Expert Opinion on Drug Safety

ISSN: 1474-0338 (Print) 1744-764X (Online) Journal homepage: https://www.tandfonline.com/loi/ieds20

Using sertraline in postpartum and breastfeeding:

balancing risks and benefits

Alessandro Cuomo, Giuseppe Maina, Stephen M Neal, Graziella De Montis,

Gianluca Rosso, Simona Scheggi, Bruno Beccarini Crescenzi, Simone
Bolognesi, Arianna Goracci, Anna Coluccia, Fabio Ferretti & Andrea Fagiolini

To cite this article: Alessandro Cuomo, Giuseppe Maina, Stephen M Neal, Graziella De Montis,
Gianluca Rosso, Simona Scheggi, Bruno Beccarini Crescenzi, Simone Bolognesi, Arianna Goracci,
Anna Coluccia, Fabio Ferretti & Andrea Fagiolini (2018) Using sertraline in postpartum and
breastfeeding: balancing risks and benefits, Expert Opinion on Drug Safety, 17:7, 719-725, DOI:
10.1080/14740338.2018.1491546

To link to this article: https://doi.org/10.1080/14740338.2018.1491546

Accepted author version posted online: 21

Jun 2018.
Published online: 05 Jul 2018.

Submit your article to this journal

Article views: 213

View Crossmark data

Full Terms & Conditions of access and use can be found at

https://www.tandfonline.com/action/journalInformation?journalCode=ieds20
EXPERT OPINION ON DRUG SAFETY
2018, VOL. 17, NO. 7, 719–725
https://doi.org/10.1080/14740338.2018.1491546

REVIEW

Using sertraline in postpartum and breastfeeding: balancing risks and benefits

Alessandro Cuomoa, Giuseppe Mainab, Stephen M Nealc, Graziella De Montisa, Gianluca Rosso b, Simona Scheggia,
Bruno Beccarini Crescenzia, Simone Bolognesia, Arianna Goraccia, Anna Colucciad, Fabio Ferrettid and Andrea Fagiolinia
a
University of Siena, Department of Molecular and Developmental Medicine (AC, GDM, SS, BBC, SB, AG, AF); bUniversity of Torino, Department of
Neuroscience (GM, GR); cThe Department of Psychiatry, West Virginia School of Osteopathic Medicine (SMN); dUniversity of Siena Department of
Medical, Sugical and Neurological Sciences (AC2, FF)

ABSTRACT ARTICLE HISTORY

Introduction: The World Health Organization recommends newborns to be breastfed but this may be Received 9 March 2018
challenging if the mother needs to be treated for depression, since strong evidence to inform treatment Accepted 18 June 2018
choice is missing. KEYWORDS
Areas covered: We provide a critical review of the literature to guide clinicians who are considering Sertraline; pregnancy;
sertraline for the management of depression during postpartum. breast-feeding; milk; infant;
Expert opinion: Sertraline is one of the safest antidepressants during breastfeeding. In most cases, newborn; SSRI; depression;
women already taking sertraline should be advised to breastfeed and continue the medication. We nursing; post-partum;
recommend to begin with low doses and to slowly increase the dose up, with careful monitoring of the lactation; perinatal and
newborn for adverse effects (irritability, poor feeding, or uneasy sleep, especially if the child was born pregnancy
premature or had low weight at birth). The target dose should be the lowest effective. When feasible,
child exposure to the medication may be reduced by avoiding breastfeeding at the time when the
antidepressant milk concentration is at its peak. A decision to switch to sertraline from ongoing and
effective treatment should be taken only after a scrupulous evaluation of the potential risks and
benefits of switching versus continuing the ongoing medication while monitoring the infant carefully.

1. Introduction The aim of the paper is to provide evidence-based sugges-

tion for decision making about sertraline in the treatment of
Postpartum depression (PPD) may be diagnosed when a woman
an episode of major depressive disease occurring during the
meets the criteria for a depressive episode with an onset during
postpartum period.
pregnancy or within 4 weeks after the delivery [1,2]. The occur-
rence of depression in the postpartum period poses several pro-
blems, including the risks of impairing the mother–infant 2. Sertraline concentrations in milk
interaction [3] (maternal withdrawal, disengagement, intrusion,
Detectable levels of all antidepressants have been found in
and hostility [4,5]), impairing the infant’s long-term emotional,
breast milk [21,35–37]. A number of factors influence the
cognitive, behavioral, social, and psychomotor development, and
concentration of a medication into breast milk: protein bind-
shortening of the breastfeeding period [6–15]. The World Health
ing (drugs that are highly protein bound are less likely to pass
Organization (WHO) recommends breastfeeding for at least the
into breast milk), rate of absorption, half-life, peak serum
first 6 months of life [16]. There is an evidence about numerous
concentration and time to achieve the peak, pH, volume of
benefits of breastfeeding on both maternal and infant health,
distribution, molecular size, dissociation constant, ionization
including decreased risk for maternal ovarian and breast cancers,
degree, and solubility [38]. Sertraline is 98% bound to plasma
type II diabetes mellitus and hypertension [17–20]; immunological
proteins, which reduces the likelihood of milk transfer [39],
and antioxidant protection for the baby; reduced risk of several
and most of reviewers consider it as one of the preferred
diseases including asthma, ear infections, diarrhea, and sudden
antidepressants during breastfeeding [35,40–43]. Sertraline is
newborn death syndrome [17,21–24], as well as positive economic
predominantly metabolized by CYP2B6 with lesser involve-
impact [21,25–29]. An appropriate treatment of postpartum
ment of CYP2C19, CYP2C9, CYP3A4, and CYP2D6. Sertraline
depression may benefit women, children, and families [9,30,31].
multiple metabolic pathways increases its chances to be effec-
Several reviews have been conducted on the safety of
tively metabolized from both mothers and infants, which is
antidepressants during breast-feeding but most knowledge
another reason to allocate this medication among the most
derives from case studies and small case series [21,32–35].
preferred antidepressants to use during breastfeeding [44].
However, pharmacodynamic and pharmacokinetic para-
The drug’s concentration in milk parallels the concentration
meters widely vary among specific medications of this class
in maternal plasma, albeit with some delay. The newborn
and the potential impact on the newborn may differ from
sertraline exposure may be calculated based on the relative
medication to medication.

CONTACT Andrea Fagiolini andreafagiolini@gmail.com University of Siena, Department of Molecular and Developmental Medicine (AC, GDM, SS, BBC, SB, AG, AF)
© 2018 Informa UK Limited, trading as Taylor & Francis Group
720 A. CUOMO ET AL.
Article highlights
● Sertraline is one of the safest antidepressants for breastfeeding
women
● Infants are unlikely to exhibit quantifiable serum sertraline
concentrations
● Very few adverse events associated with sertraline have been
reported.
● Sertraline should be started with low doses and the dose should be
titrated up slowly while monitoring the infant for adverse effects
● The target dose should be the lowest effective.
● When feasible, breastfeeding should be avoided at the time of peak
antidepressant concentration in the breast milk.
This box summarizes key points contained in the article.
dose per kg body weight [45]. Sertraline is considered the
selective serotonin reuptake inhibitors (SSRI) of choice for
depression during breastfeeding because of its relatively
short half-life, often undetectable infant serum concentration,
and low risk of central nervous system effects.
An analysis of 67 studies [35] (including a total of 238 infants)
of antidepressant levels in breastfed infants showed that an
average milk sertraline level of 45 mcg/L (range 7–207 mcg/L)
was to be expected for an average sertraline daily dosage of
83 mg (range 25–200 mg). Breastfed infants resulted to receive
approximately 0.5% of the maternal weight-adjusted dosage of
sertraline with a very small risk of adverse events.
Stowe and colleagues [46] evaluated the levels of sertraline
and its metabolite desmethylsertraline in both breast milk and
newborns serum. Sertraline and desmethylsertraline were pre-
sent in all milk samples. Interestingly, a gradient from ‘fore’ to
‘hind’ milk was observed with the highest sertraline concen-
trations being observed in hind milk, 7–10 h following the
maternal intake. Hence, the option of pumping and discarding
milk in this time window, or of nursing the infant with milk
that has been pumped in other time windows, should be
considered. Higher maternal sertraline doses were correlated
with higher breast milk sertraline and desmethylsertraline
levels. Three infants showed detectable sertraline concentra-
tions, and six showed detectable desmethylsertraline levels.
No adverse effects were observed in any infant.
In another study, which included four breastfeeding mother
treated with a mean sertraline dose of 87.5 mg, resulting in an
estimate dose of sertraline 0.04 mg/kg for the infants, no infant
showed detectable (<0.1 mcg/L) serum concentration of either
sertraline or nor-sertraline [47].
Salazar and colleagues reported of seven breastfeeding
mothers treated with sertraline at 25 (n = 2) or 50 mg
(n = 5) generating sertraline milk concentrations ranging
from 24.2 to 81.7 ng/mL resulting in low infant absolute
doses, ranging from 4.36 to 12.26 µg/kg/day [48].
Three other studies [49–51] evaluated serum sertraline con-
centrations in lactating mothers and their babies and confirmed
low sertraline and metabolite levels in the infants’ serum.
In rats studies, Capello and colleagues [52] evaluated
fetal central nervous system (CNS) exposure to antidepres-
sants (including sertraline) received via breast milk and
observed that CNS exposure occurred even when drug
concentrations in nursing pup sera were undetectable. Of
interest, serotonin transporter occupancy ranging from 18%
to 35% was observed in all sertraline groups, after 7 days of
exposure via breast milk.
Epperson et al [53,54] evaluated platelet serotonin trans-
porter blockade in 14 mother–infant dyads, before and after
maternal treatment with sertraline 25–200 mg/day. Although a
marked (70–96%) decrease in platelet serotonin concentration
was observed in the mothers, minor or no change in platelet
serotonin concentration was observed in the breastfed infants.
Sertraline and, desmethylsertraline, levels were 30.7 ng/mL
and 45.3 ng/mL in the mothers but resulted below or at the
lower limit of quantitation in their infants. The authors con-
cluded that mothers treated with sertraline can breast-feed
without significantly affecting serotonin transport in their
children.
Hendrick et al [55] studied the physical development and
weight gain of the infants of 78 mothers receiving SSRI
(including sertraline) and selective norepinephrine and sero-
tonin reuptake inhibitors (SNRI) anti-depressant while
breastfeeding.
The average 6-month weight of the infants in the study
was 17.6 pounds for boys and 16.1 pounds for girls, which
were not significantly different from the CDC-published
weight norms. However, the mean weights for infants
whose mothers experienced depression for longer than 2
months were 14.7 pounds for girls and 16.1 pounds for
boys, that is, significantly lower than the weights of the
other infants in the sample [55].
Hackett et al [56] reported on a breastfed infant whose
mother was treated with sertraline 300 mg/day (infant plasma
sertraline level = 5 μg/L, demethylsertraline = 17 μg/L) com-
bined with reboxetine at 8 mg/day. The child achieved stan-
dard weight for age milestones with a Denver developmental
age, described as a percent of actual age, that resulted 119%,
In a study involving 25 women receiving antidepressants,
and their 26 breastfed infants, no adverse effect was observed
among the 6 breastfed infants whose mothers were receiving
sertraline at doses between 50 mg and 100 mg [22].
Hendrick and colleagues reported on 30 infants
breastfed by a mother taking sertraline. Detectable levels
of sertraline were present in 24% of the children. Sertraline
was significantly more likely to be detected in infants
breastfed by mothers that were taking more than 100 mg
a day. No adverse effect was recorded for any of the
breastfed infants [56].
In a comparative analysis of sertraline and nortriptyline
during postpartum depression, 13 newborns were fed on
breast milk by mothers receiving sertraline therapy. Serum
levels of sertraline resulted undetectable (<2 mcg/L);
whereas, norsertraline levels varied from undetectable to
6 mcg/L [58]. No adverse events for the infants were
reported.
Pinheiro and colleagues [41] conducted a review and
meta-analysis [41] to evaluate the risks and benefits of
sertraline during breastfeeding. The authors did not find a
significant correlation between infant and maternal sertra-
line plasma levels, owing to the low to non-detectable
infant plasma concentrations, which were not affected by

maternal sertraline levels. A significant relationship was
instead found between infant and maternal plasma concen-
trations of desmethylsertraline. However, desmethylsertra-
line is not as active as sertraline.
The authors concluded that their findings confirm the role
of sertraline as first-line antidepressant and support the prac-
tice to target sertraline dose at the best level to completely
treat depression, as opposed to prescribing low doses out of
fear of an excessive infant exposure.
3. Adverse impacts of sertraline during breastfeding
Sertraline may affect the production of breast milk. Cases
of galactorrhea in non-expectant and non-nursing women
treated with sertraline have been reported [60–62], despite
the fact that most studies on the topic have concluded
that sertraline is less likely than other SSRISs or than some
SNRIs to cause hyperprolactinemia [57].
Holland reported to have observed a reduced milk supply
in six nursing mothers treated with sertraline. Interestingly,
one of the women experienced an increase in milk supply
after stopping sertraline for 1 week, which reversed upon re-
starting the medication. However, the author noted that the
reduction in milk supply was temporary in all six cases, and
that milk production improved within 2–3 days from an
increase in the intake of fluids [58].
Another case study [59] evaluated the impact of SSRIs
(including sertraline) on human lactation in a cohort of 431
women and observed that women on SSRI were more likely to
experience delayed secretory activation.
A cohort study compared the breastfeeding outcomes of
women treated with SSRI at the time of delivery with a group
of women who discontinued the antidepressant before deliv-
ery, and a group of women who were never exposed to
sertraline. Breastfeeding rates resulted significantly higher in
unexposed women. In addition, both women exposed to an
SSRI prior to delivery and women who were still taking sertra-
line at the time of delivery (total number of women exposed
to sertraline = 87) were less likely (respectively, 27% and 33%)
to breastfeed than unexposed women, despite the fact that
there were not significant differences in lactation rates among
the study groups. The authors concluded that women
exposed to SSRIs during pregnancy may benefit from addi-
tional education and support regarding breastfeeding and the
risks of antidepressant exposure [60].
Although several studies reported no adverse effects [61],
isolated cases of adverse events potentially related to expo-
sure to sertraline during breastfeeding have been reported.
For instance, Rohan described the history of a 5-month-old
baby who became agitated after her mother took sertraline
and of an infant who was exposed to sertraline from 10 days
postpartum through the remaining of the first 3 months of life.
During this period, the infant was somnolent, had low muscle
tone, and hearing problems, which markedly improved when
the drug was discontinued [62].
Oberlander and colleagues evaluated biobehavioral
responses to pain at 2 months of age in infants exposed to
SSRI. The study group of 30 infants who were exposed to SSRIs
both pre and post-natally, included four subjects who were
EXPERT OPINION ON DRUG SAFETY 721
exposed to sertraline. In this group (n = 30), signs of blunted
pain response were observed [47].
However, several studies reported no adverse events. For
instance, Lee and colleagues [69] reported no adverse event
in a control group that included two infants breastfed by a
mother who was treated with sertraline [63]. In addition, no
adverse outcomes were observed in an infant breastfed by a
mother receiving sertraline 50 mg daily and methylpheni-
date 72 mg/day. The evaluations conducted at 6 and
12 months of age confirmed the absence of developmental
problems in the child [64].
In addition, in a study of sertraline for postpartum depres-
sion, no adverse even was reported for any of the six infants
who were breastfed [65].
Hale and colleagues [66] evaluated antidepressant discon-
tinuation syndrome in the infants of 403 (188 on sertraline)
women who received an antidepressant only during preg-
nancy or during both pregnancy and breastfeeding (n = 527,
405 on sertraline).
Discontinuation syndrome was reported only for a small per-
centage of infants exposed to antidepressants. Interestingly,
infants of women who took antidepressants during pregnancy
and breastfeeding were 2–8 times more likely to experience
symptoms of discontinuation than infants that were exposed
only during breastfeeding.
A telephone follow-up survey was conducted among 124
females who used benzodiazepines during breastfeeding to
determine whether their newborns demonstrated any symptom
of sedation. One of the women was also taking sertraline 50 mg/
day, along with 2.5 mg of zopiclone as needed, up to three times
a day. Sedation was reported in the breastfed infant but it was
not possible to establish if sertraline contributed [67].
Muller and colleagues [68] reported of a 33-week preterm
infant who was exposed to sertraline during both pregnancy
and lactation. Signs of serotonergic overstimulation were
observed until day 9 after birth, when breastfeeding was
discontinued. The symptoms resembled an abstinence syn-
drome and included muscle tone dysregulation, high-pitched
crying, and hyperthermia. Interestingly, sertraline blood level
in the infant was within the normal range estimated for adults.
However, the serotonergic overstimulation could be due to
the infant’s reduced metabolic capacity and/or the immaturity
of the blood–brain barrier.
In a study of 247 infants exposed to an antidepressant
during the third trimester of pregnancy, a higher risk of devel-
oping poor neonatal adaptation was observed in infants who
received formula feeding compared to those infants who were
breastfed or received mixed feeding. Of note, 68 of the total
sample was exposed to sertraline during pregnancy and all
mothers continued the medication during breastfeeding [69].
Uguz and colleagues [70] retrospectively evaluated the
tolerability of sertraline and paroxetine in 72 breastfed infants,
of whom 42 were exposed to paroxetine and 30 to sertraline.
Sertraline dose was 25 mg in 3 mothers, 50 mg in 24 mothers,
and 100 mg in 3 mothers. Paroxetine dose was 10 mg in 10
mothers and 20 mg in 32 mothers.
The prevalence of adverse events was 12.5%. Four infants
in the sertraline group and five infants in the paroxetine group
experienced adverse events, and the most frequent symptoms
722 A. CUOMO ET AL.
were insomnia (88.9%), restlessness (55.6%), and excessive
crying (22.2%).
All adverse events developed within 2 weeks of initiation of
sertraline treatment and completely recovered within the
3 days from treatment discontinuation.
4. Conclusion
A number of psychological interventions have been devel-
oped and tested for the treatment of mild postnatal
depression: interpersonal therapy (IPT) [71–77]; cognitive
behavioral therapy (CBT) [78–80]; psychodynamic therapy
[79]; individual or support group counseling [81,82].
Overall, psychological interventions for the treatment of
depression in the postpartum period have shown moder-
ate effect sizes [83]; antidepressant medications have
shown larger effect sizes [84].
Pharmacotherapy should be considered for women who are
experiencing moderate to severe depression and do not respond
to, or are not good candidates for, psychotherapy. When consider-
ing an antidepressant a woman who needs to breastfeed, there is
not a 100% safe option or an universally accepted treatment
algorithm option. It is noteworthy that many antidepressants in
general, and sertraline in particular, show minor concentrations in
breast milk and even lower – often undetectable – concentrations
in the infant serum. When an antidepressant therapy is indicated
in females suffering from depression, it is not always necessary to
discontinue breastfeeding, especially when a relatively safe med-
ication, such as sertraline, is prescribed.
5. Expert opinion
A personalized risk–benefit evaluation should be conducted
before a decision is made whether an antidepressant should
be started/continued in postpartum and whether breast feed-
ing should be suggested. A partnership between the mental
health professional and the pediatrician is paramount, as no
clinical decision in the context of postpartum depression is
completely without risk.
Clinical variables that may inform treatment options
include the mother’s clinical history, the current symptoms,
the risks of untreated depression, the risks and benefits of
breastfeeding, and the mother’s preferences [85].
In most cases, women who are already taking sertraline
should be advised to continue for at least 6 months after
recovery of the depressive episode. Important variables to
consider include the number of previous episodes and the
risk of relapse if the treatment is discontinued [86,87].
Moreover, continuing the antidepressants while breast-
feeding may reduce the risk of withdrawal symptoms for
the infant [88]. In fact, stopping an antidepressant abruptly
may lead to withdrawal effects[89].
Sertraline is one of the safest and most studied medica-
tions to be used during breastfeeding, owing to its docu-
mented low levels of exposure in breastfed infants and to
the very limited number of adverse events that have been
described in the literature.
However, a decision to switch to sertraline from ongoing
treatments that have proven to be effective but are not
usually considered as first-line options in breastfeeding (e.g.
citalopram or fluoxetine) should be taken only after a thor-
ough evaluation of the risks and benefits of switching versus
continuing an ongoing effective medication while monitoring
the infant carefully [33,90].
If sertraline is administered to a nursing mother after delivery,
it is recommended to begin at a low doses and then titrate the
dose up slowly, while monitoring the infant for adverse effects
(irritability, poor **feeding, or uneasy sleep, particularly if the
infant is sick, premature or has a low weight) [17,22,35,40,91–
94]. The target dose should be the lowest effective one, although
care should be taken to ensure that such dose is high enough to
be effective [95].
Infant exposure to an antidepressant could be minimized
by avoiding breastfeeding at the time of peak antidepressant
concentration in the breast milk[96]. However, avoiding breast
feeding when peak drug levels occur may not be practical [86].
When adverse effects in the infant are noted, options to be
considered include a dosage decrease, a change to partial or
full bottle-feeding, or a change in the prescribed medication.
Although the ability to metabolize drugs is not usually fully
developed in neonates, routine breast milk and/or infant
serum sampling for drug levels evaluation is generally not
recommended [21,35,97]. However, in selected cases serum
sampling may be helpful to reassure a mother who desires
to continue breastfeeding but is worried about the drug con-
centrations in her milk and/or in her infant circulation.
The literature on this topic is rapidly growing. Once a decision
has to be taken, we recommend to monitor current knowledge
through publications and websites that update and review pub-
lished information frequently (https://toxnet.nlm.nih.gov/new
toxnet/lactmed.htm; www.mededppd.org, www.postpartum.
net, www.womensmental-health.org, and www.motherrisk.org).
Funding
none
Declaration of interest
A Fagiolini is/has been a consultant and/or a speaker and/or has received
research grants from Allergan, Angelini, Generici DOC, Lundbeck, Italfarmaco,
Janssen, Otsuka, Pfizer, Recordati, Roche, and Sanofi Aventis. G Maina is/has
been a consultant and/or a speaker and/or has received research grants from
Janssen, Otsuka, Lundbeck, Fb Health, Angelini, and Sanofi Aventis. G Rosso
is/has been a consultant and/or a speaker and/or has received research
grants from Otsuka, Lundbeck, and Angelini. The authors have no other
relevant affiliations or financial involvement with any organization or entity
with a financial interest in or financial conflict with the subject matter or
materials discussed in the manuscript apart from those disclosed.
ORCID
Gianluca Rosso http://orcid.org/0000-0002-2308-9146
References
Papers of special note have been highlighted as either of interest (•) or of
considerable interest (••) to readers.
1. APA. Dianostic and statistical manual of mental disorders: DSM-5.
5th ed. Arlington (VA): American Psychiatric Association; 2013.

2. WHO. Maternal mental health and child health and development.
Improving maternal mental health millennium development goal 5 –
improving maternal health. Geneva (Switzerland): World health
Organization; 2010.
3. Murray LHS, Cooper P. Effects of postnatal depression on mother–
infant interactions and child development. In: Bremner JG, Wachs
TD, editors. The Wiley-Blackwell handbook of infant development.
Vol. 2. 2nd ed. Hoboken (NJ): Wiley-Blackwell; 2010. p. 192–220.
4. Martins C, Gaffan EA. Effects of early maternal depression on
patterns of infant-mother attachment: a meta-analytic investiga-
tion. J Child Psychol Psychiatry. 2000;41(6):737–746.
5. Lovejoy MC, Graczyk PA, O’Hare E, et al. Maternal depression and
parenting behavior: a meta-analytic review. Clin Psychol Rev.
2000;20(5):561–592.
6. Murray L, Arteche A, Fearon P, et al. Maternal postnatal
depression and the development of depression in offspring
up to 16 years of age. J Am Acad Child Adolesc Psychiatry.
2011;50(5):460–470.
7. Brand SR, Brennan PA. Impact of antenatal and postpartum mater-
nal mental illness: how are the children?. Clin Obstet Gynecol.
2009;52(3):441–455.
8. Cornish AM, McMahon CA, Ungerer JA, et al. Postnatal depression
and infant cognitive and motor development in the second post-
natal year: the impact of depression chronicity and infant gender.
Infant Behav Dev. 2005;28:407–417.
9. Orhon FS, Ulukol B, Soykan A. Postpartum mood disorders and
maternal perceptions of infant patterns in well-child follow-up
visits. Acta Paediatr. 2007;96(12):1777–1783.
10. Grace SL, Evindar A, Stewart DE. The effect of postpartum depression on
child cognitive development and behavior: a review and critical analysis
of the literature. Arch Womens Ment Health. 2003;6(4):263–274.
11. Murray L, Cooper PJ. Postpartum depression and child develop-
ment. Psychol Med. 1997;27(2):253–260.
12. Misri S, Reebye P, Kendrick K, et al. Internalizing behaviors in 4-
year-old children exposed in utero to psychotropic medications.
Am J Psychiatry. 2006;163(6):1026–1032.
13. Sohr-Preston SL, Scaramella LV. Implications of timing of maternal
depressive symptoms for early cognitive and language develop-
ment. Clin Child Fam Psychol Rev. 2006;9(1):65–83.
14. Dennis CL, McQueen K. Does maternal postpartum depressive
symptomatology influence infant feeding outcomes? Acta
Paediatr. 2007;96(4):590–594.
15. Hipwell AE, Goossens FA, Melhuish EC, et al. Severe maternal
psychopathology and infant-mother attachment. Dev
Psychopathol. 2000;12(2):157–175.
16. who.int [Internet]. Geneve (Switzerland): Health Topic:
Breastfeeding; 2018 Jan 23. Available from: http://www.who.int/
topics/breastfeeding/en/
17. Ip S, Chung M, Raman G, et al. Breastfeeding and maternal and
infant health outcomes in developed countries. Evid Rep Technol
Assess (Full Rep). 2007;153:1–186.
18. McClure CK, Catov JM, Ness RB, et al. Lactation and maternal
subclinical cardiovascular disease among premenopausal women.
Am J Obstet Gynecol. 2012;207(1):46.e1-8.
19. Schwarz EB, Brown JS, Creasman JM, et al. Lactation and maternal
risk of type 2 diabetes: a population-based study. Am J Med.
2010;123(9):863.e1-6.
20. Stuebe AM, Schwarz EB, Grewen K, et al. Duration of lactation and
incidence of maternal hypertension: a longitudinal cohort study.
Am J Epidemiol. 2011;174(10):1147–1158.
21. Lanza Di Scalea T, Wisner KL. Antidepressant medication use during
breastfeeding. Clin Obstet Gynecol. 2009;52(3):483–497.
22. Berle JO, Steen VM, Aamo TO, et al. Breastfeeding during maternal
antidepressant treatment with serotonin reuptake inhibitors: infant
exposure, clinical symptoms, and cytochrome p450 genotypes. J
Clin Psychiatry. 2004;65(9):1228–1234.
• Serum drug levels in breastfed infants of mothers receiving
SSRI antidepressants were undetectable or low. This study
provides evidence indicating that breastfeeding should not
be generally discouraged in women using SSRIs.
EXPERT OPINION ON DRUG SAFETY 723
23. Newton ER. Breastmilk: the gold standard. Clin Obstet Gynecol.
2004;47(3):632–642.
24. Harder T, Bergmann R, Kallischnigg G, et al. Duration of breastfeed-
ing and risk of overweight: a meta-analysis. Am J Epidemiol.
2005;162(5):397–403.
25. Bartick M, Reinhold A. The burden of suboptimal breastfeeding in
the United States: a pediatric cost analysis. J Pediatr. 2010;125(5):
e1048–56.
26. Bartick MC, Stuebe AM, Schwarz EB, et al. Cost analysis of maternal
disease associated with suboptimal breastfeeding. Obstet Gynecol.
2013;122(1):111–119.
27. Scariati PD, Grummer-Strawn LM, Fein SB. A longitudinal analysis of
infant morbidity and the extent of breastfeeding in the United
States. PEDIATRICS. 1997;99(6):e5–e5.
28. Dell S, To T. Breastfeeding and asthma in young children: findings
from a population-based study. Arch Pediatr Adolesc Med.
2001;155(11):1261–1265.
29. Dignam DM. Understanding intimacy as experienced by breast-
feeding women. Health Care Women Int. 1995;16(5):477–485.
30. Pilowsky DJ, Wickramaratne P, Talati A, et al. Children of depressed
mothers 1 year after the initiation of maternal treatment: findings from
the STAR*D-Child Study. Am J Psychiatry. 2008;165(9):1136–1147.
31. Bauer A, Parsonage M, Knapp M, et al. Costs of perinatal mental
health problems. London, UK: London School of Economics and
Political Science; 2014.
32. Gentile S. Use of contemporary antidepressants during breastfeeding:
a proposal for a specific safety index. Drug Saf. 2007;30(2):107–121.
33. Hallberg P, Sjoblom V. The use of selective serotonin reuptake
inhibitors during pregnancy and breast-feeding: a review and clin-
ical aspects. J Clin Psychopharmacol. 2005;25(1):59–73.
• Review of studies and reports of the use of serotonin reuptake
inhibitors during both pregnancy and lactation.
34. Eberhard-Gran M, Eskild A, Opjordsmoen S. Use of psychotropic
medications in treating mood disorders during lactation: practical
recommendations. CNS Drugs. 2006;20(3):187–198.
35. Weissman AM, Levy BT, Hartz AJ, et al. Pooled analysis of antide-
pressant levels in lactating mothers, breast milk, and nursing
infants. Am J Psychiatry. 2004;161(6):1066–1078.
36. Spigset OHS. Excretion of psychotropic drugs into breast milk. CNS
Drugs. 1998;9:111–134.
37. Berle JØ, Spigset O. Maternal antidepressant use and breast-feed-
ing. Curr Med Lit Psychiatry. 2008;19:33–37.
38. Breitzka RL, Sandritter TL, Hatzopoulos FK. Principles of drug trans-
fer into breast milk and drug disposition in the nursing infant. J
Hum Lact. 1997;13(2):155–158.
39. DeVane CL, Liston HL, Markowitz JS. Clinical pharmacokinetics of
sertraline. Clin Pharmacokinet. 2002;41(15):1247–1266.
40. Sriraman NK, Melvin K, Meltzer-Brody S. ABM Clinical Protocol #18:
use of Antidepressants in Breastfeeding Mothers. Breastfeed Med.
2015;10(6):290–299.
•• Clinical protocol for managing common medical problems that
may impact breastfeeding success, developed by AThe
Academy of Breastfeeding Medicine.
41. Pinheiro E, Bogen DL, Hoxha D, et al. Sertraline and breastfeeding:
review and meta-analysis. Arch Womens Ment Health. 2015;18
(2):139–146.
•• Evaluation of the risk-benefit profile of sertraline treatment
during breastfeeding. Sertraline is a first-line drug for breast-
feeding women, with low levels of exposure in breastfed
infants and very few adverse events.
42. Berle JO, Spigset O. Antidepressant Use During Breastfeeding. Curr
Womens Health Rev. 2011;7(1):28–34.
43. Orsolini L, Bellantuono C. Serotonin reuptake inhibitors and breast-
feeding: a systematic review. Hum Psychopharmacol. 2015;30(1):4–20.
•• Literature review indicating that paroxetine and sertraline are
the first choice antidepressants in nursing women
44. Obach RS, Cox LM, Tremaine LM. Sertraline is metabolized by
multiple cytochrome P450 enzymes, monoamine oxidases, and
glucuronyl transferases in human: an in vitro study. Drug Metab
Dispos. 2005;33(2):262–270.
724 A. CUOMO ET AL.
45. Begg EJ, Atkinson HC, Duffull SB. Prospective evaluation of a model
for the prediction of milk: plasmadrug concentrations from physi-
cochemical characteristics. Br J Clin Pharmacol. 1992;33(5):501–505.
46. Stowe ZN, Hostetter AL, Owens MJ, et al. The pharmacokinetics of
sertraline excretion into human breast milk: determinants of infant
serum concentrations. J Clin Psychiatry. 2003;64(1):73–80.
47. Oberlander TF, Grunau RE, Fitzgerald C, et al. Pain reactivity in
2-month-old infants after prenatal and postnatal serotonin
reuptake inhibitor medication exposure. J Pediatr. 2005;
115(2):411–425.
48. Salazar FR, D’Avila FB, De Oliveira MH, et al. Development and
validation of a bioanalytical method for five antidepressants in
human milk by LC-MS. J Pharm Biomed Anal. 2016;129:502–508.
49. Altshuler LL, Burt VK, McMullen M, et al. Breastfeeding and sertra-
line: a 24-hour analysis. J Clin Psychiatry. 1995 June;56(6):243–245.
50. Stowe ZN, Owens MJ, Landry JC, et al. Sertraline and desmethylser-
traline in human breast milk and nursing infants. J Clin Psychiatry.
1997;154(9):1255–1260.
51. Wisner KL, Perel JM, Blumer J. Serum sertraline and
N-desmethylsertraline levels in breast-feeding mother-infant pairs.
Am J Psychiatry. 1998;155(5):690–692.
• Most infants whose mothers were treated with sertraline had very
low serum levels of both sertraline and N-desmethylsertraline.
52. Capello CF, Bourke CH, Ritchie JC, et al. Serotonin transporter occu-
pancy in rats exposed to serotonin reuptake inhibitors in utero or via
breast milk. J Pharmacol Exp Ther. 2011;339(1):275–285.
53. Epperson N, Czarkowski KA, Ward-O’Brien D, et al. Maternal sertra-
line treatment and serotonin transport in breast-feeding mother-
infant pairs. Am J Psychiatry. 2001;158(10):1631–1637.
54. Epperson CN, Anderson GM, McDougle CJ. Sertraline and breast-
feeding. N Engl J Med. 1997;336(16):1189–1190.
55. Hendrick V, Smith LM, Hwang S, et al. Weight gain in breastfed
infants of mothers taking antidepressant medications. J Clin
Psychiatry. 2003;64(4):410–412.
56. Hendrick V, Fukuchi A, Altshuler L, et al. Use of sertraline, parox-
etine and fluvoxamine by nursing women. Breastfeed Med.
2001;179:163–166.
57. Trenque T, Herlem E, Auriche P, et al. Serotonin reuptake inhibitors
and hyperprolactinaemia: a case/non-case study in the French
pharmacovigilance database. Drug Saf. 2011;34(12):1161–1166.
58. Holland D. An observation of the effect of sertraline on breast milk
supply. Aust N Z J Psychiatry. 2000;34(6):1032.
59. Marshall AM, Nommsen-Rivers LA, Hernandez LL, et al. Serotonin
transport and metabolism in the mammary gland modulates
secretory activation and involution. J Clin Endocrinol Metab.
2010;95(2):837–846.
60. Gorman JR, Kao K, Chambers CD. Breastfeeding among women
exposed to antidepressants during pregnancy. J Hum Lact.
2012;28(2):181–188.
61. Mammen OK, Perel JM, Rudolph G, et al. Sertraline and norsertraline
levels in three breastfed infants. J Clin Psychiatry. 1997;58(3):100–103.
62. Rohan ASA. Drug distribution in human milk. Aust Prescriber.
1997;20:84.
63. Lee A, Woo J, Ito S. Frequency of infant adverse events that are
associated with citalopram use during breast-feeding. Am J Obstet
Gynecol. 2004;190(1):218–221.
64. Bolea-Alamanac BM, Green A, Verma G, et al. Methylphenidate use
in pregnancy and lactation: a systematic review of evidence. Br J
Clin Pharmacol. 2014;77(1):96–101.
65. Hantsoo L, Ward-O’Brien D, Czarkowski KA, et al. A randomized,
placebo-controlled, double-blind trial of sertraline for postpartum
depression. Psychopharmacology. 2014;231(5):939–948.
66. Hale TW, Kendall-Tackett K, Cong Z, et al. Discontinuation syndrome in
newborns whose mothers took antidepressants while pregnant or
breastfeeding. Breastfeed Med. 2010;5(6):283–288.
67. Kelly LE, Poon S, Madadi P, et al. Neonatal benzodiazepines expo-
sure during breastfeeding. J Pediatr. 2012;161(3):448–451.
68. Muller MJ, Preuss C, Paul T, et al. Serotonergic overstimulation in a
preterm infant after sertraline intake via breastmilk. Breastfeed
Med. 2013;8(3):327–329.
69. Kieviet N, Hoppenbrouwers C, Dolman KM, et al. Risk factors for
poor neonatal adaptation after exposure to antidepressants in
utero. Acta Paediatr. 2015;104(4):384–391.
70. Uguz F, Arpaci N. Short-Term Safety of Paroxetine and Sertraline in
Breastfed Infants: A Retrospective Cohort Study from a University
Hospital. Breastfeed Med. 2016;11:487–489.
71. Markowitz JC, Weissman MM. Interpersonal psychotherapy:
principles and applications. World Psychiatry. 2004;3(3):136–
139.
72. Weissman MMKG. Interpersonal psychotherapy for depression. In:
Wolman BB, Stricker G, eds. Depressive disorders: facts, theories, and
treatment methods. Oxford (UK): John Wiley & Sons; 1990. p. 379–395.
73. Stuart S, O’Hara MW. Interpersonal psychotherapy for postpar-
tum depression: a treatment program. J Psychother Pract Res.
1995;4(1):18–29.
74. Wisner KL, Perel JM, Findling RL. Antidepressant treatment during
breast-feeding. Am J Psychiatry. 1996;153(9):1132–1137.
75. O’Hara MW, Stuart S, Gorman LL, et al. Efficacy of interpersonal
psychotherapy for postpartum depression. Arch Gen Psychiatry.
2000;57(11):1039–1045.
76. Klier CM, Muzik M, Rosenblum KL, et al. Interpersonal psychother-
apy adapted for the group setting in the treatment of postpartum
depression. J Psychother Pract Res. 2001;10(2):124–131.
77. Grigoriadis S, Ravitz P. An approach to interpersonal psychotherapy
for postpartum depression: focusing on interpersonal changes. Can
Fam Physician. 2007;53(9):1469–1475.
78. Beck JS. Cognitive therapy: basics and beyond. New York (NY):
Guilford Press; 1995.
79. Clark R, Tluczek A, Wenzel A. Psychotherapy for postpartum depres-
sion: a preliminary report. Am J Orthopsychiatry. 2003;73(4):441–454.
80. Appleby L, Warner R, Whitton A, et al. A controlled study of fluox-
etine and cognitive-behavioral counselling in the treatment of post-
natal depression. Br Med J (Clin Res Ed). 1997;314(7085):932–936.
81. Hollon SD. What is cognitive behavioral therapy and does it work?
Curr Opin Neurobiol. 1998;8(2):289–292.
82. Stuart S, Clark E. The treatment of postpartum depression with
interpersonal psychotherapy and interpersonal counseling. Sante
Ment Que. 2008;33(2):87–104.
83. Cuijpers P, Brannmark JG, Van Straten A. Psychological treatment of
postpartum depression: a meta-analysis. J Clin Psychol. 2008;64(1):103–
118.
84. Bledsoe SEGN. Treating depression during pregnancy and in the
postpartum: A preliminary meta-analysis. Res Soc Work Pract.
2006;16:109–120.
85. U.S. Department of health and human services. The surgeon gen-
eral’s call to action to support breastfeeding. Washington (DC): U.S.
Department of Health and Human Services, Office of the Surgeon
General; 2011.
86. Bobo WV, Yawn BP. Concise review for physicians and other
clinicians: postpartum depression. Mayo Clin Proc. 2014;89
(6):835–844.
87. Bazire S. Psychotropic drug directory. Shaftesbury. Dorset (UK):
Lloyd-Reinhold Communications; 2016.
88. Taylor D, Paton C, Kapur S. The Maudsley prescribing guidelines in
psychiatry. 12th ed. Hoboken (NJ): Wiley Blackwell; 2015.
89. British National Formulary [BNF online]. London: BMJ Group
and Pharmaceutical Press; 2016 2016 Jan; cited 2016 Jan;
cited 2016 Jan 15]. Available from: https://www-medicinescom
plete-com.ezproxy.rgu.ac.uk/mc/bnf/current/PHP6720-baclofen.
htm.
90. Abreu AC, Stuart S. Pharmacological and hormonal treatments for
postpartum depression. Psychiatr Ann. 2005;35:568–576.
91. Sunder KR, Wisner KL, Hanusa BH, et al. Postpartum depression
recurrence versus discontinuation syndrome: observations from a
randomized controlled trial. J Clin Psychiatry. 2004;65(9):1266–
1268.
92. Lesaca TG. Sertraline and galactorrhea. J Clin Psychopharmacol.
1996;16(4):333–334.
93. Bronzo MR, Stahl SM. Galactorrhea induced by sertraline. Am J
Psychiatry. 1993;150(8):1269–1270.

94. Nebhinani N. Sertraline-induced galactorrhea: case report and
review of cases reported with other SSRIs. Gen Hosp Psychiatry.
2013;35(5):576.e3-5.
95. nice.org.uk [Internet]. Antenatal and postnatal mental health: clin-
ical management and service guidance [cited 2018 Jan 28].
Available from: https://www.nice.org.uk/guidance/cg192/
resources/antenatal-and-postnatal-mental-health-clinical-manage
ment-and-service-guidance-pdf-35109869806789
EXPERT OPINION ON DRUG SAFETY 725
96. Stowe ZN. The use of mood stabilizers during breastfeeding. J Clin
Psychiatry. 2007;68(Suppl 9):22–28.
97. Ragan KSZ, Newport DJ. Use of antidepressants and mood
stabilizers in breast-feeding women. In: Cohen LS, Nonacs RM,
editors. Mood and anxiety disorders during pregnancy and
postpartum (Review of Psychiatry Series, Volume 24, Number
4; Oldham JM and Riba MB, series editors). Washington (DC):
American Psychiatric Publishing; 2005. p. 105–144.