Introduction

Common mental disorders

Psychiatric disorders in pregnancy and the postpartum period are common and have an impact not only on the health of the mother, but also on the well-being of her offspring.

In this chapter, we provide a concise introduction to perinatal psychiatric disorders and emphasize the role of prevention, early detection, and collaborative care. We are aware that the term peri­natal is not used in exactly the same way in different contexts. We here use it to indicate pregnancy and the first few months after childbirth. Although the perinatal and postpartum specifier in the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) (2) and the World Health Organization International Classification of Diseases, tenth edition (ICD-10) (3) respectively cover the first 4 and 6 weeks after delivery, in clinical practice it is common to extend the postpartum period to 6 months after childbirth or even up to 1 year. Indeed, the United Kingdom National Institute for Health and Care Excellence (NICE) ‘Antenatal and Postnatal Mental Health: Clinical Management and Service Guidance' defined the postpartum period as up to 1 year after childbirth (4).

We discuss both disorders with first onset in the perinatal period and the course and management of women with pre-existing illness. We discuss the presentation, epidemiology, risk factors, prognosis, and management of a range of common mental disorders, such as depression and anxiety, and less prevalent, but more severe dis­orders, such as postpartum psychosis, bipolar disorder, and schizo­phrenia.

Depression

Major depression is the leading cause of disability worldwide (5) and common during pregnancy and in the postpartum period. The noso­logical status of depressive episodes associated with reproductive events is controversial (6). The American Psychiatric Association (2) and the World Health Organization (3) in their classification sys­tems currently do not consider them as separate disorders but rather subtypes of major depression.

Epidemiology

The point-prevalence of major depression during pregnancy and postpartum varies widely across studies and countries, ranging from 0% to over 30% (7-10). Although cultural differences may play a role, it is likely that methodological heterogeneity and, in particular, differences in the assessment of depression are likely to contribute to the large variability observed.

Evidence on whether pregnancy is protective and the post­partum period is a high-risk period for depression is also incon­sistent. According to a Danish registry-based study, the relative risk of being admitted to hospital for major depression for the first time is halved during pregnancy, but more than doubled in the first 2 months after childbirth compared to 1 year postpartum (11). This research, however, considered only first-onset cases. In a retro­spective study on 546 women with recurrent major depression, over 35% of the 1189 pregnancies followed by live births were af­fected by a postpartum depressive episode, while depression during pregnancy was less frequent (12). A prospective study in the United States, however, has questioned the temporal association between childbirth and depression and estimated that one-t hird of post­partum depressive episodes begin in pregnancy and an additional 27% prior to conception (13).

Established risk factors for postpartum depression are a history of depression or anxiety, recent stressful life events, poor social sup­port, and domestic violence (reviewed in (14)). A recent systematic review identified similar risk factors for depression during preg­nancy (poor social support; adverse life events; domestic violence; history of mental illness; unplanned or unwanted pregnancy; pre- sent/past pregnancy complications, including miscarriage) (15).

Clinical presentation

The symptomatology is similar to that of non-childbearing depres­sion (6, 16). The validity of somatic symptoms of depression (i.e. fa­tigue, loss of libido, appetite, and weight and sleep changes) in the perinatal period has, however, been debated, because they overlap with the normal physical experience of pregnancy and childbirth (8). It has been described that intrusive violent thoughts and psych­osis are more common in women with postpartum-onset than in those with pregnancy-onset depression (17). In a United States national survey, 30% of women who screened positive for post­partum depression endorsed thoughts of self-harm (13). Suicide in pregnancy and postpartum is a rare event, but represent a major, neglected, cause of maternal mortality (Box 18.1). The same study found that the majority (65.7%) of women with postpartum depres­sion had comorbid anxiety disorders including generalized anxiety disorder and obsessive-compulsive disorder.

Screening

A study in the United Kingdom has estimated that about 50% of cases of maternal depression go undetected with high costs for the woman, the child, and the entire society (1). Given the high preva­lence and the detrimental consequences of untreated perinatal depression, universal screening of perinatal women has been ad­vocated in many countries worldwide, most recently in the United States by the US Preventative Services Task Force (18).

Self-reported measures of depression, specifically designed to identify women who need further clinical assessment in the post­partum period, include the Bromley Postnatal Depression Scale, the Edinburgh Postnatal Depression Scale, and the Postpartum Depression Screening Scale.

Box 18.1 Suicide, violence, and perinatal mental health

According to recent estimates, women with postpartum psychiatric dis­orders have an over 80-fold increased risk of violent death and are about 290 times more likely to commit suicide in the first year postpartum compared to mothers without mental disorders. Over 40% of women with postpartum mental disorders who die in the first year after giving birth, die of suicide, homicide, or accident (94).

Estimates of perinatal (defined as 1 year preconception, in pregnancy, and 1 year after childbirth) intimate partner violence vary considerably, from less than 1% to over 80% (41), with higher prevalence in women with low socioeconomic status and in those with perinatal mental dis­orders, including anxiety, depression, and PTSD (95). The majority of the current evidence is based on findings for high-income countries, but it is likely that the cultural context influences the prevalence and risk factors of perinatal psychiatric disorders associated with domestic violence (95).

Untreated postpartum severe disorders are associated with an in­creased risk of both suicide (94, 96) and infanticide (97). According to the Eighth Report of the Confidential Enquiries into Maternal Deaths in the United Kingdom, a substantial proportion of women who committed suicide following postpartum psychosis were misdiagnosed by clinicians as suffering from anxiety, moderate depression, or adjustment disorder and did not receive adequate treatment (51). Similarly, a retrospective study on 45 filicidal mothers found that two out of three women were initially erroneously diagnosed as having unipolar depression (58). (including midwives, obstetricians, health visitors, and general prac­titioners) should ask two questions to identify possible depression (Whooley questions), at the woman's first contact with primary care, at her booking visit, and postpartum (first year after childbirth):

• During the past month, have you often been bothered by feeling down, depressed, or hopeless?

• During the past month, have you often been bothered by having little interest or pleasure in doing things?

If there is a positive answer to either question, or a high risk of developing a mental health problem, or clinical concern, the clin­ician should consider using the Edinburgh Postnatal Depression Scale or the Patient Health Questionnaire as part of a full assess­ment or referring the woman to her family physician or, if a severe mental health problem is suspected, to a mental health professional.

Differential diagnosis

‘Organic' disorders, such as thyroid dysfunction, anaemia, or sub­stance abuse, should always be ruled out. Postpartum major depres­sion needs to be distinguished from minor mood disorders, such as postpartum blues, and from postpartum psychosis (discussed in de­tail in a later section). Postpartum blues is common and character­ized by transient emotional liability during the first week after birth that does not impair the care of the baby. It is self-limiting, but as­sessment should ensure that the woman is not and does not become more severely depressed.

Clinicians need to be aware that postpartum depression can be a manifestation of a bipolar disorder. One study found that over 50% of cases of bipolar postpartum depression were initially misdiagnosed as unipolar disorder by clinicians (19) and a further study found that over 20% of women who screen positive for postpartum depression had bipolar disorder (13). The differential diagnosis between bipolar and unipolar depression is important, as the treatment of bipolar episodes with antidepressants may be associated with the risk of a manic switch, rapid cycling, and treatment resistance (19). The use of tools designed to detect manic symptomatology such as the Mood Disorder Questionnaire, the Hypomania Checklist-32, or the Highs Scale can help the clinician in the identification of hypomanic symp­toms (19). Episodes of psychotic depression in the immediate post­partum period should raise the possibility of an underlying bipolar diathesis, even in the absence of manic symptoms (20).

Treatment

The proportion of women taking antidepressants during preg­nancy has increased in recent decades but varies widely with studies finding rates of around 3% in Denmark (21) to over 13% in the United States (22).

A longitudinal study in the United States on 201 euthymic pregnant women taking antidepressants found that 68% of those who discon­tinued the treatment had a relapse during pregnancy compared with 26% of those who maintained it (23). Another study, however, of 778 pregnant women with a history of major depression found that staying on or stopping antidepressant treatment had little influence on psychiatric outcome (24). It is likely that differences in the nature of the depressive histories in the two groups of women account for these conflicting findings. The first study was in women treated in a specialist mood disorder service who are likely to have a severe unipolar depres­sion. The latter study, in contrast, was of women recruited in a com­munity maternity setting with consequently less severe mood disorder histories. The different results from these studies emphasize the need to individualize decisions based on the particular womans history.

If a pregnant woman is taking an antidepressant, NICE (4) recom­mends to discuss the therapeutic options with her and to choose the treatment approach according to the level of severity of the symp­tomatology, the previous psychiatric history, the stage of the preg­nancy, and her preferences (4).

For new-onset moderate or severe episodes, NICE (4) recom­mends either a high-intensity psychological intervention or anti­depressant medications, according to the woman's preferences and psychiatric history. If there is no or only a limited response to the high-intensity psychological intervention or medication alone, a combination of the two is recommended.

There is little specific evidence for the pharmacological manage­ment of postpartum depression and for evaluating the comparative harms and benefit of specific antidepressants (25). Research com­paring psychological intervention to pharmacological treatments is also lacking. Decisions must therefore be made on the basis of evidence for the efficacy of approaches accumulated in the non- perinatal context. Women requiring psychological treatment should be seen for treatment quickly, ideally within 1 month of initial as­sessment (26). There are many psychological approaches that have been shown to be effective in the perinatal period. A Cochrane meta-analysis of ten trials of psychological and psychosocial inter­ventions concluded that peer support and nondirective counselling, cognitive behavioural therapy, psychodynamic psychotherapy, and interpersonal therapy are all effective in postpartum depression (27). In addition, the Scottish Intercollegiate Guidelines Network (SIGN) suggests specific interventions directed to the improvement of the mother-baby relationship are offered, if this is impaired (28).

Similarly to pregnancy, in breastfeeding women the risk-benefit balance of pharmacological therapy is altered, and antidepressant therapy should be considered if the woman expressed a preference for medication, or she declines psychological interventions or they are not available, or her symptoms have not responded to psycho­logical interventions (4), or are severe. As with all drugs taken during breastfeeding, the infant should be monitored regularly for sedation, irritability, and any alteration in sleep, feeding, or growth pattern.

As new data on medication safety in pregnancy and during lacta­tion are emerging regularly, up-to-date advice from specialist serv­ices may be useful in individual cases.

Emerging therapies proposed for perinatal depression include oestrogens and progestins (Box 18.2), omega-3 fatty acids, such as eicosapentaenoic acid and docosahexaenoic acid, exercise, and in­tegrated yoga. Evidence of effectiveness is, however, based on small studies or is inconsistent (28-31).

Prognosis

Data on prognosis are difficult to interpret, because of the heteroge­neous methodologies and definitions used. Episodes of postpartum depression last 3-6 months on average, but about 30% of women remain depressed beyond the first postpartum year (8). Having a

Box 18.2 Gonadal steroid sensitivity and mood disorders

The exact pathophysiology of perinatal mood disorders is not known, es­pecially for non- psychotic postpartum depression. It is likely to be complex and multifactorial. Although not all perinatal episodes may be aetiologic- ally linked to the biological changes observed in the perinatal period (6), the onset of mood disorders in relation to the dramatic changes in neuro­endocrine function seen in pregnancy and immediately after delivery have generated interest in the role of gonadal steroids in affective dysregulation.

It is increasingly recognized that ovarian sex steroids have important func­tions in the central nervous system. Oestrogen and progesterone receptors are widespread in the brain, where they modulate neurotransmission and neuroplasticity via both genomic and non-genomic mechanisms and regu­late not only maternal behaviour, but also emotion processing, arousal, cognition, and motivation (98-101). Gonadal steroids have been implicated in a number of neuropsychiatric illnesses, including migraine, neurodegen- erative disorders, and premenstrual dysphoric disorders (101,102).

The brain is a steroidogenic organ able to synthetize pregnane neurosteroids, either de novo or from peripherally derived sources. Some progesterone metabolites, including allopregnanolone, are po­tent stereoselective, positive allosteric modulators of the gamma­aminobutyric acid type A (GABA-A) receptor and may be involved in the susceptibility to affective dysregulation (101,103).

Studies investigating the role of gonadal steroids in perinatal mood disorders have mainly focused on non-psychotic depression. It has been suggested that the hormonal trigger of postpartum depression is charac­terized by an abnormal response to normal concentrations of gonadal steroids, rather than abnormal basal hormone levels. In a milestone ex­periment, euthymic women with a history of postpartum depression and a group of matched controls underwent a hormone manipulation protocol that simulated the changes in oestradiol and progesterone observed during pregnancy and immediately after delivery (104). The protocol consisted of three phases: (1) endogenous hormone suppres­sion with a gonadotropin-releasing hormone agonist, (2) an 8-week add-back phase with supraphysiological doses of oestradiol and proges­terone, and (3) withdraw of both steroids under double- blind conditions. While controls were not affected by the manipulation protocol, five out of eight women with a history of postpartum depression developed sig­nificant mood symptoms. Interestingly, although symptoms were more severe during the hormone withdrawal phase, significant depressive symptoms started to develop during the add-back phase simulating the hormone conditions of pregnancy (104).

Research into the role of gonadal steroids in the pathogenesis of peri­natal mood disorders is still in very early stages and its clinical impli­cations are unclear. A Cochrane review on oestrogens and progestins for preventing and treating postpartum depression has suggested that synthetic progestins should be used with significant caution in the post­partum period and that oestrogen therapy may be of modest value and should not be part of routine management (29).

A recent randomised, controlled, phase 3 trial has reported some promising findings for brexanolone, an analog of allopregnanolone, for the treatment of postpartum depression (PMID: 30177236). The place of brexanolone in the treatment of postpartum depression is still con­sidered emerging and further research is warranted (PMID: 31241747, PMID: 31255297, PMID: 31255300).

depressive episode in relation to childbirth increases the risk of sub­sequent depressive episodes, with recurrence rates around 40% for both perinatal and non-perinatal episodes (32).

Anxiety disorders

Perinatal anxiety disorders are often overlooked (4, 8), commonly occurring in association with other psychiatric conditions, espe­cially depression (13, 33, 34). Prevalence rates of anxiety disorders in studies ranges widely from 6% to 39% in pregnancy (35) and from 16% to 50% in the postpartum period (36). There is inconsistent evi­dence of a specific link between the perinatal period and anxiety dis­orders, with the exception of obsessive-compulsive disorder (8, 35). According to a meta- analysis, both pregnant and postpartum women have an increased risk of developing obsessive-compulsive disorder (risk ratios 1.45 and 2.38 respectively) (37). While some obsessional thinking is common in pregnancy and following childbirth, some women are much more significantly affected with thoughts con­cerning contamination or aggression against the child that can lead to compulsive behaviours such as cleaning, avoidance of the child, or excessive checking on the child's well-being. Although causing sig­nificant distress to women, these aggressive thoughts are not acted on and only in a small proportion of cases lead to significant distress and functional impairment. Clinical episodes of obsessive-compulsive disorder in the perinatal period are much less common than obses­sional symptoms, affecting about 2.5% of women (37). Obsessions need to be distinguished from delusions that may pose a risk to the baby. Delusions are strongly held false beliefs that persist even when there is evidence that the beliefs are not true or logical. Obsessions are intrusive, reoccurring thoughts or urges, or mental images that cause anxiety and distress. However, the distinction between delusions and obsessions is not always clear-cut and can be a diagnostic challenge.

Randomized controlled trials for the treatment of anxiety dis­orders in the perinatal period are lacking and even non-controlled, naturalistic study evidence is also scarce (8). The treatment of peri­natal anxiety disorders largely relies on information on the treat­ment in the wider population. It is, however, not clear whether and to what extent psychosocial and psychological interventions need to be modified to be effective in the perinatal period (8). Mind-body interventions have been increasingly popular, but strong, rigorous evidence to support their effectiveness for the management of anx­iety during pregnancy or postpartum is lacking (38).

Post-traumatic stress disorder

Perinatal post-traumatic stress disorder (PTSD) is not very well studied and recognized, with the majority of studies concerning symptoms occurring after miscarriage, termination, stillbirth (39), or traumatic birth (40). In case of perinatal loss, gestational age is positively associated with the likelihood for PTSD (39). The preva­lence of perinatal PTSD is estimated at around 1-8% (8, 41), with a higher prevalence in low-income countries compared to high- income countries and showing a high comorbidity with major de­pression, anxiety, alcohol or illicit drugs use, and suicidality (8, 42). PTSD is highly prevalent (40% according to a recent study (41)) among low-income pregnant women exposed to intimate partner violence in pregnancy and following childbirth.

Little research has been conducted on the management of peri­natal PTDS, especially in women with a preconception history of trauma. However, what is clearer is that a recent Cochrane system­atic review found little or no evidence to support psychological debriefing for women who perceive giving birth as psychologically traumatic (43).