Beyond the Blues:

Medications for
Postpartum Depression
Delaney Straw, PharmD
PGY-1 Pharmacy Residency 2023-2024
February 12, 2024
Disclosures

I have no actual or potential

conflicts of interest regarding the
presented information.

2
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3
Abbreviations Overview
ACOG American College of Obstetricians and Gynecologists
SSRI Selective Serotonin Receptor Inhibitor
SNRI Serotonin and Norepinephrine Receptor Inhibitor
ECT Electroconvulsive therapy
AAP American Academy of Pediatrics
WHO World Health Organization
PHQ Patient Health Questionnaire
EPDS Edinburgh Postnatal Depression Scale
HDRS (HAM-D) Hamilton Depression Rating Scale
GAD-7 General Anxiety Disorder
PC-PTSD Primary Care - Post-traumatic Stress Disorder
PPHN Persistent Pulmonary hypertension of the newborn
PPD Postpartum Depression
CNS Central Nervous System
4
CYP Cytochrome P450
Learning Objectives

Describe risk factors, screening, and pathophysiology of

1. postpartum depression

Identify current treatment options and their place in

2. therapy in treating postpartum depression

Recognize the therapeutic use of zuranolone in treating

3. postpartum depression

Apply literature findings about brexanolone and

4. zuranolone to current practices

5
Outline

Overview of Introduction to novel

postpartum agents, including
depression zuranolone

Application of
Review of current treatment options
treatment options for postpartum
depression

6
Postpartum Depression

7
Perinatal Mood Disorders

Postpartum Blues Postpartum Depression

60-80% of new mothers 10-20% of new mothers
Prolonged crying, anxiety, More intense feelings of anxiety,
irritability, quick mood changes guilt and fatigue

Post-Traumatic Stress Postpartum Psychosis

Disorder
0.1% of new mothers
6% of mothers
Extreme confusion, refusal to eat,
Triggered by trauma leading to
delusions, hallucinations, rapid or
fear and intrusive thoughts
irrational speech

Postpartum Depression Alliance of Illinois. Symptoms of Postpartum Depression and 8

Perinatal Mood Disorders. 2020.
Timeline - Postpartum Blues / Psychosis

1 week 1 month 1 year

Onset

Birth 2 weeks 6 months

Postpartum Depression Alliance of Illinois. Symptoms of Postpartum Depression and 9

Perinatal Mood Disorders. 2020.
Timeline - Postpartum Depression

1 week 1 month 1 year

Peripartum onset Postpartum onset

Birth 2 weeks 6 months

Postpartum Depression Alliance of Illinois. Symptoms of Postpartum Depression and 10

Perinatal Mood Disorders. 2020.
Diagnosis of Postpartum Depression
- Major Depressive Episode “with peripartum onset”

At least 5
symptoms of Symptoms cause Symptoms are
depression during distress or not attributable to
a 2 week period significant social substances or
that is different or occupational medical
from previous impairment conditions
condition

Symptoms include: depressed mood, decreased pleasure, weight

changes, insomnia/hypersomnia, agitation, fatigue, feeling of
worthlessness, diminished ability to concentrate, suicidality

Screening and Diagnosis of Mental Health Conditions During Pregnancy and Postpartum: 11
ACOG Clinical Practice Guideline No. 4. Obstet Gynecol. 2023 Jun 1;141(6):1232-1261.
Screening for Postpartum Depression
- ACOG recommends for all women who are pre-pregnancy,
prenatal, and postpartum be screened for depression and
anxiety using standardized tests

PHQ-9 EPDS
PHQ-9
Edinburgh
Screens Postnatal Depression
for depressive Screens forScale
depressive and
symptoms from the past 14 anxiety symptoms from the past
days 7 days
PHQ-9
Scale: 0-27 Scale: 0-30
Edinburgh Postnatal Depression Sca
Mild: 10-14
Moderate: 15-19
Severe: > 19

Screening and Diagnosis of Mental Health Conditions During Pregnancy and Postpartum: 12
ACOG Clinical Practice Guideline No. 4. Obstet Gynecol. 2023 Jun 1;141(6):1232-1261.
 EPDS

Screening and Diagnosis of Mental Health Conditions During Pregnancy and Postpartum: 13
ACOG Clinical Practice Guideline No. 4. Obstet Gynecol. 2023 Jun 1;141(6):1232-1261.
Hamilton Depression Rating Scale

- Clinician-based interview
- 21 questions
- Score only based on
first 17 questions
- Various scales per
question

Normal: 0-7
Mild: 8-16
Moderate: 17-23
Severe: > 24

14
Sharp R. The Hamilton Rating Scale for Depression, Occupational Medicine. 2015 Jun;
65(4):340.
Risk Factors for Postpartum Depression

History of mood or anxiety disorder

Intimate
Poor social Marital
partner
support difficulties
violence

Persistent
Difficult infant
Prior abuse infant health
temperament
complications

Stewart DE, Vigod SN. Postpartum Depression: Pathophysiology, Treatment, and Emerging 15
Therapeutics. Annu Rev Med. 2019 Jan 27;70:183-196.
Complications of Postpartum Depression

Poor infant growth

Poor language and cognitive development in children

Increased risk for gastrointestinal and lower respiratory

tract infections

Rare infant physical harm

Stewart DE, Vigod SN. Postpartum Depression: Pathophysiology, Treatment, and Emerging 16
Therapeutics. Annu Rev Med. 2019 Jan 27;70:183-196.
Pathophysiology

Genetics Immune Hormones

System

Payne JL, Maguire J. Pathophysiological mechanisms implicated in postpartum depression. 17

Front Neuroendocrinol. 2019 Jan;52:165-180.
Hormone Levels

Schiller CE, Meltzer-Brody S, Rubinow DR. The role of reproductive hormones in 18

postpartum depression. CNS Spectr. 2015 Feb;20(1):48-59
Allopregnanolone

Progesterone Allopregnanolone

= Allopregnanolone

= Chloride ions

γ-aminobutyric
acid (GABA)
Effect of GABA
receptor 19
Schiller CE, Meltzer-Brody S, Rubinow DR. The role of reproductive hormones in
postpartum depression. CNS Spectr. 2015 Feb;20(1):48-59
Treatment Approach

22
Treatment Progression

All Patients
Moderate Symptoms
Severe/Unresponsive
Exercise, sleep,
self-care,
psychosocial support Add SSRI to Consider increasing
strategies non-pharmacologic dose or changing
treatment antidepressant

Consider augmentation
strategies

Stewart DE, Vigod SN. Postpartum Depression: Pathophysiology, Treatment, and Emerging 23
Therapeutics. Annu Rev Med. 2019 Jan 27;70:183-196.
Treatment Approach

1) Use the lowest dose that still shows clinical improvement

2) Avoid polypharmacy to decrease exposure and adverse

effects

3) Minimize switching medications

4) Consider exposure to the baby

5) Assess risk of inadequate treatment

Stewart DE, Vigod SN. Postpartum Depression: Pathophysiology, Treatment, and Emerging 24
Therapeutics. Annu Rev Med. 2019 Jan 27;70:183-196.
Approach to Pharmacotherapy Use

Risk of Undertreating Risk of Antidepressant Use

- Limited engagement in care

- Substance use - Preeclampsia
- Preterm birth - Spontaneous abortion
- Low birthweight - PPHN
- Preeclampsia - Transient neonatal
- Impaired infant attachment adaptation syndrome
- Disrupted relationships
- Suicidality

Treatment and Management of Mental Health Conditions During Pregnancy and 25

Postpartum: ACOG Clinical Practice Guideline No. 5. Obstet Gynecol. 2023 Jun
1;141(6):1262-1288
Antidepressant Use During Pregnancy

- For diagnosis with depression or anxiety during pregnancy or

postpartum, ACOG recommends the continuation of
psychopharmacotherapy for at least 6-12 months after symptom
remission
- Discontinuing during pregnancy or soon after has a high risk of
relapse and risk of recurrence when compared to those with
continued psychopharmacotherapy (68% vs 26%, HR 5.0)

Side effects of abrupt discontinuation:

Stomach Sleep
Dizziness Fatigue Headache
upset disruptions

Electric-like
Agitation Anxiety Myalgias Tremors
shocks

Treatment and Management of Mental Health Conditions During Pregnancy and 26

Postpartum: ACOG Clinical Practice Guideline No. 5. Obstet Gynecol. 2023 Jun
1;141(6):1262-1288
Pharmacokinetics in Pregnancy

Lower ratio of lean

Slower gastric Increased plasma
muscle to adipose
emptying volume
tissue

Increased CYP Decreased protein Increased renal

enzymatic activity binding blood flow

Antidepressant effects:
- Mainly metabolized by the liver
- Decrease in levels, especially > 20 weeks pregnancy
- Increase in symptoms may require an increase in dose

Nonacs R. Medications and Pregnancy: A Focus on the Pharmacokinetics.MGH Center for 27

Women’s Mental Health. 2014 Nov, 19.
Antidepressant Use During Breastfeeding

Benefit Harm
- Breastfeeding provides - Potential risk of exposure
nutrients and more through breast milk
immune and antioxidant - Side effects: crying,
protection than formulas irritability, decreased
feeding and watery stools

- AAP and WHO recommends the use of breast milk for feeding for 6 months if
able

- It is not recommended to change from agent used during pregnancy if

effective
- Breastfeeding is typically associated with less exposure than during
pregnancy

28
Berle JO, Spigset O. Current Women’s Health Reviews, 2011, 7, 28-34
Relative Infant Dose
- Relative infant dose (RID) = a measurement
of expected infant exposure relative to the
mothers dose after breastfeeding
- For most drugs < 10% is considered
compatible and generally safe
- 10-25% should be used with caution

- Also account for infant age and

gestational age at birth
- Immature metabolism can reduce
clearance

Lipophilicity Half-life Bioavailability

Drug ionization Molecule size Protein binding

29
Drugs and Lactation Database. Bethesda: National Institute of Child Health and Human
Development. 2006.
 30
Berle JO, Spigset O. Current Women’s Health Reviews, 2011, 7, 28-34
1st Line Treatment for Postpartum Depression

Sertraline 25 mg daily (50-200 mg) Most commonly studied and

lowest degree of breast milk
passage
Fluoxetine 10 mg daily (20-80 mg) Most activation and may
exacerbate anxiety
Citalopram 10 mg daily (20-40 mg) Risk of QT prolongation (greater
Escitalopram 5 mg daily (10-20 mg) with citalopram)

Side effects: nausea, dry mouth, insomnia, diarrhea,

headache, dizziness, agitation or anxiety, drowsiness, sexual
dysfunction, QT prolongation

Treatment and Management of Mental Health Conditions During Pregnancy and 32

Postpartum: ACOG Clinical Practice Guideline No. 5. Obstet Gynecol. 2023 Jun
1;141(6):1262-1288
1st Line Treatment for Postpartum Depression

Sertraline 25 mg daily (50-200 mg) Most commonly studied and

lowest degree of breast milk
passage
Fluoxetine 10 mg daily (20-80 mg) Most activation and may
exacerbate anxiety
Citalopram 10 mg daily (20-40 mg) Risk of QT prolongation (greater
Escitalopram 5 mg daily (10-20 mg) with citalopram)

Side effects: nausea, dry mouth, insomnia, diarrhea,

headache, dizziness, agitation or anxiety, drowsiness, sexual
dysfunction, QT prolongation

Treatment and Management of Mental Health Conditions During Pregnancy and 33

Postpartum: ACOG Clinical Practice Guideline No. 5. Obstet Gynecol. 2023 Jun
1;141(6):1262-1288
 Efficacy of SSRIs

Hantsoo L, et Sertraline vs placebo in 36 - Sertraline had a higher rate of

al. (2014) women for 6 weeks responders (67% vs 28%, p = 0.03)
- Sertraline had more remission as well
(60% vs 22% (p=0.03)

Yonkers KA, et Paroxetine vs placebo in 31 - Paroxetine improved overall severity of

al. (2008) women for 8 weeks symptoms (p=0.05)
- Paroxetine had higher rate of remission
(37% vs 15%, OR=3.5)

Sharp DJ, et al. SSRI vs supportive - At 4 weeks, antidepressants were

(2010) counseling in 254 women for more likely to have symptom
18 weeks improvement (45% vs 20%, p< 0.001)

Hantsoo L, et al. Psychopharmacology (Berl). 2014 Mar;231(5):939-48. 34

Yonkers KA, et al. J Clin Psychiatry. 2008 Apr;69(4):659-65.
Sharp DJ, et al. The RESPOND trial. Health Technol Assess. 2010 Sep;14(43):iii-iv, ix-xi, 1-153.
2nd Line Treatment for Postpartum Depression

Duloxetine 30 mg daily (30-120 mg) Caution in cardiovascular disease and

Fluoxetine 37.5 mg daily (75-300 mg)
Paroxetine 10 mg daily (20-60 mg)
Mirtazapine 7.5 mg nightly (15-45 mg)
Bupropion 150 mg daily (300-450 mg)
hypertension
Longer half life than other SSRIs
Use is not preferred in pregnancy
Increased weight gain and drowsiness
Contraindicated in seizure disorders,
caution in hypertension and
cardiovascular disease, may cause
weight loss

Side effects: insomnia, nausea, diarrhea, headaches, weight

gain, sustained hypertension, nervousness, tremor

Treatment and Management of Mental Health Conditions During Pregnancy and 35

Postpartum: ACOG Clinical Practice Guideline No. 5. Obstet Gynecol. 2023 Jun
1;141(6):1262-1288
Risks to the Newborn
If exposed to SSRIs/SNRIs in utero, O2 should be checked within
1 hour of birth and vitals should be assessed every 4 hours for the
first day of life
- Potential NICU admission may be necessary to monitor

Persistent Pulmonary
Neonatal Adaptation
Hypertension of the Congenital Heart Defects
Syndrome
Newborn
- Symptoms of - Failure of normal - Structural
withdrawal and respiratory function abnormality that
hemodynamic - Increased risk with affects function
instability use after 20 weeks - 1.5x increase in
- 30% of newborns if gestation (OR= 2.5) occurrence if used in
used in 3rd trimester - 10% mortality rate the 1st trimester
- Self-limiting - Paroxetine is most
- Fluoxetine and common
paroxetine
Antidepressant Use During Pregnancy: Considerations for the Newborn Exposed to 36
SSRIs/SNRIs. Perinatal Services BC. 2013
 Stable Antidepressant Management
Increase dose of
antidepressant

No/minimal
clinical Maximize other therapy
improvement
Taper to different
Assess for
antidepressant
efficacy at
4 weeks

Clinical
improvement Continue current regimen and
with minimal re-evaluate monthly
side effects

Treatment and Management of Mental Health Conditions During Pregnancy and 37

Postpartum: ACOG Clinical Practice Guideline No. 5. Obstet Gynecol. 2023 Jun
1;141(6):1262-1288
Remission Tapering
- Remission is defined as sequential scores of at least mild
symptoms
PHQ-9/EPDS <10

- Consider tapering off once in remission for ≥6 months for

depression and ≥12 months for anxiety

- Reducing the dose by a fixed amount over the course of

2-4 weeks is generally practiced

- Half life can be considered for risk of effects with

discontinuation
- Least risk → fluoxetine
- Intermediate risk → citalopram, escitalopram, sertraline
- Highest risk → fluvoxamine and paroxetine

Treatment and Management of Mental Health Conditions During Pregnancy and 38

Postpartum: ACOG Clinical Practice Guideline No. 5. Obstet Gynecol. 2023 Jun
1;141(6):1262-1288
Novel Agents: Brexanolone
Hormonal Zuranolone
Targets

40
GABA-A Receptor Modulators

Brexanolone Zuranolone
(ZULRESSO®) (ZURZAVAE®)

ZULRESSO. Package Insert. Sage Therapeutics; 2019. 41

ZURZUVAE. Package Insert. Biogen Incorporated; 2023.
Mechanism of Brexanolone and Zuranolone

- Neurosteroids
= Allosteric modulators

= Chloride ions
- Increase GABA-A
receptor activity through
positive allosteric
modulation of the
receptors
γ-aminobutyric acid
(GABA) receptor

- Regulate mood and

brain signaling more
effectively
GABA effect

Cutler AJ, et al. Understanding the mechanism of action and clinical effects of neuroactive 42
steroids and GABAergic compounds in major depressive disorder. Transl Psychiatry. 2023
Jun 26;13(1):228.
Brexanolone (ZULRESSO®)

43
Brexanolone (ZULRESSO®)

- FDA-approved for moderate to severe depression with onset in late

pregnancy or within 4 weeks postpartum

- Given as a one time continuous intravenous infusion titrated over 60 hours

Dosing:

0-4 hours 30 mcg/kg/hour

4-24 hours 60 mcg/kg/hour

24-52 hours 90 mcg/kg/hour*

52-56 hours 60 mcg/kg/hour

56-60 hours 30 mcg/kg/hour

*If not tolerated, continue at 60mcg/kg/hour

ZULRESSO. Package Insert. Sage Therapeutics; 2019 44
Monitoring - Brexanolone

- Must be given with an onsite healthcare provider during infusion

- Hypoxia should be assessed continuously and sedation should be

assessed every 2 hours during non-sleep periods

- Early in the day initiation is recommended

Adverse effects:

Loss of
Sedation Dry Mouth Flushing
Consciousness

ZULRESSO. Package Insert. Sage Therapeutics; 2019 45

Warnings - Brexanolone

- Use should be avoided in those with end stage renal disease

- eGFR <15 mL/minute/1.73m2

- Use should be avoided in pregnant patients

- May cause fetal harm

ZULRESSO. Package Insert. Sage Therapeutics; 2019 46

HUMMINGBIRD Trial - Brexanolone
The combined data studied
209 women with PPD with a
mean HAM-D score of 25.6
in both groups (severe). 102
patients received
brexanolone and 107 the
placebo.
There was a significantly
more rapid response with
brexanolone compared to
placebo (24 vs 36 hours)
Epperson CN, et al. Effect of brexanolone on depressive symptoms, anxiety, and insomnia
in women with postpartum depression. J Affect Disord. 2023 Jan 1;320:353-359.
The percentage of patients
achieving a HAM-D response
was higher with brexanolone
compared to placebo at hour
Pooled analysis of
60 (81.4% vs 67.3%) and
three double-blind,
after 30 days (88.2% vs
randomized trials
75.7%)
comparing
brexanolone 90
mcg/kg/hr vs
placebo in moderate Conclusion: In moderate to
to severe severe postpartum
postpartum depression, there was a
depression more rapid and clinically
meaningful reduction in
symptoms when
brexanolone was given
compared to placebo.
47
HUMMINGBIRD Trial - Primary Outcome

Epperson CN, et al. Effect of brexanolone on depressive symptoms, anxiety, and insomnia 48
in women with postpartum depression. J Affect Disord. 2023 Jan 1;320:353-359.
Zuranolone (ZURZUVAE®)

49
Place in Therapy - Zuranolone

- ZURZUVAE can be used alone or as an adjunct to oral

antidepressant therapy

- Recommended use within 12 months postpartum, for

symptoms that develop in the 3rd trimester or within 4 weeks
postpartum

- The safety and effectiveness of ZURZUVAE use beyond 14

days in a single treatment course have not been established

ZURZUVAE. Package Insert. Biogen Incorporated; 2023. 50

Dosing - Zuranolone

Zuranolone given ORALLY once daily in the evening for

14 days

ZURZUVAE. Package Insert. Biogen Incorporated; 2023. 51

Dosing - Zuranolone

Standard dosing Zuranolone 50 mg once daily

If CNS depressant effects Zuranolone 40 mg once daily

Used concomitantly with strong

CYP3A4 inhibitor

In severe hepatic impairment

(Child-Pugh C) Zuranolone 30 mg once daily

In moderate or severe renal

impairment
(eGFR < 60 mL/min)

Doses are recommended to be given in the

evening

ZURZUVAE. Package Insert. Biogen Incorporated; 2023. 52

Administration - Zuranolone

Taken with fat containing meal:

400-1000 25-50%
Calories Fat

- In pharmacokinetic studies, compared to fasted conditions:

- Given with a low fat meal → the Cmax increased 3.5-fold
and the AUC increased 1.8-fold
- Given with a high fat meal → the Cmax increased
4.3-fold and the AUC increased 2-fold

ZURZUVAE. Package Insert. Biogen Incorporated; 2023. 53

Pharmacokinetics - Zuranolone

- Tmax: 5-6 hours

Absorption
- Increased Cmax and AUC with fatty meal

- Volume of distribution: 0.5 L

Distribution
- Plasma protein binding: > 99.5%

Metabolism - Extensive CYP3A4 metabolism

- Half life: 19.7 to 24.6 hours

- Clearance is ~33 L/hr
Elimination
- Urine: 45% of the dose as metabolites
- Feces: 41% as metabolites, 2% unchanged drug

Avoid use with: CNS depressants and CYP3A4 inducers

ZURZUVAE. Package Insert. Biogen Incorporated; 2023. 54

Monitoring - Zuranolone

Adverse Effects:

Somnolence Dizziness Diarrhea

36% 13% 6%

Fatigue Nasopharyngitis UTIs

5% 9% 5%

ZURZUVAE. Package Insert. Biogen Incorporated; 2023. 55

Warnings - Zuranolone

- Use should be avoided in pregnant patients

- Fetal harm was identified in animal studies
- Effective contraception is recommended during treatment
and for one week after taking the final dose of zuranolone

- Use with caution in lactation

- Likely low levels

ZURZUVAE. Package Insert. Biogen Incorporated; 2023. 56

Zuranolone in Postpartum Depression

Deligiannidis KM, et al. Effect of Zuranolone vs Placebo in Postpartum Depression: A

Randomized Clinical Trial. JAMA Psychiatry. 2021;78(9):951–959.

Objective Methods Results

Demonstrate the - Double-blind randomized control - Primary Outcome: change

efficacy and safety of trial of zuranolone 30mg vs from baseline in HAM-D
zuranolone in placebo daily for 2 weeks score at day 15 was seen
postpartum - 150 women were included, to be significantly
depression and they were ≤ 6 months higher in those receiving
postpartum with at least one zuranolone (-17.8 vs
depressive episode without -13.6, p=0.003)
psychosis, not-breastfeeding - At day 15, there was a
- Severe classification with a higher response rate
baseline HAM-D score ≥ 26 (72% vs 48%) and
remission rate (45% vs
23%) in the zuranolone
group vs placebo

Deligiannidis KM, et al. Effect of Zuranolone vs Placebo in Postpartum Depression: A 57

Randomized Clinical Trial. JAMA Psychiatry. 2021;78(9):951–959.
HAM-D Response and Remission Rates

Deligiannidis KM, et al. Effect of Zuranolone vs Placebo in Postpartum Depression: A 58

Randomized Clinical Trial. JAMA Psychiatry. 2021;78(9):951–959.
SKYLARK Study - Zuranolone
Participants Results

- 196 patients were randomized to - The HAM-D score at day 15 was

zuranolone 50 mg (n=98) or placebo significantly improved with zuranolone
(n=98) vs placebo (-15.6 vs -11.6, p=0.001)

- Included ages 18-45 years, with a - There were similar statistical

diagnosis of major depressive disorder
during 3rd trimester or ≤4 weeks
postpartum, treated ≤12 months
postpartum
- Severe HAM-D score of ≥26
improvements at day 45 (-17.9 vs
-14.4, p=0.007)
- This study showed a significantly
greater change from baseline patient
reported EPDS scores at day 3 (-3.8
vs -2.3, p=0.03) and day 45 (-12.2 vs
-9.8, p=0.03)

Deligiannidis KM, et al. Zuranolone for the Treatment of Postpartum Depression. Am J 59

Psychiatry. 2023 Sep 1;180(9):668-675.
HAM-D Change from Baseline

Deligiannidis KM, et al. Zuranolone for the Treatment of Postpartum Depression. Am J 60

Psychiatry. 2023 Sep 1;180(9):668-675.
 Zuranolone Co-Initiated with an Antidepressant

- Assessed efficacy - 425 mothers included with a mean age of 38 years

and safety of (zuranolone 210, placebo 215) also receiving escitalopram,
zuranolone with sertraline, desvenlafaxine, duloxetine, or citalopram
standard of care
antidepressant - There was significant improvement in depressive
therapy in major symptoms at day 3 with zuranolone compared to placebo
depressive disorder (-8.9 vs -7.0, p=0.0004)

- Primary outcome: - At day 15, there was not a significant difference between
change from the change from baseline between zuranolone with an
baseline HAM-D antidepressant vs an antidepressant alone (-13.7 vs -12.9,
score p=0.24)

- Remission was not statistically different at day 15 (29.1%

vs 21.8%, p=0.14) or at day 42 (37.9% vs 39.2%,
p=0.79) between the zuranolone and placebo group

Parikh, S.V., et al. Efficacy and safety of zuranolone co-initiated with an antidepressant in 61
adults with major depressive disorder: results from the phase 3 CORAL study.
Neuropsychopharmacol. 49, 467–475 (2024).
Application to Practice

64
Comparison Summary

Traditional
Brexanolone Zuranolone
Antidepressant
- Available orally - Short - Available
- Well tolerated treatment orally
- Inexpensive course - 14 day
Pros
- May be used in - Rapid course
pregnancy and resolution - Rapid
lactation resolution
- Delayed onset - Significant - Dosing
- Tapering monitoring adjustments
requirement required may be
Cons - Lengthy required
infusion - Significant
- Expensive sedation
- No oral option - Expensive
65
Cost analysis

Price of
Capsule/Vial Additional
Product Treatment
Package Costs
Course
Doctor visits
Sertraline 50mg tablets $255 (#90) $100-510 when
titrating
100mg/20mL $30,000 Location of
Brexanolone $7,450 (#1)
vials -37,000 the infusion
20mg capsules $7,950 (#14)
Zuranolone 25mg capsules $15,900 (#28) $15,900
30mg capsules $15,900 ($14)

RED BOOK. Micromedex. Merative US L.P.; 2024. 66

Formulary Addition

- In October 2019, Brexanolone was not added to Ascension

formulary
- Limited data
- Lack of recommendation by guidelines
- Increased side effects
- High cost

- Zuranolone is currently being assessed for formulary addition

67
Conclusion

All pregnant and postpartum women should be screened for

postpartum depression.

SSRIs are considered the the first line treatment option in pregnancy
and breastfeeding mothers.

Brexanolone and Zuranolone are new agents approved for

postpartum depression that may be used in postpartum women
alone or as an adjunct to antidepressants.

Novel agents have an unknown place in therapy due to being new

products at a high cost, requiring further research compared to the
standard of care.

68
Questions?

69
Beyond the Blues:
Medications for
Postpartum Depression
Delaney Straw, PharmD
PGY-1 Pharmacy Residency 2023-2024
February 12, 2024