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18 Obsessive-Compulsive Disorder
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Anxiety Disorders
19
BenyaminDanielDaniel, CaterinaDell’Ann,
andCarloMarchesi
19.1 Introduction
In common perception, pregnancy and motherhood are often seen as times of joyful
anticipation and happiness. However, the perinatal period, which spans from conception to 1 year postpartum (O’Hara and Wisner 2014), is also marked by profound
physical and psychological changes (Bellantuono etal. 2022). This period often
presents a dichotomy: while it brings the joyful anticipation of motherhood, it also
increases vulnerability to mental health distress. Historically, idealized notions of
pregnancy and motherhood led to the belief that the perinatal period was a low-risk
time for the onset or exacerbation of anxiety disorders (ADs) (Bellantuono
etal. 2022).
Nevertheless, it is now widely recognized that anxiety symptoms and ADs are
prevalent both during pregnancy and the postpartum period, with signicant adverse
outcomes for the mother, the fetus, and its development (Marchesi etal. 2014; Ross
and McLean 2006).
Even when symptoms do not meet the threshold for a formal diagnosis of an AD,
mild to moderate levels of distress and impairment due to subthreshold anxiety can
signicantly impact maternal well-being.
A broad spectrum of ADs, including generalized anxiety disorder (GAD), panic
disorder (PD), and phobias, can manifest during this time.
Given the potential impact of maternal psychopathology not only on the mother
but also on the child (Stein etal. 2014; Glasheen etal. 2010), addressing perinatal
ADs is critical. Effective treatment can alleviate maternal distress, improve functioning during this sensitive life stage, and reduce potential negative outcomes for
B. D. Daniel (*) · C. Dell’Ann · C. Marchesi
Treatment of Psychiatric Disorders in Perinatal Period Unit, University Hospital of Parma,
Department of Mental Health, Parma Local Health Agency, University of Parma, Parma, Italy
e-mail: benyamindaniel.daniel@unipr.it; caterina.dellanna@unipr.it; carlo.marchesi@unipr.it
© 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_19
401
402
the fetus. Identifying evidence-based treatments that are both safe and acceptable
for women during pregnancy and breastfeeding is therefore of paramount
importance.
B. D. Daniel et al.
19.2 Epidemiology andPrevalence ofPerinatal
Anxiety Disorders
An estimated 30% of adults experience ADs at some point in their lives (APA 2022),
a rate signicantly higher than that of other mental health conditions. The impact of
ADs on social, emotional, and physical functioning is profound, placing a considerable burden on healthcare services (Ohayon etal. 2000; McCusker etal. 1997).
In addition to the direct public health costs associated with ADs, substantial indirect costs arise from functional impairments, such as reduced work capacity and
unemployment (Greenberg etal. 1999). Women are particularly vulnerable, with a
notably higher prevalence of ADs compared to men (Somers etal. 2006; Kessler
etal. 2005).
In the context of the perinatal period, these conditions have historically been
underestimated and under-investigated (Bellantuono et al. 2022). Earlier metaanalyses estimated that ADs affected between 8.5% (Goodman et al. 2016) and
15.2% (Dennis etal. 2017) of women during pregnancy, and 9.9% (Dennis etal.
2017) during the postpartum period. However, a more recent meta-analysis (Fawcett
etal. 2019) reported an overall prevalence of 20.7% during the perinatal period.
Additionally, Fawcett and colleagues (Fawcett etal. 2019) found that 1in 20 women
(5.5%) met the criteria for at least two ADs. Regarding the prevalence of specic
ADs, a study (Goodman etal. 2016) identied GAD, obsessive-compulsive disorder (OCD), and PD as the most common ADs during the postpartum period. In
contrast, a more recent study (Fawcett etal. 2019) found specic phobia, GAD, and
social phobia to be the most prevalent perinatal disorders. It is worth noting that
OCD is no longer classied as an AD under DSM-5.
Anxiety can manifest both as a disorder, characterized by chronic and persistent
levels of worry that signicantly impairs daily functioning and quality of life, and
as a symptom, occurring in physiological or para-physiological contexts and within
distinct psychopathological trajectories that differ from true ADs. From a psychopathological perspective, the distinction lies in the chronicity, severity, and impact
on daily life. During pregnancy, somatic symptoms such as palpitations, breathing
difculties, muscle tension, gastrointestinal discomfort, and dizziness may overlap
with those of ADs, making diagnosis more complex and increasing the risk of mistaking normal physiological responses for pathological anxiety. Furthermore, anxiety symptoms can signicantly affect quality of life, often co-occurring with other
psychological or somatic conditions and negatively impacting relationships, work
performance, and overall well-being.
geographical regions and cultural contexts, with perinatal anxiety prevalence
reported at 17.4% in China (Yang etal. 2023) and 28.2% in Africa (Umuziga etal.
19 Anxiety Disorders
2020). These variations likely stem from differences in assessment methods, diag-
nostic criteria, timing of evaluations, and populations studied.
Global events also play a crucial role in shaping prevalence rates. During the
SARS-CoV-2 pandemic, clinically elevated anxiety symptoms were reported in
57% of pregnant women (Lebel etal. 2021), highlighting the inuence of extraordinary circumstances on perinatal mental health.
In conclusion, perinatal anxiety and perinatal ADs represent a critical global
public health issue. Variability in prevalence across populations, cultures, and contexts underscores the need for culturally sensitive, evidence-based approaches to
screening, prevention, and treatment. As understanding of perinatal anxiety evolves,
addressing these conditions remains a central focus in maternal mental healthcare
worldwide.
403
19.3 Diagnostic Challenges, Classification,
andClinical Presentation
19.3.1 Limitations ofCurrent Diagnostic Criteria (DSM-5)
Diagnosing ADs during the perinatal period presents various challenges. While the
DSM-5 includes the specier “with onset in the peripartum” for mood disorders, it
does not provide a similar designation for ADs (Bellantuono etal. 2022). This omission reects the historical focus of clinical research on perinatal depression, leaving
ADs during this critical period underexplored (Marchesi etal. 2014).
The current lack of a peripartum specier for ADs creates several diagnostic
hurdles. GAD, characterized by excessive and uncontrollable worry that signicantly impairs daily functioning, is among the most common ADs during the perinatal period. However, the absence of the DSM specier “with peripartum onset”
creates several issues. Specically, applying DSM-5 criteria designed for the general population to pregnant or postpartum women may exclude individuals experiencing excessive worry for less than 6 months. To address this limitation, some
authors suggest adapting the criteria for perinatal GAD by reducing the required
duration to 1 month, provided other DSM criteria are met (Misri etal. 2015; Buist
and Gotman 2011; Wenzel etal. 2003).
Another signicant issue in diagnosing ADs during the perinatal period lies in
the overlap between the physical symptoms of some ADs, such as fatigue, irritability, tension, concentration difculties, and insomnia, and the common physiological
changes of pregnancy and postpartum (Davis etal. 2004). Furthermore, distinguishing between normal pregnancy-related worries and pathological anxiety can be particularly challenging, especially for primiparous women during the rst trimester
(Bellantuono etal. 2022).
404
B. D. Daniel et al.
19.3.2 Pregnancy-Specific Anxiety Versus General
Anxiety Disorders
Anxiety symptoms during the perinatal period can be classied as common general
ADs, as dened by the DSM-5, or as abnormal anxiety states specic to the context
of pregnancy (Bellantuono etal. 2022). Some authors (Brockington et al. 2006)
argue that perinatal ADs share the same characteristics as classic ADs seen in the
general population, but with a distinct focus on concerns such as fetal abnormalities,
fetal death, maternal inadequacy, childbirth, and lack of support.
Conversely, other authors have emphasized the need to differentiate general ADs
from pathological anxiety specic to the perinatal period. Studies have shown that
anxiety symptoms during this time are primarily associated with worries about
bodily changes and fears for the child’s health (Huizink etal. 2014), negative expectations about motherhood (Hart and McMahon 2006), or fears of inadequacy in
fullling maternal responsibilities (Huizink etal. 2014; Heron etal. 2004).
Regardless of their specic focus, ADs during the perinatal period can cause
signicant functional impairment. Although not exclusive to pregnancy or postpartum, individuals with anxiety are more likely to experience suicidal ideation and
attempts than those without anxiety (Kanwar etal. 2013). ADs are strong predictors
of postpartum depression (Robertson et al. 2004), often co-occur with perinatal
depression (Falah-Hassani etal. 2017), and have been linked to adverse pregnancy
outcomes, such as preterm birth and low birth weight (Ossola etal. 2021; Ding etal.
2014). Additionally, they have been associated with behavioral problems in off-
spring (Schreier etal. 2008).
19.3.3 The Concept ofPregnancy-Related Anxiety (PrA)
The concept of a perinatal-specic AD, referred to as pregnancy-related anxiety
(PrA), has been proposed since the 1950s (Levin 1991; Standley et al. 1979;
Pleshette etal. 1956). PrA is characterized by specic dimensions of anxiety, such
as concerns about pregnancy, childbirth, and hospitalization. Over time, numerous
measures of PrA and distress have been developed (Somerville etal. 2014; DiPietro
etal. 2008; Lobel etal. 2008; Huizink etal. 2004; Cote-Arsenault 2003), and several literature reviews have been conducted on the subject (Brunton et al. 2015;
Alderdice etal. 2012; Dunkel Schetter and Tanner 2012). A central tenet of these
studies is that PrA extends beyond merely describing pregnant women’s concerns,
positing it as a distinct clinical entity with both construct and discriminant validity.
A prospective longitudinal study evaluated the hypothesis that PrA represents a
distinct clinical phenotype, separate from general anxiety and depression. PrA levels were assessed using specialized questionnaires alongside measures of general
anxiety and depression. The ndings demonstrated that PrA is distinct from general
anxiety and depression, with a specic focus on pregnancy-related concerns, including the health of the baby, childbirth, and future parenthood. These results support
the construct and discriminant validity of PrA as a unique clinical entity (Blackmore
19 Anxiety Disorders
etal. 2016). Furthermore, a review (Williams and Koleva 2018) found that twothirds of pregnant women express concerns about their unborn child, body image,
or relationship with their partner. When these worries become excessive and interfere with daily functioning, they are classied as perinatal ADs.
405
19.4 Risk Factors forPerinatal Anxiety Disorders
Although not extensively studied, several potential risk factors for perinatal ADs
can be identied. These include: (1) socio-demographic factors, such as a low sociocultural background, limited education, ethnic minority status, young maternal age
(<25years), nancial insecurity (Shariatpanahi etal. 2023; Bellantuono etal. 2022;
Barcelona de Mendoza etal. 2016; Kane 2016); (2) psychosocial factors, including
a history of childhood or recent trauma, lack of partner or familiar support, relationship tensions, being a single mother, low self-esteem, high perceived stress
(Bellantuono etal. 2022; Dunkel Schetter and Tanner 2012; Blackmore etal. 2011);
(3) biological factors, such as elevated cortisol levels, imbalances in polyunsaturated fatty acids, and increased pro-inammatory cytokines (Bellantuono et al.
2022; Karlsson etal. 2017; Glover 2015; Glover etal. 2018); (4) pregnancy-related
factors, including unintended pregnancies, high-risk pregnancies, delivery complications, negative birth experiences, and preterm births (Shariatpanahi etal. 2023);
(5) a history of depression (van der Zee-van den Berg etal. 2021; Marchesi etal.
2014); (6) a history of ADs, which is a particularly strong predictor of anxiety dur-
ing pregnancy, regardless of other risk factors (Marchesi etal. 2014).
19.5 Risks ofUntreated Perinatal Anxiety Disorders
As outlined in this section, untreated perinatal ADs can lead to a range of negative
consequences for both mothers and fetus/infant, with potential long-term effects on
the offspring.
For mothers, perinatal ADs are associated with an increased risk of postpartum
depression (Heron et al. 2004), frequently co-occur with perinatal depression
(Falah-Hassani etal. 2017), suicidal behavior (Farias etal. 2013), pre-eclampsia
(Winkel etal. 2015), fear of childbirth (Rubertsson et al. 2014), lower odds of
breastfeeding (Grigoriadis et al. 2018), and poor coping strategies (George
etal. 2013).
In terms of infant health, perinatal ADs are associated with a variety of negative
outcomes, including preterm birth (Ding et al. 2014; Sanchez etal. 2013), low
Apgar scores (Uguz etal. 2013), fetal hyperactivity, and irregular fetal heart rate
(Uguz etal. 2019). Other complications include polyhydramnios (Bánhidy et al.
2006), a 1.6-fold increased risk of congenital abnormalities (Uguz et al. 2013),
small head circumference, and being small for gestational age (Grigoriadis etal.
2018; Chen etal. 2010), as well as low birth weight (Ding etal. 2014; Teixeira etal.
1999). Interestingly, one study (Ossola etal. 2021) found a signicant correlation
406
B. D. Daniel et al.
between the severity of anxiety symptoms and birth weight, showing a “doseresponse” effect. Higher levels of anxiety were linked to lower birth weight, with
the difference between the least and most anxious women corresponding to a
decrease of more than 600 grams. This impact on birth weight may stem from both
biological and behavioral mechanisms. Maternal anxiety, through adrenergic stimulation, might affect blood pressure and cortisol levels, which are known to contribute to low birth weight (Fan etal. 2016, 2018). Furthermore, anxiety in mildly
depressed subjects (Ossola etal. 2018) may limit healthy behaviors and foster undesirable life habits linked to negative pregnancy outcomes (Bae etal. 2010).
Moreover, perinatal ADs can also cause long-term developmental issues for offspring. Infants may experience difculties with sleeping, feeding, and activity as
well as poorer attention, hyperactivity, behavioral and emotional problems (Uguz
etal. 2019), including irritability (Van den Bergh and Marcoen 2004), attention
decit hyperactivity disorder (ADHD) (Martini etal. 2010), internalizing difculties, a tendency to social withdrawal and depression (Rees etal. 2019). Regarding
the risk of depression in offspring, alterations in neuroendocrine pathways, particularly the hypothalamic-pituitary-adrenal (HPA) axis, have been observed in children
born to anxious mothers. One study (Van den Bergh etal. 2008) highlighted the role
of the HPA axis in the link between prenatal maternal anxiety and the development
of depressive symptoms in post-pubertal female adolescents.
Perinatal ADs may also impact the child’s neurodevelopment. One study found
that prolonged maternal GAD during pregnancy affects the circulating brain-derived
neurotrophic factor (BDNF) in the fetus. BDNF plays a crucial role in neuronal
development, and lower levels of circulating BDNF have been observed as a result
(Uguz etal. 2013).
A systematic review (Adamson etal. 2019) summarized the existing literature
linking prenatal maternal anxiety with neuroimaging measures of the child’s brain
structure and function. The results revealed increased brain activation and reduced
cortical thickness in the frontal, temporal, and limbic regions of the brain. These
areas are typically associated with emotional and behavioral regulation, and their
alterations may underlie the behavioral and mental health difculties more commonly observed in children born to mothers with prenatal anxiety.
19.6 Pharmacological Treatment
19.6.1 General Considerations
As highlighted throughout this chapter, anxiety during pregnancy is a condition that
warrants serious consideration due to its potential adverse effects on both maternal
and fetal health. However, the decision to use pharmacological treatments for ADs
during pregnancy or breastfeeding poses a considerable challenge in clinical practice. This difculty often stems from physicians’ concerns regarding the safety prole of psychotropic medications, despite numerous studies assessing the risks
associated with in utero and breastfeeding exposure to these drugs. It is worth
19 Anxiety Disorders
407
noting that a comprehensive analysis of the safety of psychotropic medications during the perinatal period falls beyond the scope of this chapter.
When treating perinatal ADs, two primary intervention strategies are available:
pharmacotherapy and psychotherapy. According to the guidelines set forth by the
National Institute for Health and Care Excellence (NICE 2020), pharmacological
intervention may be deemed appropriate for perinatal ADs when symptoms are
moderate to severe, psychological interventions are insufcient, anxiety coexists
with depression, or there is an elevated risk of suicidal behavior. Conversely, in
instances of mild to moderate symptoms, psychotherapeutic approaches, particularly cognitive behavioral therapy (CBT), should be prioritized. Given the focus of
this chapter, however, the discussion will center on pharmacological interventions.
The American College of Obstetricians and Gynecologists (2023) offers similar
recommendations for managing ADs throughout pregnancy and the postpartum
period. ACOG acknowledges both psychotherapy and pharmacotherapy as valid
treatment options for perinatal anxiety and emphasizes that treatment decisions
should be individualized. Factors inuencing this decision include the severity of
symptoms, the patient’s preferences, and the potential risks and benets associated
with each treatment option. ACOG generally recommends CBT for mild to moderate symptoms, while indicating that psychopharmacotherapy is warranted in severe
cases or when psychotherapy alone proves insufcient. Additionally, ACOG underscores the importance of continuous mental health monitoring during pregnancy
and postpartum to provide timely and adequate support.
For women with a history of ADs, ACOG guidelines recommend that medications should not be halted or discontinued solely due to pregnancy or breastfeeding.
Decisions regarding the continuation or adjustment of pharmacological treatment
must be tailored to the individual, taking into account the severity of symptoms, the
patient’s medical history, and the associated risks and benets of the therapy.
Generally, it is advisable for most patients to continue psychotropic pharmacotherapy throughout pregnancy and breastfeeding, as discontinuation may pose a signicant risk of relapse or worsening of symptoms. If necessary, a gradual tapering of
medication may be implemented alongside psychological interventions.
Alternatively, switching to a drug with a lower risk of adverse effects can be considered if the current medication causes signicant side effects.
Once the decision to initiate or continue pharmacotherapy has been reached,
careful attention to optimal dosing is paramount to prevent undertreatment (ACOG
2023). While it is crucial to consider the individual severity of the patient’s condi-
tion and past psychiatric history, broad principles of psychopharmacotherapy during pregnancy include the following recommendations:
1. Use the lowest effective dose: The objective of any treatment regimen is to
administer the lowest effective dose of medication required to achieve the desired
clinical outcome. Following the implementation of the initial treatment plan,
regular monitoring of the patient’s symptoms is essential to assess efcacy. If
necessary, the dosage should be adjusted or titrated to ensure optimal symptom
management and facilitate remission.