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The Diagnostic and Statistical Manual, Fifth Edition (DSM-5) is the most recent version by the American Psychiatric Association (2013). It assists in classifying mental disorders and specifies criteria for each diagnosis.
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Of categories, depressive disorders are common. According to the National Institute of Mental Health (2010), the lifetime prevalence of depressive disorders in the United States is 21 percent. Historically, depressive disorders include major depression—a unipolar disorder—and manic-depression—a bipolar disorder with both manic and depressive episodes. It also includes dysthymia, which is chronic, mild depression.
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This is the most common depressive disorder, and the 12-month prevalence of major depressive episodes among U.S. women is 8.2 percent (Center for Behavioral Health Statistics and Quality, 2015). In 2011 to 2014, 16 percent of U.S. women had used an antidepressant in the prior month (Pratt, 2017). The diagnosis is made by identifying symptoms listed in Table 61-2, but very few patients manifest all of these.
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Major depression is multifactorial and prompted by genetic and environmental factors. Families of affected individuals often also have members suffering with alcohol abuse and anxiety disorders. Provocative conditions leading to depression include life events that prompt grief reactions, substance abuse, use of certain medications, and other medical disorders. Although life events can trigger depression, genes influence the response to these events and render the distinction between genetic and environmental factors difficult. One genome-wide linkage analysis of more than 1200 mothers suggests that variation in chromosomes 1 and 9 raises susceptibility to postpartum mood symptoms (Mahon, 2009).
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Pregnancy and Depression
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It is unquestionable that pregnancy is a major life stressor that can precipitate or exacerbate depressive tendencies. In addition, various pregnancy-induced effects are implicated. Hormones certainly affect mood, as evidenced by premenstrual syndrome and menopausal depression. Estrogen has been linked to increased serotonin synthesis, decreased serotonin breakdown, and serotonin-receptor modulation (Deecher, 2008). Concordantly, women who experience postpartum depression often have higher predelivery serum estrogen and progesterone levels and experience a greater decline postpartum (Ahokas, 1999).
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Dennis and associates (2007) queried the Cochrane Database and reported that the prevalence of antenatal depression averaged 11 percent. Melville and coworkers (2010) found it in nearly 10 percent of more than 1800 women enrolled for prenatal care at a single university clinic. Others have reported the incidence to be much higher depending on the population studied (Gavin, 2005; Hayes, 2012; Lee, 2007).
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Postpartum Depression
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Major or minor depression develops postpartum in 10 to 20 percent of women (Mental Health America, 2016). Available data indicate that unipolar major depression may be slightly more prevalent during the puerperium than among women in the general population (Yonkers, 2011). Postpartum depressive symptoms are associated with young maternal age, antenatal depression, unmarried status, smoking, newborns requiring intensive care, and those with a history of stressors during pregnancy (Ko, 2017; Silverman, 2017). Specifically, physical or verbal abuse during pregnancy is a potent risk for postpartum depression (McFarlane, 2014). Finally, serious adverse obstetrical events, especially those involving the neonate, are strongly linked to postpartum depression (Nelson, 2013, 2015).
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Depression is frequently recurrent. Up to 70 percent of women with previous postpartum depression have a subsequent episode. Women with both prior puerperal depression and a current episode of “maternity blues” carry an inordinately high risk for major depression. Indeed, 2 to 9 months postpartum, assistance with postpartum depression was the fourth most common challenge identified in women in the Pregnancy Risk Assessment Monitoring System—PRAMS (Kanotra, 2007).
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Postpartum depression is generally underrecognized and undertreated. Major depression during pregnancy or after delivery can have devastating consequences for affected women, their children, and families. One of the most significant contributions to the mortality rate among new mothers is suicide, which is most frequent among women with mental illness (Koren, 2012; Palladino, 2011). If left untreated, up to 25 percent of women with postpartum depression will be depressed 1 year later. As the duration of depression increases, so too does the number of sequelae and their severity. Maternal depression during the first weeks and months after delivery can lead to insecure attachment and later behavioral problems in the child.
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Therapy for mood disorders during pregnancy and postpartum has undergone a significant evolution during the past decade. Babbitt (2014) and Pozzi (2014) and their associates have reviewed principles of antenatal and intrapartum care of women with major mental disorders. In general, for mild and mild-moderate depression, psychological treatment options, such as cognitive behavioral therapy, are considered first (Yonkers, 2011). Antidepressant medications together with some form of psychotherapy are indicated for moderate to severe depression during pregnancy or the puerperium (American College of Obstetricians and Gynecologists, 2016b).
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Shown in Figure 61-1 is one algorithm regarding treatment of mood disorders. Some of these medications are listed in Table 61-3. For women with severe depression, a selective serotonin-reuptake inhibitor (SSRI) is selected initially. In contrast, tricyclic antidepressants and monoamine oxidase inhibitors are infrequently selected in contemporary practice. If depressive symptoms improve during a 6-week trial, the medication is continued for a minimum of 6 months to prevent relapse (Wisner, 2002). At least 60 percent of women taking antidepressant medication before pregnancy have symptoms during pregnancy. According to Hayes and colleagues (2012), approximately three fourths of women taking antidepressants before pregnancy stopped taking them before or during early pregnancy. For those who discontinue treatment, almost 70 percent have a relapse compared with approximately 25 percent who continue therapy. If the response is suboptimal or a relapse occurs, another SSRI is substituted, or psychiatric referral is considered.
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Various dietary deficiencies have suggested links to perinatal depression (Yonkers, 2011). Supplements that include omega-3 fatty acids, iron, folate, riboflavin, vitamin D, calcium, and docosahexaenoic acid (DHA) have been studied (Keenan, 2014; Miller, 2013). However, evidence currently is insufficient to support use of these dietary supplements for this purpose.
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Importantly, in a metaanalysis by Huang and coworkers (2014), women using antidepressants during pregnancy have higher rates of preterm birth and low-birthweight neonates. Nevertheless, in their review, Ray and Stowe (2014) concluded that the relative reproductive safety data are reassuring and that antidepressants remain a viable treatment option. Furthermore, recurrence sometime after medication is discontinued develops in 50 to 85 percent of women with an initial postpartum depressive episode. Women with a history of more than one depressive episode carry greater risk (American Psychiatric Association, 2000). Surveillance includes monitoring for thoughts of suicide or infanticide, emergence of psychosis, and response to therapy. For some women, the course of illness is severe enough to warrant hospitalization.
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Fetal and Neonatal Effects of Therapy
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Some known and possible fetal and neonatal effects of treatment are listed in Table 61-3. Some studies suggest that SSRIs pose an elevated teratogenic risk for fetal cardiac defects, and these have mainly focused on paroxetine (Paxil). Associations were most consistent for ventricular septal defects. The estimated risk is no greater than 1 in 200 exposed newborns (Koren, 2012). Nevertheless, the American College of Obstetricians and Gynecologists (2016b) recommends that paroxetine be avoided in women who are either pregnant or planning pregnancy. In women exposed to paroxetine in the first trimester, fetal echocardiography is considered. Jimenez-Solem and coworkers (2013) in their analysis of SSRIs found no association between exposure to SSRIs during pregnancy and perinatal mortality. Andersen and associates (2014) found that women discontinuing SSRI treatment in early pregnancy had a small increased risk of miscarriage, but that this was similar to the risk in women discontinuing SSRI treatment months before pregnancy. Taken together, these investigators concluded that treatment with SSRIs during pregnancy should not be discontinued for fear of miscarriage.
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Of other potential effects, the risk of persistent pulmonary hypertension of the newborn rose sixfold in neonates exposed to SSRIs after 20 weeks’ gestation (Chambers, 2006). This translates to an overall risk of pulmonary hypertension that would be less than 1 in 100 exposed newborns (Koren, 2012). In contrast, a population-based cohort study of 1.6 million pregnancies identified a twofold greater rate in exposed neonates. This yields an estimated attributable risk of 2 cases per 1000 births (Kieler, 2012). In a study of more than 120,000 gravidas prescribed antidepressants, Huybrechts and coworkers (2015) found an attributed risk of 1 case per 1000 births.
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In sum, the maternal risk associated with discontinuing or tapering SSRI use during pregnancy must be weighed against marginally increased neonatal risks (Ornoy, 2017). Women who abruptly discontinue either serotonin- or norepinephrine-reuptake inhibitor therapy typically experience some form of withdrawal.
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Not surprisingly, up to 30 percent of exposed neonates may also exhibit withdrawal symptoms. Symptoms are similar to opioid withdrawal, but typically are less severe. Neonatal SSRI withdrawal is usually self-limited, and the newborn rarely remains in the nursery more than 5 days (Koren, 2009). Currently, convincing evidence of long-term neurobehavioral effects of fetal exposure to these medications is lacking (Koren, 2012). Grzeskowiak and coworkers (2016) found no increased risk of behavioral problems in 7-year-old children exposed to antidepressants prior to their birth.
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Some psychotropic medications pass into breast milk. In most cases, however, levels are very low or undetectable. Effects may be transient irritability, sleep disturbances, and colic.
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Electroconvulsive Therapy
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This form of depression treatment is occasionally necessary during pregnancy for women with major mood disorders unresponsive to pharmacotherapy. Women undergoing electroconvulsive therapy (ECT) should be fasting for at least 6 hours. They are given a rapid-acting antacid before the procedure, and their airway is protected to decrease the likelihood of aspiration. After midpregnancy, a wedge is placed under the right hip to prevent sudden maternal hypotension from aortocaval compression. Other important preparatory steps include assessment of the cervix, discontinuation of nonessential anticholinergic medication, uterine and fetal heart rate monitoring, and intravenous hydration. During the procedure, excessive hyperventilation is avoided. In most cases, maternal and fetal heart rate and maternal blood pressure and oxygen saturation remain normal throughout the procedure.
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With proper preparation, the risks to both mother and fetus appear to be reasonable (Pinette, 2007). That said, adverse maternal and perinatal outcomes have followed ECT. Balki and associates (2006) reported a pregnancy in which fetal brain damage likely was caused by sustained maternal hypotension associated with treatment of status epilepticus stimulated by ECT.
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At least two extensive reviews have evaluated ECT outcomes in pregnancy. In the earlier one, Miller (1994) found 300 cases and reported complications in 10 percent. These included fetal arrhythmias, vaginal bleeding, abdominal pain, and self-limited contractions. Women not adequately prepared had increased risks for aspiration, aortocaval compression, and respiratory alkalosis. In the more recent review, Andersen and Ryan (2009) described 339 cases, undoubtedly with some homology with the earlier study. In most cases, ECT therapy was done to treat depression, and it was 78-percent effective. They reported a 5-percent maternal ECT-related complication rate. There was a 3-percent associated perinatal complication rate, which included two fetal deaths. For all of these reasons, we agree with Richards (2007) that ECT in pregnancy is not “low risk” and that it should be reserved for women whose severe depression is resistant to intensive pharmacotherapy.
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Bipolar and Related Disorders
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According to the National Institute of Mental Health (2010), the lifetime prevalence for manic-depression illness is 3.9 percent. The prevalence of bipolar disorder does not vary between gravidas and nonpregnant reproductive-aged women (Yonkers, 2011). It has a strong genetic component and has been linked to possible mutations on chromosomes 16 and 8 (Jones, 2007). The risk that monozygotic twins are both affected is 40 to 70 percent, and the risk for first-degree relatives is 5 to 10 percent (Muller-Oerlinghausen, 2002).
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Periods of depression last at least 2 weeks. At other times, patients are manic, in which mood is abnormally raised, expansive, or irritable. Potential organic causes of mania include substance abuse, hyperthyroidism, and central nervous system (CNS) tumors. These are all excluded during an acute event. Importantly, pregnancy frequently prompts medication discontinuation, which poses a twofold increased risk for relapse (Viguera, 2007). Affected women are considered high risk, and as many as 20 percent of patients with manic-depression illness commit suicide.
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Bipolar Disorder in Pregnancy
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This has also been associated with adverse perinatal outcomes, for example, preterm birth (Mei-Dan, 2015). Di Florio and associates (2013) found that those women who experience pregnancy complications are more likely to exhibit periods of mania or depression. Women who tend to be manic present with exacerbations earlier in the postpartum period.
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Typical therapy for bipolar disorder includes mood stabilizers such as lithium, valproic acid, and carbamazepine, as well as antipsychotic medications (see Table 61-3). Treatment of bipolar disorder in pregnancy is complex and is ideally managed concurrently with a psychiatrist. Decisions include risks versus benefits of using mood stabilizers, some of which are teratogenic. For example, lithium has been linked to Ebstein anomaly in exposed fetuses. More recent data, however, suggest a lower risk of cardiac malformations than previously indicated (Micromedex, 2016; Patorno, 2017). Nevertheless, many recommend fetal echocardiography for lithium-exposed fetuses. Some limited evidence suggests that lithium in breast milk, when its elimination is impaired as in dehydration or immaturity, can adversely affect the infant (Davanzo, 2011). However, lithium use in mothers with a healthy, term fetus is considered moderately safe. A more detailed discussion of other mood stabilizers and antipsychotic medications side effects can be found in Chapter 12 (Immunosuppressant Medications).
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This severe mental disorder is usually a bipolar disorder, but it may be due to major depression (American Psychiatric Association, 2013). Its incidence is estimated to be 1 in every 1000 deliveries, and it is more common in nulliparas, especially those with obstetrical complications (Bergink, 2011; Blackmore, 2006). In most cases, illness manifests within 2 weeks of delivery. In one study of postpartum women with their first lifetime episode of psychosis, the median onset of psychiatric symptoms was 8 days after delivery, and the median duration of the episode was 40 days (Bergink, 2011). Because those with underlying psychiatric disease have a 10- to 15-fold risk for recurrence postpartum, close monitoring is imperative.
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The most important risk for postpartum psychosis is a history of bipolar disease. These women typically exhibit symptoms within 1 to 2 days after delivery (Heron, 2007, 2008). Manic symptoms include feeling excited or elated, being active or energetic, feeling “chatty,” and suffering insomnia. Affected women have signs of confusion and disorientation but may also have lucid episodes.
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Postpartum psychosis has a 50-percent recurrence risk in the next pregnancy. As a result, Bergink and associates (2012) recommend initiating lithium therapy immediately after delivery in women with a history of postpartum psychosis.
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The clinical course of bipolar illness with postpartum psychosis is comparable with that for nonpregnant women. Patients usually require hospitalization, pharmacological treatment, and long-term psychiatric care. Psychotic women may have delusions leading to thoughts of self-harm or harm to their infants. Unlike women with nonpsychotic depression, these women commit infanticide, albeit uncommonly (Kim, 2008). In most instances, women with postpartum psychosis ultimately develop relapsing, chronic psychotic manic-depression.
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These relatively common disorders—18 percent prevalence overall—include panic attack, panic disorder, social anxiety disorder, specific phobia, separation anxiety disorder, and generalized anxiety disorder. All are characterized by irrational fear, tension, and worry, which are accompanied by physiological changes such as trembling, nausea, hot or cold flashes, dizziness, dyspnea, insomnia, and frequent urination (Schneier, 2006). They are treated with psychotherapy and medication, including SSRIs, tricyclic antidepressants, monoamine oxide inhibitors, or others.
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Anxiety Disorders in Pregnancy
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Despite the relative high prevalence in childbearing-aged women, little specific attention has been directed to anxiety disorders in pregnancy. Most reports conclude that rates between pregnant and nonpregnant women do not differ. One recent analysis of 268 gravidas with generalized anxiety disorder demonstrated that both symptoms and severity of anxiety decline across pregnancy (Buist, 2011).
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From their review, Ross and McLean (2006) concluded that some of the anxiety disorders may have important maternal-fetal implications. Some have been linked to preterm birth, fetal-growth restriction, and poor neurobehavioral development (Van den Bergh, 2005). Children with a history of in utero exposure to maternal anxiety are felt to be at increased risk for various neuropsychiatric conditions such as attention-deficit/hyperactivity disorder (ADHD). Hunter and coworkers (2012) analyzed infants of 60 mothers with an anxiety disorder and found that auditory sensory gating—a reflection of inhibitory neurotransmission—was impaired, particularly in offspring of untreated women. Conversely, Littleton and associates (2007) found no excessive adverse pregnancy outcomes with “anxiety symptoms.” One important exception is their link with postpartum depression (Vythilingum, 2008).
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Anxiety Disorder Treatment
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Anxiety disorders can be effectively treated during pregnancy with psychotherapy, cognitive-behavioral therapy, or medications. Mood and anxiety disorders coexist in more than half of women identified with either diagnosis (Frieder, 2008). Thus, antidepressants listed in Table 61-3 are often the first line of pharmacotherapy.
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Benzodiazepines are also commonly used to treat anxiety or panic disorders before and during pregnancy. Earlier case-control studies linked use of these CNS depressants to a possible increased risk for cleft lip and palate. A metaanalysis of more than 1 million exposed pregnancies, however, did not identify a teratogenic risk (Enato, 2011). Benzodiazepines, especially when taken during the third trimester, can cause neonatal withdrawal syndrome, which persists for days to weeks after delivery.