CurrentmhnPolicy CP.PHAR.417

Brexanolone (Zulresso) for Postpartum Depression

Defines medical necessity criteria, dosing, monitoring and coverage stance for brexanolone (Zulresso) for treatment of postpartum depression in members covered by the payer.

Policy Summary

Payermhn

PolicyBrexanolone (Zulresso) for Postpartum Depression

Policy CodePolicy CP.PHAR.417

Change TypeNo material change

Effective DateJun 1, 2019

Next Review DateN/A

Key ActionSubmit prior authorization with documentation showing severe depression (e.g., MADRS ≥35) or a failed 4‑week oral antidepressant trial and confirm member meets dosing and REMS monitoring requirements.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

15+minimum eligible patient age

≤6 motime since delivery limit

60 hrsinfusion duration

90 mcg/kg/hrmaximum infusion rate

REMSREMS

J1632

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Coverage and Medical Necessity Criteria

inv-01: Initial Therapy (Postpartum Depression)

Covered when ALL of the following are met:

Initial Approval Criteria for PPD

Diagnosis timing: Diagnosis of a major depressive episode that began no earlier than the third trimester and no later than the first 4 weeks following delivery, as diagnosed by Structured Clinical Interview for DSM-5
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Prescriber: Prescribed by or in consultation with psychiatrist or obstetrician-gynecologist
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Age ≥ 15 years
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Severity or prior treatment
- Severity HAM-D: HAM-D score ≥ 24HAM-D ≥24
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- Severity MADRS: MADRS score ≥ 35MADRS ≥35
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- Severity PHQ-9: PHQ-9 score ≥ 20PHQ-9 ≥20
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- Severity EPDS: EPDS score ≥ 20EPDS ≥20
Postpartum timing limit: No more than 6 months have passed since member has given birth≤6 months
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No prior brexanolone this pregnancy: Member has not received prior treatment with Zulresso or Zurzuvae for the current pregnancy
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Dosing limits: Dose does not exceed 90 mcg/kg per hour over 60 hours with specified titration schedule (0–4 h 30 mcg/kg/hr; 4–24 h 60 mcg/kg/hr; 24–52 h 90 mcg/kg/hr or 60 mcg/kg/hr if not tolerated; 52–56 h 60 mcg/kg/hr; 56–60 h 30 mcg/kg/hr)Max 90 mcg/kg/hr over 60 hours
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inv-02: Initial therapy / approval criteria

Covered when criteria in the policy are met (summary of revisions reflected):

Diagnosis timing: Major depressive episode began no later than the first 4 weeks following delivery per updated ACOG guidance

Reflects revised criterion per ACOG guidance

Severity demonstration: Severe depression demonstrated by MADRS ≥ 35 OR documentation of severe depression via psychiatrist or obstetrician-gynecologist clinical interview OR severe score on BDI or EPDSMADRS ≥ 35

Additional scales (BDI, EPDS) and OBGYN interview added in 2Q 2024

Prior exposure: Member has not received prior treatment with Zulresso or Zurzuvae for the current pregnancy

Explicit exclusion added in revisions

Non‑FDA approved indications that are not addressed in this policy are not authorized for coverage unless the provider supplies sufficient documentation of efficacy and safety consistent with applicable off‑label use policies (CP.CPA.09 for commercial, HIM.PA.154 for marketplace/ICHRA, or CP.PMN.53 for Medicaid) or other evidence of coverage documents.

Prior receipt of brexanolone (Zulresso) or Zurzuvae for the current pregnancy is a disqualifying condition and excludes the member from approval pathways under this policy; members must not have received prior treatment with these products for the same pregnancy to be eligible.

Requests for re‑authorization are not permitted; members must meet the initial approval criteria to receive coverage. Requests that fall outside the indications listed in this policy or that do not meet the initial criteria are considered not medically necessary and will be denied.

Use of brexanolone without documentation that the member meets the policy's severity requirements is considered not authorized. For example, a MADRS score below 35 without alternative psychiatrist or obstetrician‑gynecologist clinical interview evidence of severe depression does not satisfy the severity threshold for approval.

Product, Codes and Severity Thresholds

Policy identifiersmixed

CP.PHAR.417

Policy reference number

Product / administrationmixed

NA	IV infusion of brexanolone over 60 hours; product vial 100 mg/20 mL (5 mg/mL)

HCPCS CodesHCPCS

J1632

Injection, brexanolone, 1 mg

Depression severity score thresholds — HAM-D, MADRS, PHQ-9, EPDS, BDI

HAM-D (HAMD)Threshold for severe depression: HAM-D score ≥ 24 (17-item scale)

MADRSThreshold for severe depression: MADRS score ≥ 35

PHQ-9Threshold for severe depression: PHQ-9 score ≥ 20

EPDSThreshold for severe postpartum depression: EPDS score ≥ 20

BDIThreshold for severe depression: BDI score ≥ 29 (21-item self-report)

MADRS threshold — >= 35

Prior Authorization, Documentation, and Billing Actions

Prior Authorization

Prior Authorization Required

Prior authorization required — Prior authorization is required and approvals are granted only when all initial approval criteria are met. Re-authorization is not permitted; members must meet the initial approval criteria for each request.

Approval duration: Not applicable
Re-authorization: Not permitted

Step Therapy

Step Therapy / Trial of Antidepressant

Step therapy / antidepressant trial — Member must either meet a severe-depression threshold on an accepted rating scale or have documentation of a failed 4-week trial of an oral antidepressant at an adequate dose (unless contraindicated or intolerant).

Accepted antidepressant classes: SSRI, SNRI, TCA, bupropion, mirtazapine
Required trial duration: 4 weeks at up to maximally indicated dose but no less than commonly recognized minimum therapeutic dose

Key Terms and Dosing Definitions

Brexanolone (Zulresso) — drug description and mechanism

AgentBrexanolone (Zulresso) — neuroactive steroid

Mechanism of actionGABAA receptor positive allosteric modulator (enhances GABAergic neurotransmission)

IndicationFDA-approved for treatment of postpartum depression in patients 15 years and older

Depression severity scales — HAM-D, MADRS, PHQ-9, EPDS, BDI described

HAM-D (Hamilton Depression Rating Scale)17-item clinician-rated scale; severe depression defined as >23 (policy uses HAM-D ≥ 24)

MADRS (Montgomery–Åsberg Depression Rating Scale)10-item clinician-rated questionnaire measuring depressive episode severity; severe defined as >34 (policy threshold ≥ 35)

Setting and Monitoring Requirements

inv-24: Inpatient/Monitored setting

Admission for brexanolone infusion: Patient meets the Initial Approval Criteria for PPD and is appropriate for supervised inpatient or monitored setting for continuous 60-hour IV infusion due to REMS-mandated sedation and loss-of-consciousness risk60 hours; continuous pulse oximetry

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Monitoring during infusion: Continuous monitoring including continuous pulse oximetry and observation for excessive sedation or loss of consciousness per REMS requirements; continue infusion per dosing schedule unless adverse events occur

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Administration Modality

inv-25: Intravenous continuous infusion (brexanolone)

Brexanolone infusion modality: Continuous IV infusion over 60 hours with REMS-mandated monitoring for excessive sedation and sudden loss of consciousness60 hours; continuous pulse oximetry

chunks 18,16

inv-26: Intravenous infusion (brexanolone)

Administration: Brexanolone must be administered as a continuous intravenous infusion over 60 hours with stepwise dosing increments and decrements as specified (0–4 h: 30 mcg/kg/hr; 4–24 h: 60 mcg/kg/hr; 24–52 h: 90 mcg/kg/hr or 60 mcg/kg/hr if not tolerated; 52–56 h: 60 mcg/kg/hr; 56–60 h: 30 mcg/kg/hr)60 hours; max 90 mcg/kg/hr

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Policy Summary

Payermhn

PolicyBrexanolone (Zulresso) for Postpartum Depression

Policy CodePolicy CP.PHAR.417

Change TypeNo material change

Effective DateJun 1, 2019

Next Review DateN/A

SourceLink

On This Page

Severity BDI: BDI score ≥ 29BDI ≥29

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Clinical interview evidence: If not meeting score thresholds, documentation of severe depression as evidenced by a psychiatrist or obstetrician-gynecologist clinical interview

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Failed antidepressant trial: Failure of a 4-week trial of ONE oral antidepressant at up to maximally indicated dose but no less than commonly recognized minimum therapeutic dose unless intolerant or contraindicated (SSRI, SNRI, TCA, bupropion, mirtazapine)4-week trial

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MADRS threshold>= 35 (required to qualify as severe depression per policy)

ContextMADRS is a 10-item diagnostic questionnaire used to measure severity of depressive episodes

Documentation alternativeIf MADRS < 35, severe depression may be documented via psychiatrist or obstetrician-gynecologist clinical interview or other qualifying score

Documentation Required

Supporting documentation required — Providers must submit clinical documentation (for example, office chart notes, lab results, depression rating scale scores, and specialist interview notes) demonstrating that the member meets all approval criteria. Failure to provide adequate supporting documentation may lead to denial of the request.

Examples: office notes, lab results, depression rating scale printouts, psychiatrist or obstetrician-gynecologist interview documentation

Documentation Required

Documentation to Demonstrate Severity

Documentation to demonstrate severity — Evidence of severe postpartum depression may include specific validated scale scores or documentation of a specialist clinical interview. Acceptable severity evidence includes MADRS ≥ 35, HAMD ≥ 24, PHQ-9 ≥ 20, EPDS ≥ 20, or BDI ≥ 29, or documentation from a psychiatrist or obstetrician-gynecologist clinical interview confirming severe depression.

Accepted scales and thresholds: MADRS ≥ 35; HAMD ≥ 24; PHQ-9 ≥ 20; EPDS ≥ 20; BDI ≥ 29
Alternative: documented clinical interview by psychiatrist or obstetrician-gynecologist confirming severe depression

Denial Risk

Prior Treatment Exclusion

Prior treatment exclusion — Member is not eligible for approval if they have received prior treatment with brexanolone formulations Zulresso or Zurzuvae for the current pregnancy.

Prior treatment with Zulresso or Zurzuvae for the current pregnancy disqualifies approval

PHQ-99-item patient questionnaire for screening/monitoring; severe depression >19 (policy threshold ≥ 20)

EPDS (Edinburgh Postnatal Depression Scale)10-item postnatal screening tool; severe symptomatology >19 (policy threshold ≥ 20)

BDI (Beck Depression Inventory)21-item self-reported inventory; severe depression >28 (policy threshold ≥ 29)

Standard dosing regimen — continuous IV infusion over 60 hours with stepwise titration

Infusion durationContinuous intravenous infusion over 60 hours (2.5 days)

Initial rate (0–4 hours)30 mcg/kg per hour

Titration (4–24 hours)Increase to 60 mcg/kg per hour

Maintenance peak (24–52 hours)Increase to 90 mcg/kg per hour (alternate 60 mcg/kg/hr if 90 not tolerated)

Taper (52–60 hours)52–56 hrs: 60 mcg/kg/hr; 56–60 hrs: 30 mcg/kg/hr