Received: 28 October 2015 | Revised: 11 March 2016 | Accepted: 22 April 2016

DOI: 10.1111/bdi.12398

REVIEW

Mood stabilizers during breastfeeding: a systematic

review of the recent literature
1 2
Faruk Uguz | Verinder Sharma

1
Department of Psychiatry, Meram Faculty
of Medicine, Necmettin Erbakan University,
Konya, Turkey
2Department of Psychiatry and Obstetrics
and Gynecology, Western University,
Parkwood Institute, London, ON, Canada
Correspondence
Faruk Uguz, Department of
Psychiatry, Necmettin Erbakan
Üniversitesi Meram Meram, Konya,
Turkey. Email: farukuguz@gmail.com
Abstract
Objective: This review examined the safety of mood stabilizers in exposed
breastfed infants.
Methods: PubMed was searched for English language reports between 1 January 1995
and 30 August 2015 by using combinations of key words breastfeeding, lactation,
postpartum period, puerperium, mood stabilizers, lithium, lamotrigine, valproate,
carbamazepine, and oxcarbazepine. Case reports, case series, and prospective or cross-
sectional studies including relevant data such as relative infant dose, milk-to-plasma ratio,
infant drug plasma levels, and adverse events were identified.
Results: A total of 26 of 604 relevant reports in PubMed were included in the study.
These reports included lamotrigine (122 cases in 12 reports), lithium (26 cases in
five reports), carbamazepine (64 cases in five reports), valproate (nine cases in
three reports), and oxcarbazepine (two cases in two reports). Of 26 reports, one
report included both carbamazepine and valproate. The reports suggest that a
considerable amount of lithium and lamotrigine are excreted into breast milk. There
is a paucity of data on valproate and oxcarbazepine; however, the infant/ maternal
ratio of serum drug concentration seems to be lower in valproate expo-sure
compared to other mood stabilizers. The incidence of adverse events in infants
exposed to mood stabilizers is reported to be very low.
Conclusions: The current data suggest that mood stabilizers can be prescribed
without any adverse events in most infants in lactating women. The available reports
also suggest a low prevalence rate of laboratory abnormalities including hepatic,
kidney, and thyroid functions in the infants. Additional studies examining short- term
and especially long-term effects of mood stabilizers on breastfed infants are
required.

KEYWORDS
breastfeeding, lactation, mood stabilizers, postpartum

The postpartum period is associated with considerable risk for the
occurrence or exacerbation of psychiatric disorders and hospital read-
mission.1–4 Bipolar disorder is a chronic and severe psychiatric illness
that affects many women during their childbearing years, especially in
the postpartum period.5 In addition to misdiagnosis of bipolar depres-
sion as major depressive disorder during the postpartum period,6 there
is substantial evidence suggesting a relationship between
postpartum psychosis and bipolar disorder.7
Benefits of breast milk for both the mother and the infant have
been well documented.8–10 However, breastfeeding is one of the
major challenges in the treatment of women with bipolar disorder.
While many mothers with bipolar disorder would like to breastfeed,

Bipolar Disord 2016; xx: 1–9 wileyonlinelibrary.com/bdi © 2016 John Wiley & Sons A/S. | 1
Published by John Wiley & Sons Ltd
2 |
most mothers with postpartum psychosis or bipolar disorder require
treatment with psychotrophic medications, especially antipsychotics and
mood stabilizers. In addition, maternal psychiatric disturbances during
the postpartum period negatively influence not only mothers but also
mother−infant relationships and child−mother attachment, and can lead
to suicidal and infanticidal behaviors, especially if there are psychotic
features.11–15 On the other hand, the benefits of breast-feeding should
be carefully balanced against the deleterious effect of sleep deprivation
in triggering mood episodes.6 If pharmacotherapy is necessary to treat
bipolar disorder in breastfeeding women, the following main points
should be considered in the decision regarding the choice of medication:
(i) a clinical evaluation of risks and bene-fits of treatment of bipolar
disorder with psychotropics, (ii) detailed assessment of the severity of
the maternal psychiatric disorder and the degree of functional impairment
due to the psychiatric disorder, (iii) cautious assessment of therapeutic
and side effects of previous med-ications in the patient, and (iv) review of
scientific evidence regarding the relative safety of each psychotropic in
the breastfed infants.
All psychotropic medications are excreted into the breast milk to
varying degrees.9 Hence, safety data on psychotropic drugs during
lac-tation are essential to minimize infant exposure and adverse
effects while maintaining optimum maternal mental health. 6,8
Although sev-eral reviews examining the safety of mood stabilizers
in breastfeeding women have been published,9,10 systematic
reviews on this topic are inadequate. This article aimed to
systematically evaluate data in the recent literature on the safety of
mood stabilizers in infants during the lactation period.
1 | METHODS
In the current review, the Preferred Reporting Items for Systematic
Reviews and Meta--analyses (PRISMA) guidelines and checklist
were used.16 Papers published in electronic databases including
PubMed between 1 January 1995 and 30 August 2015 were found
using the following terms: breastfeeding, lactation, postpartum
period, puerperium, mood stabilizers, lithium, lamotrigine, valproate,
car-bamazepine, and oxcarbazepine. Additionally, references in the
papers were examined to obtain further relevant publications.
Reports that met the following predefined criteria were included in
the present review: (i) published in English in a peer--reviewed
journal, (ii) clearly defined drug--related values such as the milk-- to-
-plasma ratio (M/P ratio; an estimate of the distribution of the drug
between maternal plasma and milk17), the absolute infant dose
(defined as the dose an infant receives by ingestion of mater-nal milk
after one single maternal dose or during a dose interval at steady
state17), and the relative infant dose (RID; represents the weight-
-adjusted infant dose relative to the weight--adjusted maternal
dose18), as well as developmental outcomes or adverse events in
the infants, (iii) clearly defined breastfeeding status and type of mood
stabilizer used, and (iv) a case report, case series, or prospective or
cross--sectional study. Experimental studies involv-ing animals,
reviews, editorials and commentaries were excluded
Uguz and Sharma
from the review. Additionally, we excluded reports pertaining to the
use of antipsychotics during breastfeeding. After the titles of all non-
-duplicated articles had been identified, the abstracts were screened
to ensure that they met the inclusion criteria. Full texts of the
relevant abstracts were obtained and examined carefully to
determine their eligibility for inclusion. Figure 1 shows the flow
diagram based on PRISMA of the studies that were selected for this
review.
2 | RESULTS
Table 1 presents characteristics of reports included in the review.
2.1 | Lithium
Recently, five reports (two studies and three case reports)19–23
including a total of 26 patients with bipolar disorder who were
treated with lithium during lactation have been published in the
literature. The daily dose of lithium was between 600 and 1350 mg/
day. All reports provided infant serum lithium levels. Whether lithium
had also been used by the patients during pregnancy was unclear in
the study by Moretti et al.19; however, patients in all other reports
had a prior history of lithium treatment during the index pregnancy.
Viguera et al.20 reported extensive data on maternal−infant
pairs examining serum and breast milk concentrations of lith-ium
and concurrent thyroid and renal function in the infant. In 10
patients, the average M/P ratio was 0.53 (range: 0.34–0.70), the
infant serum level of lithium was 0.16 mEq/L (within the range of
0.05–0.30 mEq/L that is not considered as toxic), and the infant/
maternal serum -lithium concentration ratio was 0.24 (range: 0.11–
0.56). This study did not report the absolute daily infant dose or RID.
The authors reported that clinical adverse events in the breastfed
infants were not observed despite minor and transient abnormalities
in laboratory parameters, including slightly elevated serum levels of
thyroid--stimulating hormone (TSH) (n = 1), urea nitrogen (n = 2),
and -creatinine (n = 1) even after prolonged exposure to lithium.
Serum levels of lithium were 0.23 mEq/L in the infant with an
elevated level of TSH and 0.10 mEq/L in an infant with elevated
urea nitro-gen. One infant had elevated urea nitrogen and
creatinine; however, the authors did not report the infant serum level
of lithium in this infant. Moreover, we did not find any information on
the M/P ratio and infant/maternal serum lithium concentration ratio in
the infants with abnormal laboratory parameters.
Moretti et al.19 did not report any adverse events in 11 infants
exposed to lithium. The infant/maternal serum lithium concentration
ratios calculated in two infants were 0.17 and 0.47. The same
infants had serum lithium levels of 0.14 and 0.47 mEq/L. This study
is unique in also reporting RID in infants exposed to lithium. The
average RID value was 12.2% (range: 0%–30%); however, seven of
11 infants had RID values ≥ 15%. This study did not examine any
laboratory parame-ter associated with lithium in the infants.
Uguz and Sharma | 3

Records identified from PubMed

(n = 604)

Duplicates removed (n = 362)

Titles and abstracts screened

(n = 242)

170 records excluded

Potentially relevant records

determined for full-text screening
(n = 72)

43 records excluded after detailed full-text review

for the following reasons:
 Review articles (n = 24)
 Animal studies (n = 7)
 Editorials or comments on reports (n
= 3)
 Reports in a language other than English
(n = 6)
3 records identified  Duplicate reports (n = 1)
from reference  Data unclear for review purposes (n = 2)
reviews

26 records included in systematic

FIGURE 1 Flow diagram showing identification final review
of studies included in this review

Tanaka et al.21 reported an undetectable serum level of lithium
in an exposed infant. Other case reports22,23 indicated that infant
serum levels of lithium were between 0.08 and 0.26 mEq/L and
infant/maternal ratios of serum lithium concentration were between
0.10 and 0.5815,16 Additionally, in these reports, mild hypotonia
(n = 1) and normal thyroid and renal function (n = 1) in the infants
were reported.
2.2 | Lamotrigine
Reports on lamotrigine assessed for this review included 122
women (seven studies and five case reports)24–31 with a diagnosis
of epilepsy (n = 107) or bipolar disorder (n = 15). The studies
suggest that considerable amounts of lamotrigine are excreted
in breast milk.25,26,29–33,35 Adverse events were reported in only
four of 122 infants (3.27%). Nordmo et al.29 reported a case of
severe apnea leading to cyanotic episodes in an infant. The authors
noted the likelihood that apnea was precipitated by a rapid increase
in the maternal serum levels of lamotrigine which more than
doubled from the 9th to the 17th postpartum day. In contrast,
the infant with apnea had a lower lamotrigine serum concentra-
tion (4.87 μg/mL) than measured shortly after birth (5.81 μg/
mL). Wakil et al.34 reported rash in three infants; however, it
was determined that rash in two cases was not related to lamo-
trigine, because it was attributed to eczema and a soy allergy
and the rash in the other case resolved before the pediatrician
was alerted. The authors did not report the lamotrigine levels in
the infants with rashes.
The M/P ratio (n = 108), infant/maternal ratio of serum lamotrigine
concentration (n = 83) and RID (n = 42) were reported to be 0.12–1.05,
0.03–1.0 and 2.0%–21.1%, respectively in the recently published
studies. As shown in Table 1, the maximum infant plasma lamotrig-
ine level (n = 84) was 12.7 μg/mL with most of values reported to be
< 5 μg/mL.18–20, 22–26 Newport et al.35 presented comprehensive data
on the usage of lamotrigine during breastfeeding (n = 30), including
the mean values for M/P ratio (0.41), RID (9.2%), infant plasma level
(1.2 μg/mL) and infant/maternal ratio of serum lamotrigine concentra-
tion (0.18). Page--Sharp et al. 28 reported similar values for RID, infant
plasma levels and infant/maternal ratio of serum lamotrigine concen-
tration in a study with a small study cohort of patients (n = 6). The
mean absolute daily infant doses in these two studies were 0.51 and
0.45 mg/kg, respectively. Rambeck et al.25 noted that infant plasma
levels of lamotrigine fell below the detection limit when nutrition with
the mothers’ milk was reduced to only one milk meal in the morning.
Maternal dose was a significant predictor of the concentration of lam-
otrigine in breast milk. In contrast, time after maternal dose was not
associated with lamotrigine levels in breast milk.35
It is unclear whether adverse events in the infants are associated
with M/P ratio, infant/maternal ratio of serum lamotrigine concen-
tration, and/or RID. These parameters in the infant with apnea were
 4
TABLE 1 Characteristics of reports examining safety of mood stabilizers for infants during breastfeeding

|
Maternal Pregnancy Infant age at the Follow--up
Study N dose, mg/day Diagnosis exposure assessment period M/P ratio RID, % Infant serum levels IS/MS ratio Adverse events

Lithium
Viguera 10 600–1200 BD Yes 1–55 weeks NA 0.34–0.70 NA 0.05–0.30 mEq/L 0.11–0.56 Elevation in serum
20
et al. Mean: 850 Mean: 0.53 Mean: 0.16 mEq/L Mean: 0.24 levels of TSH
(n = 1), urea
nitrogen (n = 2), and
creatinine (n = 1)
Moretti 11 600–1500 BD NA 5 days– NA NA 0–30 0.14–0.47 mEq/L 0.17–0.47 None
19
et al. 15 months Mean: 12.2 (n = 2)
Tanaka 1 900 BD Yes 18 days NA NA NA Undetectable NA None
21
et al.
Bogen 3 900–1350 BD Yes 31–183 days NA NA NA 0.08–0.11 mEq/L 0.10–0.17 Mild hypotonia
22
et al. (n = 1)
23
Frew 1 600 BD Yes 10 days NA NA NA 0.26 mEq/L 0.58 None
Lamotrigine
24
Gentile 1 300 EP Yes 0 4 months NA NA NA NA None
Rambeck 1 200–300 EP Yes 1 month 5 months 0.56 NA 1 month: 2.68 μg/ NA None
25
et al. mL
5 months: < 0.2
μg/mL
Fotopoulou 4 250–900 EP Yes 3 months NA 0.38–0.70 NA 1.7–3.3 μg/mL 0.18–0.36 None
26
et al. Median: Median:
0.59 0.26
Liporace 4 150–800 EP Yes 10 days 2 months NA NA Undetectable 0.20–043 None
27
et al. (n = 1) Mean: 0.30
< 1.0–2.0 μg/mL
(n = 3)
Page--Sharp 6 175–800 EP (n = 5) NA 0.4–5.1 months NA NA 5.4–9.9 0.3–0.9 μg/mL 0.03–0.33 None
28
et al. Mean: 400 BD (n = 1) Mean: Mean: 7.6 Mean :0.6 Mean: 0.18
4.1 months
Nordmo 1 850 EP Yes 17 days NA 0.88 13 4.87 μg/mL 0.32 Severe apnea leading
29
et al. to cyanotic
episodes
Ohman 10 100–800 EP Yes 0–3 weeks NA 0.50–0.77 2.0–20.0 2.0–11.0 μg/mL 0.23–0.53 None
30
et al. Median: Median: 9.0 Median:

Uguz and Sharma

0.61 ~0.30
Tomson 1 250 EP Yes 1 week 5 months 0.60 NA 3.7 μg/mL ~0.25 None
31
et al.
(Continues)
 Uguz and Sharma
TABLE 1 (Continued)

Maternal Pregnancy Infant age at the Follow--up

Study N dose, mg/day Diagnosis exposure assessment period M/P ratio RID, % Infant serum levels IS/MS ratio Adverse events

Kacirova 27 50–500 EP Yes 3–30 days NA 0.46–0.54 NA < 0.1–12.7 μg/mL 0.45–0.55 NA
32
et al.
33
Berry 34 NA EP Yes NA NA 0.40–0.80 NA NA NA None
34
Wakil et al. 3 200–250 BD Yes 0 15–18 months NA NA NA NA Rash in all infants
Newport et al. 30 50–800 EP (n = 19) Yes 1–52 weeks NA 0.12–1.05 3.1–21.1 < 0.3–3.9 μg/mL 0.09–1.0 None
35 Mean: 386.5 BD (n = 11) Mean:13 weeks Mean: 0.41 Mean: 9.2 Mean: 1.2 μg/mL Mean: 0.18
(n = 12) (n = 12)
Valproate
Wisner and 2 750 BD No 1–3 months 12–18 months NA NA 1–4 μg/mL 0.015–0.06 None
36
Perel
Piontek 6 750–1000 BD No 0–13 weeks 4 months NA NA 0.7–1.5 μg/mL 0.01–0.023 None
37
et al. Mean:
0.015
38
Stahl et al. 1 1200 EP Yes 3 months NA NA NA 6.6 μg/mL NA Thrombocytopenic
purpura and anemia
Carbamazepine
Wisner and 1 500 BD NA 3 months NA NA NA 0.7 ng/mL 0.15 None
36
Perel
Brent and 1 600 BD Yes 2 weeks NA NA NA 0.5 ng/mL NA Seizure--like activities
41
Wisner
Shimoyama 7 500–800 NA NA 1–34 days NA 0.25–1.20 NA NA NA NA
40
et al. Mean: 0.64
42
Frey et al. 1 400 EP Yes 8 days 12 months NA NA 0.5 mg/L 0.4 Mild neuromotor
impairment of the
extremities
Kacirova 54 NA EP NA 6–10 days NA 0.0–1.4 NA 0.0–2.6 mg/L 0.0–0.7 NA
39
et al.
Oxcarbazepine
43
Lutz et al. 1 600 BD Yes 8 days 5 years 5–9 1.5–1.7 0.1 μg/mL 1.0 None
44
Gentile 1 1200 EP Yes 4 months NA NA NA NA NA None
BD, bipolar disorder; EP, epilepsy; M/P ratio, milk--to--plasma ratio; RID, relative infant dose; IS/MS ratio, infant/maternal ratio of serum drug concentration; TSH, thyroid--stimulating hormone; NA, not
available.

|5
6 |
0.88%, 0.32%, and 13%, respectively.29 Wakil et al.34 did not
report these safety parameters in the infants with rashes.
2.3 | Valproate
Data on nine infants exposed to valproate have been published in
the recent literature.36–38 The diagnoses were bipolar disorder in
eight women and epilepsy in one woman. The available reports did
not present the M/P ratio, absolute daily infant dose or RID. The
serum levels of valproate in the infants were in the range of 0.7–6.6
μg/mL30–32; these levels corresponded to 1.5%–6% of maternal
serum levels with a mean of 2.1%.37 The exposed infants had no
adverse events except trombocytopenic purpura and anemia in one
infant reported by Stahl et al.38 The authors reported that the serum
level of valproate in the infant with these adverse events was 6.6
μg/mL. Liver function tests carried out in three exposed infants were
normal.36,38
2.4 | Carbamazepine
Recently, two studies39,40 and three case reports37,42,43
describing the use of carbamazepine in a total of 64 patients were
published. Of the 64 patients, two women were diagnosed with
bipolar dis-order and 55 with epilepsy, and for the remaining seven
women the diagnoses were not documented. Kacirova et al. 39
reported that the ranges for M/P ratio, infant serum levels of
carbamazepine and infant/maternal ratio of serum carbamazepine
concentration were 0.0–1.4, 0.0–2.6 and 0.0–0.7, respectively, in 54
women. The authors also noted a significant correlation between
carba-mazepine levels in maternal serum and breast milk but not
between maternal and infant serum levels. According to the authors,
the interindividual variabilities in infant/maternal serum ratio of car-
bamazepine concentrations may result from different activities of the
infant metabolizing enzymes. In a study by Shimoyama et al. 40 (n =
7), the mean M/P ratio was 0.64 (range: 0.25–1.20). Two case
reports36,42 reported infant/maternal serum carbamazepine
concentration ratios of 0.04 and 0.15. The absolute daily infant dose
and RID were not available in these reports.
Data on adverse events in the infants exposed to carbamazepine in
the included reports were not available except for three cases. Wis-ner
and Perel36 reported that the infant exposed to carbamazepine had
normal liver functions. Brent and Wisner41 reported seizure--like
symptoms in one infant, who was additionally exposed to fluoxetine.
Moreover, the mother used the same medications during pregnancy.
Therefore, the authors could not conclude that there was a clear
relationship between the use of carbamazepine during lactation and
seizure--like symptoms in the infant. Frey et al.42 reported neonatal
cholestatic hepatitis and mild neuromotor impairment of the extremi-ties
in one infant. In this case, the mother was treated with carbamaz-epine
during the pregnancy period and the newborn required ventila-tory and
circulatory support following delivery. Thus, in light of these confounding
factors, it was very difficult to conclude whether these adverse events
resulted solely from exposure to carbamazepine via
Uguz and Sharma
breast milk. In addition, the infant serum level of carbamazepine in
these two cases was only 0.5 ng/mL.34,35
2.5 | Oxcarbazepine
Only two case reports43,44 could be found about usage of oxcar-
bazepine during breastfeeding in the recent literature. Lutz et al. 43
calculated safety--related parameters at the 8th and 23rd days
postpartum in the infant of a mother with the diagnosis of bipolar
disorder. The absolute daily infant dose was 510–570 μg, RID was
1.5%–1.7% and infant/maternal ratio of serum oxcarbazepine
concentration was < 0.5–1.0. In contrast, the M/P ratio was very
high (5.0–9.0). The authors reported no adverse effects or delayed
development in the child at the end of 5 years. The second case
report by Gentile44 did not include any safety--related parameters.
However, the author reported normal development in the infant
during the first breastfed month of life.
3 | DISCUSSION
Published data on the safety of prescribed medications during
lactation are essential in the decision about the best treatment
options and the choice of pharmacological agents. Reported
adverse events, infant plasma drug concentrations, M/P ratio,
infant/maternal serum drug concentration ratio, RID and absolute
daily infant dose are the main safety--related parameters.35 The
last three are rela-tively new parameters that have been used
frequently in recent years. The RID value is a very useful practical
guide to indicate the extent of drug exposure during
breastfeeding.18 The levels that are generally accepted to be
clinically significant are 10% or more for RID, 1 or more for the M/P
ratio, and 10% or more for the infant/maternal serum drug
concentration ratio.45,46 Not many studies report each of these
parameters as they require exhaustive labaratory assays.
Lithium is widely used in the treatment of bipolar disorder. Although
litihim has been used as a mood stabilizer for many years, more data on
its usage during breastfeeding have been emerging recently.10 Similar to
other psychotropics, the amount of lithium excreted into milk varies in
breastfeeding mothers, possibly due to differences in M/P ratio and
variations in maternal clearance and serum levels of lithium.21 It has
been recommended that lithium should be avoided during breastfeed-
ing.47,48 In reality, however, the limited available data suggest that the
M/P ratios are lower than the acceptable level suggested for the M/P ratio
(1.0). Moreover, it has been reported that almost none of the exposed
infants experienced any clinical adverse events, with a low prevalence
rate of laboratory abnormalities. On the other hand, it has also been
noted that more than half of infants had ≥ 15% RID values 19 and
relatively high infant/maternal serum lithium concentration ratios. As a
result, there is no clear evidence suggesting any contrindication to the
use of lithium during lactation. However, owing to a relatively high
exposure of breastfed infants and limited short--term and long-- term
safety data on infants exposed to lithium during breastfeeding,
Uguz and Sharma | 7

lithium should be considered when there is a lack of alternative studies. On the other hand, an unclear association between carba-
treat-ments. The possible risks and benefits of lithium treatment mazepine exposure and cholestatic hepatitis (n = 1)42 and seizure--
during lac-tation should be adequately discussed with the mother.
like symptoms (n = 1)41 as well as an association between valproate
Anticonvulsants, especially valproate, carbamazepine, and lam-
otrigine, are other mood stabilizers widely used in the treatment of exposure and thrombocytopenic purpura and anemia (n = 1)38 has
bipolar disorder. The available data on the use of anticonvulsants in been reported. Breastfeeding infants of mothers using valproate or
lactating women have been obtained almost entirely in epileptic patients. carbamazepine should be monitored for jaundice, hepatotoxicity,
In most cases, the patients had also been treated with the same leukopenia, anemia and thrombocytopenia. In addition, the present
medications during their pregnancy. For this reason, assessing the review suggests that there is very limited information about the
possibility of a connection between the usage of anticonvulsants and usage of oxcarbazepine during breastfeeding, and therefore
adverse events in exposed infants is very difficult. Multicenter and oxcarbazepine might not be an appropriate pharmacological option
population--based prospective studies with follow--up for a period of in treatment of bipolar disorder during breastfeeding. Reports
published more than 20 years ago indicating very low M/P ratios for
three and six years, respectively, demonstrated no harmful effects of
valproate (0.7%– 10%)10 suggest that valproate may have a more
breastfeeding while the patients were taking anticonvulsants.52–54
favorable level of drug exposure during lactation than
However, no such studies carried out in women with a diagnosis of
carbamazepine, oxcarbazepine and lamotrigine. However, a higher
bipolar disorder have been reported.
teratogenic potential and other reproductive risks, such as polycystic
As shown in Table 1, lamotrigine has the most extensive safety data ovarian syndrome, for valproate compared to other anticonvulsants
in infants exposed via breast milk, with data on a relatively large of should be considered before it can be concluded that valproate
infants reported in the literature. The reported prevalence of adverse
should be preferred in women with bipolar disorder.50,51
events in the infants is very low. It is well known that use of lamotrigine is
associated with the development a rash that can occa-sionally be life-
-threatening, such as toxic epidermal necrolysis and Steven–Johnson 4 | CONCLUSIONS
syndrome.34 Although a rash was reported in three exposed infants, this
The available data do not allow definitive conclusions to be drawn
appeared not to be connected with lamotrig-ine.34 On the other hand,
about the risk/benefit profile of mood stabilizers in terms of the safety
wide ranges with 10–20--fold differences have been reported for the M/P
of the infants of breastfeeding women with bipolar disorder.
ratio, RID and infant/maternal ratio of serum lamotrigine concentration,
However, the available information does not demonstrate a con-
which are important reflectors of the level of drug exposure in
traindication for breastfeeding during maternal use of mood sta-
breastfeeding infants. However, rel-atively consistent results such as
bilizers. Following risk−benefit analysis, individualized treatment for
M/P ratios of 0.40–0.60, RID val-ues of 6%–9%, and infant/maternal
bipolar disorder during breastfeeding is the main clinical approach in
ratios of serum lamotrigine con-centration of 0.1–0.3 have also been
the management. Additionally, the parents should be informed and
reported. In addition, the high maternal lamotrigine doses used in many
educated regarding possible adverse events. It is unclear which
breastfeeding women with epilepsy should be considered during the
mood stabilizer is superior to others with regard to infant safety
interpretation of the avail-able data. The relatively consistent results for
these safety parameters and a low prevalence rate of adverse events in
because of the lack of comparative, short--term and especially long--

the exposed infants, suggest that lamotrigine may be considered term studies with large sample sizes. Due to theoretical risks and
preferable to other drugs in breastfeeding women with bipolar relatively high exposure via breast milk, lithium should be recom-
depression, and discontinuation of breastfeeding in mothers using mended with caution. This review suggests that the risk of adverse
lamotrigine does not seem to be necessary. However, infants exposed to events in infants exposed to anticonvulsants is low, and therefore
lamotrigine should be closely monitored for skin rash which can these mood stabilizers may be preferable for some patients with a
occasionally be life--threatening and apnea which can lead to cyanosis. diagnosis of bipolar disorder. Further studies with large sample sizes
are needed to reach more definitive conclusions about the use of
The American Academy of Pediatrics considers carbamazepine and mood stabilizers by mothers with bipolar disorder during
valproate to be compatible with use during breastfeeding.47 In weighing breastfeeding.
up the benefits of breastfeeding against the potential risks to the nursing
infant, some authors have suggested that traditional anticonvulsants DISCLOSURES
such as carbamazepine and valproate are generally considered safe for
use during breastfeeding by epileptic women because they have not The authors of this paper do not have any commercial associations
been found to be excreted into breast milk in clinically relevant that might pose a conflict of interest in connection with this
amounts.49 In the recent literature, there are more data on manuscript.
carbamazepine than on valproate in breastfeeding women. Nonetheless,
limited data suggest that valproate has a lower infant/ maternal ratio of AUTHOR CONTRIBUTIONS
serum concentration compared to lamotrigine and
FU performed the literature search. FU and VS wrote the paper.
carbamazepine,26,32,35–38,40,49 which should be confirmed by further
8 |
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How to cite this article: Uguz, F., Sharma, V. (2016) Mood
stabilizers during breastfeeding: a systematic review of the recent
literature. Bipolar Disord 00: 1–9. DOI: 10.1111/bdi.12398