Exploring psychotherapeutic issues and agents in clinical practice
Postpartum is defined as the fourth trimester of pregnancy that occurs from birth to 6 weeks and up to 1 year after birth (Kanes et al., 2017). During this time, a woman's body is readjusting from developing the fetus to supporting the born infant, nurturing her family, and returning to preconception state. This process is not an immediate snap back but rather a gradual shifting of physiological, psychosocial, and financial resources requiring external supports.
The Centers for Disease Control and Prevention reported an overall prevalence of postpartum depression in the United States in 2012 of 11.5% based on self-report surveillance up to 270 days after birth, a decline from 2004 of 14.8% (Ko, Rockhill, Tong, Morrow, & Barr, 2017). However, these data are based on self-reported depressive symptoms that range from brief sad episodes to extended clinical depressive symptoms and are not limited to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 2013) criteria for major depressive disorder with peripartum onset. Prevalence was highest among those who were: age 20 to 24; American Indian/Alaskan Native or Asian/ Pacific Islander; had <12 years of education; unmarried; smokers; had three or more stressful life events in the 1 year before birth; gave birth to term, low-birthweight infants; and had infants requiring neonatal intensive care at birth (Ko et al., 2017).
Globally, the prevalence of postpartum depression is estimated at 10% to 20% of all mothers in high-income and low-income countries; the prevalence of severe postpartum depression is 5% to 10% of women (Kanes et al., 2017). In addition, there is the possibility of postpartum depression having a chronic course and transitioning to bipolar depression (Fisher et al., 2019).
The consequences of postpartum depression include parent–child bonding/attachment difficulties, relationship disruptions, disconnections with friends and relatives, sleep disturbance, cognitive and social delays in infants and siblings, onset or worsening intimate partner violence, substance use, depressive psychosis, maternal suicide, and infanticide (Kelsey, 2017; Norhayati, Nik Hazlina, Aniza, & Asrenee, 2016; Park, Brain, Grunau, Diamond, & Oberlander, 2018). Consequences to the infant during post-partum depression include emotional and physical neglect, neurocognitive developmental disturbances, and later diagnosis of attention-deficit, anxiety, and depressive disorders (Duan, Hare, Staring, & Deligiannidis, 2019; O'Connor, Senger, Henninger, Coppola, & Gaynes, 2019; Park et al., 2018). In addition, the newborn may have physical health concerns including low birth weight, slow to gain weight, and lower rate of breastfeeding (Cobrun et al., 2018). Unfortunately, these outcomes may be “blamed” on the mother, which may further complicate her own depression.
The risk of maternal suicide in the United States is 2 per 100,000 women (Palladino, Singh, Campbell, Flynn, & Gold, 2011); however, these statistics are confounded by a mix of diagnoses including psychosis. Infanticide is relatively rare, and the statistics include a wide range of causation, including maternal epileptic psychosis and schizophrenia (Brockington, 2017). In one study, suicidal ideation occurred in approximately 2% of women during the first 6 months postpartum, with symptoms of depression and anxiety within the first 1 to 2 days after birth significantly correlating with later suicidal thinking (Bodnar-Deren, Klipstein, Fersh, Shemesh, & Howell, 2016). Another study reported that pregnant women were more likely than the general population to endorse suicidal ideation, experience intimate partner violence, have less than a high school level of education, and have major depression, which contributed to elevated risk for suicidal ideation (Gelaye, Kajeepeta, & Williams, 2016). Ultimately, postpartum psychiatric disorders, especially depressive disorders within 90 days postpartum, contribute to an elevated 1-year risk of suicide in these women compared to healthy mothers (Moses-Kolko & Hipwell, 2016). Equally troubling is homicide by the intimate partner, in which 45.3% of pregnancy-associated homicides are attributed to a current or former intimate partner (Palladino et al., 2011).
Other factors may contribute to postpartum depression. Stigma and the woman's lack of knowledge about the early signs of depression may prevent her and her partner from seeking help. Many single mothers or those who have low incomes or are marginalized experience pressures of parenting and may fear having their infant taken away if they endorse severe depression (Maxwell, Robinson, & Rogers, 2019). Limited social and tangible support, lack of community resources, inadequate access or availability of professional services, and limited rapport with health care providers also limit help-seeking (Newman, Hirst, & Darwin, 2019). Fear of treatment in mental health settings, worry that their partner will judge them as bad mothers, and concern that their partner will leave them contribute to women not seeking care and under-reporting depressive symptoms in postpartum follow up (Reay, Matthey, Ellwood, & Scott, 2011; Rock, 2019).
Neurobiology of Postpartum Depression
Because of the ethical challenges in performing perinatal biological research, it is not surprising that there is a dearth of well-controlled studies about the neurobiology of perinatal depression. Yet, pharmacological interventions hinge on understanding any unique neurophysiological variation that may be attributed to pregnancy. The prominent theory of depression is the monoamine hypothesis that proposes an imbalance in the monoamine neurotransmitters (i.e., serotonin, norepinephrine, and dopamine), which contributes to the symptoms of depression (Köhler, Cierpinsky, Kronenberg, & Adli, 2016; Pawluski, 2019).
The serotonergic system is the predominant focus in depression and mood disorders, and certainly this is supported by the use of serotonergic medications. This class of drugs blocks the serotonin reuptake inhibitor transporter (SERT) thereby providing more likelihood of serotonin binding to a post synaptic neuron, enhancing firing of serotonin neurons throughout the brain with great variability in the different serotonin receptor subtypes that are affected. Depending on the area in the brain where the receptor subtypes reside, the various selective serotonin reuptake inhibitors (SSRIs) have slightly differential effects on depressive symptoms.
However, the results have been disappointing even after the 35+ years that these drugs have been on the market. Although SSRIs and subsequent serotonin norepinephrine reuptake inhibitors (SNRIs) are safer than the tricyclics and monoamine oxidase inhibitors, the incidence and prevalence of depression have not changed and the incidence of suicide has increased (Curtin, Warner, & Hedegaard, 2016; Ferrari et al., 2013; Frieder, Fersh, Hainline, & Deligiannidis, 2019; GBD 2016 Disease and Injury Incidence and Prevalence Collaborators, 2017; Sakurai, Suzuki, Yoshimura, Mimura, & Uchida, 2017). SSRIs are prescribed to 2% to 8% of pregnant women and approximately 4% of postpartum women (Munk-Olsen, Gasse, & Laursen, 2012), even though there are few large double-blind, placebo-controlled studies with child-bearing women to substantiate their safety and efficacy. There is some concern, however, that during pregnancy there is less serotonin immunoreactivity in women's brains resulting in lower clinical efficacy of serotonergic agents (Lonstein, 2019; Yildiz et al., 2017).
Given the incidence and prevalence of postpartum depression and the serious consequences to the mother, infant, and family, it is essential to identify postpartum depression early and treat it intensely. The first step is early detection through universal screening of all women in the first postpartum visit, usually within 2 weeks after birth (Puryear, Nong, Correa, Cox, & Greeley, 2019; Rock, 2019). However, many women delay or do not attend their postpartum appointments, especially if they are already experiencing depressive and/or anxiety symptoms (Rodin, Silow-Carroll, Cross-Barnet, Courtot, & Hill, 2019; Shim, Stark, Ross, & Miller, 2019). The Edinburgh Postnatal Depression Scale (EPDD) and the Patient Health Questionnaire-9 (PHQ-9) are the most commonly used valid and reliable measures for depressive symptoms in postpartum women (Olin et al., 2017), and they are easily administered by support staff in obstetrics/gynecology and well-baby clinics. When depressive symptoms are identified, professional staff triage patients for mild, moderate, and severe presentations, and provide referrals to mental health services for moderate and severe screens or if suicidal ideation is present (Puryear et al., 2019; Rock, 2019; Wilkinson, Anderson, & Wheeler, 2017).
Tricyclics, noradrenergic dopaminergic reuptake inhibitors (e.g., bupropion), SSRIs, and SNRIs have been found to be safe and effective treatment for depression during and immediately after pregnancy with low risk of teratogenicity, pregnancy complications, neonatal adaptation, or child neurodevelopmental disorders (Lugo-Candelas et al., 2018; Lusskin et al., 2018; Molyneaux, Howard, McGeown, Karia, & Trevillion, 2014). Unfortunately, many women discontinue medication early in treatment, fail to follow through with any form of treatment, or fail to achieve full remission of symptoms over a 12-month period (Fisher et al., 2019; Frieder et al., 2019). Table A (available in the online version of this article) shows the drugs currently approved for treatment of depressive symptoms during the perinatal period.
Antidepressant Drugs Used in the Perinatal Period
Several studies found fluctuations in progesterone throughout pregnancy, reaching highest concentration in the third trimester then abruptly decreasing immediately after childbirth. The hypothesis is that GABAA receptors fail to adapt to this change resulting in postpartum depressive symptoms in at-risk women. In March 2019, the U.S. Food and Drug Administration (FDA) approved brexanolone (Zulresso®), a neuroactive steroid GABAA receptor positive allosteric modulator, which is a novel approach to the treatment of postpartum depression (Kanes et al., 2017). Approval requires a risk evaluation and mitigation strategy (REMS). Without direct serotonergic effect, GABAA acts to slow neural firing, thereby decreasing irregular activation of neurotransmission throughout the central nervous system, and in doing so reduces depressive and anxiety symptoms. Brexanolone is administered intravenously over a 60-hour period at titrated dosages beginning at 30 µg/kg/h for hours 0 to 4, 60 µg/kg/h for hours 5 to 24, if tolerated 90 µg/kg/h for hours 25 to 52, then decreases to 60 µg/kg/h for hours 53 to 56, and 30 µg/kg/h for hours 57 to 60 (Kanes et al., 2017; Meltzer-Brody et al., 2019). This medication is provided during a 2.5-day hospitalization, and the patient must be monitored continuously for excess sedation and sudden loss of consciousness. Mother–baby interaction must be monitored, and breastfeeding suspended during this period. The most common adverse effects include dizziness, somnolence, and headache.
Women who were treated in early studies showed a significant reduction in Hamilton Rating Scale for Depression (HAM-D) scores at the end of 60 hours in two randomized controlled trials; however, the placebo group also had a robust reduction in HAM-D scores. It is unclear why the EPDD was not used to measure depressive symptoms as it is specific to postpartum depression. Because the effect size in both studies was 1 to 2 at a power of 80% (Kanes et al., 2017; Meltzer-Brody et al., 2019), these results indicate brexanolone to be a potentially useful treatment option for high-risk patients even though it is an expensive option. Sage Therapeutics™, the pharmaceutical company that developed brexano-lone, is working on an oral formulation (Frieder et al., 2019).
Other pharmacological treatments studied included vitamin E, which showed mixed results when used as monotherapy (Amini, Jafarirad, & Amani, 2019). Estrogens may have modest value in the treatment of postpartum depression but progestins should be used with caution in the postpartum period (Dennis, Ross, & Herxheimer, 2008).
Most women at risk for postpartum depression are low-income and marginalized individuals who cannot afford expensive pharmacological treatments and tend to not follow through with treatments in general (Krensky & Shannon, 2018). Alternative considerations in alignment with the causative factors include tangible supportive services such as child care, respite infant care, housekeeping and transportation assistance, partner education and supportive services, and mother support groups (Bhat et al., 2017; Lehnig, Nagl, Stepan, Wagner, & Kersting, 2019).
Not surprisingly, a majority of studies on nonpharmacological supportive interventions were found in the nursing literature. Group-based interventions that emphasized acceptance and self-efficacy (Gillis & Parish, 2019) and bundling services, including written educational materials and home visits (Gillis, Holley, Leming-Lee, & Parish, 2019; Kelsey, 2017) were cost-effective, well-received by women and families, destigmatizing, and effective in decreasing depressive symptoms. Introducing mother–baby interaction therapy improved mothers' sensitivity and responsiveness to their infant and promoted maternal functioning and sense of well-being (Horowitz, Posmontier, Chiarello, & Geller, 2019). Technology-assisted programs that included telephone contacts with postpartum women over 12 weeks, brief tips, and supportive electronic messages several times per week for 3 weeks, 3 months, and 6 months demonstrated no significant changes in EPDS but were identified as helpful and nonburdensome (McCarter, Demidenko, Sisco, & Hegel, 2019). Another study added a telephone-based cognitive-behavioral therapy to increase new mothers' confidence in their maternal role, enhance their emotional control, and increase their sense of support (Ngai & Chan, 2019).
Summary and Recommendations
Postpartum depression is a serious disorder that has profound physical, emotional, and developmental consequences to both the mother and baby. Severe postpartum depression is a risk for later development of bipolar disorder (Freeman et al., 2018; Sharma, Doobay, & Baczynski, 2017). Early identification through universal screening is essential in providing effective treatment and referral for continuing care and prevention of greater harm. Pharmacological treatment continues to be the standard of treatment for moderate to severe depression with SSRIs as the safest and most effective medication. Most recently, brexanolone intravenous infusion, a novel pharmacological approach, received FDA approval with REMS. Use of psychotherapy, group supportive therapy, and assistive strategies are safe and efficient approaches adjunctive to pharmacotherapy or as monotherapy for mild postpartum depression and should be considered as first-line nursing treatment.
Psychiatric–mental health nurse generalists can provide supportive services such as:
- universal screening for postpartum depression at follow up maternal and child care appointments;
- support group therapy for new mothers and their infants;
- written instructions about the signs of postpartum depression, effects on the woman and her family, and resources;
- brief tips and peer support sessions with mothers regarding coping with stresses of new motherhood while patients are waiting for follow-up maternal and childcare appointments; and
- home visits to new mothers within the first 6 weeks after childbirth.
Advanced practice psychiatric– mental health nurses can provide screenings, referrals, and mental health treatment for new mothers and their family as well as:
- focused assessments for high-risk pregnant women and new mothers;
- brief cognitive-behavioral and interpersonal psychotherapies for women and their partners where postpartum depression is identified;
- hold support and educational groups for high-risk mothers, marginalized women, and those with mild depressive symptoms; and
- provide pharmacotherapy and medication management for women with moderate to severe postpartum depression.
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Antidepressant Drugs Used in the Perinatal Period
|Generic (Brand)||FDA Pregnancy Categorya,b||Fetal/Neonate Complications||Breastfeeding Considerations|
|Bupropion (Wellbutrin®)||C||No increased risk of congenital malformations||Bupropion and its metabolites present in human breasmilk. Exercise caution. Plasma levels undetectable in infants. One case of seizure in a 6-month-old.|
|Citalopram (Celexa®)||C||Nonteratogenic effects include complications requiring prolonged hospitalization, respiratory support, and tube feeding upon delivery. Other clinical findings include respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying.c||Excreted in human breast milk. Exercise caution. Some reports of infants experiencing excessive somnolence, decreased feedings, and weight loss.|
|Desvenlafaxine (Pristiq®)||C||Neonates exposed to SNRIs or SSRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Nonteratogenic effects include respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying.c||Potential for serious adverse reactions in breastfeeding infants.|
|Duloxetine (Cymbalta®)||C||Neonates exposed to SNRIs or SSRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Nonteratogenic effects include respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying.c||Safety is unknown; therefore, breastfeeding is not recommended.|
|Escitalopram (Lexapro®)||C||Nonteratogenic effects include complications requiring prolonged hospitalization, respiratory support, and tube feeding upon delivery. Other clinical findings include respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying.c||Excreted in human breast milk. Exercise caution. Some reports of infants experiencing excessive somnolence, decreased feedings, and weight loss.|
|Fluoxetine (Prozac®)||C||Fetal cardiovascular malformations; nonteratogenic effects include complications requiring prolonged hospitalization, respiratory support, and tube feeding upon delivery. Other clinical findings include respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying.c||Excreted in human breast milk; therefore, breastfeeding is not recommended. Studies show mixed results in nursing infants: some show no adverse effects and others report increased crying, sleep disturbance, vomiting, and watery stools.|
|Fluvoxamine (Luvox®)||C||Increased embryofetal death, increased incidence of fetal eye abnormalities, decreased fetal body weight; nonteratogenic effects include complications requiring prolonged hospitalization, respiratory support, and tube feeding upon delivery. Other clinical findings include respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying.c||Secreted [Query #1: Excreted?] in human breast milk. Potential for serious adverse effects from exposure in the breastfeeding infant should be taken into consideration when deciding to continue [Query #2: breastfeeding?] or discontinue use [Query #3: of the drug?].|
|Mirtazapine (Remeron®)||C||No evidence of teratogenic effects.||May be excreted in [Query #4: human?] breast milk. Exercise caution.|
|Nefazodone (Serzone®)||C||Premature birth, infant drowsiness and lethargy, infant failure to thrive, and poor temperature control.||Unknown whether nefazodone or its metabolites are excreted in human breast milk. Exercise caution.|
|Paroxetine (Paxil®)||D||Epidemiological studies have shown that infants exposed to paroxetine in the first trimester have an increased risk of congenital malformations, particularly cardiovascular malformations; nonteratogenic effects include complications requiring prolonged hospitalization, respiratory support, and tube feeding upon delivery. Other clinical findings include respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying.c||Secreted [Query #5: Excreted?] in human breast milk. Exercise caution.|
|Sertraline (Zoloft®)||C||Nonteratogenic effects include complications requiring prolonged hospitalization, respiratory support, and tube feeding upon delivery. Other clinical findings include respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying.c||Unknown whether, and in what amount, sertraline or its metabolites are excreted in human breast milk. Exercise caution.|
|Trazodone (Oleptro®)||C||Increased fetal resorption, increase in congenital anomalies, may cause fetal harm.||Not recommended|
|Venlafaxine (Effexor®)||C||No teratogenic effects reported; nonteratogenic effects include respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying.||Excreted in [Query #6: human breast?] milk, potential for serious adverse reactions in nursing infants. A decision should be made to discontinue breastfeeding or the drug.|