Navigating the Shadows: Understanding the Psychology and Pharmacology of Treating Postpartum Depression

The dream of bringing a child into the world can be idyllic: The 9-month gestation period can be filled with anticipation and discovery, culminating in a scene filled with overwhelming joy and excitement. However, for many new mothers, when the frenzy and elation of the delivery room have dissipated, a postpartum period clouded by a silent and pervasive adversary can follow: postpartum depression (PPD).

Postpartum depression, which can also be called peripartum depression or major depressive disorder (MDD) with peripartum onset, is a specifier of MDD with PPD symptoms typically occurring during pregnancy or the 4 weeks following delivery. In the United States, roughly 1 in 8 women reported experiencing symptoms of postpartum depression, according to a CDC study published in May 2020.¹ Worldwide, roughly 10% of pregnant mothers and 13% of postpartum women experience some form of depression, according to a report from the World Health Organization published in June 2019.²

PPD can be debilitating and can manifest in a variety of ways following the birth of a child.³ Symptoms range from deep and intense feelings of sadness, hopelessness, and anger to loss of appetite, restlessness, shame, and guilt. PPD may also present with anxiety, panic attacks, and intrusive thoughts that can be very distressing. While PPD most commonly affects new mothers, it can also occur in new fathers, presenting as irritability, loss of appetite, and depressed mood.⁴

Image Credit: © Nadezhda - stock.adobe.com

The timing of PPD onset varies. In the first few days after delivery, up to 80% of mothers experience the “baby blues,” which is defined as a period of mood lability, tearfulness, anxiety, and restlessness. For many mothers, these symptoms abate; however, a proportion of women will experience a worsening of these symptoms that develop into PPD. Some people also experience perinatal depression, a form of PPD that can begin while a mother is still pregnant.

There are a variety of treatment options for those suffering from PPD, most often through a holistic approach combining psychotherapy and medications.³ Cognitive behavioral therapy can be an effective treatment method to manage the distressing thoughts and feelings associated with PPD.⁵ Pharmacological interventions like antidepressants, such as selective serotonin reuptake inhibitors, and other medications can also play an important role in reducing the severity of PPD.

For adults experiencing the often debilitating effects of PPD, those options are now expanding. Last year, in a breakthrough for the treatment of PPD, the FDA approved zuranolone (Zurzuvae; Sage Therapeutics), the first oral medication designed specifically to treat PPD.⁶ Previously, the only medication FDA approved to treat PPD was an intravenous treatment administered in a hospital or health care facility.⁷

Zuranolone belongs to a class of drugs called neurosteroids.⁸ It acts on the gamma-aminobutyric acid (GABA) receptors in the brain, modulating their activity.⁹ Zuranolone aims to restore the balance of neurotransmitters, lessening the symptoms of depression and allowing new mothers to return to their normal lives. By contrast, antidepressants may take 4 to 6 weeks to see the full benefit, while the onset of zuranolone towards improving depressive symptoms is much more rapid. Specifically, the rapid improvement often seen with zuranolone is beneficial for new mothers who are acclimating to their new identity while caring for an infant; faster symptom relief means that they don’t miss out on important bonding time with their infants and they are more quickly able to adjust to their new role, which is critical not only for the mothers but also for their family and communities as well.

Another factor to consider with treatment options for PPD, and specifically with medication interventions, is the effect on a mother’s ability to breastfeed. Many medications limit or completely eliminate breastfeeding as an option because of the potential impact on the baby. Combined with other mental health challenges associated with PPD, this can have a profound effect on physical and emotional bonding for a parent and their new baby. Zuranolone, by comparison, has been shown to have little to no impact on a mother’s ability to safely breastfeed.¹⁰

The most notable benefit of zuranolone for patients is the near-immediate improvement in symptoms of PPD—the drug has been shown to be effective within 3 days of treatment initiation. Previous PPD treatments can take weeks or months to take effect, so zuranolone has cut that time dramatically. In addition, because zuranolone is an oral medication, it does not require the mother to be admitted to a hospital for administration. Allowing mothers to remain at home with their family can promote wellbeing and reduce separation between mom and baby, making the treatment more accessible and feasible for many people.

The period after birth is vital for new parents to bond with their baby, helping to stimulate brain development and growth that can have lifelong effects.¹¹ Spending that time free from the pain of depression can improve lives. The development of novel treatment options like zuranolone—providing rapid improvement in just days—combined with evidence-based psychotherapy, holds tremendous promise for reducing the suffering of those experiencing PPD.

About the Authors

Shari Allen, PharmD, BCPP, is a clinical pharmacist with a specialty in psychiatry in addition to serving as an associate professor at Philadelphia College of Osteopathic Medicine (PCOM) Georgia, where she instructs on the therapeutics of central nervous system disorders in Integrated Therapeutics.

Alexa Bonacquisti, PhD, PMH-C, is a licensed psychologist with expertise in reproductive health psychology and an assistant professor at PCOM. Her clinical work focuses on treating women across the lifespan, with an emphasis on the psychological aspects of the reproductive journey.

REFERENCES

1. Bauman BL, Ko JY, Cox S, et al. Vital Signs: Postpartum Depressive Symptoms and Provider Discussions About Perinatal Depression — United States, 2018. MMWR Morb Mortal Wkly Rep. 2020;69(19);575-581. doi:10.15585/mmwr.mm6919a2
2. World Health Organization. Mental Health and Substance Use. June 24, 2019. Accessed May 6, 2024. https://www.who.int/teams/mental-health-and-substance-use/promotion-prevention/maternal-mental-health
3. Mayo Clinic Staff. Postpartum depression. Mayo Clinic. November 24, 2022. Accessed May 6, 2024. https://www.mayoclinic.org/diseases-conditions/postpartum-depression/symptoms-causes/syc-20376617
4. Scarff JR. Postpartum Depression in Men. Innov Clin Neurosci. 2019;16(5-6):11-14.
5. Huang L, Zhao Y, Qiang C, Fan B. Is cognitive behavioral therapy a better choice for women with postnatal depression? A systematic review and meta-analysis. PLoS One. 2018;13(10):e0205243. doi:10.1371/journal.pone.0205243
6. FDA Approves First Oral Treatment for Postpartum Depression. News Release. FDA; August 04, 2023. Accessed May 6, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-treatment-postpartum-depression
7. Cornett EM, Rando L, Labbé AM, et al. Brexanolone to Treat Postpartum Depression in Adult Women. Psychopharmacol Bull. 2021;51(2):115-130.
8. National Center for Biotechnology Information. PubChem Compound Summary for CID 86294073, Zuranolone. Accessed May 6, 2024. https://pubchem.ncbi.nlm.nih.gov/compound/Zuranolone
9. Allen MJ, Sabir S, Sharma S. GABA Receptor. StatPearls [Internet]. Treasure Island (FL): StatPearls; January 2024. Accessed May 6, 2024. https://www.ncbi.nlm.nih.gov/books/NBK526124/
10. Drugs and Lactation Database (LactMed). Bethesda, MD: National Institute of Child Health and Human Development; 2006. Zuranolone. Updated September 15, 2023. https://www.ncbi.nlm.nih.gov/books/NBK594292/
11. Winston R, Chicot R. The importance of early bonding on the long-term mental health and resilience of children. London J Prim Care (Abingdon). 2016;8(1):12-14. doi:10.1080/17571472.2015.1133012