Postpartum Depression

Updated: Aug 16, 2023
  • Author: Saju Joy, MD, MS; Chief Editor: Christine Isaacs, MD  more...
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Overview

Overview

Patients and their caregivers frequently overlook postpartum depression, despite the fact that effective nonpharmacologic and pharmacologic treatments are available for this condition. [1, 2] Untreated postpartum affective illness places the mother and infant at risk and is associated with significant long-term effects on child development and behavior. [3, 4, 5]

Therefore, appropriate screening for and prompt recognition and treatment of depression are essential for maternal and infant well-being and can improve outcomes. [6, 7] The American College of Obstetricians and Gynecologists (ACOG) recommends mental health screening during pregnancy and postpartum, with systems in place to ensure timely evaluation and diagnosis, effective therapy, and appropriate monitoring and follow-up. [8] The American Academy of Pediatrics (AAP) has encouraged pediatric practices to create a system to better identify postpartum depression to ensure a healthier parent-child relationship. [9]

Postpartum psychiatric illness was initially conceptualized as a group of disorders specifically linked to pregnancy and childbirth and thus was considered diagnostically distinct from other types of psychiatric illness. Evidence now suggests, however, that postpartum psychiatric illness is virtually indistinguishable from psychiatric disorders that occur at other times during a woman's life. [3, 2, 4]

Statistics

During the postpartum period, up to 85% of women experience some type of mood disturbance; the AAP estimates that more than 400,000 infants are born each year to mothers who are depressed. [9] Although for most women, symptoms of mood disturbance are transient and relatively mild (ie, postpartum blues), 10-15% of women experience a more disabling and persistent form of depression, and 0.1-0.2% of women experience postpartum psychosis. [10, 11, 12, 13]

Further information

For patient education information, see the Depression Center.

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Risk Factors for Postpartum Mood Disorders

Although predicting who is at risk for postpartum psychiatric illness is difficult, hormonal, psychosocial, and biologic factors are considered to be risk factors for postpartum mood disorders. [3, 7, 14, 15, 16]

Hormonal factors

Although levels of estrogen, progesterone, and cortisol fall dramatically within 48 hours after delivery, [9, 17] women with postpartum depression do not differ significantly from nondepressed women with regard to levels of estrogen, progesterone, prolactin, and cortisol or in the degree to which these hormone levels change. However, affected individuals may be abnormally sensitive to changes in the hormonal milieu and may develop depressive symptoms when treated with exogenous estrogen or progesterone. [17]

Metha et al demonstrated that women with postpartum depression express different transcripts associated with estrogen signaling in the third trimester of pregnancy compared with euthymic women. In fact, the presence of the identified transcripts predicted postpartum depression with 88% accuracy. This may be a way to identify at-risk women in the future. [18]

Psychosocial factors

Women who report inadequate social supports, marital discord or dissatisfaction, or recent negative life events, such as a death in the family, financial difficulties, or loss of employment, are more likely to experience postpartum depression. [14] However, there has been no apparent, consistent association between obstetric factors and risk for postpartum depression. However, data suggest certain adverse perinatal outcomes are associated with increased symptoms of depression and postpartum depression. [19]

Woolhouse et al found intimate partner violence to be common among women reporting postnatal depressive symptoms, which may be an important factor to consider in the management of these patients. [20, 21]

Alternatively, postpartum employment and social support have been associated with a lower rate of depressive symptoms. [22]

Biologic vulnerability

Women with a previous history of depression, a family history of a mood disorder, or depression during the current pregnancy are at increased risk for postpartum depression. [14] A meta-analysis by Zacher Kjeldsen et al found that women who have a family history of any psychiatric disorder have almost two times the risk of postpartum depression as do women without such a history. [23] Furthermore, women with a previous history of postpartum depression or psychosis have a risk of recurrence of up to 90%. [24, 25]

A large population-based study by Silverman et al examined the impact of a depression history on postpartum depression and pre- and perinatal risk factors. Postpartum depression is 20 times more likely to occur in women with a history of depression. The study also found that gestational diabetes was independently associated with increased postpartum depression risk. [26, 27]

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Screening for Postpartum Mood Disorders

Despite multiple contacts with medical professionals during the postpartum period, patients and their caregivers often overlook postpartum affective illness. Too often, postpartum depression is dismissed as a normal or natural consequence of childbirth. [3, 28, 29] In fact, women commonly report the persistence of depressive symptoms for many months before the initiation of treatment. Although symptoms of depression may remit spontaneously, many women are still depressed 1 year after childbirth. [2, 4, 30, 31]

Screening of all mothers during the antepartum and postpartum period is indicated. [7, 12, 30, 32, 33, 34] Screening women for depressive symptoms during pregnancy may also help to identify those women at higher risk for postpartum depression. [3]  ACOG recommends that screening for perinatal depression occur at the initial prenatal visit, later in pregnancy, and at postpartum visits. [8]

Screening tools

The Edinburgh Postnatal Depression Scale (EPDS) is a 10-item, self-rated questionnaire used extensively for detection of postpartum depression. A score of 10 or more on the EPDS or an affirmative answer on question 10 (presence of suicidal thoughts) requires more thorough evaluation. The EPDS may be included in routine well-baby and pediatric visits. [35]

A 3-question version of the EPDS was tested in a pediatric emergency department, and the results showed that the abbreviated version of the EPDS was similar to the full version in screening for postpartum depressive symptoms. Further studies are needed in order to confirm these findings. [36]

A study Venkatesh et al assessed the feasibility of large-scale implementation of universal screening for depression in pregnancy and postpartum using the EPDS. The study demonstrated the feasibility of universal depression screening both antepartum and postpartum using the EPDS as an initial screen followed by mental health referral for further diagnostic evaluation and treatment. Among the 8,985 women in the study, 8840 women (98%) were screened for depression antepartum, and 7780 (86%) were screened postpartum. A total of 576 women (6.5%) screened positive for probable depression: of these, 69% screened positive antepartum and 31% postpartum. The study also found that women who screened positive antepartum were significantly more likely to link to mental health services compared to women who screened positive postpartum. [37, 38]

No increased benefit to using one screening tool over another has been shown. Using the following 2 questions may be as effective as employing more lengthy tools, although they have not been validated in different cultural settings [7] :

  • Over the past 2 weeks have you felt down, depressed, or hopeless?

  • Over the past 2 weeks have you felt little interest or pleasure in doing things?

Depression screening should include systems in place to follow up positive results with subsequent diagnosis and treatment. [3, 13, 28] The Montgomery-Asberg Depression Rating Scale (MADRS) is a common, 10-item, clinician-administered evaluation used following a positive screen, and it accurately differentiates depressed and nondepressed patients, evaluates severity of disease, and detects changes in symptoms over time. [39]

In a study of postpartum depression among urban, low-income mothers, Chaudron et al found that, although the EPDS, Beck Depression Inventory II (BDI-II), and Postpartum Depression Screening Scale (PDSS) have high accuracy in identifying depression, cutoff scores may need to be altered in this population to identify depression more accurately. [40]

In the study, which included 198 mothers of infants up to age 14 months, the sensitivities and specificities of each screening tool were calculated in comparison with diagnoses of major depressive disorder (MDD) or minor depressive disorder (MnDD) made on the basis of a psychiatric diagnostic interview. Optimal cutoff scores for the BDI-II (≥14 for MDD and ≥11 for MDD/MnDD) and EPDS (≥9 for MDD and ≥7 for MDD/MnDD) were lower than currently recommended. [40] For the PDSS, the optimal cutoff score was consistent with current guidelines for MDD (≥80) but higher than recommended for MDD/MnDD (≥77).

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Postpartum Blues

Up to 85% of women experience postpartum affective instability. Rapidly fluctuating mood, tearfulness, irritability, and anxiety are common symptoms. [41, 42, 43, 44]

Symptoms peak on the fourth or fifth day after delivery and last for several days, but they are generally time-limited and spontaneously remit within the first 2 postpartum weeks. [41] Symptoms do not interfere with a mother's ability to function and to care for her child.

Women with more severe symptoms or symptoms persisting longer than 2 weeks should be screened for postpartum depression. [3, 4]

Management

Postpartum blues are typically mild in severity and resolves spontaneously. No specific treatment is required, other than support and reassurance. However, further evaluation is necessary if symptoms persist longer than 2 weeks. [4, 41, 42]

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Postpregnancy Depression

Postpartum depression is more persistent and debilitating than postpartum blues, often interfering with the mother's ability to care for herself or her child. [3] Untreated depression is associated with poor maternal health and intrauterine growth restriction. [3, 45]

The postpartum period is the most vulnerable time for a woman to develop psychiatric illness with postpartum depression occurring in 10-15% of women in the general population. Postpartum depression develops most frequently in the first 4 months following delivery but can occur anytime in the first year. Postpartum depression is no different from depression that can occur at any other time in a woman's life. [3, 46] Women who have suffered 1 episode of major depression following childbirth have a risk of recurrence of about 25%. [47]

Risk factors

Women at highest risk for postpartum depression are those with a personal history of depression, who have suffered a previous episode of postpartum depression, or who have experienced depression during pregnancy. [12, 14] In addition to a history of depression, recent stressful life events and daily stressors, such as childcare, lack of social support (especially from the partner), unintended pregnancy, and insurance status, have been validated as risk factors. [3, 14, 32]

Adolescents in the prenatal and puerperal period have higher rates of depressive symptoms and depression than their adult counterparts; however, their risk of depression is comparable to their nonpregnant peers. [48]

Presentation

Signs and symptoms of postpartum depression are clinically indistinguishable from major depression that occurs in women at other times. [49] Typically, the disorder develops insidiously over the first 3 postpartum months, [3] although postpartum depression may have a more acute onset.

Symptoms of major depression may include depressed mood, tearfulness, anhedonia, insomnia, fatigue, appetite disturbance, suicidal thoughts, and recurrent thoughts of death. [50] In the postpartum period, depression is characterized as intense sadness, anxiety, or despair. This interferes with the mother’s ability to function, causing risk of harm to the mother or infant. [3]

Anxiety is prominent, including worries or obsessions about the infant's health and well-being. [14] The mother may have ambivalent or negative feelings toward the infant. She may also have intrusive and unpleasant fears or thoughts about harming the infant. [51]

Management overview

Postpartum depression manifests along a continuum; some patients may experience relatively mild or moderate symptoms, while others may present with a more severe form of depression, characterized by prominent neurovegetative symptoms and marked impairment of functioning. [2, 47]

Exclude medical causes for mood disturbance (eg, thyroid dysfunction, anemia). The initial evaluation includes a thorough medical history, physical examination, and routine laboratory tests. [30, 47]

Earlier initiation of treatment is associated with a better prognosis, [52] and the severity of the illness should guide treatment. [31, 47] Failure to treat or inadequate treatment may result in deterioration of the relationship between the mother and the baby or the partner. It can also increase the risk of morbidity in both mother and infant, as well as compromise the infant's social and educational development. [53, 54, 55]

Nonpharmacologic treatment strategies are useful for women with mild to moderate depressive symptoms. Individual or group psychotherapy (cognitive-behavioral and interpersonal therapy) are effective. [11, 49, 56, 57] Psychoeducational or support groups may also be helpful. These modalities may be especially attractive to mothers who are nursing and who wish to avoid taking medications. [58]  ACOG recommends that psychotherapy be considered as a first-line therapy for mild to moderate perinatal depression. [59]

Pharmacologic strategies are indicated for moderate to severe depressive symptoms or when a woman’s condition does not respond to nonpharmacologic treatment. Medication may also be used in conjunction with nonpharmacologic therapies.

Inpatient hospitalization may be necessary for severe postpartum depression. [60, 61, 62] A consideration is electroconvulsive therapy (ECT), which is rapid, safe, and effective for women with severe postpartum depression, especially those with active suicidal ideation. [63]

Pharmacotherapy considerations

Antidepressants remain the first line of treatment. [5, 31, 40] However, there are preliminary data to suggest that estrogen, alone or in combination with an antidepressant, may be beneficial.

ACOG recommends that selective serotonin reuptake inhibitors (SSRIs) be used as first-line pharmacotherapy for perinatal depression. Serotonin-norepinephrine reuptake inhibitors (SNRIs) can be considered as reasonable alternatives. Administration of a GABA-receptor–positive modulator can be considered in the postpartum period for moderate to severe perinatal depression with onset in the third trimester or within 4 weeks postpartum. [59]

Sleep disturbances and insomnia have been associated with an increased risk of postpartum depression. Khazaie et al recently demonstrated that treatment of insomnia in the third trimester of pregnancy reduces rates of postpartum depressive symptoms. These findings suggest that screening and treatment of sleep disturbances in pregnancy could reduce the incidence of postpartum depression. [64]

Typically, symptoms start to diminish in 2-4 weeks. A full remission may take several months. If this is the first episode of depression, 6-12 months of treatment is recommended. In partial responders, increasing the medication dosage may be helpful. For women with recurrent major depression, long-term maintenance treatment with an antidepressant is indicated. [31]

Anxiolytic agents such as lorazepam and clonazepam may be useful as adjunctive treatment in patients with anxiety and sleep disturbance.

SSRIs

Selective serotonin reuptake inhibitors (SSRIs) are first-line agents and are effective in women with postpartum depression. Use standard antidepressant dosages (eg, fluoxetine [Prozac] 10-60mg/day, sertraline [Zoloft] 50-200mg/day, paroxetine [Paxil] 20-60mg/day, citalopram [Celexa] 20-60mg/day, or escitalopram [Lexapro] 10-20mg/day).

Adverse effects of this drug category include insomnia, jitteriness, nausea, appetite suppression, headache, and sexual dysfunction.

SNRIs

Serotonin/norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine (Effexor) 75-300mg/day or duloxetine (Cymbalta) 40-60mg/day are also highly effective for managing depression and anxiety.

Adverse effects of SNRIs include those of the SSRIs as well as sleep disturbances, constipation, and abnormal vision.

Although SSRIs have been well studied in the treatment of depression, only recently have randomized controlled trials in the postpartum population become available. These randomized controlled trials demonstrate patients undergoing pharmacologic treatment alone have a higher response and remission with an SSRI compared with placebo. [65] However, patients undergoing psychotherapy did not demonstrate a significant additive benefit when an SSRI was added to their therapy, as compared with placebo. [66]

TCAs

Tricyclic antidepressants (TCAs) (eg, nortriptyline 50-150mg/day) may be useful for women with sleep disturbance, although some studies suggest that women respond better to the SSRI drug category.

Adverse effects of the TCAs include sedation, weight gain, dry mouth, constipation, and sexual dysfunction.

GABA receptor positive modulators

The US Food and Drug Administration (FDA) approved an injection (brexanolone) in 2019 and an oral capsule (zuranolone) in 2023 for postpartum depression. Each is a neuroactive steroid (NAS) GABA-A receptor-positive allosteric modulator (PAM). The GABA system is the major inhibitory signaling pathway of the brain and CNS and contributes to regulating brain function (eg, mood, arousal, behavior, cognition). The mechanism of action for the treatment of PPD is not fully understood, but is believed to be related to positive allosteric modulation of both synaptic and extrasynaptic GABA-A receptors. 

Zuranolone 

Zuranolone (Zurzuvae) is administered orally every evening for 14 days with fat-containing food to enhance absorption. It often causes sedation and CNS depression. 

Approval was supported by a double-blind phase 3 trial in women with severe postpartum depression who were randomized in a 1:1 ratio to receive zuranolone 50 mg/day or placebo for 14 days. The primary endpoint was change from baseline in total score on the 17-item Hamilton Depression Rating Scale (HAM-D) at day 15. Among 196 patients randomized (zuranolone, N=98; placebo, N=98), 170 (86.7%) completed the 45-day study. Zuranolone resulted in statistically significant improvement in depressive symptoms at day 15 with a change from baseline in HAM-D score or -15.6 compared with -11.6 for placebo. Significant improvement in depressive symptoms was also reported at days 3, 28, and 45. [67]    

Brexanolone

Brexanolone (Zulresso) was the first drug to be approved by the FDA for the treatment of postpartum depression. 

The drug is available only through a restricted program called the Zulresso REMS Program that requires the drug be administered by a healthcare provider in a certified healthcare facility. The REMS requires that patients be enrolled in the program prior to administration of the drug. Brexanolone is administered as a continuous intravenous infusion over a total of 60 hours (2.5 days). Because of the risk of serious harm owing to the sudden loss of consciousness, patients must be monitored for excessive sedation and sudden loss of consciousness and have continuous pulse oximetry monitoring.

Approval was based on two randomized, placebo-controlled phase 3 clinical trials that investigated the efficacy and safety of brexanolone injection in 246 women with moderate-to-severe postpartum depression at 30 US centers.

In study 1, Hamilton Rating Scale for Depression (HAM-D) total scores decreased to a significantly greater extent at the end of the 60-hour infusion in the group receiving brexanolone 60 mcg/kg/hour (mean reduction, 19.5 points; P = .0013) and in the group on brexanolone 90 mcg/kg/hour (17.7 points; P = .0252) compared with the placebo group (14 points). Similarly, in study 2, HAM-D scores improved significantly more in the higher-dose group (mean, 14.6 points; P = .016) compared with the placebo group (12.1 points). [68]

Depression scores had not returned to baseline by day 30 in any of the brexanolone groups and remained significantly lower in both treatment groups compared with the placebo group of study 1 at day 30.

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Postpartum Psychosis

Postpartum psychosis is the most severe form of postpartum psychiatric illness. [69] The condition is rare, occurring in approximately 1-2 per 1000 women after childbirth. [10] At highest risk are women with a personal history of bipolar disorder or a previous episode of postpartum psychosis. [70, 71]

Presentation

Postpartum psychosis has a dramatic onset, emerging as early as the first 48-72 hours after delivery. In most women, symptoms develop within the first 2 postpartum weeks. [69, 71] The condition resembles a rapidly evolving manic or mixed episode, with symptoms such as restlessness and insomnia, irritability, rapidly shifting depressed or elated mood, and disorganized behavior. [69, 71]

The mother may have delusional beliefs that relate to the infant (eg, the baby is defective or dying, the infant is Satan or God), or she may have auditory hallucinations that instruct her to harm herself or her infant. [4, 43, 51, 69, 71]

The risks for infanticide and suicide are high among women with untreated postpartum psychosis. [43, 51] Rates of infanticide in this population are as high as 4%. [51]

Management

Puerperal psychosis is a psychiatric emergency that typically requires inpatient treatment. [24, 63, 71] Most patients with postpartum psychosis have bipolar disorder. Acute treatment includes a mood stabilizer (eg, lithium, valproic acid, carbamazepine) in combination with antipsychotic medications and benzodiazepines. [24]

Electroconvulsive therapy (ECT) (often bilateral) is well tolerated and rapidly effective. [62]

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Breastfeeding and Psychotropic Medications

Women who plan to breastfeed must be informed that all psychotropic medications, including antidepressants, are secreted into breast milk. Concentrations in breast milk vary widely. [72] Infant serum blood levels of antidepressants are not typically obtained unless the question of toxicity in the infant arises.

Data on the use of tricyclic antidepressants, fluoxetine, sertraline, and paroxetine during breastfeeding are encouraging, and serum antidepressant levels in the breastfed infant are either low or undetectable. Reports of toxicity in breastfed infants are rare, although the long-term effects of exposure to trace amounts of medication are not known. [5]

Women treated with valproic acid and carbamazepine should avoid breastfeeding, because these agents have been associated with hepatotoxicity in the infant. [5] In addition, avoid breastfeeding in premature infants or in those with hepatic insufficiency who may have difficulty metabolizing medications present in breast milk. [5]

Breastfeeding in women treated with lithium should be pursued with caution because lithium is secreted at high levels in breast milk and may cause significant toxicity in the nursing infant. If the breastfed infant is exposed to lithium in the breast milk, periodic monitoring of lithium levels and thyroid function is indicated. [5, 72]

Data from a lactation study in 12 women indicate that brexanolone is transferred to breastmilk in nursing mothers; however, the relative infant dose (RID) is low, 1-2% of the maternal weight–adjusted dosage. Available data do not suggest a significant risk of adverse reactions to breastfed infants from exposure. [73]

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Prevention of Postpartum Psychiatric Illness

Women at high risk for postpartum illness should be identified before delivery. This includes women with a previous episode of postpartum illness and women with a history of either unipolar or bipolar depression. Women who experience depression during pregnancy should also be considered at high risk for postpartum illness. [14]

In addition to monitoring, women with a history of recurrent depression or a history of postpartum depression may benefit from prophylactic treatment with an antidepressant medication. If antidepressants are not used during pregnancy, they may be initiated shortly before or immediately after delivery to reduce the risk of recurrent illness. [31]

Women with bipolar disorder or a history of postpartum psychosis may benefit from prophylactic treatment with lithium, initiated either before or within 24 hours of delivery. [24, 25]

The prophylactic efficacy of nonpharmacologic interventions in this setting has not been fully assessed, although one study reported lower rates of postpartum depression in a group of women receiving interpersonal therapy for depression during pregnancy. [58]

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Impact of Postpartum Depression on Child Development

A large body of literature suggests that a mother's attitude and behavior toward her infant significantly affects mother-infant bonding and infant well-being and development. Postpartum depression may negatively affect these mother-infant interactions. [3, 74]

Mothers with postpartum depression are more likely to express negative attitudes about their infant and to view their infant as more demanding or difficult. Depressed mothers exhibit difficulties engaging the infant, either being more withdrawn or inappropriately intrusive, and more commonly exhibit negative facial interactions. In addition, mothers with symptoms of depression are more likely to discontinue breastfeeding earlier in the postpartum period. [75, 76] These early disruptions in mother-infant bonding may have a profound impact on child development. [77]

Children of mothers with postpartum depression are more likely than children of nondepressed mothers to exhibit behavioral problems (eg, sleep and eating difficulties, temper tantrums, hyperactivity), delays in cognitive development, emotional and social dysregulation, and early onset of depressive illness. [53] Furthermore, children of depressed mothers have been shown to have slightly increased weight gain at 6 months of life, which may be predictive of increased risk of obesity later in life. [78]

As previously stated, the American Academy of Pediatrics (AAP) has stated that more than 400,000 infants are born each year to depressed mothers. Due to the potential negative effects of postpartum depression on mother-infant bonding and infant well-being and development, the AAP has encouraged pediatric practices to create a system to better identify postpartum depression in order to ensure a healthier parent-child relationship. [79]

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Key Considerations

Postpartum psychiatric illness consists of a highly prevalent group of disorders that affect women during their childbearing years. Although postpartum blues is typically benign and self-limited, postpartum depression and postpartum psychosis cause significant distress and dysfunction. Despite multiple contacts with medical professionals during the postpartum period, puerperal mood disorders are frequently missed, and many women go without treatment.

Untreated mood disorders place the mother at risk for recurrent disease. Furthermore, maternal depression is associated with long-term cognitive, emotional, and behavioral problems in the child. One of the most important objectives is to increase awareness across the spectrum of health-care professionals who care for women during pregnancy and the puerperium so that postpartum mood disorders may be identified early and treated appropriately. Effective pharmacologic and nonpharmacologic therapies are available.

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Questions & Answers

Overview

What is postpartum depression?

What is the prevalence of postpartum depression?

What are the types of risk factors for postpartum depression?

What are the hormonal risk factors for postpartum depression?

What are the psychosocial risk factors for postpartum depression?

What are the biologic risk factors for postpartum depression?

When is screening for postpartum depression indicated?

How are women screened for postpartum depression?

What is the accuracy of screening tools for postpartum depression?

What are the postpartum blues?

How are the postpartum blues treated?

How are postpartum blues and postpartum depression differentiated?

When does postpartum depression typically develop?

What are the risk factors for postpartum depression?

What are the signs and symptoms of postpartum depression?

How is postpartum depression treated?

When is inpatient care indicated for the treatment of postpartum depression?

What is the role of medications in the treatment of postpartum depression?

What is the role of SSRIs in the treatment of postpartum depression?

What is the role of SNRIs in the treatment of postpartum depression?

What is the role of TCAs in the treatment of postpartum depression?

What is the role of brexanolone (Zulresso) in the treatment of postpartum depression?

What is postpartum psychosis?

What are the signs and symptom of postpartum psychosis?

What is the risk of infanticide and suicide in women with untreated postpartum psychosis?

How is postpartum psychosis treated?

What is the safety of breastfeeding in women taking medications for the treatment of postpartum depression?

How is postpartum depression prevented?

How does postpartum depression affect child development?

What are the risks of untreated postpartum depression?

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