The Critical Role OB/GYNs Play in Postpartum Depression Diagnosis and Treatment

For pregnant and postpartum women, the perinatal period is often a time filled with joy - but it’s also one of enormous change. In addition to the expected physical changes, the range of hormonal, emotional, and psychological shifts that occur during pregnancy and after childbirth may bring intense, unfamiliar feelings.^1,2 In some cases, these symptoms can interfere with a new mother’s ability to care for and bond with her newborn.¹

Symptoms of depression that are present for at least two weeks and start during the perinatal period may be indicative of postpartum depression (PPD).³ Approximately one in eight women who give birth in the U.S report experiencing depression symptoms.^4,5 The prevalence of postpartum depression symptoms in the U.S. was reported to be higher among BIPOC women in survey data from 2018.⁵ Adequate postpartum care, such as screening for depression, has also been significantly less likely to be received by racial and historically marginalized groups, Medicaid-insured patients, and rural patients.⁶

“PPD has been historically underrecognized.^7,8 As a clinician, I see firsthand the significant long-term risks and the devastating impact it may have on our patients,” says Dr. Camille Hoffman, Board-certified Obstetrician Gynecologist (OB/GYN) Maternal-Fetal Medicine (MFM) Specialist and Professor of Maternal-Fetal Medicine at the University of Colorado. “Unfortunately, women who suffer from PPD may minimize or ignore their symptoms, for fear of stigma, judgment from others, or even concerns their baby could be taken away if they speak up.¹ We must address the stigma women with PPD face in order to provide our patients with effective ways to help manage their symptoms.”

Considering the risks and underdiagnosis associated with PPD, screening, education, anticipatory guidance, and conversations around symptoms are important first steps.^7,9 The entire care team can play meaningful roles in PPD care – and because OB/GYNs are frequently the main clinicians during pregnancy and postpartum, they can be pivotal in PPD screening, diagnosis, and treatment.⁷ The number of treatment options specifically indicated for adults with PPD has been increasing, giving clinicians and their patients more options to manage this condition.^10,11

Symptoms and the risk of underdiagnosed PPD

As many clinicians know, PPD is a serious medical condition that typically requires treatment.^3,10 PPD is distinct from the baby blues, in which temporary symptoms – mood changes, crying spells, anxiety, and difficulty sleeping – generally occur and resolve on their own within two weeks postpartum.¹ In contrast, PPD symptoms are longer lasting, present as a change in daily functioning, and may include depressed mood, loss of interest or pleasure in activities, and feelings of worthlessness or guilt.³ Women with PPD may also have trouble bonding with their baby, have persistent doubts about their ability to care for them, or may even have thoughts of harm.^3,12

The onset of PPD symptoms can occur during pregnancy or the postpartum period, which is considered by the American College of Obstetrics and Gynecology (ACOG) as 12 months after delivery.^3,7 Identifying symptoms early and accurately is critical.^7,9

“We need to screen and diagnose PPD quickly and effectively since this condition can have a detrimental impact,” says Dr. Hoffman.^7,9

Employing screening tools early and often is key

ACOG emphasizes the urgency of diagnosing women with PPD and recommends clinicians begin education and discussion of symptoms early on in pregnancy.^7,9 ACOG guidelines, updated in 2023, advise providers to screen patients at their initial pregnancy visit, later in pregnancy, and at postpartum visits.⁷

ACOG recommends screening patients with standardized, validated instruments like the Edinburgh Postnatal Depression Screen (EPDS) or Patient Health Questionnaire (PHQ-9).⁷ “I use these tools early and often with my patients,” Dr. Hoffman says, “because they offer effective ways for me to monitor changes throughout the pregnancy and perinatal period, and they are also a great first step in beginning crucial conversations on maternal mental health.”⁷

Across visits, clinicians should work to build a trusting relationship with their patients and encourage open communication around potential PPD symptoms as an important part of care.^7,9 Because of the stigma around PPD, patients may hesitate to discuss their symptoms.^1,13

“We’re seeing maternal mental health be talked about in the public more than ever before, and I hope this helps reduce the stigma – but sadly, there remains a lot of taboo around PPD,” says Dr. Hoffman. “By educating women about the symptoms of PPD throughout their pregnancy and into birth, new mothers and their support systems can be empowered to have these difficult conversations earlier in their motherhood journey, share their PPD symptoms, and get the help they need sooner.”

Treating PPD

While perinatal care includes a number of healthcare providers who can screen for PPD (e.g., pediatricians and primary care providers), OB/GYNs, midwives, and nurses are often critical in diagnosis and treatment.^7,14 A patient may be more comfortable confiding in and receiving care from the team she developed a relationship with during pregnancy.⁹

There are several treatment approaches for PPD, including psychotherapy and medication, along with non-clinical options like support groups and self-care.¹⁰ One available option, ZURZUVAE®(zuranolone) CIV, is the first and only FDA-approved oral, 14-day treatment specifically indicated for adults with PPD, for use alone or as an adjunct to oral antidepressant therapy.¹⁵ ZURZUVAE 50 mg (two 25-mg capsules) should be taken orally, once daily in the evening for 14 days with fat-containing food.¹⁵ The dose may be reduced to 40 mg (two 20-mg capsules) once daily in the evening (i.e., for a total of 14 days of ZURZUVAE treatment) if central nervous system (CNS) effects occur.¹⁵ ZURZUVAE can cause driving impairment due to CNS depressant effects.¹⁵ Clinicians should advise patients not to drive or engage in other potentially hazardous activities until at least 12 hours after ZURZUVAE administration for the duration of the 14-day treatment course and inform patients that they may not be able to assess their own driving competence, or the degree of driving impairment caused by ZURZUVAE.¹⁵ In addition to driving impairment, ZURZUVAE can cause other CNS depressant effects such as somnolence and confusion.¹⁵ Other warnings and precautions include suicidal thoughts and behaviors and embryo-fetal toxicity.¹⁵ Please see full Prescribing Information and Important Safety Information , including Boxed Warning.

ZURZUVAE was evaluated in two randomized, placebo-controlled, multicenter, clinical trials in 347 adult women, within 12 months postpartum, who met the DSM-5 criteria for a major depressive episode, had onset of symptoms in the third trimester or within four weeks of delivery, and had a 17 item Hamilton Depression Rating Scale (HAMD-17) total score ≥26.^15,16 The HAMD-17 is a commonly used tool in clinical research to assess depression symptoms.¹⁷ The primary endpoint for the studies was change from baseline HAMD-17 total score at Day 15.¹⁵, In Study 1, patients received 50 mg of ZURZUVAE or placebo for 14 days with the option to reduce the dose to 40 mg based on tolerability.^15,16 In Study 2, patients received a dose approximately equivalent to 40 mg of ZURZUVAE or placebo for 14 days.^15,16 In both studies, patients were followed for four weeks after their last dose of treatment and concomitant use of stable antidepressants (defined as a stable dose for ≥30 days prior to baseline) was permitted.^15,16 The primary endpoint for both studies was met; patients who received ZURZUVAE had statistically significant improvement in depression symptoms measured by the change from baseline in the HAMD-17 total score at Day 15 compared to patients who received placebo.^15,16 In Study 1, the key secondary endpoints included change from baseline in HAMD-17 total score at Days 3, 28, and 45 compared to patients who received placebo, were met.^15,16 This study demonstrated rapid improvements in depression symptoms as early as Day 3 with effects also observed at Day 45.^15,16 Across PPD clinical studies at all doses studied, serious adverse reactions included confusional state (1%).¹⁵ The most common adverse reactions (incidence ≥5% and greater than placebo) seen in either Study 1 or Study 2 were somnolence, dizziness, diarrhea, fatigue, nasopharyngitis, and urinary tract infection.¹⁵

“I believe the FDA approval of ZURZUVAE has contributed to a greater focus on maternal mental health and a dialogue on how we treat postpartum depression,” says Dr. Hoffman. “Historically, there has been only one treatment option approved specifically to treat PPD, so the availability of an oral treatment option like ZURZUVAE that may rapidly improve symptoms of PPD has the potential to make a difference in the lives of people struggling with this condition.”^7,10,11 

OB/GYNs should discuss with their patients the risks and benefits of breastfeeding while taking ZURZUVAE.¹⁵ Available data from a clinical lactation study in 14 women taking ZURZUVAE (30 mg) indicated that ZURZUVAE is present in low levels in human milk.¹⁵ This represents a maximum relative infant dose for ZURZUVAE of <1% compared to the maternal dose.¹⁵ There are no data on the effects of ZURZUVAE on a breastfed infant and limited data on the effects on milk production.¹⁵ “The decision to breastfeed is personal,” says Dr. Hoffman, “and OB/GYNs should always encourage their patients to voice their questions and concerns.”^7,10

The time to act is now

The early postpartum months can be especially important for diagnosing PPD and creating a treatment plan.^7,9 “To me, the early weeks postpartum are a critical period for the mother. When faced with PPD, we need to act urgently to help our patients manage their PPD symptoms,” says Dr. Hoffman.⁷ "We as OB/GYNs are positioned as first-line providers to help women with this condition through open conversations, regular education, and an expanding range of treatment options.”^7,9,10

To learn more about ZURZUVAE, how to prescribe it, and about programs in place to support patient access and affordability, visit www.zurzuvaehcp.com

INDICATION

ZURZUVAE™ (zuranolone) is indicated for the treatment of postpartum depression (PPD) in adults.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS
Impaired Ability to Drive or Engage in Other Potentially Hazardous Activities

• ZURZUVAE causes driving impairment due to central nervous system (CNS) depressant effects
• Advise patients not to drive a motor vehicle or engage in other potentially hazardous activities requiring complete mental alertness, such as operating machinery, until at least 12 hours after ZURZUVAE administration for the duration of the 14-day treatment course. Inform patients that they may not be able to assess their own driving competence or the degree of driving impairment caused by ZURZUVAE

Central Nervous System Depressant Effects

• ZURZUVAE can cause CNS depressant effects such as somnolence and confusion
• Somnolence developed in 36% of patients who received ZURZUVAE (50 mg) and in 6% of patients who received placebo daily. Some ZURZUVAE-treated patients developed confusional state. One of these cases was severe, and was also associated with somnolence, dizziness, and gait disturbance
• A higher percentage of ZURZUVAE-treated patients, compared to placebo-treated patients, experienced somnolence, dizziness, or confusion that required dosage reduction, interruption, or discontinuation
• Because ZURZUVAE can cause CNS depressant effects, patients may be at higher risk of falls
• Other CNS depressants such as alcohol, benzodiazepines, opioids, tricyclic antidepressants, or drugs that increase zuranolone concentration, may increase impairment of psychomotor performance or CNS depressant effects such as somnolence, cognitive impairment, and the risk of respiratory depression in ZURZUVAE-treated patients
• To reduce the risk of CNS depressant effects and/or mitigate CNS depressant effects that occurs with ZURZUVAE treatment:
  • If patients develop CNS depressant effects, consider dosage reduction or discontinuation of ZURZUVAE
  • If use with another CNS depressant is unavoidable, consider dosage reduction
  • Reduce the ZURZUVAE dosage in patients taking strong CYP3A4 inhibitors

Suicidal Thoughts and Behavior

• In pooled analyses of placebo-controlled trials of chronically administered antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients and 4,500 pediatric patients, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients age 24 years and younger was greater than in placebo-treated patients. There was considerable variation in risk of suicidal thoughts and behaviors among drugs, but there was an increased risk identified in young patients for most drugs studied. There were differences in absolute risk of suicidal thoughts and behaviors across the different indications, with the highest incidence in patients with major depressive disorder (MDD)
• ZURZUVAE does not directly affect monoaminergic systems. Consider changing the therapeutic regimen, including discontinuing ZURZUVAE, in patients whose depression becomes worse or who experience emergent suicidal thoughts and behaviors

Embryo-fetal Toxicity

• Based on findings from animal studies, ZURZUVAE may cause fetal harm when administered to a pregnant woman
• Advise a pregnant woman of the potential risk to an infant exposed to ZURZUVAE in utero. Advise females of reproductive potential to use effective contraception during treatment with ZURZUVAE and for one week after the final dose

ADVERSE REACTIONS

• The most common adverse reactions (≥5% and greater than placebo) in ZURZUVAE-treated patients were somnolence, dizziness, diarrhea, fatigue, nasopharyngitis, and urinary tract infection

DRUG INTERACTIONS
CNS Depressant Drugs and Alcohol

• Caution should be used when ZURZUVAE is administered in combination with other CNS drugs or alcohol. If use with another CNS depressant is unavoidable, consider dosage reduction

Strong CYP3A4 Inhibitors

• Reduce the ZURZUVAE dosage when used with a strong CYP3A4 inhibitor

CYP3A4 Inducers

• Avoid concomitant use of ZURZUVAE with CYP3A4 inducers

USE IN SPECIFIC POPULATIONS
Pregnancy

• There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants, including ZURZUVAE, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-987-9882 or visiting online at https://womensmentalhealth.org/research/pregnancyregistry/antidepressants/
• Based on findings from animal studies, ZURZUVAE may cause fetal harm. Advise pregnant women of the potential risk to a fetus. Available data on ZURZUVAE use in pregnant women from the clinical development program are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

Lactation

• Available data from a clinical lactation study in 14 women indicate that zuranolone is present in low levels in human milk. There are no data on the effects of zuranolone on a breastfed infant and limited data on the effects on milk production
• The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ZURZUVAE and any potential adverse effects on the breastfed child from ZURZUVAE or from the underlying maternal condition

Hepatic Impairment

• The recommended ZURZUVAE dosage in patients with severe hepatic impairment (Child-Pugh C) is lower than patients with normal hepatic function

Renal Impairment

• The recommended ZURZUVAE dosage in patients with moderate and severe renal impairment is lower than those with normal renal function

DRUG ABUSE AND DEPENDENCE

• ZURZUVAE contains zuranolone, a Schedule IV controlled substance under the Controlled Substances Act
• Zuranolone has abuse potential with associated risks of misuse, abuse, and substance use disorder including addiction
• ZURZUVAE may produce physical dependence

Please see full Prescribing Information, including Boxed Warning.

References

1. Thurgood S, et al. Postpartum Depression (PPD).Am J Clin Med. 2009;6:17-22
2. Meltzer-Brody S, Kanes SJ. Allopregnanolone in postpartum depression: Role in pathophysiology and treatment. Neurobiol Stress. 2020;12:100212
3. American Psychiatric Association. Depressive disorders. In: Diagnostic and Statistical Manual of Mental Disorders. 5th ed., text rev. American Psychiatric Publishing Inc. 2022.
4. Data on File. Biogen and Sage Therapeutics, Inc. 2024.
5. Bauman BL, 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.
6. Interrante JD, et al. Association of Health Insurance, Geography, and Race and Ethnicity With Disparities in Receipt of Recommended Postpartum Care in the US. JAMA Health Forum. 2022;3(10):e223292.
7. ACOG Committee Opinion No. 4. Screening and Diagnosis of Mental Health Conditions During Pregnancy and Postpartum. Obstetrics and gynecologyvol. 141,(6 (). 2023):: e1232-e1261.
8. Cox EQ, et al. The Perinatal Depression Treatment Cascade: Baby Steps Toward Improving outcomes. J Clin Psychiatry. 2016;77(9):1189-1200
9. ACOG Committee Opinion No. 736. Optimizing Postpartum Care. Obstetrics and gynecologyvol. 131,(5 () 2018):: e140-e149.
10. ACOG Committee Opinion No. 5. Treatment and Management of Mental Health Conditions During Pregnancy and Postpartum. Obstetrics and gynecologyvol. 141,(6 (). 2023):: e1262-e1288.
11. ACOG Practice Advisory. Zuranolone for the Treatment of Postpartum Depression. August 2024.
12. National Institutes of Mental Health. https://www.nimh.nih.gov/health/publications/perinatal-depression. Accessed February 22, 2024.
13. Schomerus, G, et al. Stigma as a barrier to recognizing personal mental illness and seeking help: A prospective study among untreated persons with mental illness. European Archives of Psychiatry and Clinical Neuroscience. 2019; 269:469-479.
14. Earls, M., et al. Clinical Report - Report—Incorporating Recognition and Management of Perinatal and Postpartum Depression Into Pediatric Practice. 2019;143(1);e2018325
15. ZURZUVAE Prescribing Information. Cambridge, MA: Biogen and Sage Therapeutics, Inc; 11/2023
16. Deligiannidis KM, et al. Effect of zuranolone vs placebo in postpartum depression: a randomized clinical trial. JAMA Psychiatry. 2023 Feb 1;80(2):191
17. Gerbasi, M. Associations between commonly used patient-reported outcome tools in postpartum depression clinical practice and the Hamilton Rating Scale for Depression. Archives of Women's Mental Health (2020) 23:727–735.

ZUR-US-0901 05/24