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Antipsychotics During Lactation
AdeleC.Viguera, AlexiaM.Jones, JoshuaNiforatos,
andCarrieSwetlik
9.1 Introduction
Historically, women with serious mood and psychotic disorders have often been
discouraged from breastfeeding due to limited lactation safety data for mood stabilizers and second-generation antipsychotics (SGAs.) (Viguera etal. 2010; Sachs
and Committee On Drugs 2013; Viguera etal. 2002) While 83.2% of mothers in the
United States initiate breastfeeding (Center for Disease Control and Prevention
2022), only approximately 49% of mothers with psychiatric disorders attempt to
breastfeed (Santucci etal. 2017), with rates as low as 15% for mothers with bipolar
disorder (Shao etal. 2015).
The American Academy of Pediatrics strongly advocates for exclusive breastfeeding during the rst six months of life, citing well-documented nutritional,
immunological, physical, neurodevelopmental, and psychological benets for both
mother and infant (Center for Disease Control and Prevention 2022; Meek etal.
2022). However, this recommendation becomes more nuanced for women
9
A. C. Viguera (*)
Department of Psychiatry and Psychology, Cleveland Clinic, Cleveland, OH, USA
e-mail: viguera@ccf.org
A. M. Jones
Cleveland Clinic, Cleveland, OH, USA
e-mail: jonesa131@ccf.org
J. Niforatos
Department of Emergency Medicine, John Hopkins University– School of Medicine,
Baltimore, MD, USA
e-mail: jnifora1@jhmi.edu
C. Swetlik
Department of Neurology, MetroHealth Hospital, Cleveland, OH, USA
e-mail: cswetlik@metrohealth.org
© The Author(s), under exclusive license to Springer Nature
Switzerland AG 2025
F. Uguz, L. Orsolini (eds.), Perinatal Psychopharmacology,
https://doi.org/10.1007/978-3-031-99720-4_9
237
238
managing psychiatric conditions whose treatment typically involves multiple psychotropic medications (Galbally et al. 2019; Viguera et al. 2022; Viguera 2024;
Baldessarini etal. 2008).
The postpartum period represents a time of increased risk for either onset or
relapse of mood, anxiety, and psychotic disorders (Jones and Craddock 2005;
Viguera etal. 2007a, 2011; Kendell etal. 1987). Therefore, prioritizing maternal
mental health and stability often represents the most prudent clinical approach when
evaluating risks and benets of treatment during the perinatal period (Viguera etal.
2007a; Miller etal. 2023; Cohen etal. 2006). Moreover, medication exposure dif-
fers signicantly between prenatal exposure and exposure through breast milk
(Verstegen etal. 2022).
During pregnancy, drug concentrations in the fetal bloodstream equilibrate with
maternal levels, resulting in substantial exposure. In contrast, during breastfeeding
infants receive only a small fraction of the mother’s medication dose through breastmilk (Verstegen etal. 2022). Data also suggest that for most medications, adverse
effects from breast milk exposure are rare (Sachs and Committee On Drugs 2013;
Anderson et al. 2016). Consequently, there is no compelling rationale to advise
against breastfeeding for postpartum mothers who require psychotropic medications (Sachs and Committee On Drugs 2013; Miller etal. 2023).
Growing evidence indicates that most psychotropic medications, with only a few
exceptions, are safe for breastfeeding mothers (Klinger etal. 2013; Pacchiarotti
etal. 2016; Fortinguerra etal. 2009; Larsen etal. 2015; Uguz 2016; Gentile 2008;
McAllister-Williams etal. 2017). This chapter examines the lactation safety data of
antipsychotic medications, with particular emphasis on second-generation antipsychotics (SGAs), and outlines a clinical decision-framework for treatment
management.
A. C. Viguera et al.
9.2 Current Clinical Practices andEvolving
Treatment Paradigms
9.2.1 Insights fromtheNational Pregnancy Registry
forAtypical Antipsychotics
Recent evidence from the National Pregnancy Registry for Atypical Antipsychotics
(NPRAA) has provided valuable insights into real-world breastfeeding practices
among women taking second-generation antipsychotics (Viguera etal. 2022). This
prospective cohort study, conducted between 2008 and 2020, enrolled 2004 women
with a history of psychiatric disorders aged 18–45years, with 1394 completing
postpartum follow-up (Viguera etal. 2022). The study revealed signicant differences in breastfeeding patterns between women taking SGAs, most of whom were
diagnosed with bipolar disorder, and those who were not. The control group consisted of mostly women treated with SSRI/SNRI for unipolar and anxiety disorders.
Of women taking SGAs, 59.3% initiated breastfeeding, compared to 88.2% in the
control group. By 3 months postpartum, only 23% of women on SGAs maintained
9 Antipsychotics During Lactation
breastfeeding compared to 47% in the control group of women with psychiatric
disorders taking other psychotropics other than SGAs. Of the women taking SGAs,
60.4% were also on other psychotropic medications (polytherapy), compared to
only 24.4% in the control group. Importantly, no serious adverse effects were
reported in either the cases or controls per medical record review.
Polytherapy has historically been considered incompatible with breastfeeding
(Klinger etal. 2013; Uguz 2016; Viguera etal. 2007b; Sadowski etal. 2013). Thus,
the high rate of polytherapy with SGAs observed in this study is striking, and aligns
with data demonstrating that multiple psychotropic medications are increasingly
used during pregnancy and breastfeeding, especially for mood, anxiety, and psychotic disorders (Sadowski etal. 2013). This nding underscores the clinical reality
faced by many women with psychiatric disorders who need more than one medication to maintain symptom stability (Galbally etal. 2019; Viguera 2024; Baldessarini
etal. 2008). Although lactation safety data for multiple concurrent psychotropics
remains sparse, these ndings demonstrate that women who are successfully managed on complex medication regimens may continue breastfeeding their
infants safely.
This current trend may reect a growing awareness among mothers and clinicians that the substantial benets of breastfeeding outweigh concerns about the
uncertain risks of multiple medications during lactation. This nding may also suggest women are independently deciding to breastfeed while taking multiple medications, contrary to clinical recommendations. Similar behavior has been observed
among women who were lithium monotherapy responders who chose to breastfeed,
despite it being considered a contraindication by many clinicians (Viguera et al.
2007b). Researchers found that healthy, full-term infants who were closely moni-
tored with appropriate labs (TSH, BUN/Cr) in collaboration with a pediatrician
were able to successfully breastfeed while their mothers took lithium, with no serious adverse events reported (Viguera etal. 2007b). This suggests that limited data
or experience with a particular medication during breastfeeding does not necessarily constitute a contraindication, but rather indicates that breastfeeding may be
attempted with appropriate close monitoring and follow-up.
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9.3 Pharmacological Principles ofDrug Transfer into
Breast Milk
Understanding medication transfer into breast milk is complex and requires consideration of multiple pharmacological principles. Drug transfer into breast milk
occurs primarily via passive diffusion (Hale’s Medications and Mothers’ Milk 2026;
Begg etal. 2002; Kelsey 2016; Hale 2004). Factors that inuence the amount of
drug available for secretion into breast milk include molecular weight, protein binding, lipid solubility, drug half-life, and pKa levels (Verstegen etal. 2022; Anderson
etal. 2016; Hale’s Medications and Mothers’ Milk 2026; Begg etal. 2002; Kelsey
2016; Hale 2004). Molecular weight signicantly inuences medication transfer,
with lower molecular weight compounds passing more readily than those with
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A. C. Viguera et al.
higher molecular weight. While most antipsychotics have low molecular weights
allowing moderate milk transfer, quetiapine is an exception with its high molecular
weight (Klinger etal. 2013). Protein binding represents another critical factor; medications with high protein binding (>90%) demonstrate limited breast milk transfer.
This is particularly relevant for antipsychotics, which feature high protein binding
(Klinger etal. 2013). Thus, only a small fraction of the antipsychotic in the form of
free drug is available for excretion into breast milk, keeping most of the drug bound
in maternal plasma and preventing transfer into breast milk (Klinger etal. 2013).
The lipid solubility of medications signicantly impacts their concentration in
breast milk (Verstegen etal. 2022). Lipophilic medications tend to concentrate in
breast milk due to its higher fat content compared to plasma. Most psychotropics,
including antipsychotics, are generally lipophilic compounds (Klinger etal. 2013).
Additionally, the pH gradient between breast milk and plasma inuences medication transfer. Breast milk (pH7.2) is slightly more acidic than plasma (pH7.4), and
this pH difference can lead to ion trapping of basic medications in breast milk,
potentially increasing infant exposure (Kelsey 2016). Other factors including bioavailability, volume of distribution, and the permeability of the blood-brain barrier
also play a role in determining the impact of medication exposure in the infant
(Kelsey 2016).
9.3.1 Metrics forMeasuring Infant Exposure
There are several methods for evaluating medication exposure through breastfeeding. However, two metrics, the Milk-to-Plasma (M/P) ratio and the Relative Infant
Dose (RID), have been typically used in clinical practice and are important metrics
in assigning risk categories to various medications (Verstegen etal. 2022; Hale’s
Medications and Mothers’ Milk 2026; Begg etal. 2002; Kelsey 2016). The M/P
ratio, which represents the ratio of the concentration of drug in the milk to that in
the maternal plasma, is commonly reported in the literature (Verstegen etal. 2022;
Uguz 2016). However, its clinical utility remains limited as it only accounts for drug
transfer from the mother’s blood to breastmilk without accounting for actual infant
exposure (Verstegen etal. 2022).
In contrast, the RID attempts to quantify infant exposure and offers a more comprehensive assessment by measuring what percentage of the mother’s medication
dose reaches her breastfed infant, incorporating both maternal and infant weight
into its calculations (Verstegen etal. 2022; McAllister-Williams etal. 2017; Hale’s
Medications and Mothers’ Milk 2026). The current standard considers a relative
infant dose of less than 10% of the maternal dose to be safe and compatible with
breastfeeding (Verstegen etal. 2022). Notably, almost all psychiatric medications
fall below this safe threshold, offering reassurance to both clinicians and mothers
(Hale’s Medications and Mothers’ Milk 2026). For the most commonly prescribed
antipsychotics, quetiapine has the lowest RID (0.09–0.43%), followed by