Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5238_Библиотеки_им_академика_М_И_Перельмана.pdf
6
S. Alwan and A. Berard
antidepressant use in the perinatal period over time has also been established worldwide. In Denmark, studies reported a six-fold increase in the use of an antidepressant at some point during pregnancy, where the exposure rate increased from 0.4%
in 1997 to 3.1% in 2016 (Jimenez-Solem etal. 2013; Sun etal. 2019). In a study
utilizing the UK Clinical Practice Research Datalink (CPRD) Pregnancy Register,
antidepressant prescribing during pregnancy increased from 3.2% in 1996 to 13.4%
in 2018 (Martin etal. 2024). Notably, most women discontinued antidepressant use
at some point before the end of pregnancy, but post-pregnancy resumption was common. Similarly in the United States, reports of antidepressant use in pregnancy have
shown increases from around 1.5% in 1996 to 8.1% in 2005 (Cooper etal. 2007;
Alwan etal. 2011; Andrade etal. 2008; Huybrechts etal. 2013). A study published
in 2023 analyzed data from privately insured individuals in the United States diagnosed with perinatal mood and anxiety disorders (PMAD) between 2008 and 2020
(Hall etal. 2024). The ndings revealed that antidepressant prescriptions increased
signicantly during this period, particularly after the issuance of clinical practice
recommendations in 2015–2016 regarding PMAD screening and treatment. This
suggests that updated clinical guidelines may have contributed to increased access
to antidepressant treatment for pregnant and postpartum individuals.
Dispensing of an antidepressant medication during pregnancy is more common
among older women, non-Hispanic White race, women living in the Midwest, and
those with higher education (>12years) (Huybrechts etal. 2013; Molenaar etal.
2020). Other commonly reported predictors of antidepressant use in the perinatal
period are periconceptional smoking or alcohol use and having comorbid disorders,
such as pre-pregnancy type 1 or 2 diabetes and hypertension (Bakker etal. 2008;
Jimenez-Solem etal. 2013; Bénard-Laribière etal. 2018).
During the course of a pregnancy, a sudden decrease in use of an antidepressant,
regardless of the type, was observed in many studies around the third month of conception, which appears to be related to the time at which pregnancy was recognized
and may indicate the possibility of healthcare providers being reluctant to continue
treatment after the occurrence of pregnancy (Noh etal. 2022; Liu et al. 2022).
However, the attempt to decrease the fetal risk of antidepressant use during pregnancy by discontinuing treatment in women with severe depression has been associated with increased risk of relapse of the depression with its associated adverse
pregnancy outcomes (Bayrampour etal. 2020).
1.2.1.1 Selective Serotonin Reuptake Inhibitors
SSRIs account for about 80% of all antidepressant prescriptions and are being prescribed for a variety of conditions, other than depression (Harman etal. 2009).
Fluoxetine was the rst introduced SSRI in 1988 and became the most frequently
prescribed antidepressant worldwide (Morrison etal. 2005). Other SSRIs currently
available on the market include citalopram, and its pharmacologically active
s- enantiomer, escitalopram, uvoxamine, paroxetine, and sertraline. SSRIs share a
similar mechanism of action by blocking the reuptake of serotonin (5-HT) via the
serotonin transporter (SERT). However, each SSRI differs from another with regard
1 Epidemiology ofUse ofPsychotropic Drugs inPregnant andNursing Women
7
to its chemical structure and pharmacokinetic properties (Hiemke and Hartter
2000), and therefore has the potential to affect the developing fetus in various ways.
Maternal use of SSRI medications in pregnancy has gained considerable clinical
attention over the past two decades. Evidence from the literature include slightly
elevated risks for organ-specic birth defects, heart defects in specic, with rsttrimester exposure to certain SSRIs (De Vries etal. 2021) and risks of neonatal
withdrawal syndrome and behavioral alterations (Forsberg etal. 2014), persistent
pulmonary hypertension of the newborn (PPHN) (Huybrechts etal. 2015; Alwan
etal. 2016; Bérard etal. 2017a), preterm birth, low birth weight and small for gestational age birth associated with late intrauterine exposure to any SSRI (Hogue
etal. 2017). Although concerns have been raised with regard to elevated rates of
autism spectrum disorder diagnoses in children born to mothers who were treated
an SSRI in pregnancy (Kaplan etal. 2017), several large record-linkage studies suggested that such associations may not actually be causal, but instead reect genetic
and shared familial environmental factors (Brown etal. 2017; Sujan etal. 2017).
The US FDA has initially issued two public health advisories in 2005 and 2006
regarding the potential risk for cardiac defects with maternal paroxetine use, and
later of PPHN in relation to any SSRI use in pregnancy, which ultimately affected
the pattern of use of SSRIs among pregnant women at the time. A later advisory
from the FDA in 2011 was issued, based on the results of subsequent studies, recommending healthcare providers to treat depression during pregnancy as clinically
appropriate (U.S.Food and Drug Administration 2011). Additionally, in 2011, the
UK’s Medicines and Health Care products Regulatory Agency (MHRA) warned
that rst-trimester exposure to uoxetine might slightly increase the risk of congenital cardiac malformations in newborns and also highlighted a small increased
risk of postpartum hemorrhage associated with the use of SSRIs in the month before
delivery. The MHRA reminded healthcare professionals of the potential risks of
PPHN and neonatal withdrawal or toxicity reactions linked to these medications,
emphasizing the importance of balancing these risks against the consequences of
untreated depression during pregnancy.
Sertraline remains to be reported the most frequently prescribed SSRI during
pregnancy in the United States and France (Bénard-Laribière etal. 2018; Andrade
etal. 2016), while in other European countries, citalopram in Scandinavian countries (Jimenez-Solem etal. 2013; Kallen etal. 2013) and uoxetine in the UK (Ban
etal. 2014) have been reported to be the most commonly used SSRIs in the perinatal
period. Despite the fact that paroxetine use during pregnancy has been initially contraindicated, it has been reported to be the most frequently dispensed SSRI to
women in the perinatal period in Italy and the Netherlands, with no reduction in its
use following the US FDA warnings (Charlton etal. 2015). In Canada, a decrease in
the use of paroxetine during pregnancy has been noted (Bérard etal. 2017b), while
rates for sertraline and citalopram remain to be the highest in this population.
Within the perinatal period, patterns of maternal SSRI continuation versus discontinuation also differ by geographical region. For example, in a European pharmacoepidemiologic study based on six electronic healthcare databases (Charlton
etal. 2015), at least 40% of women with a prescription to an SSRI during the year
8
S. Alwan and A. Berard
before pregnancy discontinued use before pregnancy and did not restart the medication during the year following delivery. Continuing treatment with an SSRI throughout pregnancy and following delivery was more common among women in Denmark
and the Netherlands compared to those living in Italy, with the lowest rates.
In terms of breastfeeding, SSRIs vary in the degree to how much they cross into
breast milk, but sertraline and paroxetine appear to be more tolerated by nursing
babies than other SSRIs (Uguz 2021). However, most studies regarding the safety of
antidepressants among nursing women are confounded by prenatal exposure to the
same drug, which may increase the risk of early adverse effects, as well as other
lifestyle risk factors, including smoking and alcohol and substance abuse, and no
studies exist on the long-term cognitive and behavioral development on the breastfed children.
1.2.1.2 Bupropion
Bupropion is an aminoketone that is structurally and chemically different from
other antidepressants on the market. It is a weak inhibitor of neuronal uptake of
dopamine, norepinephrine, and serotonin and does not inhibit monoamine oxidase
(Ascher etal. 1995). It was rst marketed as an oral antidepressant (Wellbutrin®)
and was subsequently developed as a non-nicotine aid to smoking cessation
(Zyban®). Because women who smoke are encouraged to stop doing so when they
become pregnant (Tong etal. 2008), it is therefore not surprising that many women
are treated with bupropion in early pregnancy (Berard etal. 2016). Regardless of the
indication for use, bupropion is the second most commonly used non-SSRI antidepressant in the perinatal period, with a reported frequency of 0.7–1.0% among pregnant women in the United States (Alwan etal. 2011; Hanley and Mintzes 2014).
Maternal treatment with bupropion during pregnancy appears to be relatively
uncommon in Europe, though specic prevalence rates are not extensively
documented.
Available data on the safety of bupropion in human pregnancy is also limited.
Some studies have reported a slight increase in the rate of congenital heart defects,
in particular, left ventricular outow obstruction defects following bupropion use in
early pregnancy (Alwan etal. 2010; Louik etal. 2014; Thyagarajan etal. 2012; De
Vries etal. 2021), but the absolute risk was estimated at 2.1–2.8 per 1000 births.
1.2.1.3 Other Less Commonly Used Antidepressants
Tricyclic antidepressants (TCAs) were once the treatment of choice for depression
and panic disorder before the introduction of SSRIs. They remain commonly used
for comorbid conditions and when treatment with an SSRI has failed. About 0.2%
of women are exposed to a TCA sometime during their pregnancy (Alwan et al.
2011, Hanley and Mintzes 2014), and some neonatal withdrawal symptoms have
been reported with their use in late pregnancy (Ter Horst et al. 2012). The most
commonly used TCA is amitriptyline, which has a mechanism of action similar to
SSRIs with regard to the blocking of SERT.Some reports have shown that amitriptyline use during gestation was associated with an increased risk of birth defects and
1 Epidemiology ofUse ofPsychotropic Drugs inPregnant andNursing Women
9
other long-term neurodevelopmental outcomes (Bérard et al. 2017b; Boukhris
etal. 2017).
Selective norepinephrine reuptake inhibitors (SNRIs) work in a similar mechanism to SSRIs, but they also block the reuptake of the neurotransmitter norepinephrine along with serotonin in the brain to help relieve depression, and are also
commonly prescribed for other conditions, including anxiety disorders and longterm chronic pain. SNRIs are increasingly being used in pregnancy with an overall
reported frequency of up to 0.8% based on a US population (Hanley and Mintzes
2014). In a Scandinavian population-based study encompassing Denmark, Iceland,
Norway, and Sweden, 0.5% of pregnant women were exposed to SNRIs (Zoega
etal. 2015). Notably, SNRI use varied by country, ranging from 0.3% in Norway to
0.9% in Iceland. Additionally, the study observed a decrease in SNRI use as pregnancy progressed: 0.5% at conception, 0.4% in the rst trimester, 0.3% in the second trimester, and 0.2% in the third trimester. Venlafaxine has been the most
frequently used SNRI in pregnancy and lactation, with the majority of studies
reporting on its safety when taken in early pregnancy (Richardson etal. 2019; Furu
etal. 2015). However, some studies have indicated slightly elevated risks of cardiac
defects and spontaneous abortion with early pregnancy exposure (Bérard et al.
2017b; Anderson etal. 2020; Kolding etal. 2021).
1.2.2 Anxiolytics
Anxiety constitutes the most common mental disorder among women of reproductive age, and specically women in the perinatal period. In fact, it appears to be that
among women taking antidepressant medications in pregnancy, anxiety diagnoses
are nearly as common as depressive diagnoses, and antidepressant users with an
anxiety disorder are twice as many as antidepressant users with a depression disorder (Hanley and Mintzes 2014). Even though there is evidence in the literature that
maternal stress and anxiety in the perinatal period can negatively affect both mother
and baby (Monk etal. 2020), women’s perceived concerns of the teratogenic risk of
medications may lead to low adherence and discontinuation of needed therapy upon
recognition of pregnancy (Denton etal. 2020). Nevertheless, antianxiety medications, or anxiolytics, are the second most commonly used medications in the perinatal period after antidepressants. Anxiolytics include benzodiazepine and
benzodiazepine-like medications. Most women often use benzodiazepines to manage anxiety as needed more than regularly. A few studies have looked into patterns
of use of anxiolytics in the perinatal period, and in one US study, the rate of use of
benzodiazepines and benzodiazepine-like medications was estimated at 3.9% in
pregnancy, with zolpidem being the most common one dispensed among pregnant
women (2.4%) followed by alprazolam (0.8%) (Hanley and Mintzes 2014).
Diazepine use in pregnancy was much lower at 0.6% and only 0.05% relled more
than one prescription for it in pregnancy, which is probably related to its association
with cleft lip and palate in the infant in earlier reports that have not been conrmed
in several later studies and reviews (Iqbal etal. 2002). Notably, anxiolytic use was
10
S. Alwan and A. Berard
more frequently initiated during pregnancy (2.7% incident users) than continued
from preconception (1.2% prevalent users), suggesting that some women may begin
anxiolytic treatment after becoming pregnant (Hanley and Mintzes 2014). Another
study focusing on benzodiazepine dispensing patterns among commercially insured
pregnant women in the United States from 2007 to 2015 highlighted a signicantly
increased shift of prescribing these medications in recent years (Qato and Gandhi
2021). In this study, benzodiazepine dispensing increased in the pre-conception
period from 2.3% to 3.8%, rst trimester from 1.1% to 2.1%, and second trimester
from 0.3% to 0.5%; however, it decreased post-delivery from 2.4% to 2.1%.
However, it is important to note that maternal use of benzodiazepines during pregnancy has been associated with certain risks, including an increased likelihood of
spontaneous abortions (Sheehy et al. 2019) and potential congenital anomalies
(Grigoriadis etal. 2019). Therefore, short acting prescription should be prioritized
during this period.
1.2.3 Antipsychotics
Use of antipsychotic medications is indicated for a number of conditions, including
psychosis, schizophrenia, and bipolar disorder. However, use of antipsychotics has
increased over the past two decades, partly because the approved indications for
these agents have expanded beyond these conditions to also include depression,
obsessive-compulsive disorder, anxiety disorders, and autism spectrum disorders
(Olfson etal. 2012; Alexander etal. 2011). Apparently, as many as 25% of patients
with depression and up to 50% of patients with bipolar disorder also have psychotic
symptoms (Smith and Dubovsky 2017). The rate of antipsychotic medication use
during pregnancy has also increased over time (Toh etal. 2013; Robiyanto etal.
2023), and their use in pregnancy constitutes an important clinical challenge because
of concern over their risk to the fetus. Reported adverse outcomes of prenatal antipsychotic use include congenital malformations, preterm birth, small for gestational
age (Terrana etal. 2015; Coughlin etal. 2015), as well as short-term delay in development and lower neuromotor performance (Peng etal. 2013; Johnson etal. 2012).
Confounding by indication could not be ruled out in the observed increased prevalences of adverse outcomes. Schizophrenia is the best studied in pregnancy, and
the untreated condition appears to be associated with low birth weight, small for
gestational age infants, and preterm delivery (Lin etal. 2010). It is important to note
that schizophrenia patients are more likely to have unplanned pregnancies along
with lower educational levels and higher body mass indices (BMI), as well as
adverse lifestyles, including smoking and alcohol use and lower adherence to multivitamin (Habermann etal. 2013), all of which may contribute to an increased risk
of adverse pregnancy outcomes. Furthermore, since psychosis interferes with commitment with prenatal care and parenting, it is believed that risks of not managing
schizophrenia outweigh risks of managing it therapeutically (Edinoff etal. 2022).
However, indications for use of both rst-generation and second-generation antipsychotics include depression in more than 50% of cases, followed by bipolar disorder and schizophrenia (Toh etal. 2013).
1 Epidemiology ofUse ofPsychotropic Drugs inPregnant andNursing Women
11
1.2.3.1 First Generation Antipsychotics (FGAs)
The neuroleptic FGAs, also known as the typical antipsychotics, were the rst antipsychotic treatment of choice for psychiatric disorders. These medications act
through blocking dopamine receptors in the dopaminergic pathways of the brain, as
excessive dopamine release is associated with psychotic experiences. The most
commonly used agents of this class in the general population and among women in
the perinatal period are chlorpromazine and haloperidol. Because they have been
available longer on the market, they have an established safety record as monotherapy, specically with regard to haloperidol (Patton et al. 2002; Straub etal.
2022). However, over a ten-year period between 2001 and 2010, the rate of use of
FGA drugs during pregnancy in the US population has remained constant at 0.1%
(Park etal. 2017), which is probably due to the recently introduced atypical antipsychotics among women of reproductive age (Robiyanto etal. 2023). Over the course
of a pregnancy, the prevalence of FGA use is reported highest in the rst trimester
then drops by the second and third trimesters (Toh etal. 2013), indicative of inadvertent exposures before the pregnancy is diagnosed.
1.2.3.2 Second-Generation Antipsychotics (SGAs)
The rst atypical antipsychotic, clozapine, was introduced in the 1960s and has
been widely used since then. Subsequently, several SGA agents became available in
the market in the past three decades and have received approval for various indications, including irritability in autism spectrum disorders, mood stabilization in bipolar disorder, and additional therapy for major depression. The diagnoses of these
conditions have notably increased, leading to a signicant rise in SGA use among
the general population, which also translated during the perinatal period. For example, a threefold increase in the prevalence of use of SGA among pregnant women in
the United States, from 0.4% to 1.3% over a ten-year period, has been reported
(Park etal. 2017), with the most frequently reported SGA used being quetiapine and
aripiprazole. In the same study, polytherapy with other antipsychotics and antidepressants is reported in more than half of pregnant women on an SGA, and about
25% of them also take a mood stabilizer or a benzodiazepine simultaneously.
In Europe, the prevalence of women on antipsychotic medications in general is
lower than in the United States, and ranges between 0.1% and 0.3% (Margulis etal.
2014). About 50% of women discontinue therapy with an SGA upon recognition of
pregnancy, while 60–70% stop taking an SGA by the third trimester of pregnancy
(Park etal. 2017). Furthermore, among those who switch at the beginning of pregnancy, the majority are reported to switch to quetiapine (Park et al. 2017). The
overall prevalence of antipsychotic use in pregnancy in the Netherlands doubled due
to increased use (in terms of both continuation and initiation of SGAs), which escalated from 0.3in 1994 to 2.6 per 1000in 2011 (Robiyanto etal. 2023).
It is not surprising that quetiapine is most reported among women in the perinatal
period as it has a wide range of off-label indications such as generalized anxiety
disorder, insomnia, and post-traumatic stress disorder (PTSD) in addition to its
approved uses for bipolar disorder and schizophrenia (Maan etal. 2025). Quetiapine
also has an established safety prole including a lower placental transfer compared
12
S. Alwan and A. Berard
to other antipsychotics (Creeley and Denton 2019), and is recommended for nursing
women with low concentrations of the drug passed into breastmilk (Van Boekholt
etal. 2015).
1.2.4 Mood Stabilizers
Due to the chronic nature of bipolar disorder with a relapsing-remitting course,
most patients require long-term treatment with several psychotropics, particularly
with mood stabilizers. There has been an increase in bipolar disorder diagnoses
among women in the perinatal period, which is consistent with the increase observed
in the general population, possibly due to improved classication of people who
were previously misdiagnosed as having unipolar depression or overdiagnosis of
this condition (Masters etal. 2022). Evidence also shows increased recurrence of
the condition during the perinatal and postpartum periods, especially after abrupt
discontinuation of mood stabilizers (Wesseloo et al. 2016). Whether treated or
untreated, bipolar disorder may increase the risk of various adverse pregnancy,
obstetric, and neonatal outcomes which may be worse in untreated cases (Rusner
etal. 2016; Boden etal. 2012).
Mood stabilizers that are used to treat bipolar disorder include lithium and antiepileptic drugs, most commonly, carbamazepine and valproate. Lithium is the only
medication consistently shown to be effective for acute mania, bipolar depression,
and long-term relapse prevention (Smith and Dubovsky 2017). Lithium use in early
pregnancy has been associated with an increased risk of congenital heart defects
(Patorno etal. 2017; Hastie etal. 2021). Prenatal diagnosis by fetal echocardiography should be offered to women who have been treated with lithium in early pregnancy. Both valproic acid and carbamazepine are contraindicated in pregnancy
because of their association with high prevalences of malformations and other
adverse outcomes, including long-term neurodevelopmental disorders (Blotière
etal. 2020). On the contrary, both medications are considered for nursing because
of their low serum levels in breast milk, but close monitoring is still recommended
(Wisner and Perel 1998; Kacirova etal. 2019). As per the product labelling, lithium
is not recommended for nursing mothers because of the risk of accumulation while
the neonatal kidney is still immature. However, a recent study suggests that with
careful monitoring, lithium use among nursing women might be feasible (Viguera
etal. 2007; Heinonen etal. 2022).
The use of lithium during pregnancy and breastfeeding varies signicantly across
different regions and clinical practices, inuenced by concerns about potential risks
to both mother and infant, even though it has been recommended as the rst-line
mood-stabilizing treatment during pregnancy (Poels etal. 2018). In Denmark, a
study revealed that only 16% of pregnant women with bipolar disorder continued
lithium therapy, with just 6.3% maintaining usage into the third trimester (Broeks
etal. 2017). Similarly, in the UK, high discontinuation rates were observed, with
only 17 out of 52 pregnant women persisting with lithium treatment (McCrea etal.
2015). In terms of breastfeeding, a retrospective review at a single academic
1 Epidemiology ofUse ofPsychotropic Drugs inPregnant andNursing Women
13
medical center from 2013 to 2023 found that 39% of postpartum patients on lithium
chose to nurse their babies (Kummerlowe etal. 2024). Most of these patients had
been on long-term lithium therapy, initiating treatment prior to pregnancy.
These patterns underscore the need for individualized risk-benet assessments
and multidisciplinary collaboration when considering lithium therapy during pregnancy and breastfeeding. Ongoing research and education are essential to support
informed decision-making and ensure the safety and well-being of both mother
and child.
1.2.5 Stimulants
Prescription stimulants, including amphetamines and methylphenidate, are a group
of psychoactive drugs that affect the central nervous system and the autonomic nervous system, and used to treat attention-decit hyperactivity disorder (ADHD) and
narcolepsy. A signicant increase in the use of stimulants among women of reproductive age has been observed in the past decade in different parts of the world. The
percentage of females aged 15–44 years with prescription stimulant llings
increased from 3.6% in 2016 to 4.1% in 2021in the United States (Danielson etal.
2023). In Norway, the prevalence of ADHD medication use among females aged
18–64years increased nearly sixfold, from 3.0 per 1000in 2006 to 18.1 per 1000in
2022 (Hartz etal. 2024). In a Canadian study, a rising 14-fold from 0.08% in 1998
to 1.2% in 2015 was reported, with methylphenidate use being the most common
(Lemelin etal. 2021). Many women opt for discontinuation of stimulants upon recognition of pregnancy because of lack of knowledge on their safety. Another US
study utilizing data from 2013 to 2018 found that among 15,413 pregnancies with
pre-pregnancy stimulant use, 42% discontinued treatment before conception, 39%
during the rst trimester, and only 19% continued into later trimesters (Murugappan
etal. 2022). A Danish cohort study reported nearly 60% of women discontinued
ADHD medication during pregnancy, whereas 17.2% halted medication during
pregnancy but resumed after delivery (Bang Madsen et al. 2024). These ndings
underscore the prevalent pattern of discontinuing stimulant medications during
pregnancy, primarily due to uncertainties regarding their safety.
1.3 Conclusion
In balancing the necessity of pharmacotherapy for pregnant or nursing women with
psychiatric conditions, it is imperative to evaluate the risks posed by medication
exposure to the unborn child against the dangers of untreated maternal illness.
Although confounding by indication has been a common limitation in earlier studies affecting both treatment decisions and outcomes, recent observational studies
have signicantly improved methodologically, particularly in their ability to adjust
for indication. This improved understanding aids decision-makers to better inform
their patients with effective and safe therapy choices. However, pregnant women are
14
S. Alwan and A. Berard
often affected by more than one mental health disorder and may require combination therapy with various psychotropic drugs, which can complicate treatment decisions. Consequently, given the high prescription rates and expanding indications for
these drugs among women of reproductive age, it is essential to have a comprehensive risk assessment understanding of pharmacotherapy options. This ensures that
treatment decisions and preconception planning are based on the best available evidence, optimizing outcomes for both mother and child.
References
Alcantarilla L, López-Castro M, Betriu M, Torres A, Garcia C, Solé E, Gelabert E, Roca-
Lecumberri A.Risk factors for relapse or recurrence in women with bipolar disorder and recur-
rent major depressive disorder in the perinatal period: a systematic review. Arch Womens Ment
Health. 2023;26:737–54.
Alexander GC, Gallagher SA, Mascola A, Moloney RM, Stafford RS. Increasing off-label use
of antipsychotic medications in the United States, 1995-2008. Pharmacoepidemiol Drug Saf.
2011;20:177–84.
Alwan S, Grant KS.Maternal medication use in pregnancy: a narrative review on assessing and com-
municating the “risk” of birth defects to the patient. Pharmacoepidemiology. 2024;3:336–49.
Alwan S, Reefhuis J, Botto LD, Rasmussen SA, Correa A, Friedman JM.Maternal use of bupro-
pion and risk for congenital heart defects. Am J Obstet Gynecol. 2010;203(52):e1–6.
Alwan S, Reefhuis J, Rasmussen SA, Friedman JM.Patterns of antidepressant medication use
among pregnant women in a United States population. J Clin Pharmacol. 2011;51:264–70.
Alwan S, Bandoli G, Chambers CD.Maternal use of selective serotonin-reuptake inhibitors and risk
of persistent pulmonary hypertension of the newborn. Clin Pharmacol Ther. 2016;100:34–41.
Anderson KN, Lind JN, Simeone RM, Bobo WV, Mitchell AA, Riehle-Colarusso T, Polen KN,
Reefhuis J.Maternal use of specic antidepressant medications during early pregnancy and the
risk of selected birth defects. JAMA Psychiatry. 2020;77:1246–55.
Andrade SE, etal. Use of antidepressant medications during pregnancy: a multisite study. Am J
Obstet Gynecol. 2008;198:194–5.
Andrade SE, Reichman ME, Mott K, Pitts M, Kieswetter C, Dinatale M, Stone MB, Popovic J,
Haffenreffer K, Toh S.Use of selective serotonin reuptake inhibitors (SSRIs) in women deliv-
ering liveborn infants and other women of child-bearing age within the U.S.Food and Drug
Administration’s mini-sentinel program. Arch Womens Ment Health. 2016;19:969–77.
Ascher JA, Jo C, Colin JN, Feighner JP, Ferris RM, Fibiger HC, Golden RN, Martin P, Potter WZ,
Richelson E, etal. Bupropion: a review of its mechanism of antidepressant activity. J Clin
Psychiatry. 1995;56:395–401.
Bakker MK, Kölling P, etal. Increase in use of selective serotonin reuptake inhibitors in preg-
nancy during the last decade, a population-based cohort study from The Netherlands. Br J Clin
Pharmacol. 2008;65:600–6.
Ban L, Gibson JE, West J, Fiaschi L, Sokal R, Smeeth L, Doyle P, Hubbard RB, Tata LJ.Maternal
depression, antidepressant prescriptions, and congenital anomaly risk in offspring: a popula-
tion-based cohort study. BJOG. 2014;121:1471–81.
Bang Madsen K, Bliddal M, Skoglund CB, Larsson H, Munk-Olsen T, Madsen MG, Hove
Thomsen P, Bergink V, Srinivas C, Cohen JM, Brikell I, Liu X.Attention-decit hyperactiv-
ity disorder (ADHD) medication use trajectories among women in the perinatal period. CNS
Drugs. 2024;38:303–14.
Bayrampour H, Kapoor A, Bunka M, Ryan D.The risk of relapse of depression during preg-
nancy after discontinuation of antidepressants: a systematic review and meta-analysis. J Clin
Psychiatry. 2020;81
1 Epidemiology ofUse ofPsychotropic Drugs inPregnant andNursing Women
Bénard-Laribière A, Pambrun E, Sutter-Dallay AL, Gautier S, Hurault-Delarue C, Damase-Michel
C, Lacroix I, Bégaud B, Pariente A.Patterns of antidepressant use during pregnancy: a nation-
wide population-based cohort study. Br J Clin Pharmacol. 2018;84:1764–75.
Berard A, Zhao JP, Sheehy O.Success of smoking cessation interventions during pregnancy. Am J
Obstet Gynecol. 2016;215:611.e1–8.
Bérard A, Sheehy O, Zhao JP, Vinet É, Bernatsky S, Abrahamowicz M.SSRI and SNRI use dur-
ing pregnancy and the risk of persistent pulmonary hypertension of the newborn. Br J Clin
Pharmacol. 2017a;83:1126–33.
Bérard A, Zhao JP, Sheehy O.Antidepressant use during pregnancy and the risk of major congeni-
tal malformations in a cohort of depressed pregnant women: an updated analysis of the Quebec
pregnancy cohort. BMJ Open. 2017b;7:e013372.
Bérard A, Abbas-Chorfa F, Kassai B, Vial T, Nguyen KA, Sheehy O, Schott AM. The French
pregnancy cohort: medication use during pregnancy in the French population. PLoS One.
2019;14:e0219095.
Bergink V, Laursen TM, Johannsen BM, Kushner SA, Meltzer-Brody S, Munk-Olsen T. Pre-
eclampsia and rst-onset postpartum psychiatric episodes: a Danish population-based cohort
study. Psychol Med. 2015;45:3481–9.
Blotière PO, Miranda S, Weill A, Mikaeloff Y, Peyre H, Ramus F, Mahmoud Z, Coste J, Dray-Spira
R.Risk of early neurodevelopmental outcomes associated with prenatal exposure to the anti-
epileptic drugs most commonly used during pregnancy: a French nationwide population-based
cohort study. BMJ Open. 2020;10:e034829.
Boden R, Lundgren M, Brandt L, Reutfors J, Andersen M, Kieler H.Risks of adverse pregnancy
and birth outcomes in women treated or not treated with mood stabilisers for bipolar disorder:
population based cohort study. BMJ. 2012;345:e7085.
Boukhris T, Sheehy O, Berard A.Antidepressant use in pregnancy and the risk of attention decit
with or without hyperactivity disorder in children. Paediatr Perinat Epidemiol. 2017;31:363–73.
Brody DJ, Gu Q.Antidepressant use among adults: United States, 2015–2018. In: NCHS data
brief. Hyattsville: National Center for Health Statistics; 2020.
Broeks SC, Thisted Horsdal H, Glejsted Ingstrup K, Gasse C.Psychopharmacological drug utiliza-
tion patterns in pregnant women with bipolar disorder– a nationwide register-based study. J
Affect Disord. 2017;210:158–65.
Brown HK, Ray JG, Wilton AS, Lunsky Y, Gomes T, Vigod SN. Association between seroto-
nergic antidepressant use during pregnancy and autism Spectrum disorder in children.
JAMA. 2017;317:1544–52.
Caparros-Gonzalez RA, Torre-Luque A, Romero-Gonzalez B, Quesada-Soto JM, Alderdice F,
Peralta-Ramírez MI.Stress during pregnancy and the development of diseases in the offspring:
a systematic-review and meta-analysis. Midwifery. 2021;97:102939.
Charlton RA, Jordan S, Pierini A, Garne E, Neville AJ, Hansen AV, Gini R, Thayer D, Tingay K,
Puccini A, Bos HJ, Nybo Andersen AM, Sinclair M, Dolk H, Den Berg DJ-V, L.T. Selective
serotonin reuptake inhibitor prescribing before, during and after pregnancy: a population-based
study in six European regions. BJOG. 2015;122:1010–20.
Cooper WO, et al. Increasing use of antidepressants in pregnancy. Am J Obstet Gynecol.
2007;196:544–5.
Coughlin CG, Blackwell KA, Bartley C, Hay M, Yonkers KA, Bloch MH.Obstetric and neo-
natal outcomes after antipsychotic medication exposure in pregnancy. Obstet Gynecol.
2015;125:1224–35.
Creeley CE, Denton LK.Use of prescribed Psychotropics during pregnancy: a systematic review
of pregnancy, neonatal, and childhood outcomes. Brain Sci. 2019;9:235.
Danielson MLB etal. Trends in stimulant prescription lls among commercially insured children
and adults– United States, 2016–2021. MMWR Morb Mortal Wkly Rep; 2023.
De Vries C, Gadzhanova S, Sykes MJ, Ward M, Roughead E.A systematic review and meta-anal-
ysis considering the risk for congenital heart defects of antidepressant classes and individual
antidepressants. Drug Saf. 2021;44:291–312.
15