Zuranolone Treating Postpartum Depression Materials

MORE THAN THE BLUES: THE ROLE OF ZURANOLONE IN THE TREATMENT OF POSTPARTUM DEPRESSION

JENNIFER SALVON, RPh

Jennifer Salvon is a clinical pharmacist and freelance medical writer at Salvon Scientific, based in Massachusetts. During her career, she has practiced in a variety of venues, including the hospital, retail, managed care, teaching, and clinical research settings. As a lifelong learner, Jennifer enjoys researching and writing to educate herself and others.

Topic Overview

Most women experience the “baby blues” after childbirth, with mood swings, weepiness, anxiety, and difficulty sleeping. Beginning a few days after birth, these feelings typically last a couple of weeks. Sometimes, symptoms persist and worsen, developing into postpartum depression (PPD), a more severe condition. Untreated PPD can adversely affect maternal and newborn well- being. Treatment of PPD involves lifestyle changes, psychotherapy, and treatment with antidepressants. Traditional antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), are first-line therapy choices. Zuranolone, the first FDA-approved oral medication indicated for PPD, offers a convenient, rapid onset, and effective therapeutic option. Understanding the benefits and risks of zuranolone allows the pharmacy team to provide effective patient counseling contributing to positive patient outcomes.

Accreditation Statement

RxCe.com LLC is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education.

Universal Activity Number (UAN): The ACPE Universal Activity Number assigned to this activity is 

Pharmacist  0669-0000-23-220-H01-P

Pharmacy Technician  0669-0000-23-221-H01-T

Credits: 1 contact hour of continuing education credit

Type of Activity: Knowledge

Media: Internet/Home study Fee Information: $4.99

Estimated time to complete activity: 1 contact hour, including Course Test and course evaluation

Release Date: December 21, 2023 Expiration Date: December 21, 2026

Target Audience: This educational activity is for pharmacists.

How to Earn Credit: From December 21, 2023, through December 21, 2026, participants must:

Read the “learning objectives” and “author and planning team disclosures;”

Study the section entitled “educational activity;” and

Complete the Course Test and Evaluation form. The Course Test will be graded automatically. Following successful completion of the Course Test with a score of 70% or higher, a statement of participation will be made available immediately. (No partial credit will be given.)

Credit for this course will be uploaded to CPE Monitor®.

Learning Objectives: Upon completion of this educational activity, participants should be able to:

Discuss the prevalence and risk factors for postpartum depression

Review available postpartum depression treatment options

Describe the use of zuranolone to treat postpartum depression

Review effective counseling techniques to improve patient outcomes

Disclosures

The following individuals were involved in developing this activity: Jennifer Salvon, RPh, and Pamela Sardo, PharmD, BS. Pamela Sardo was an employee of Rhythm Pharmaceuticals until March 2022 and has no conflicts of interest or relationships regarding the subject matter discussed. There are no financial relationships relevant to this activity to report or disclose by any of the individuals involved in the development of this activity.

© RxCe.com LLC 2023: All rights reserved. No reproduction of all or part of any content herein is allowed without the prior, written permission of RxCe.com LLC.

Introduction

The birth of a child is a momentous occasion for the mother and family; however, for most mothers, it can be exhausting and accompanied by mood changes, apprehension, and unhappiness. When this experience is mild, it is referred to as the “baby blues.” Beginning a few days after birth, baby blues typically last a couple of weeks. Sometimes, symptoms persist and worsen, developing into postpartum depression, a more severe condition. Untreated postpartum depression can adversely affect maternal and newborn well-being. Treatment of postpartum depression involves lifestyle changes, psychotherapy, and treatment with antidepressants. Zuranolone is the first FDA-approved oral medication indicated for postpartum depression. It has a rapid onset and may be an effective therapeutic option for mothers experiencing postpartum depression. This course discusses the benefits and risks of zuranolone so that the pharmacy team may provide effective patient counseling and contribute to a positive patient outcome.

Mental Health Changes After Childbirth

Observation of mental health changes after childbirth dates back to A.D., 460 when Hippocrates noted an association between the postpartum period and mood disturbances.1,2 In 1858, the first paper describing mental health disturbances in postpartum women was published.2 Despite the recognition of mental health changes in postpartum women, it was not until 1994 that postpartum depression (PPD) was recognized in the Diagnostic and Statistical Manual of Mental Disorders (DSM).2

Fast forward to today, and PPD is a common complication of childbirth, affecting over 17% (17.22%) of the population globally.3 This number is likely higher as PPD is underdiagnosed and undertreated.4 Many postpartum women do not recognize the symptoms, or they worry about the stigma associated with PPD.5 Moreover, cultural and societal norms and expectations about motherhood can differ greatly between races and ethnicities, causing women in certain cultures to be less likely to report their depression.5

Untreated PPD can adversely affect maternal and newborn well-being.4,6 Pregnancy-related deaths occur during pregnancy, delivery, and up to a year postpartum. Over 84% of these deaths are determined preventable. Maternal suicide is the leading cause of maternal mortality, causing approximately 20% of postpartum deaths.6,7 Death is more likely in the urban setting (82%), and over 50% occur 7-365 days postpartum.8

The mental health impact of PPD on mothers and infants is considerable. Women with PPD are less likely to breastfeed, attend well-child visits, complete infant immunizations, and more likely to exhibit poor mother-infant bonding.6,9 Infants of women with PPD are more likely to have trouble breastfeeding and self-soothing. Cognitive, behavioral, and emotional development may be impaired, and in later years, there is an increased likelihood of having a mental health diagnosis.7,10

Pathophysiology of Postpartum Depression

Immediately after childbirth, almost 80% of women experience mild, temporary emotional symptoms, including low mood, tearfulness, and mild irritability. This is commonly referred to as the baby blues.9,11 These symptoms usually last less than 2 weeks but may continue longer in some women, developing into PPD.9 Postpartum blues are considered mild and limited in duration, and most importantly, do not impair day-to-day functioning.

Diagnosing PPD involves individual clinical assessment of the patient. Evaluation of symptom onset, severity, and duration is essential. In The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), the diagnosis of PPD as a major depressive disorder with postpartum onset involves the following criteria:11

Experiencing one of the following over a single two-week period:

Depressed mood

Loss of interest or pleasure in all or most activities

And, in the same period, at least 5 of the following:

Depressed mood

Loss of interest or pleasure in all or most activities

Weight loss

Insomnia or hypersomnia

Psychomotor agitation

Fatigue

Feelings of worthlessness or guilt

Diminished ability to think or concentrate

Recurring thoughts of death or suicidal ideation

In June of 2023, the American College of Obstetricians and Gynecologists (ACOG) released new recommendations for screening pregnant women for mental health conditions during pregnancy and postpartum.12 The guideline suggests screening twice during pregnancy, during each postpartum visit, and during well-child and well-woman visits.12

Several depression screening questionnaires exist. Two commonly used questionnaires are the Edinburgh Postnatal Depression Screen (EPDS) and the Patient Health Questionnaire (PHQ-9).12 These screening tools include a self- harm question and assess the presence and severity of depressive and anxiety

symptoms. Patients self-administer the questionnaire, and a score of ≥ 10 is a positive screen.9,12

Several proposed physiological pathways for PPD exist, including hormonal changes, hypothalamic-pituitary axis (HPA) activation, dysfunction in gamma-aminobutyric acid (GABA) signaling, inflammation, and others.11,13 One specific area of interest is the role of allopregnanolone, a neuroactive steroid (NAS). Allopregnanolone exerts a positive effect on GABA-A receptors, producing anxiolytic and antidepressant effects.11,13 During the postpartum period, women experience a decline in steroid hormones, including allopregnanolone.11,13

The duration of PPD varies; most cases resolve within a few months of treatment, but up to 24% of PPD women remain depressed after one year, and 13% remain depressed after two years.9 Additionally, 40% of women with PPD experience a relapse, either related or unrelated to another pregnancy.9

The following are risk factors for developing PPD:4,6

Younger age

Single status

Lower education level

Premature infants

Living in urban areas

Family history of psychiatric disorders

Treatment of Postpartum Depression

Current postpartum depression treatment options include lifestyle modifications, psychotherapy, and treatment with antidepressants.4,6 One of the first steps, patient education, is essential for successful patient outcomes.9 Patient education starts with a thorough explanation of PPD, working to dispel feelings of stigma and embarrassment. It is important to include lifestyle modifications such as diet, exercise, and sleep hygiene in the discussion.9

Studies exist linking deficiencies in Vitamin D levels with PPD.10 Vitamin D levels less than 32 ng/ml are considered low.10 In pregnant women with low levels of Vitamin D, recommended doses range from 1000 to 2000 international units (IU).10 One study found supplementation with vitamin D 50,000 IU every 14 days for 8 weeks resulted in decreased PPD symptoms.14

In June of 2023, ACOG published a clinical practice guideline for the Treatment and Management of Mental Health Conditions During Pregnancy and Postpartum.16 The guideline includes recommendations on the treatment of several conditions, including depression, anxiety, bipolar disorders, and acute postpartum psychosis.16

Psychotherapy is a first-line treatment for all levels of postpartum depression.10,16 Studies have evaluated different interventions in PPD treatment. Cognitive behavior therapy (CBT) and interpersonal therapy (IPT) are both effective in treating PPD.9 Cognitive behavior therapy targets negative thoughts and their role in the maintenance of negative emotions and behaviors.10 Focusing on the role of interpersonal relationships, IPT addresses conflicts and transitions, including having a baby.10

Initiation of pharmacotherapy is necessary in cases where psychotherapy results are insufficient or the symptoms of PPD are severe. First-line therapy begins with selective serotonin reuptake inhibitors (SSRIs).9,16 Alternatively, serotonin-norepinephrine reuptake inhibitors (SNRIs) offer a second-line choice.9,16 Other second-line medications include mirtazapine and bupropion.16 The use of these medications to treat PPD is off- label.

In previously treated patients, therapy initiation should be based on the formerly effective medication. In treatment-naive patients, either sertraline or escitalopram are first-line choices.16 Starting with low doses and titrating to symptom response aids in minimizing adverse effects. Monotherapy is preferred, and switching between medications is avoided if possible.16 Table 1 lists commonly used medications and dose ranges.

Table 1

Medications Used in Treating Postpartum Depression16

SSRI = selective serotonin reuptake inhibitor; SNRI = serotonin-norepinephrine reuptake inhibitor

Brexanolone, approved in March 2019, is the first FDA-approved treatment of PPD and introduces a novel approach to the treatment of PPD.17 Brexanolone is a synthetic allopregnanolone available as an intravenous (IV) infusion. Approval of Brexanolone is based on the results of 3 clinical trials in the HUMMINGBIRD program.18 Study results showed a rapid reduction in PPD symptoms resulting from brexanolone treatment versus placebo.7

Administration of brexanolone requires an inpatient hospital stay with a healthcare provider available on-site for the duration of the 60-hour infusion to monitor the patient continuously.7,15 Brexanolone is available in 20 ml vials as a 5 mg/ml solution and requires dilution before administration.15

Dosing of brexanolone is cyclical and given as follows:15

Initiation, hours 0 to 4: 30 mcg/kg/hour

Hours 4 to 24: 60 mcg/kg/hour

Hours 24 to 52: 90 mcg/kg/hour

The dose may be lowered to 60 mcg/kg/hour in patients who do not tolerate the 90 mcg/kg/hour dose

Hours 52 to 56: 60 mcg/kg/hour

Hours 56 to 60: 30 mcg/kg/hour

Brexanolone is a Schedule IV medication, and prescribing information contains a boxed warning for excessive sedation and sudden loss of consciousness.7 Due to the risk of serious adverse effects, brexanolone is only available through a restricted risk evaluation and mitigation strategy (REMS) program.7 Other common adverse reactions include sedation, fatigue, dry mouth, and flushing.7,15 Brexanolone treatment is pricey at approximately

$34,000, not including the costs associated with a hospital stay.19

The ACOG guideline recommends the consideration of brexanolone treatment in moderate to severe PPD.16 Unfortunately, the high cost, the potential for serious adverse events, and restricted access limit the use of brexanolone.7 Clinicians need to weigh the benefits of an effective, rapid-onset medication against the challenges of access, cost, need for inpatient monitoring, and lack of lactation data.16

Zuranolone as a Treatment Option for PPD

Approved in August 2023, zuranolone is the first oral medication indicated to treat PPD.20 The FDA gave zuranolone's application Priority Review and Fast Track status, reserved for drugs that treat serious diseases and fulfill an unmet medical need.20 Clinical trials indicate zuranolone may offer an effective, rapid-onset, and convenient treatment option.6,21 Zuranolone is an oral synthetic allopregnanolone, acting as a neuroactive steroid GABA-A receptive positive modulator.22,23 Zuranolone was developed by Sage Therapeutics and Biogen under the brand name Zurvuvae.23

Clinical Trials

Approval of zuranolone is based on data from two Phase III clinical trials: ROBIN and SKYLARK.6,21 ROBIN and SKYLARK were randomized, double-blind, placebo-controlled, and were performed in an outpatient setting. Both studies evaluated the efficacy and safety of zuranolone in women with severe PPD.6,21

The Hamilton Rating Scale for Depression (HAMD-17) assessed the severity of PPD and its treatment effect. Research settings more commonly use the HAMD-17 scale, while clinical settings utilize the EPDS and PHQ-9 scales.22 Both studies allowed concomitant use of existing oral antidepressants if the dose had been stable for at least the last 30 days.

Women meeting the following inclusion criteria participated in the studies:

Age 18-45 years

Baseline HAMD-17 score ≥ 26

Symptom onset in the third trimester or within 4 weeks postpartum

Agreed not to breastfeed during the study

The dosing in the ROBIN study assessed zuranolone 30 mg orally versus placebo once daily in the evening with a high-fat meal for 14 days. Patients unable to tolerate 30 mg once daily could decrease to 20 mg daily.21 In the SKYLARK study, patients received either zuranolone 50 mg or a placebo once daily in the evening with a high-fat meal for 14 days. The option existed to decrease the dose to 40 mg based on tolerability.6

Both studies followed patients for an additional 4 weeks after the 14- day treatment. The primary endpoint in both trials was the change in HAMD- 17 total score at day 15.6,21 Secondary endpoints in the ROBIN study included changes in HAMD-17 scores at days 3, 8, 21, and 45.21 The SKYLARK study collected changes in HAMD-17 scores on days 3, 28, and 45.6 Treatment of

zuranolone resulted in a statistically significant reduction in HAMD-17 scores at day 15 compared to placebo in both trials.6,21

Overall, zuranolone was well-tolerated in both studies. The most reported adverse reactions included dizziness, drowsiness, fatigue, diarrhea, urinary tract infections, and upper respiratory tract infections.6,21

Contraindications and Warnings

Zuranolone has a boxed warning regarding CNS depression, cautioning about an impaired ability to drive or engage in other potentially hazardous activities. The warning advises patients not to drive for 12 hours after taking zuranolone. Patients should be advised that they may not be able to assess their own driving competence.23

Controlled Substance

Zuranolone is a Schedule IV controlled substance based on its potential for misuse and dependence.23 Its potential for misuse is dose-dependent, and the reactions included “euphoric mood, feeling drunk, and somnolence.”23 Zuranolone may produce a physical dependence.23

Dosing

The recommended starting dose of zuranolone is 50 mg orally with high- fat food once daily in the evening for 14 days. Administration with high-fat food (400-1000 calories, 25-50% fat) results in greater bioavailability of zuranolone.23 The dose of zuranolone may be reduced to 40 mg once daily in the evening if intolerable CNS depressant effects occur.23

Dose modifications are recommended for renal and hepatic impairment. In severe hepatic impairment (Child-Pugh C), the recommended dosing is 30 mg once daily in the evening. In moderate to severe renal impairment (eGFR

<60ml/min/1.73 m2), 30 mg once daily in the evening. Zuranolone may be used alone or in adjunct to antidepressant therapy.23

Drug-Drug Interactions

Zuranolone should not be taken with other CNS depressant drugs due to a potential increase in CNS depressant effects and impaired psychomotor performance. Clinicians should consider dose reduction if the combination is unavoidable.23 Patients should be advised to refrain from drinking alcohol during zuranolone therapy.23

The primary hepatic enzyme involved in zuranolone’s metabolism is CYP3A4. Strong CYP3A4 inhibitors such as clarithromycin or ketoconazole have the potential to increase concentrations of zuranolone. This may increase the risk of adverse reactions. If concurrent administration is necessary, a zuranolone dose reduction to 30 mg is advised.23

Carbamazepine, phenobarbital, and phenytoin induce CYP3A4 activity. Enzyme induction may reduce the efficacy of zuranolone. The use of zuranolone with CYP3A4 inducers is not recommended.23

Pregnancy and Breastfeeding

Zuranolone may cause fetal harm based on data from animal studies.23 Advise patients to use effective contraception during treatment with zuranolone and for one week after the final dose. A pregnancy exposure registry exists to monitor pregnancy outcomes in women taking antidepressants during pregnancy.23

Zuranolone is known to pass into breast milk at low levels.23 No information exists regarding zuranolone’s effect on infants. The risks versus benefits should be considered when making the decision to breastfeed while taking zuranolone.

Supply, Handling, and Storage

Zuranolone is available in 20 mg, 25 mg, and 30 mg capsules and stored at controlled room temperature (68°F to 77°F).23 As mentioned above,

zuranolone is a Schedule IV controlled substance.23 It should be stored accordingly.

Zuranolone’s Place in Therapy

In August of 2023, ACOG published a practice advisory recommending the consideration of zuranolone in postpartum PPD treatment.22 Again, the benefits and risks need to be considered before initiating therapy. Zuranolone offers a convenient, oral, rapid onset, effective, outpatient-based treatment option. The risk of potential suicidal thoughts and sedation serious enough to limit driving, along with the lack of efficacy past 42 days, need to be weighed.22

Many women with PPD have a chronic mental health condition.12 Recently, zuranolone failed to receive approval from the FDA for the treatment of major depressive disorder.24 Further study is required to assess zuranolone's usefulness as a long-term therapy.

One drawback is the cost of zuranolone.25 The oral, once-daily, 14-day treatment is expected to retail at $15,900.25 This raises issues regarding whether zuranolone will be broadly accessible to patients who may benefit from its use.25

The Pharmacy Team: Front-line Support

Pharmacists and pharmacy technicians are among the most accessible healthcare providers. People routinely turn to neighborhood pharmacies for advice on many health topics. Many women with PPD fail to seek treatment or professional help. These facts make the pharmacy team essential in supporting women suffering from PPD. Recognizing signs of PPD and engaging with patients aids in improving overall patient outcomes.

Zuranolone provides an effective, well-tolerated oral treatment for PPD though its use does carry some risk. Comprehensive patient counseling will aid in therapy compliance and contribute to positive patient outcomes. The following list contains pertinent patient counseling tips:

Zuranolone may impair your ability to drive. Do not drive for at least 12 hours after taking your dose of zuranolone.

Contact your healthcare provider immediately if you experience suicidal thoughts.

The most common adverse reactions to zuranolone include dizziness, drowsiness, fatigue, diarrhea, urinary tract infections, and upper respiratory tract infections.

Do not drink alcohol or combine zuranolone with other anti-anxiety or pain medications.

If you miss a dose of zuranolone, do not take extra, continue with the next day’s dose as scheduled.

Take zuranolone with high-fat food or a meal.

Use effective contraception for the duration of the 2-week therapy and for 1 week after. Zuranolone may cause fetal harm. Contact your healthcare provider if you become pregnant.

Summary

Postpartum depression is a common complication of childbirth, affecting millions of new mothers. For many reasons, including cultural and societal expectations, many women remain untreated. Untreated PPD can adversely affect mother and infant health and quality of life. Screening women for PPD during pregnancy and postpartum is essential. Treatment with traditional antidepressants, such as SSRIs, is effective, but response to treatment may take up to 12 weeks or more. Zuranolone offers an effective, rapid onset, and convenient treatment option. Side effects include dizziness, drowsiness, fatigue, diarrhea, urinary tract infections, and upper respiratory tract infections. Severe CNS depression may occur, making patient counseling an essential component of therapy. An informed and knowledgeable pharmacy team contributes to therapy adherence and successful patient care.

Course Test

Which of the following is a recognized risk factor for developing postpartum depression (PPD)?

Married status

Rural living

Younger age

Higher education

Postpartum depression, distinct from temporary “baby blues,” affects what percentage of postpartum women globally?

80%

17.22%

23.44%

50.5%

Under DSM-5 criteria,          is NOT a symptom of PPD.

a depressed mood

feeling tired

the inability to concentrate

feeling pleasure in activities

Which of the following is a first-line, off-label medication for the treatment of PPD in treatment-naive patients?

Bupropion

Escitalopram

Nortriptyline

Venlafaxine

Administration of brexanolone involves which of the following?

Daily infusion in an outpatient clinic for 3 days

Cyclical infusion at home with a home health care service

Cyclical infusion over 60 hours in an inpatient setting

Infusion at a steady rate over 60 hours in an inpatient setting

Psychotherapy is an important part of PPD treatment. Which of the following psychotherapies has been studied and found to be effective in treating PPD?

Acceptance and Commitment Therapy (ACT)

Compassion-Focused Therapy (CFT)

Integrative Body Psychotherapy (IBP)

Cognitive Behavioral Therapy (CBT)

What is the duration of therapy with zuranolone?

14 days

42 days

21 days

60 days

Which of the following drugs can reduce the efficacy of zuranolone if they are taken together?

Phenobarbital

Amoxicillin

Omeprazole

Losartan

Zuranolone dose reduction is recommended in which of the following scenarios?

Administration with another antidepressant

Moderate hepatic impairment

Difficulty falling asleep

Moderate renal impairment

What advice would you give to a patient picking up a new prescription for zuranolone?

Take in the evening on an empty stomach.

Do not drive for at least 12 hours after taking.

If you miss a dose, take it as soon as you remember.

It may take several weeks to start to feel better.

References

Miller LJ. Postpartum depression. JAMA. 2002;287(6):762-765. doi:10.1001/jama.287.6.762

Hansotte E, Payne SI, Babich SM. Positive postpartum depression screening practices and subsequent mental health treatment for low- income women in Western countries: a systematic literature review. Public Health Rev. 2017;38:3. Published 2017 Jan 31. doi:10.1186/s40985-017-0050-y

Wang Z, Liu J, Shuai H, et al. Mapping global prevalence of depression among postpartum women [published correction appears in Transl Psychiatry. 2021 Dec 20;11(1):640]. Transl Psychiatry.

2021;11(1):543. Published 2021 Oct 20. doi:10.1038/s41398-021-

01663-6

Frieder A, Fersh M, Hainline R, Deligiannidis KM. Pharmacotherapy of Postpartum Depression: Current Approaches and Novel Drug Development. CNS Drugs. 2019;33(3):265-282. doi:10.1007/s40263- 019-00605-7

Manso-Córdoba S, Pickering S, Ortega MA, Asúnsolo Á, Romero D. Factors Related to Seeking Help for Postpartum Depression: A Secondary Analysis of New York City PRAMS Data. Int J Environ Res Public Health. 2020;17(24):9328. Published 2020 Dec 13. doi:10.3390/ijerph17249328

Deligiannidis KM, Meltzer-Brody S, Maximos B, et al. Zuranolone for the Treatment of Postpartum Depression. Am J Psychiatry. 2023;180(9):668-675. doi:10.1176/appi.ajp.20220785

Kaufman Y, Carlini SV, Deligiannidis KM. Advances in pharmacotherapy for postpartum depression: a structured review of standard-of-care antidepressants and novel neuroactive steroid antidepressants. Ther Adv Psychopharmacol. 2022;12:20451253211065859. Published 2022

Jan 28. doi:10.1177/20451253211065859

Trost S, Beauregard J, Chandra G, et al. Pregnancy-related deaths: data from Maternal Mortality Review Committees in 36 US states, 2017– 2019. September 19, 2022. https://www.cdc.gov/reproductivehealth/maternal-mortality/erase- mm/data-mmrc.html. Accessed November 17, 2023.

Stewart DE, Vigod SN. Postpartum Depression: Pathophysiology, Treatment, and Emerging Therapeutics. Annu Rev Med. 2019;70:183-

196. doi:10.1146/annurev-med-041217-011106

Higgins NE, Rose MJ, Gardner TJ, Crawford JN. Perinatal Depression Treatment Guidelines for Obstetric Providers. Obstet Gynecol Clin North Am. 2023;50(3):589-607. doi:10.1016/j.ogc.2023.03.009

Meltzer-Brody S, Kanes SJ. Allopregnanolone in postpartum depression: Role in pathophysiology and treatment. Neurobiol Stress.

2020;12:100212. Published 2020 Feb 3. doi:10.1016/j.ynstr.2020.100212

Screening and Diagnosis of Mental Health Conditions During Pregnancy and Postpartum: ACOG Clinical Practice Guideline No. 4. Obstet Gynecol. 2023;141(6):1232-1261. doi:10.1097/AOG.0000000000005200

Walton N, Maguire J. Allopregnanolone-based treatments for postpartum depression: Why/how do they work?. Neurobiol Stress. 2019;11:100198. Published 2019 Oct 24.

doi:10.1016/j.ynstr.2019.100198

Amini S, Amani R, Jafarirad S, Cheraghian B, Sayyah M, Hemmati AA. The effect of vitamin D and calcium supplementation on inflammatory biomarkers, estradiol levels and severity of symptoms in women with postpartum depression: a randomized double-blind clinical trial. Nutr Neurosci. 2022;25(1):22-32. doi:10.1080/1028415X.2019.1707396

Zulresso [package insert]. Cambridge, MA: Sage Therapeutics. 6/2022. https://assets.sagerx.com/zulresso/prescribing-information.pdf. Accessed December 1, 2023.

Treatment and Management of Mental Health Conditions During Pregnancy and Postpartum: ACOG Clinical Practice Guideline No. 5. Obstet Gynecol. 2023;141(6):1262-1288. doi:10.1097/AOG.0000000000005202

U.S. Food and Drug Administration. FDA approves first treatment for post-partum depression. FDA. Published March 19, 2019. https://www.fda.gov/news-events/press-announcements/fda-approves- first-treatment-post-partum-depression. Accessed November 13, 2023.

Epperson CN, Rubinow DR, Meltzer-Brody S, et al. Effect of brexanolone on depressive symptoms, anxiety, and insomnia in women with postpartum depression: Pooled analyses from 3 double-blind, randomized, placebo-controlled clinical trials in the HUMMINGBIRD clinical program. J Affect Disord. 2023;320:353-359. doi:10.1016/j.jad.2022.09.143

Powell JG, Garland S, Preston K, Piszczatoski C. Brexanolone (Zulresso): Finally, an FDA-Approved Treatment for Postpartum Depression. Ann Pharmacother. 2020;54(2):157-163. doi:10.1177/1060028019873320

U.S. Food and Drug Administration. FDA Approves First Oral Treatment for Postpartum Depression. FDA. Published August 4, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves- first-oral-treatment-postpartum-depression. Accessed November 13, 2023.

Deligiannidis KM, Meltzer-Brody S, Gunduz-Bruce H, et al. Effect of Zuranolone vs Placebo in Postpartum Depression: A Randomized Clinical Trial [published correction appears in JAMA Psychiatry. 2022 Jul

1;79(7):740] [published correction appears in JAMA Psychiatry. 2023 Feb 1;80(2):191]. JAMA Psychiatry. 2021;78(9):951-959.

doi:10.1001/jamapsychiatry.2021.1559

American College of Obstetricians and Gynecologists. Zuranolone for the Treatment of Postpartum Depression. ACOG. August 2023. https://www.acog.org/clinical/clinical-guidance/practice- advisory/articles/2023/08/zuranolone-for-the-treatment-of-postpartum- depression. Accessed November 22, 2023.

Zurzuvae [package insert]. Cambridge, MA: Biogen, Inc. https://documents.sage-biogen.com/us/zurzuvae/pi.pdf. Accessed November 28, 2023.

Clinical Trial Arena. Zuranolone approved for postpartum depression but misses out on bigger MDD indication. Published 2023. Accessed December 20, 2023. https://www.clinicaltrialsarena.com/analyst- comment/zuranolone-postpartum-depression-misses-out-mdd- indication/?cf-view

Sage Therapeutics Announces Third Quarter 2023 Financial Results and Highlights Pipeline and Business Progress. Sage Therapeutics. November 7, 2023. https://investor.sagerx.com/news-releases/news- release-details/sage-therapeutics-announces-third-quarter-2023- financial-results. Accessed December 18, 2023.

DISCLAIMER

The information provided in this course is general in nature, and it is solely designed to provide participants with continuing education credit(s). This course and materials are not meant to substitute for the independent, professional judgment of any participant regarding that participant’s professional practice, including but not limited to patient assessment, diagnosis, treatment, and/or health management. Medical and pharmacy practices, rules, and laws vary from state to state, and this course does not cover the laws of each state; therefore, participants must consult the laws of their state as they relate to their professional practice.

Healthcare professionals, including pharmacists and pharmacy technicians, must consult with their employer, healthcare facility, hospital, or other organization, for guidelines, protocols, and procedures they are to follow. The information provided in this course does not replace those guidelines, protocols, and procedures but is for academic purposes only, and this course’s limited purpose is for the completion of continuing education credits.

Participants are advised and acknowledge that information related to medications, their administration, dosing, contraindications, adverse reactions, interactions, warnings, precautions, or accepted uses are constantly changing, and any person taking this course understands that such person must make an independent review of medication information prior to any patient assessment, diagnosis, treatment and/or health management. Any discussion of off-label use of any medication, device, or procedure is informational only, and such uses are not endorsed hereby.

Nothing contained in this course represents the opinions, views, judgments, or conclusions of RxCe.com LLC. RxCe.com LLC is not liable or responsible to any person for any inaccuracy, error, or omission with respect to this course, or course material.

© RxCe.com LLC 2023: All rights reserved. No reproduction of all or part of any content herein is allowed without the prior, written permission of RxCe.com LLC.