Background
Postpartum depression (PPD) (sometimes referred to as pregnancy-related mood disorder) is one of the most common and serious postpartum conditions, affecting 10% to 20% of mothers within the first year of childbirth. Studies have found that up to 50% of women with PPD are undiagnosed. Risk factors include a prior history of depression (approximately 25% to 30% risk of recurrence), including PPD and depression during pregnancy. Other risk factors include recent stressful life events, lack of social support, and unintended pregnancy. Women who are economically stressed, disadvantaged, low income, or black are at a higher risk of PPD, as well. Moreover, studies of economically disadvantaged families have shown that approximately 25% of women will have ongoing depressive symptoms that last well beyond the initial postpartum year.
Treatment approaches include nonpharmacological therapies, such as interpersonal psychotherapy or cognitive behavioral therapy, pharmacological therapies, or a combination of both. Antidepressant medications are one of the most commonly prescribed pharmacologic treatments of PPD. The mother and her provider should work together to make an individually tailored choice. Breastfeeding mothers may be concerned about continuing and/or starting medication for PPD. Some providers are reluctant to prescribe for lactating mothers, due to lack of information about antidepressants and breastfeeding. The risks of untreated depression, the risks of the medication to the breastfeeding dyad, and the benefits of treatment must be fully considered when making treatment decisions.
This protocol will discuss the spectrum of disease, emphasize the importance of screening, and provide evidence-based information recommendations for treatment of PPD in breastfeeding mothers.
Spectrum of Disease
There has been controversy about whether PPD is a distinct entity. In the Diagnostic and Statistical Manual of Mental Disorders , fourth and fifth editions (DSM-IV and V, respectively), PPD is considered a subtype of major depression, and there is an associated specifier to denote onset in the postpartum period. The newer DSM-V expanded the definition of PPD to include onset of symptoms during pregnancy through 4 weeks postpartum. Diagnosis may be further complicated by other comorbid conditions, including anxiety and bipolar disorder. Postpartum mood disorders are common in the postpartum period. However, they differ according to timing and severity of symptoms and encompass a wide range of disorders. “Postpartum blues” is a condition characterized by emotional changes, insomnia, appetite loss, and feelings of being overwhelmed that can affect 30% to 80% of women. It is a transient condition that usually peaks on postpartum day 5 and resolves by day 10. Unlike PPD, postpartum blues does not adversely affect infant care.
“PPD” is a major depressive episode that impairs social and occupational functioning. Symptoms cause significant distress and can include suicidal ideation. If untreated, symptoms may persist beyond 14 days and can last several months to a year.
“Postpartum psychosis” is a psychiatric emergency and is characterized by paranoia, hallucinations, delusions, and suicidal ideation, with the potential risk of suicide and/or infanticide. It can occur in one to three of every 1000 deliveries and usually has a rapid onset (within hours to a few weeks) after delivery. Women with postpartum psychosis may have a prior history of postpartum psychosis or bipolar disorder, but in some women there is no prior psychiatric history. Approximately 25% to 50% of women with bipolar disorder are at risk of developing postpartum psychosis.
“Postpartum intrusive thoughts” and “obsessive compulsive disorder” commonly occur in women. With a wide range of severity of symptoms, they are concerns for postpartum women. Intrusive or obsessive thoughts are unwelcome and involuntary thoughts, images, or unpleasant ideas that may become obsessions. These thoughts are usually upsetting or distressing to the woman, and they can be difficult to manage or eliminate.
Screening for PPD
Research confirms that most mothers (80%) are comfortable with the idea of being screened for depression. Internationally, guidelines and authorities recommend screening for PPD.
Although definitive evidence of benefit is limited, the American College of Obstetricians and Gynecologists recommends that clinicians screen patients at least once during the perinatal period for depression and anxiety symptoms using a standardized, validated tool. For the first time, a large U.S. multicenter study of screening and follow-up care for PPD in a family practice setting has shown improved maternal outcomes at 12 months. (I) (Quality of evidence [levels of evidence I, II-1, II-2, II-3, and III] is based on the U.S. Preventive Services Task Force Appendix A Task Force Ratings and is noted throughout this protocol in parentheses.)
Most physicians and maternal/child health care providers recognize the detrimental effects of PPD and agree that screening new mothers is within the scope of their practice. The American Academy of Pediatrics and the U.S. Surgeon General’s Office recognize and call for the early identification and treatment of mental health disorders, including PPD. It is important that screening for PPD be done systematically on a global scale, as detection and treatment have been shown to be beneficial in many countries. (I)
Screening Instruments
The screening instrument that has been most studied throughout the world is the Edinburgh Postnatal Depression Scale (EPDS). The EPDS is free and considered to be in the public domain. It is available in many languages and has cross-cultural validity. It has 10 questions to be completed by the mother based on symptoms over the past 7 days and takes approximately 5 minutes to complete. There are multiple points of contact in which screening can occur. In well-child-care visits, EPDS screening could occur during the 1-, 2-, 4-, and 6-month visits. , The cesarean section incision check at 2 weeks and the postpartum visit at 4 to 8 weeks are also important screening opportunities. The EPDS can be readily administered and has demonstrated validity to detect postpartum mood disorders at as early as 4 to 8 weeks postpartum. (II-3) A score of 10 or higher or a positive response to Question 10 about suicidal thoughts is considered positive and indicates that the mother may be suffering from a depressive illness of varying severity. (II-3) Providers caring for the infant must refer a mother with a positive screen for appropriate care.
Effects of PPD
In addition to the obvious adverse effects on the mother, PPD affects the child, spouse and/or partner, and other family members. It can cause family dysfunction, prevent effective mother-baby bonding, lead to early cessation of breastfeeding, and adversely affect infant growth and brain development. Rates of paternal depression are higher when the mother has PPD, which can compound the negative effects of depression on children. Infants of depressed mothers show less engagement and eye contact with their mother and are at risk for failure to thrive, attachment disorder, and development delay.
A shared neuroendocrine mechanism among maternal mood, oxytocin levels, and maternal affect during breastfeeding has been demonstrated. This strengthens the position that women with depression would benefit from early and sustained support with breastfeeding. Likewise, women with negative early breastfeeding experiences may be more likely to have depressive symptoms at 2 months postpartum; thus women experiencing breastfeeding difficulties should be screened for depressive symptoms.
Clinical Approach to Treating PPD
Once a woman is identified as being at risk for PPD, treatment choices must be considered and offered to her. For mild to moderate depression in the breastfeeding mother, psychology/cognitive behavioral therapy, if available, should be considered as first-line therapy. (II-2)
Treatment
Nonpharmacological
Psychological Therapy
Psychological therapy is effective for the treatment of major depressive disorder in the postpartum period, and different types of therapies seem equally effective. (I) There are three approaches to the administration of psychological therapy in the postpartum period, including interpersonal therapy, cognitive behavioral therapy, and psychodynamic psychotherapy (nondirective therapy). Nonpharmacological treatment is not harmful to the infant and is often acceptable to mothers with PPD.
Infant Feeding Considerations
Breastfeeding difficulties and perinatal depression symptoms often present together, and management of depression should include a discussion of the mother’s experience of breastfeeding. Some mothers with depression find that breastfeeding enhances bonding and improves their mood, whereas others find breastfeeding to be difficult. For dyads struggling with milk production and latch issues, efforts should be undertaken to simplify feeding plans to ensure that mother and infant have time to enjoy one another. The demands of nighttime breastfeeding can be challenging for mothers for whom interruption of sleep is a major trigger for mood symptoms. In these cases, it may be helpful to arrange for another caregiver to feed the infant once at night, allowing the mother to receive 5 to 6 hours of uninterrupted sleep. A caregiver may also bring the infant to the mother to feed at the breast and then assume responsibility for settling the baby back to sleep, thereby minimizing maternal sleep disruption. (III)
Medications
If psychological/cognitive behavioral therapy is unavailable, symptoms are severe, or mothers refuse this therapy, antidepressants are an effective option. Many factors must be considered when choosing an antidepressant during breastfeeding. All antidepressants are present in human milk to some extent. Data to inform clinical decisions are derived primarily from case reports or case series. Therefore the initial treatment choice should be based on an informed clinical approach that takes into account the patient’s previous treatments for depression, especially use during the pregnancy, the targeted symptoms, family history of depression, and their experiences with antidepressants, current and past medical disorders, current medications, allergies, side effects of the medications, and maternal wishes. An individualized risk-benefit analysis of the treatments must be conducted ( Table J-18 ). (I)
| Class | Drug | Dosage per Day | Indications | Maternal Side Effects | Infant Exposure Effects | Comments |
|---|---|---|---|---|---|---|
| SSRIs | Citalopram | 10-60 mg | Depressive or anxiety disorders; may be prescribed for fibromyalgia, neuropathic pain, or premenstrual symptoms and disorders | Gastrointestinal distress, headaches, sexual dysfunction, nervousness, and sedation | All SSRIs have been detected in human milk. Paroxetine and sertraline have not exceeded the recommended 10% maternal level and are usually undetectable in infant serum. Fluoxetine and citalopram have exceeded the 10% maternal level. The infant adverse events reported include uneasy sleep, colic, irritability, poor feeding, and drowsiness. The FDA indicated that fluoxetine should not be used by nursing mothers | Sertraline is the most likely SSRI to be prescribed. It’s low to undetectable in milk and has a relative safety profile in pregnancy. Long-term effects on neurobehavior and development from exposure to any SSRI during pregnancy and lactation have a limited evidence base, but more recent studies are relatively reassuring |
| Escitalopram | 10-20 mg | |||||
| Fluoxetine | 10-80 mg | |||||
| Fluvoxamine | 50-300 mg | |||||
| Paroxetine | 10-60 mg | |||||
| Sertraline * | 25-200 mg (usually a daily dose). Start at 25 mg for 5-7 days, then increase to 50 mg | |||||
| SNRIs | Venlafaxine | 37.5-225 mg | Depression | Galactorrhea | Venlafaxine and its active metabolite are in milk, and its metabolite can be found in the plasma of most breastfed infants, but no proved drug-related side effects. Monitor for sedation and adequate weight gain | Sporadic case reports for these medications. Limited number to report significant outcomes for nursing infants |
| Duloxetine | 20-120 mg | |||||
| Desvenlafaxine | 50-100 mg | |||||
| Other antidepressants (norepinephrine/dopamine/serotonin reuptake blockers) | Bupropion | 150-450 mg | Depression | Dose-dependent drowsiness, dry mouth, increased appetite, weight gain, and dizziness | Very limited data, ranging from asymptomatic with undetectable infant serum levels to concerns with irritability and seizures | Use is not a reason to discontinue breastfeeding. However, another drug may be preferred |
| Mirtazapine | 15-30 mg | Limited infant data; no adverse side effects noted | ||||
| TCAs/heterocyclics | Amitriptyline, amoxapine, clomipramine, desipramine, doxepin, maprotiline, nortriptyline, protriptyline, and trimipramine | Nortriptyline, 30-50 mg/day, in 3-4 divided doses, or the total daily dosage may be given once a day | Depression and anxiety disorders; often used in low doses for sleep and chronic pain | Hypotension, sedation, dry mouth, urinary retention, weight gain, sexual dysfunction, and constipation. In an overdose, these medications can cause cardiac arrhythmias and death | Only nortriptyline has a sufficient number of reported cases to comment on its use during lactation: it is generally undetectable in infant serum; no adverse events have been reported. Use of doxepin is often cautioned because of a case report of hypotonia, poor feeding, emesis, and sedation in a breastfeeding infant that resolved after discontinuation of nursing | One of the older classes |
| Herbal/natural | St. John’s wort ( Hypericum perforatum ) contains hypericin and hyperforin as well as flavonoids such as quercetin | 300 mg | Depression | One study found a slightly increased frequency of colic, drowsiness, and lethargy among breastfed infants but none required treatment | Both hypericin and hyperforin are poorly excreted into human milk | Has been used for the treatment of mild to moderate depression for many years, especially in Europe. Its use as a treatment for depression is controversial in the United States |
| Omega-3 fatty acids | Depression during pregnancy and the postpartum period | Appears to be of little risk to mothers and infants. The primary negative side effect is the “fishy smell” | Lack of sufficient evidence at this time to consider it a treatment for depression | |||
| Antipsychotic | Quetiapine | Start at 25 mg, titrate. Maximum dose, 600 mg | Bipolar disorder, schizophrenia | Sedation | Sedation | |
| Mood stabilizer | Lithium | Start at 300 mg, titrate as per LI levels. Maximum dose, 900-1200 mg | Diarrhea, vomiting | Elevated TSH | Dosing is dictated by lithium blood levels in the mother, which need to be regularly checked |
* Best safety profile of selective serotonin reuptake inhibitors (SSRIs) in lactation.
Clinical Factors Affecting Antidepressant Choice
- •
Obtain a psychiatric history with a focus on previous episodes of mood and anxiety disorders and effective treatment interventions. If psychotropic medications were used, determine what treatments were effective with a tolerable side effect profile. Past treatment response is often the best predictor of future response. (II-2)
- •
Obtain a family history of psychiatric illness and treatment response. An immediate family member’s history may be indicative of the mother’s treatment response. (II-2)
- •
Consider the primary symptoms that the medication will be targeting and its potential side effect profile.
- •
Choose psychotropic medications with an evidence base in lactating women. Older medications with available data are preferred over newer antidepressants with limited safety information.
Choosing an Antidepressant During Lactation
When considering the use of any medication in a lactating woman, providers must consider both maternal and infant safety factors. The medication must be both efficacious for the mother and safe for the infant. Although infant serum levels of psychotropic medications are the most accurate measures of infant exposure, it is often difficult to measure infant serum levels in routine clinical practice. However, factors affecting the passage of medication into human milk must be considered, including the following:
- 1.
Route of drug administration and pharmacokinetics :
- •
absorption rate
- •
half-life and peak serum time
- •
dissociation constant
- •
volume of distribution
- •
molecular size
- •
degree of ionization
- •
pH of plasma (7.4) and milk (6.8)
- •
solubility of the drug in water and in lipids
- •
binding to plasma protein
- •
- 2.
Amount of drug received by the infant in human milk :
- •
milk yield
- •
colostrum versus mature milk
- •
concentration of the drug in the milk
- •
how well the breast was emptied during the previous feeding
- •
the infant’s ability to absorb, detoxify, and excrete the drug
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Up-to-date information about medication use during lactation is easily available from the Internet on TOXNET LACTMED ( http://toxnet.nlm.nih.gov.easyaccess2.lib.cuhk.edu.hk/newtoxnet/lactmed.htm ) (available in English) and e-lactancia ( http://e-lactancia.org/ ) (available in both English and Spanish).
Most antidepressant studies provide milk levels, or a milk to mother’s plasma ratio, that are not constant and depend on factors such as dose, frequency, duration of dosing, maternal variation in drug disposition, drug interactions, and genetic background. Few studies provide infant serum levels, although they are the best measure of infant exposure.
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