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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5238_Библиотеки_им_академика_М_И_Перельмана.pdf
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- •Contents
- •1.1 Introduction
- •1.2.1 Antidepressants
- •1.2.3.2 Second-Generation Antipsychotics (SGAs)
- •1.2.4 Mood Stabilizers
- •1.2.5 Stimulants
- •1.3 Conclusion
- •References
- •1.2.1.1 Selective Serotonin Reuptake Inhibitors
- •1.2.1.2 Bupropion
- •1.2.1.3 Other Less Commonly Used Antidepressants
- •1.2.2 Anxiolytics
- •1.2.3 Antipsychotics
- •1.2.3.1 First Generation Antipsychotics (FGAs)
- •2.2.8 Opioid Pharmacokinetics During Lactation
- •2.3 Conclusions
- •References
- •3.1 Introduction
- •3.2 Pregnancy Risk Categories
- •3.4.1.4 Monotherapy Versus Polytherapy
- •3.4.2.1 Experimental Studies
- •Animal Studies
- •3.4.2.2 Human Studies
- •Case Reports
- •Epidemiologic Studies
- •Meta-Analysis
- •3.4.2.3 Methodological Issues
- •Sample Size, Characteristics, Follow-Up
- •Recall Bias
- •Confounders
- •Confounding by Indication
- •Meta-Analysis
- •3.5 Lactation
- •3.5.1.4 Lipid Solubility
- •3.5.1.5 Pharmacogenomics
- •3.5.1.6 Oral Bioavailability
- •3.5.3.1 Milk Plasma Ratio (M/P Ratio)
- •3.5.3.2 Relative Infant Dose
- •3.5.3.3 Infant Plasma Concentration
- •3.5.3.5 Lactation Categories
- •3.7 Conclusion
- •References
- •4.1 Introduction
- •4.5 Conclusions
- •References
- •5.1 Introduction
- •5.2 Paternal Mental Health
- •5.2.1 Paternal Mental Health: Depressive Disorders
- •5.2.2 Paternal Mental Health: Anxiety Disorders
- •5.2.3 Paternal Mental Health: Bipolar Disorders
- •5.2.4 Paternal Mental Health: Posttraumatic Stress Disorders
- •5.2.5 Paternal Mental Health: Obsessive-Compulsive Disorders
- •5.2.6 Paternal Mental Health: Substance Use Disorders
- •5.4 Management Strategies
- •5.5 Conclusions
- •References
- •6.1 Introduction
- •6.5.1.1 Congenital Malformations
- •6.5.1.2 Preterm Birth
- •6.5.1.3 Low Birth Weight
- •6.5.1.4 Stillbirth
- •6.5.1.5 Low APGAR Scores
- •6.5.1.7 Neonatal Adaptation Syndrome
- •6.5.2.2 Neurodevelopmental Disorders
- •6.5.3 Maternal Outcomes
- •6.5.3.1 Postpartum Hemorrhage
- •6.5.3.2 Eclampsia, Hypertension
- •6.6.1 SSRIs
- •6.6.1.1 Sertraline
- •6.6.1.2 Paroxetine
- •6.6.1.3 Fluoxetine
- •6.6.1.5 Fluvoxamine
- •6.6.2 SNRIs
- •6.6.2.1 Duloxetine
- •6.6.2.2 Venlafaxine
- •6.6.3 TCAs
- •6.6.4 Atypical/Other Antidepressants
- •6.6.4.1 Vortioxetine
- •6.6.4.2 Bupropion
- •6.6.4.3 Mirtazapine
- •6.7 Statistical Significance Versus Clinical Significance
- •6.8 Conclusion
- •References
- •7: Antidepressants During Lactation
- •7.1 Introduction
- •7.2.2 Discussion
- •7.3.1 The Safety Scoring System
- •7.3.2 Methods
- •7.3.3 Safety Scores
- •7.3.3.1 Selective Serotonin Reuptake Inhibitors (SSRIs)
- •7.3.3.3 Tricyclic Antidepressants (TCAs)
- •7.3.3.4 Other Antidepressant Drugs
- •7.3.3.5 Neurosteroids Antidepressants
- •7.3.4 Discussion
- •7.4 General Discussion
- •7.5 Conclusion
- •Bibliography
- •8.1 Introduction
- •8.6 Gestational Diabetes
- •8.9.8 Special Cases
- •8.9.8.1 Risperidone
- •8.9.8.2 Aripiprazole
- •8.9.8.3 Clozapine
- •8.9.8.4 Olanzapine
- •8.11 Premature Infants/Low Birth Weight Infants
- •8.13.1 Definitions
- •8.15 Conclusion
- •References
- •Suggested Reading
- •9: Antipsychotics During Lactation
- •9.1 Introduction
- •9.3.2 Medication Risk Category Classifications
- •9.4 First-Generation Antipsychotics (FGAs)
- •9.4.1 Haloperidol
- •9.4.2 Chlorpromazine
- •9.5 Second-Generation Antipsychotics (SGAs)
- •9.5.1 Olanzapine
- •9.5.3 Quetiapine
- •9.5.4 Aripiprazole
- •9.5.5 Clozapine
- •9.5.6 Amisulpride
- •9.5.7 Ziprasidone
- •9.5.8 Newer Second-Generation Antipsychotics
- •9.6 Comprehensive Risk-Benefit Assessment Framework
- •References
- •10.1 Introduction
- •10.2 Lithium
- •10.2.1 Placental Transfer
- •10.2.2 Embryonic Period: Organogenesis
- •10.2.4 Child Development
- •10.2.5 Maternal Management
- •10.4 Antiepileptic Drugs
- •10.4.1 Placental Transfer
- •10.4.2 Carbamazepine
- •10.4.2.1 Embryonic Period: Organogenesis
- •10.4.3 Valproates
- •10.4.3.1 Embryonic Period: Organogenesis
- •10.4.4 Lamotrigine
- •10.4.4.1 Embryonic Period: Organogenesis
- •10.5 Conclusion
- •References
- •11: Mood Stabilizers During Lactation
- •11.1 Introduction
- •11.4.1 Lithium
- •11.4.2 Valproate
- •11.4.3 Carbamazepine
- •11.4.4 Oxcarbazepine
- •11.4.5 Lamotrigine
- •11.4.6 Topiramate
- •11.4.7 Gabapentin
- •11.6 Conclusion
- •References
- •12.1 Introduction
- •12.4.1 Benzodiazepines
- •12.4.2 Z-Drugs
- •12.5 Perinatal Complications
- •12.6 Conclusions
- •References
- •13.1 Introduction
- •13.2 Benzodiazepines
- •13.2.1 Diazepam
- •13.2.2 Clonazepam
- •13.2.3 Alprazolam
- •13.2.4 Lorazepam
- •13.2.5 Oxazepam
- •13.2.6 Midazolam
- •13.3 Z-Drugs
- •13.4 Conclusion
- •References
- •14.1 Introduction
- •14.2 Methadone, Buprenorphine, Buprenorphine/Naloxone
- •14.3 Naltrexone
- •14.4 Buspirone
- •14.5 Gabapentinoids
- •14.5.1 Pregabalin
- •14.5.2 Gabapentin
- •14.6 Pramipexole
- •14.7 Methylphenidate
- •14.8 Acamprosate
- •14.9 Disulfiram
- •14.10 Baclofen
- •14.11 Other Medicines
- •14.11.1 Nalmefene
- •14.11.2 Biperiden
- •14.12 Conclusions
- •References
- •15: Major Depression
- •15.1 Introduction
- •15.5.2 Safety Profile
- •15.5.3 Symptom Profile
- •15.5.5 Dosing
- •References
- •16: Bipolar Disorder
- •16.1 Introduction
- •16.2 Identifying Perinatal Bipolar Disorder
- •16.6.1 Acute Treatment
- •16.6.3 Maintenance Treatment
- •16.9 Conclusions
- •References
- •17.1 Introduction
- •17.5.1 Pregnancy
- •17.5.2 Postpartum Period
- •17.6 Conclusion
- •References
- •18: Obsessive-Compulsive Disorder
- •18.1 Introduction
- •18.3 Pharmacological Treatment
- •18.3.1 General Considerations
- •18.3.2.1 First-Line Treatment
- •Switch Between Antidepressants
- •SSRI Treatment at Supratherapeutic Doses
- •18.3.3 Prophylactic Treatment
- •18.3.3.1 Pre-conceptional Phase
- •18.3.3.2 Pregnancy
- •18.3.3.3 Postpartum Period
- •18.4 Conclusion
- •References
- •19: Anxiety Disorders
- •19.1 Introduction
- •19.6 Pharmacological Treatment
- •19.6.1 General Considerations
- •19.10 Conclusion
- •References
- •20: Posttraumatic Stress Disorder
- •20.1 Introduction
- •20.3 Pharmacological Treatment
- •20.3.1 General Considerations
- •20.4 Conclusion
- •References
- •21: Alcohol Use Disorders
- •21.1 Introduction
- •21.2 Epidemiology
- •21.7.1 Naltrexone Use
- •21.7.2 Disulfiram Use
- •21.7.3 Acamprosate Use
- •21.7.4 Nalmefene Use
- •21.7.5 Baclofen Use
- •21.7.6 Other Medications
- •21.8 Conclusions
- •References
- •22: Substance Use Disorders
- •22.1 Introduction
- •22.7 Conclusions
- •References
- •23.1 Introduction
- •23.3 Most Common Sleep Disorders During Peripartum
- •23.3.1 Insomnia
- •23.3.1.2 Pathophysiology
- •Hypnotic Benzodiazepines

9 Antipsychotics During Lactation
to preventing relapse and minimizing psychiatric morbidity. Therefore, forgoing
breastfeeding may be in the best interest of the mother-infant dyad. Clinicians
should be aware of the potential psychological distress and maternal guilt surrounding such feeding decisions, and stress the overarching clinical principle that maternal well-being supports infant well-being.
251
9.6.4 Maternal andInfant Monitoring
Maternal monitoring should include evaluation of psychiatric symptoms, medication side effects, and impact on milk supply. For infants, standardized monitoring
protocols remain absent. Routine and regular pediatric assessments for growth,
developmental milestones, feeding patterns, alertness, sleep, and behavior are recommended. Any change in the infant’s behavior from baseline should be investigated further. If a medication exposure is suspected of causing an adverse effect,
temporarily suspending breastfeeding allows for evaluation. In a clinical scenario of
a mother breastfeeding on an SGA with no to minimal safety data, close monitoring
is recommended.
Measuring drug levels in the breastfeeding baby is generally not recommended
since in most instances, antipsychotic levels are low or non-detectable in the infant
serum. However, if there is a meaningful change in the infant’s behavior (e.g., sedation, irritability, feeding problems), an infant’s serum level may be helpful.
It is also important for the treating psychiatrist and the infant’s pediatrician
to work collaboratively in supporting the mother’s decision to breastfeed or not.
Ideally, it is advisable for the mother to discuss her plans to breastfeed with her
psychiatrist and pediatrician prior to delivery. Such a discussion ensures an
interdisciplinary team approach that can respond nimbly with any changes in
circumstances.
9.7 Resources forClinicians onMedication Safety
During Breastfeeding
Resources for clinical decision making have expanded signicantly. Breastfeeding
mothers and their healthcare providers can access several comprehensive, evidencebased resources on medication safety during lactation. These highly reputable references provide up-to-date information to support informed clinical decisions. While
not exhaustive, the following represent key professional resources available for
consultation:
LactMed® (www.ncbi.nlm.nih.gov/books/NBK501922) is a free online
resource maintained by the National Library of Medicine that serves as the most
comprehensive and frequently updated online database for medication safety during
lactation. It provides detailed information about maternal and infant drug levels,
potential effects on infants, impacts on milk production, and suggested alternatives
when available. There is also a free smartphone app, LactRx, designed for

252
A. C. Viguera et al.
healthcare providers and breastfeeding mothers. This app provides quick access to
information about medication safety during lactation using the LactMed database in
a mobile-friendly format, allowing users to search for medications and review their
compatibility with breastfeeding.
MotherToBaby (https://mothertobaby.org/pregnancy- breastfeeding- exposures)
is a service of the non-prot Organization of Teratology Information Specialists
(OTIS) and is one of the leading authorities and most trusted source of evidencebased information on the safety of medications and other exposures during pregnancy. MotherToBaby provides Q&A format medication fact sheets in both English
and Spanish, making it an invaluable tool for patient education. These materials
cover a wide range of medications and their use during both pregnancy and lactation, presenting complex medical information in an accessible format. In addition,
they also offer “Ask and Expert” service via live chat which offers free, personalized, and condential exposure information for both patients and clinicians.
The InfantRisk Call Center at the Texas Tech Health Sciences Center
https://www.infantrisk.com (1-806-352-2519; M-F 8am-3pm CST) offers cur-
rent information regarding medication safety for breastfeeding mothers. Staffed
by nurses with specialized training from Drs. Hale and Krutsch, the center
serves as an important free resource for both healthcare providers and patients
seeking guidance on medications during lactation. Additionally, the center conducts ongoing research in this eld and welcomes mother volunteers who wish
to participate in their studies.
Hale’s Medications & Mothers’ Milk 2025–2026 (21st Edition) by Thomas
W.Hale, RPh, PhD & Kaytlin Krutsch, PhD, PharmD, MBA, BCPS is an authoritative textbook on medication safety during lactation, trusted by healthcare professionals worldwide for years. It provides evidence-based analysis of over 1200
medications, current pharmacokinetic data and milk transfer information, clear risk
categorization for clinical decision-making, and practical alternatives for high-risk
medications. There is also a digital access platform available through HalesMeds.
com for real-time updates between print editions. This is a paid subscription service.
The Food and Drug Administration (FDA) Pregnancy and Lactation
Labeling Rule
The FDA Pregnancy and Lactation Labeling Rule (PLLR) (https://www.fda.gov/
drugs/labeling- information- drug- products/pregnancy- and- lactation- labelingresources) represents a signicant improvement in medication safety information
by replacing the previous A, B, C, D, X categorization system. This new approach
requires that drug labels provide detailed, narrative summaries of available research
addressing effects on women, fetuses, infants, and milk production, along with clinical considerations for minimizing exposure. While demanding more careful analysis from clinicians rather than offering simple categorical recommendations, the
PLLR provides more accurate and nuanced guidance for clinical decision-making
regarding drug use during pregnancy and lactation.

9 Antipsychotics During Lactation
253
9.8 Conclusion andFuture Directions
The overwhelming evidence, although limited, suggests that most rst-generation
and second-generation antipsychotics are compatible with breastfeeding, with the
notable exception of clozapine. Medication choice should be individualized based
on maternal history, infant health status, mother’s preferences, clinical needs, and
available lactation safety data. Throughout the decision-making process, maternal
health and well-being must be prioritized while implementing appropriate measures
to minimize infant exposure and thoroughly monitor infant growth and development. These objectives should not be viewed as competing priorities, but rather as
interconnected elements of a comprehensive approach to care. Providers can use the
risk assessment framework in this chapter to guide their clinical decisions
(Table 9.1). Future research priorities should focus on systematic evaluation of
newer antipsychotics, long-term neurobehavioral outcomes, and the development of
standardized infant monitoring protocols. Additionally, emerging evidence suggesting that combination medication therapy during breastfeeding may be safer than
previously believed is promising and warrants further study.
Table 9.1 Expert recommendations based on scientic evidence and clinical experience
Prioritize maternal well-being: Women who are taking an antipsychotic should not be
discouraged from breastfeeding. However, sacricing a mother’s mental well-being in favor of
breastfeeding is never recommended
Guidance of FGAs: Haloperidol and chlorpromazine are generally compatible with
breastfeeding. Other FGAs may also be compatible but have less evidence
Guidance of SGAs: Olanzapine, quetiapine, and risperidone have the most safety data during
lactation and appear to be reasonable choices for breastfeeding women. Clozapine should
generally be avoided during breastfeeding due to risks of agranulocytosis and seizures in
infants. Aripiprazole warrants careful consideration, particularly regarding its effects on
prolactin and potential impacts on milk supply
Polytherapy: The co-administration of more than one antipsychotic and/or complex
psychotropic regimen (>2 psychotropics) should not necessarily be discouraged during
lactation, but close monitoring of infant is recommended
Risk-benet assessment: The decision to use antipsychotics during breastfeeding should be
individualized, considering the mother’s psychiatric history, medication response, potential for
relapse, support systems, sleep management, and infant factors (age, developmental stage,
health status) and should be discussed collaboratively with a psychiatrist, physician, and the
patient
Infant safety and monitoring: Infants exposed to an antipsychotic through breast milk should
be carefully monitored for adverse events including any changes in infant behavior, alertness,
feeding, or sleep

254
A. C. Viguera et al.
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259

Mood Stabilizers inPregnancy
10
Anne-LaureSutter-Dallay andFlorenceGressier
10.1 Introduction
For 7% of women presenting a bipolar disorder (BD), their rst episode occurred in
the context of the perinatal period (Viguera et al. 2011). In women with bipolar
disorder prior to pregnancy, the risk of relapse may reach up to 20% during pregnancy (Van der Lugt etal. 2012) and is between 50% and 70% post-partum (Jones
and Craddock 2005; Viguera etal. 2011). Conversely, bipolar disorders themselves
seem to have a possible inuence on the course of pregnancy: the review of
Mohamed etal. (2023) suggests that the risk of obstetric complications would be
higher in bipolar patients—treated or not—than in the general population. The
recent work of Chan etal. (2024) is along the same lines, nding that in a population-based cohort of 465,069 women—including 302 women with a diagnosis of
BD, of whom 168 had one or more prescriptions for mood stabilizers during pregnancy (treated BD) and 134 were not exposed to mood stabilizers during pregnancy
(untreated BD)—BD was signicantly associated with an increased risk of gestational diabetes (ORa: 1.75 [95% CI: 1.15–2.70]) and maternal somatic hospitalization ≤90 days after discharge from the index delivery (2.12 [1.19–3.90]); in
treatment status-stratied analyses, treated BD women had a signicantly increased
A.-L. Sutter-Dallay (*)
Department of Perinatal Psychiatry, University Department of Child and Adolescent
Psychiatry, Charles Perrens Hospital, Bordeaux, France
Bordeaux Population Health INSERM 1219 Research Center, HEALTHY Team, Bordeaux
University, Bordeaux, France
e-mail: alsutter@ch-perrens.fr
F. Gressier
Department of Psychiatry, Faculté de Médecine Paris-Saclay, CESP, Inserm U1018, Bicêtre
University Hospital, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris
Saclay, Université Paris-Saclay, Le Kremlin Bicêtre, France
© The Author(s), under exclusive license to Springer Nature
Switzerland AG 2025
F. Uguz, L. Orsolini (eds.), Perinatal Psychopharmacology,
https://doi.org/10.1007/978-3-031-99720-4_10
261
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