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Identification and Treatment of Postpartum Depression
We Can and Should Do Better With Identification and Treatment of Postpartum Depression

Released: August 26, 2024

Expiration: August 25, 2025

Jennifer L Payne
Jennifer L Payne, MD
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Last year, the CDC announced that not only is maternal mortality rising in the US and far outpacing rates in other developed nations, but that the number one cause of maternal mortality is mental health conditions. Postpartum depression (PPD) is the most common complication of childbirth, and suicide accounts for 20% of all postpartum deaths. PPD is also associated with infanticide, attachment issues, problems breastfeeding, and decreased use of safety practices. Further, it is consistently associated with lower IQ, slower language development, and behavioral and mental health conditions in exposed children. Thus, identification and treatment are imperative to improve outcomes for mothers and exposed children. Yet, it is estimated that less than 50% of PPD cases are identified, and even fewer receive standard treatments.

Screening and Standard Treatment for PPD
PPD can be identified by using self-rated screening tools that readily identify those who are experiencing symptoms if implemented as a standard part of perinatal care. Barriers including stigma, embarrassment, and lack of awareness can result in false-negative results. Therefore, education about the need to identify and treat PPD should be offered along with screening.

Standard screening tools include the 9-item Patient Health Questionnaire (PHQ-9) and Edinburg Postnatal Depression Scale (EPDS). The Mood Disorder Questionnaire (MDQ) can also be used to screen for an elevated risk of bipolar disorder, which should trigger a referral to a mental health professional when positive. Clinics that screen should have plans in place that lead to treatment when a positive score occurs, including initiating treatment within the clinic or referring out for further care.

Standard treatment approaches for PPD mirror those used for major depressive disorder (MDD). These include antidepressants, with an emphasis on selective serotonin reuptake inhibitors, and psychotherapy, with an emphasis on cognitive behavioral and interpersonal therapies.

Implicating GABAergic Signaling in PPD
The GABAergic system is the major inhibitory neurotransmitter system in the central nervous system that regulates the hypothalamic-pituitary-adrenal (HPA) axis and its response to stress. According to the GABAergic hypothesis of depression, depressive disorders are actually disorders of stress response in which the GABAergic system is underactive in the setting of acute or chronic stress, leading to overactivity of the HPA axis and the clinical emergence of depression. The postpartum period is thought to represent a biologically vulnerable time for the GABAergic system in that levels of neuroactive steroids, such as allopregnanolone, dramatically fall after delivery. These neuroactive steroids are positive allosteric modulators of the GABAA receptor, meaning they increase receptor activity and lead to greater inhibition of the HPA axis. Individuals who develop PPD may have specific vulnerabilities in the GABAergic system that make them susceptible to this disorder after the dramatic fall in allopregnanolone levels post delivery. 

New Pharmacologic Options: Brexanolone and Zuranolone
Two new pharmacologic treatments for PPD have been approved by the FDA. These agents (like allopregnanolone) are positive allosteric modulators of the GABAergic system and thus increase inhibitory GABAergic effects on the HPA axis. The first approved agent was brexanolone, which is given in a continuous intravenous infusion over 60 hours. Administration of brexanolone requires inpatient admission due to the need for continuous pulse oximetry and monitoring for risk of oversedation during infusion. In contrast, zuranolone is an oral agent that is given once daily for 14 days and may be used at home. Although both agents cause sedation, brexanolone can cause more severe cases of oversedation which should be addressed with treatment interruption.

Remarkably, both agents reduce PPD symptoms rapidly with statistically significant differences compared to placebo within 24 hours for brexanolone and 3 days for zuranolone. In addition, unlike standard antidepressant therapies, therapy with brexanolone or zuranolone consists of a short, fixed duration of treatment, with therapeutic response expected to continue in the absence of ongoing administration.

With the addition of these new agents, treatment decisions for patients with PPD have become more complicated. Brexanolone should be reserved for patients with severe PPD, suicidality, or when rapid relief is needed. Standard antidepressants can be used in patients with a history of recurrent MDD who will likely need long-term treatment, particularly if there is a history of response to a particular agent. Zuranolone can be used to treat a first episode of PPD or cases of inadequate or partial response to standard antidepressants during pregnancy or postpartum.

Summary
Diagnosis and treatment of PPD are crucial, not only for patients but for the sake of their exposed children. Identification can be facilitated with the use of self-rated screening tools. Treatment of PPD generally follows treatment practices for MDD but may additionally utilize 2 new agents that increase activity of the GABAergic neurotransmitter system resulting in decreased HPA axis activity to provide rapid and sustained relief of PPD symptoms. As healthcare professionals, we can and should do better in identifying and treating PPD rapidly and effectively.

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