infants because they are larger, and the drug will be more
diluted. Infant stability should also be evaluated. Infants
who are physiologically and behaviorally unstable or with
poor gastrointestinal stability, may be at a greater risk from
toxicity induced by maternal medications. The mother
should take the medication immediately after breastfeeding
and not before (Marks and Spatz, 2003).
3.3. Lithium
Lithium is still considered the mainstay of treatment for BD
(Grande et al., 2015), and women with chronic bipolar
illness are candidates for continuing lithium during preg-
nancy in order to avoid relapses or starting again at the 2nd
or 3rd trimester to prevent postpartum recurrences. For
lithium, the evidence comes from several case series. On
the basis of the early reports, the use of lithium during
lactation has been discouraged and typically contraindi-
cated, due to the high variability of the transfer into breast
milk (Sykes et al., 1976; Tunnessen and Hertz, 1972; Schou
et al., 1973; Schou and Amdisen, 1973; Fries, 1970;
Weinstein and Goldfield, 1969). Conversely, recent data
suggest that serum lithium levels in nursing infants were
low (ranging from 0.09 to 0.25 mEq/L) and no clinically
overt adverse effects were found in infants. Elevations of
thyroid-stimulating hormone, blood urea nitrogen, and
creatinine were few, minor, and transient; lithium levels
were measurable at approximately one quarter of the
concentration of that in the mother (mothers average levels
of 0.76 mEq/L) in breast-feeding newborns5. Thus lactation
can be permitted through an individualized approach to
breastfeeding in women receiving lithium (Viguera et al.,
2011; Moretti et al., 2003; Bogen et al., 2012; Tanaka et al.,
2008) (Table 1).
3.4. Antiepileptic drugs (AEDs)
Together with lithium, several AEDs are considered as "mood
stabilizers" and represent widely prescribed drugs for the
treatment of BD in its different phases and as prophylaxis
(Viguera et al., 2000, 2011; Pope et al., 2014a, 2014b;
Maina et al., 2014).
All AEDs pass into the breast milk, even if in different
amounts. Data on the use of AEDs by nursing women ae
Please cite this article as: Pacchiarotti, I., et al., Mood stabilizers and antipsychotics during breastfeeding: Focus on bipolar disorder.
European Neuropsychopharmacology (2016), http://dx.doi.org/10.1016/j.euroneuro.2016.08.008
7
scarce and mainly represented by single pharmacologic or
pharmacokinetic studies and/or by case reports or case
series on the side effects attributed to their presence in
breast milk (Davanzo et al., 2013).
Generally, the available data suggest that the use of most
AEDs in monotherapy does not preclude exclusive breast-
feeding. In an open-label study of 82 mother-infant pairs,
breastfeeding was carried out during monotherapy with
lamotrigine, carbamazepine, phenytoin or valproate and
compared to 112 non-breastfed infants of mother on AEDs
treatment. Both groups were previously exposed in utero to
these drugs. No differences were found between the two
groups in infant Intelligence Quotients (IQs) at the age of
three and six years (Meador et al., 2010, 2014) (Table 1).
3.4.1. Valproate
Valproate (VPA) is the most prescribed drug as an alter-
native to lithium or even as a first choice treatment for BD,
being its efficacy for acute manic episodes and for preven-
tion of recurrences. For VPA, the evidence comes from case
reports and series and three open-label studies. In contrast
to the findings of treatment with VPA during pregnancy, the
limited passage of VPA into breast milk makes it theoreti-
cally safe during lactation, with concentrations less than 1%
and no evidence of any cognitive impairment or signs of
intoxication in the infants (Meador et al., 2010, 2014;
Alexander, 1979; Philbert et al., 1985; Wisner and Perel,
1998; Piontek et al., 2000; Veiby et al., 2013), except from
one case of trombocitopenic purpura and anemia, that
promptly disappeared after stopping breastfeeding (Stahl
et al., 1997), and a slight retardation in the psychomotor
development in 4 out of 12 infants exposed to VPA also
during the entire pregnancy (von Unruh et al., 1984)
(Table 1).
3.4.2. Carbamazepine
Like lithium and VPA, carbamazepine (CBZ) has shown
efficacy for the treatment of manic phases of BD and during
the maintenance treatment (Chen and Lin, 2012). For CBZ,
there are three open-label studies and few case reports.
Despite the variability in the rate of transfer of CBZ into
breast milk (Wisner and Perel, 1998; Shimoyama et al.,
2000), no serious adverse events were reported in case
series, with the exception of transient toxic liver changes
(Merlob et al., 1992; Frey et al., 1990, 2002). Three open-
label studies found no deleterious effects of breastfeeding
during CBZ treatment on cognitive outcomes (Meador et al.,
2010, 2014; Veiby et al., 2013) (Table 1).
3.4.3. Oxcarbazepine
In BD, oxcarbazepine (OXC) has shown some effectiveness as
adjuvant treatment in preventing impulsive behavior in BD
and in the prevention of depressive recurrences (Popovic
et al., 2012; Vieta et al., 2008a, 2008b). Reports on the use
of OXC while on breastfeeding are limited to one case
report reporting a low relative infant dose and no significant
side effects in a 5-year follow-up period (Lutz et al., 2007)
(Table 1).
 8
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Table 2 Antipsychotics during breastfeeding.

Drug First author, Study design Sample and maternal dose Main outcomes
year

Olanzapine Gilad et al., Prospective 22 mothers breastfeeding while taking OLZ, 15 mothers taking OLZ  Data on lactation and outcome at the age of 1–2 years
2011 controlled but did not breastfeed and 51 breastfeeding mothers using a drug were obtained.
observational known to be safe during lactation (paracetamol) (Mean dose  The rate of adverse outcomes in OLZ-exposed breastfed
study 6.25 mg/day) infants did not differ from those of the control groups.
Whitworth Case report 1 mother-infant pair (5–15 mg/day)  Relatively high plasma level in the infant aged four
et al., 2010 months (Maternal dosage 15 mg, infant's OLZ concentra-
tion 11 ng/ml) probably related to an immature hepatic
transformation system, especially CYP1A2
 OLZ plasma levels decreased to very low or even
undetectable during the following four months
 The infant developed normally and showed no side
effects during the treatment period
Lutz et al., Case report 1 mother-infant pair (5 mg/day)  The relative infant dose was 0.3% and the OLZ concen-
2008 tration was below the limit of detection in the infant's
plasma sample (o5 ng/ml)
 No adverse effects were noticed in the infant.
Ambresin Case report 1 mother-infant pair (20 mg/day)  The relative amount of drug transferred to the infant
et al., 2004 was about 4% of maternal weight-adjusted dose
Gardiner Case series 7 mother-infant pairs (5–20 mg/day)  OLZ was not detected in the plasma of the 6 infants
et al., 2003  No adverse effects were found in the infants.
Croke et al., Case series 5 Mother-infant pairs (2.5–10 mg/day)  There were no adverse effects on the infants as a
2002 consequence of exposure to OLZ.
Goldstein Case series 2 Mother-infant pairs (5–10 mg/day)  In one infant, the exposure to OLZ at 5 mg was
et al., 2000 associated with icterus and sedation; although bottle-
fed was initiated, icterus and sedation continued.
 The second infant was exposed at 2 months to OLZ
10 mg. No adverse events were reported.
Kirchheiner Case report 1 Mother-infant pair (10 mg/day)  OLZ was not detected in the plasma of the infant either
et al., 2000 2 or 6 weeks after lactation was started
 At the age of 11 months and during the remaining
regular pediatric examinations there were no abnormal
findings.
Aripiprazole Watanabe Case report 1 mother-infant pair (18 mg/day)  In the plasma of the 6-day-old baby 7.6 μg/L of ARP was
et al., 2011 measured


I. Pacchiarotti et al.
No adverse events reported
Lutz et al., Case report 1 mother-infant pair (15 mg/day)  Neither ARP nor its metabolite was detected in any of
2010 the 3 milk specimens obtained on day 27 after the
infant's birth.
 In a 3-month follow-up period, the baby was growing
normally.
Quetiapine Rampono Case report 1 mother-infant pair (400 mg/day)  Infant's QTP plasma concentration was 1.4 μg/L
et al., 2007  No adverse effects were noted in the infant
  QTP levels in breast-milk ranged from not detected to

Mood stabilizers and antipsychotics during breastfeeding

Misri et al., Case series 6 mother-infant pairs (25–400 mg/day)
European Neuropsychopharmacology (2016), http://dx.doi.org/10.1016/j.euroneuro.2016.08.008
Please cite this article as: Pacchiarotti, I., et al., Mood stabilizers and antipsychotics during breastfeeding: Focus on bipolar disorder.

2006 32–264 nmol/L depending on QTP doses.

 4 out of the 6 babies scored as being within normal
limits on the Bayley Scales of Infant Development,
whereas 2 showed a mild developmental delay.
Gentile, 2006 Case report 1 mother-infant pair (400 mg/day)  Combination of QTP and fluvoxamine (200 mg/day)
 Mixed feeding was continued for 3 months and no
adverse events were observed in the baby.
Lee et al., Case report 1 mother-infant pair (200 mg/day)  An exclusively breast-fed infant would ingest only 0.09%
2004 of the weight-adjusted maternal dose
 Follow-up at 4.5 months indicated that the infant was
developing well, and no adverse effects were reported
Risperidone Aichhorn Case report 1 mother-infant pair (2–3 mg/day)  Infant's serum concentration was 0 ng/ml for RIS and
et al., 2005 0.1 ng/ml for its metabolite.
 Three months after the initiation of breastfeeding the
infant did not show any adverse effects and psychomo-
tor development was normal.
Ilett et al., Case series 3 mothers and 2 infants (1.5–4 mg/day)  M/P concentration ratio for RIS and its metabolite was
2004 o0.5
 RIS and its metabolite were not detected in the plasma
of the 2 breast-fed infants studied
 No adverse effects were noted.
Hill et al., Case report 1 mother (6 mg/day)  The estimated infant exposure to RIS was calculated as
2000 0.84% of the maternal dose as RIS and additional 3.46%
from its active metabolite.
Amisulpride Teoh et al., Case report 1 mother-infant pair (400 mg/day)  Transfer of AMI into milk was high (5.188 mg/L AMI
2011 concentration in milk and 266 mg/L in plasma).
 The relative infant dose was 10.7% of the maternal
weight-adjusted dose.
 The infant was in good health with an appropriate
Denver development score for her age.
Ilett et al., Case report 1 mother-infant pair (200 mg/day)  The infant developed normally and no detectable drug-
2010 related adverse effects were found
Ziprasidone Werremeyer, Case report 1 mother-infant pair (40 mg/day)  Breastfeeding was maintained up to 6 month, and the
2009 child was deemed healthy, with normal growth and
development at this age
 ZIP was given in combination with citalopram (60 mg/
day)
 Use of ZIP during lactation did not result in any
detectable outcome.
Clozapine Mendhekar, Case report 1 mother-infant pair (100 mg/day)  An infant who was exposed during pregnancy and breast-
2007 feeding (until the baby was 1 year old) to CZP experi-
enced delayed speech acquisition possible related with
the drug-exposition.
 Beside speech acquisition, development was normal.
Barnas et al., Case report 1 mother (50–100 mg/day)  CZP concentration in breast milk ranged from 63.5 ng/
1994 ml (CZP dose 50 mg/day) to 115.6 ng/ml (CZP dose
100 mg/day)

9
 10
Table 2 (continued )
European Neuropsychopharmacology (2016), http://dx.doi.org/10.1016/j.euroneuro.2016.08.008
Please cite this article as: Pacchiarotti, I., et al., Mood stabilizers and antipsychotics during breastfeeding: Focus on bipolar disorder.

Drug First author, Study design Sample and maternal dose Main outcomes
year

 The infant was not exposed to breast-milk

Haloperidol Yoshida Prospective 9 mother-infant pairs and 18 controls bottle-fed infants whose  HAL concentration in infants’ serum ranged from 0.8 to
et al., 1998 controlled mothers were taking HAL (in three cases in association with 8.0 ng/ml
observational chlorpromazine) (1–40 mg/day)  Psychomotor development was assessed with the Bayley
study scale. All the breast-fed babies developed normally,
except 2 infants (both treated with HAL and clorproma-
zepine) whose scores fell to low borderline levels at 12–
18 months.
 All the infants were normal on the Amiel-Tison
neurological test.
 There were no significant differences in psychomotor
development between the breast-fed and the bottle-fed
infants at 1–4 months of age.
Whalley Case report 1 mother-infant pair (10 mg/day)  The baby did not appear to be sedated and was
et al., 1981 feeding well.
 HAL was stopped in the sixth week after birth.
 The baby developed normally
Chlorpromazine Yoshida Prospective 4 mother-infant pairs and 18 controls bottle-fed infants whose  CPZ concentration in infant serum ranged from o0.1 to
et al., 1998 controlled mothers were taking neuroleptics or mood-stabilizing drugs. (50– 0.7 ng/ml
observational 600 mg/day)  In three cases, CPZ was given in combination with HAL
study  Psychomotor development was assessed by the Bayley
scale. Two infants scored fell to low borderline levels at
12–18 months. The other two infants were developing
normally
 All the infants were normal on the Amiel-Tison
neurological test.
 There were no significant differences in psychomotor
development between the breast-fed and the bottle-fed
infants at 1–4 months of age
Trifluoperazine Yoshida Prospective 2 mother-infant pairs and 18 controls bottle-fed infants whose  Infant serum concentration of TPZ was available for one
et al., 1998 controlled mothers were taking neuroleptics or mood-stabilizing drugs. (5– of the two infant exposed and was o2 ng/ml
observational 10 mg/day)  The two infants developed normally
study  There were no significant differences in psychomotor
development between the breast-fed and the bottle-fed
infants at 1–4 months of age


I. Pacchiarotti et al.
Perphenazine Olesen et al., Case report 1 Mother-infant pair (16–24 mg/day) Expressed as micrograms per kilogram of body weight,
1990 the dose passed on to the child with the milk was about
0.1% of that given to the mother.
 The child developed normally, and no signs of drug-
induced symptoms were observed
 Mood stabilizers and antipsychotics during breastfeeding 11

3.4.4. Lamotrigine
 The estimated daily infant exposure averaged 0.5% of

 The estimated daily infant exposure averaged 0.3% of

 The infant showed no specific drug effects and had a
The efficacy of lamotrigine (LTG) in preventing depressive
recurrences of BD, mainly in bipolar patients with predomi-
the corresponding maternal weight related dose.

nantly depressive polarity is considered the true strength of

the corresponding maternal weight related dose
this drug (Popovic et al., 2012; Reinares et al., 2014). Its
efficacy for the treatment of bipolar depression is still under
debate (Reinares et al., 2014).
The evidence on the safety of the treatment with LTG
 No adverse events were reported

during breastfeeding derives from one naturalistic, three

open studies and various case reports and series, reporting
normal motor development.

high variability in infants’ plasma concentrations and in M/P

ratios but no serious adverse effects or cognitive and
development alterations (Meador et al., 2010, 2014; Veiby
et al., 2013; Tomson et al., 1997; Rambeck et al., 1997;
Ohman et al., 2000; Liporace et al., 2004; Gentile, 2005;
Page-Sharp et al., 2006; Newport et al., 2008; Fotopoulou
et al., 2009), with the exception of elevated platelet counts
in 7 out of 8 children without clinical consequences
(Newport et al., 2008), a case of mild apnea and cyanosis
with therapeutic values of LTG of 4.9 μg/ml in infant's serum
OLZ=Olanzapine; ARP=Aripiprazole; RIS =Risperidone; AMI =Amisulpride; ZIP=Ziprasidone; CZP=Clozapine; HAL=Haloperidol.

(Nordmo et al., 2009) and another case of an intermittently

occurring skin rash of little clinical relevance (Wakil et al.,
2009) (Table 1).

3.5. Antipsychotics
CPZ=Chlorpromazine; TPZ=Trifluoperazine; PFZ=Perfenazine; FPX=Flupenthixol; ZPX=Zuclopenthixol.

During the last years, an increased number of studies have

supported the use of antipsychotics (APs)- especially second
generation APs- as a valid therapeutic alternative for the
treatment of BD, both as monotherapy and as adjunctive
treatment to traditional mood stabilizers (Vieta et al.,
2008a, 2008b, 2010, 2011; Yildiz et al., 2011) (Table 2).
1 Mother-infant pair (4 mg/day)

1 Mother-infant pair (14–24 mg)

From the available studies, treatment with most APs does

not preclude breastfeeding. In fact, despite all the available
APs are excreted into human milk, only minimal concentra-
tions of the active ingredients have been found in breast-
milk (Larsen et al., 2015; Gentile, 2008; Klinger et al.,
2013; Parikh et al., 2014).

3.5.1. Quetiapine
For quetiapine (QTP) there are case reports and series,
showing low infant exposure to QTP, with a relative infant
dose from only 0.09% to a maximum of 0.43% of the weight-
adjusted maternal dose (Misri et al., 2006; Lee et al., 2004).
Case report

Case report

No adverse effects of QTP were reported from the available

studies (Lee et al., 2004; Gentile, 2006; Rampono et al.,
2007) (Table 2).
and Skjaer-

3.5.2. Olanzapine
Skjaeraasen,

aasen, 1988

For olanzapine (OLZ), there is sufficient documentation

Matheson

Matheson

deriving from several case series, reports and a prospective

1988

study, showing low infant plasma concentrations and low

and

relative infant doses from 0.3% to 4% of the weight-adjusted

maternal dose (Kirchheiner et al., 2000; Croke et al., 2002;
Zuclopenthixol

Gardiner et al., 2003; Ambresin et al., 2004; Lutz et al.,

Flupenthixol

2008), except for one case with relatively high OLZ plasma
levels during the first four months of age (Whitworth et al.,
2010). Generally, no adverse events were reported in the
exposed infants (Kirchheiner et al., 2000; Croke et al.,
2002; Gardiner et al., 2003; Ambresin et al., 2004; Lutz

Please cite this article as: Pacchiarotti, I., et al., Mood stabilizers and antipsychotics during breastfeeding: Focus on bipolar disorder.
European Neuropsychopharmacology (2016), http://dx.doi.org/10.1016/j.euroneuro.2016.08.008
12
et al., 2008; Whitworth et al., 2010; Goldstein et al., 2000;
Gilad et al., 2011) (Table 2).
3.5.3. Risperidone
For risperidone (RIS) during breastfeeding there are only
case reports, showing relative infant doses ranged from
2.3% to 4.7% and low or undetectable plasma levels, with no
adverse effects reported in the infants (Hill et al., 2000;
Ilett et al., 2004; Aichhorn et al., 2005) (Table 2).
3.5.4. Aripiprazole
Data on aripiprazole (ARP) exposure during pregnancy and
lactation are scarce. The only two case reports indicate that
the administration of ARP during lactation might be rela-
tively safe (Lutz et al., 2010; Watanabe et al., 2011)
(Table 2).
3.5.5. Amisulpride
There are only two case reports for amisulpiride (AMI)
during breastfeeding showing a variability of relative infant
doses and a high transfer into breast milk, but no adverse
effects were found in the two infants (from 6% to 10.7%)
(Ilett et al., 2010; Teoh et al., 2011) (Table 2).
3.5.6. Ziprasidone
The use of ziprasidone during lactation did not result in any
detectable outcome from the only available case report
(Werremeyer, 2009) (Table 2).
3.5.7. Clozapine
Data on clozapine (CZP) use during lactation are anecdotal,
showing considerable CZP concentrations in breast milk and
M/P ratios and a possible delayed speech acquisition (Barnas
et al., 1994; Mendhekar, 2007). The general risk of agranu-
locytosis with CZP treatment might be one of the additional
reasons to avoid its use during lactation (Gentile, 2008)
(Table 2).
3.5.8. Typical antipsychotics
For haloperidol (HAL) there is a prospective study and a
case report, showing a high variability of HAL infant serum
and milk concentrations (Whalley et al., 1981; Yoshida
et al., 1998), with a possible impairment in psychomotor
development in two infants also exposed to chlorpromazine
(Yoshida et al., 1998). The aforementioned open label
controlled study (Yoshida et al., 1998) also evaluated the
transfer of chlorpromazine (CPZ) and trifluoperazine (TPZ)
into breast milk, showing a high variability of milk concen-
trations for both drugs. There is only one case report for
perphenazine (PFZ), showing a low relative infant dose and
no adverse events (Olesen et al., 1990) (Table 2).
4. Discussion
The postpartum is a period of significantly increased risk for
severe mood episode recurrences in women with BD. eIn
several longitudinal studies, the postpartum psychosis was
shown not to be a discrete nosologic entity, but a post-
partum presentation of an underlying mood disorder that
appears mainly within the bipolar spectrum (Chaudron and
Pies, 2003; Di Florio et al., 2013). A recent cohort study of a
Please cite this article as: Pacchiarotti, I., et al., Mood stabilizers and antipsychotics during breastfeeding: Focus on bipolar disorder.
European Neuropsychopharmacology (2016), http://dx.doi.org/10.1016/j.euroneuro.2016.08.008
I. Pacchiarotti et al.
long-term follow-up of a total of 120,378 women with a
first-time psychiatric inpatient or outpatient admission with
any type of psychiatric disorder revealed a predictive effect
of symptoms occurring within the first 14 days of delivery on
the subsequent conversion to BD (relative risk: 4.26; 95% CI:
3.11-5.85) (Munk-Olsen et al., 2012).
The clinical management of BD which recurs or starts
during the postpartum period is a complex issue that
highlights the need for balancing potential teratogenic
and other adverse effects of medication on the child,
against the consequences of untreated bipolar episodes,
first of all the risk of suicide or even infanticide (Weinstein
and Goldfield, 1969; Pacchiarotti et al., 2001; Jones et al.,
2014). The assessment of the mother's intent to breast-feed
is critical to the discussion of treating a new postpartum
bipolar episode or continuing medication for BD. The
majority of women treated for BD need to continue
medication during postpartum, as this is a time of high
relapse risk. Some women may need treatment in the early
postnatal period due to onset of a new bipolar episode. In
this context, inherent benefits of breast-feeding for a
mother with BD and her infant should be weighed against
risks of neonatal exposure to psychotropic drugs through
breast milk (Pope et al., 2014a).
Given ethical concerns, double-blind placebo-controlled
trials assessing the safety of mood stabilizers and antipsy-
chotics during breastfeeding are not possible. Large-sample
retrospective studies following guidelines may provide more
information on safety concerns. Nevertheless, current find-
ings assessing this issue are mainly based on case reports
and/or case series, impeding a reliable ascription of any
reported side effect to medication taken by the breastfeed-
ing mother.
Lithium, usually considered as contraindicated, has been
recently rehabilitated and can be considered as a possible
treatment option during breastfeeding. In fact, while
lithium passes through breast milk and is measurable in
breast-feeding newborns at approximately one quarter of
the concentration of that in the mother, a recent study
found no serious adverse events in breastfed infants
(Viguera et al., 2011). Nonetheless, following maternal
and infant lithium levels, a careful attention to infant
hydration and frequent monitoring of the infant's renal
and thyroid function are necessary, particularly if the infant
shows symptoms of lithium exposure (Viguera et al., 2011;
Pope et al., 2014a).
Regarding anticonvulsants, CBZ and VPA are considered to
have a good level of safety during lactation. LTG can be
used but at the lowest doses and considered for individual
cases, due to the highly variable transfer of this drug to the
child. Little data are available on the use of OXC (Davanzo
et al., 2013).
With respect to atypical APs during breastfeeding, QTP
and OLZ are cited as safe and should be considered as
first-line treatment options in those patients in whom an
antipsychotic is indicated. RIS is categorized as possible
for breastfeeding under medical supervision due to
insufficient data. Finally, typical APs together with the
newer atypical APs such as aripiprazole, paliperidone,
lurasidone, ziprasidone, asenapine and loxapine are
currently not recommended due to the paucity or lack
of data.
 Mood stabilizers and antipsychotics during breastfeeding
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Please cite this article as: Pacchiarotti, I., et al., Mood stabilizers and antipsychotics during breastfeeding: Focus on bipolar disorder.

Table 3 Mood stabilizers, antipsychotics and their compatibility with breastfeeding.

Specific drugs Efficacy/safety Safety profile during breastfeeding Precautions Level of

in BD evidence

Lithium – Manic episode Breastfeeding could be permitted with lithium – Careful observation of exposed infants (muscle tone, tremor, dehydration, Da
– Prophylaxis of BD through an individualized approach Moderately lethargy, feeding problems, weight gain) is needed.
– Suicide prevention safe – Despite no significant adverse effects were found in breastfed infants, a
frequent monitoring of the infant's renal and thyroid function is
recommended.
Valproate – Manic/mixed With a close observation for possible side-effects, – Thrombocytes count D
episode the infant can be breastfed
– Prophylaxis of BD – Safe
Lamotrigine – Prophylaxis of – Breastfeeding with LTG needs to be carefully con- – It is advisable to check the presence of thrombocytosis and skin rush in the D
depressive sidered by individual cases due to the wide varia- nursing infant.
recurrences in BD bility of M/P ratio and infant's plasma – The lowest dose should be prescribed (up to 200 mg/day)
concentrations.
– Moderately safe
Carbamazepine – Manic episode – With a close observation for possible side-effects, – Liver enzymes parameters D
– Prophylaxis of BD the infant can be breastfed
– Safe
Quetiapine – Manic/mixed First line treatment in BD during breastfeeding. – Infant monitoring D
episode – Safe
– Bipolar depression
– Prophylaxis of BD
Olanzapine – Manic/mixed First line treatment in BD during breastfeeding. – Infant monitoring D
episode – Safe
– Prophylaxis of BD
Risperidone – Manic/mixed Possible for breastfeeding under medical super- – Infant monitoring D
episode vision due to insufficient data
– Moderately safe
Amisulpiride – Manic/mixed Due to the considerable transfer into breast milk D
episode other antipsychotic should be preferred.
Not recommended
Clozapine – Manic/mixed – Clozapine is currently not recommended during D
episode breastfeeding due to the lack of data and to its
side-effect profile.
Not recommended
Aripiprazole – Manic/mixed – Despite the preliminary evidence seems to indicate D
episode that the administration of ARP during lactation may
be relatively safe, breastfeeding cannot be cur-
rently recommended due to the paucity of studies.
Not recommended
Paliperidone – Manic/mixed Not recommended due to lack of data D
episode

13
14 I. Pacchiarotti et al.

Since there are still no clear guidelines on the use of

National Health and Medical Research Council (NHMRC) of the Australian Government's NHMRC levels of evidence and grades for recommendations for developers of guidelines Level of
National Health and Medical Research Council (NHMRC) of the Australian Government. NHMRC levels of evidence and grades for recommendations for developers of guidelines. Canberra:
evidence
Level of
mood stabilizers and antipsychotics in BD during breastfeed-
ing, due to the dearth of evidence, only tentative treatment
advice can be made (Table 3). The decision to breastfeed
D

D
D
the child should be taken by the mother, after careful
assessment of the circumstances and the nature of the
treatment that she may be taking, and sensible medical
advice. From this systematic review, the benefits of breast-
feeding mostly appear to outweigh the cons, with few
exceptions. Combined breastfeeding with other supplemen-
tary nutrition is possible and reduces the risk of exposure to
high drug levels in the newborn. Breastfeeding should be
avoided or at least restricted in premature newborns.
Future reports are urgently needed assessing the safety of
these medications during breastfeeding such as long-term
follow-up studies evaluating the infant's health, psychoso-
cial and cognitive functioning in order to allow clinicians
and patients to make informed treatment decisions.

Declaration of contribution of each author to

the manuscript

Dr. Pacchiarotti A, Dr. León Caballero and Dr Murru: Con-

ception and design of the study, acquisition of data, analysis
Precautions

and interpretation of data, drafting the article.

Dr. Valentí and Dr. Goikolea: Conception and design of the
study, acquisition of data, analysis and interpretation of
data, drafting the article.
Dr. Samalin and Dr. Carvalho: drafting the article, revising
critically for contents.
evidence D: Body of evidence is weak and recommendation must be applied with caution.

Dr. Solé Roigé and Dr Benabarre: acquisition of data,

Not recommended due to the paucity of data

analysis and interpretation of data.

Dr. Furio, Dr. Verdolini and Dr. Pancheri: drafting the
Not recommended due to lack of data

Not recommended due to lack of data

Not recommended due to lack of data

Not recommended due to lack of data

article, revising critically for contents.

Safety profile during breastfeeding

Dr. Gutiérrez-Rojas and Dr. Crespo: acquisition of data,

analysis and interpretation of data.
Dr. Gonzalez-Pinto, Dr. Perrino and Dr. Montes: acquisition
of data, analysis and interpretation of data.
Dr Vieta: Conception and design of the study, revising
National Health and Medical Research Council, December 2009.

critically for contents, final approval to the version.

Author disclosures/conflict of interest

Dr. Pacchiarotti has received CME-related honoraria, or

consulting fees from
ADAMED, Janssen-Cilag and Lundbeck.
– Prophylaxis of BD
adjunctive

Dr. León-Caballero has no conflicts of interest.

depression (FDA)

Dr. Murru has received CME-related honoraria, or con-

Agitation in BD
Efficacy/safety

– Manic/mixed

– Manic/mixed

sulting fees from ADAMED AstraZeneca, Bristol-Myers

Manic/mixed
treatment

Squibb, Janssen-Cilag, Lundbeck and Otsuka.

episode

episode
– Bipolar

Dr. Valentí has received grants from Eli Lilly & Co.; and
episode
in BD

has served as a speaker for Abbott, Bristol-Myers Squibb,

as
Table 3 (continued )

GlaxoSmithKline, and Janssen-Cilag.

Dr Samalin has served as consultant or speaker for the
Specific drugs

companies: Astra-Zeneca, Bristol-Myers Squibb, Eli Lilly,

Ziprasidone

Typical APs
Lurasidone

Janssen-Cilag, Lundbeck, Otsuka, Sanofi-Aventis, Takeda.

Asenapine

Loxapine

Dr. Goikolea has been a speaker or on the advisory board

for Astra-Zeneca, BristolMyers-Squibb, Eli Lilly, Glaxo-
a

Smith-Kline, Janssen-Cilag,Merck Sharpe and Dohme,

Otsuka, Pfizer, Sanofi-Aventis.

Please cite this article as: Pacchiarotti, I., et al., Mood stabilizers and antipsychotics during breastfeeding: Focus on bipolar disorder.
European Neuropsychopharmacology (2016), http://dx.doi.org/10.1016/j.euroneuro.2016.08.008
Mood stabilizers and antipsychotics during breastfeeding
Dr. Benabarre has served as consultant or speaker for the
companies: Janssen-Cilag, Otsuka, Ferrer, Lundbeck.
Dr. Montes has no conflicts of interest.
Dr. Crespo has no conflicts of interest.
Dr. Perrino has no conflicts of interest.
Dr. Pancheri has no conflicts of interest.
Dr. Verdolini has no conflicts of interest.
Dr. Furio has no conflicts of interest.
Dr. Carvalho has no conflicts of interest.
Dr Solé Roigé has no conflicts of interest.
Dr L. Gutiérrez-Rojas has been a spokesperson for and
advisory board member of Bristol-Myers Squibb, Janssen-
Cilag, Astra-Zeneca, Rovi, Lundbeck, Otsuka, GSK and
Pfizer.
Dr. Gonzalez-Pinto has received grants and served as
consultant, advisor or CME speaker for the following enti-
ties: Almirall, AstraZeneca, Bristol-Myers Squibb, Cephalon,
Eli Lilly, Glaxo-Smith-Kline, Janssen-Cilag, Ferrer, Johnson
and Johnson, Lundbeck, Merck, Otsuka, Pfizer, Sanofi-Aven-
tis, Servier, Shering-Plough, Solvay, the Spanish Ministry of
Science and Innovation (CIBERSAM), the Ministry of Science
(Carlos III Institute), the Basque Government, the Stanley
Medical Research Institute, and Wyeth.
Prof. Eduard Vieta has received research grants and:
Alexza, Almirall, Astra-Zeneca, Bial, Bristol-Myers Squibb,
Eli Lilly, Ferrer, Forest Research Institute, Gedeon Richter,
Glaxo-Smith-Kline, Janssen-Cilag, Jazz, Lundbeck, Merck,
Novartis, Otsuka, Pfizer, Roche, Sanofi-Aventis, Servier,
Solvay, Shire, Takeda, United Biosource Corporation,
research funding from the Spanish Ministry of Science and
Innovation, the Stanley Medical Research Institute and the
7th Framework program of the European Union.
Role of funding and acknowledgments
This work was supported with funding from the Spanish
Ministry of Economy and Competitiveness, the Centro de
Investigación en Red de Salud Mental, CIBERSAM, -Instituto
de Salud Carlos III – Recerca del DIUE de la Generalitat de
Catalunya to the Bipolar Disorders Group (2014 SGR 398).
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