ModifiedCentenePolicy CP.PHAR.650

Zuranolone (Zurzuvae) for Postpartum Depression

Covers medical necessity and prior authorization criteria for Zurzuvae (zuranolone) to treat postpartum depression in adults for Centene-affiliated health plans. Applies to prescribers requesting coverage for this medication.

Policy Summary

PayerCentene

PolicyZuranolone (Zurzuvae) for Postpartum Depression

Policy CodePolicy CP.PHAR.650

Change TypeAdded prescriber specialtyupdated assessment tools and dosing

Effective DateDec 1, 2023

Next Review Date

Key ActionSubmit prior authorization with documentation that initial approval criteria for postpartum depression are met, including timing of onset, prescriber type, age, severity, and dosing limits.

SourceLink

POLICY UPDATE CHANGES

Added obstetrician-gynecologist as an additional prescriber specialty and specialist that can perform a clinical interview to confirm severe depression.

In Appendix B updated dosing regimens and removed commercially unavailable branded therapeutic alternatives.

14 daysmax treatment course

50 mg/daymax daily dose

≥ 18min age

≤ 12 mopostpartum interval

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Coverage Criteria for Zurzuvae (zuranolone)

inv-01: Initial Therapy - Postpartum Depression

Covered when ALL of the following are met:

PPD initial criteria

Severity or prior antidepressant trial
- a: HAM-D (HAMD) score ≥ 24 (severe depression).
- b: MADRS score ≥ 35 (severe depression).
- c: PHQ-9 score ≥ 20 (severe depression).
- d: EPDS score ≥ 20 (severe depression).
- e: BDI score ≥ 29 (severe depression).
- f: If none of the above scores meet severe thresholds, documentation of severe depression from a psychiatrist or obstetrician-gynecologist clinical interview.
- g: Failure of a 4-week trial of ONE oral antidepressant (SSRI, SNRI, TCA, bupropion, or mirtazapine) at up to maximally indicated dose but not less than commonly recognized minimum therapeutic dose, unless clinically significant adverse effects or contraindications exist.

placeholder

inv-02: Re-authorization

Re-authorization is not permitted; members must meet the initial approval criteria for each pregnancy/request.

Non‑FDA approved indications that are not specifically addressed by this policy are not authorized for coverage by Centene unless there is adequate documentation supporting safety and efficacy in the requested indication. Such support must follow the applicable off‑label use policies referenced by plan type (for example, CP.CPA.09 for commercial lines, HIM.PA.154 for Health Insurance Marketplace, or CP.PMN.53 for Medicaid) or be documented in an evidence of coverage document that permits the off‑label use.

When a state Medicaid program’s coverage provisions conflict with the coverage provisions in this clinical policy, the state Medicaid coverage provisions take precedence. Providers and reviewers should consult the applicable state Medicaid manual for any coverage rules or exceptions that apply to Medicaid members.

Clinical Scales and Coding Thresholds

Severe depression thresholds (rating scales)

HAM-D (Hamilton Rating Scale for Depression)Score ≥ 24 indicates severe depression

MADRS (Montgomery-Åsberg Depression Rating Scale)Score ≥ 35 indicates severe depression

PHQ-9 (Patient Health Questionnaire-9)Score ≥ 20 indicates severe depression

EPDS (Edinburgh Postnatal Depression Scale)Score ≥ 20 indicates severe depression

BDI (Beck Depression Inventory)Score ≥ 29 indicates severe depression

Provider Requirements, Authorization, and Denial Triggers

Prior Authorization

Prior Authorization Required

Prior authorization is required. Requests must document that the member meets all initial approval criteria for postpartum depression, including timing of onset (began no earlier than the third trimester and no later than 4 weeks after delivery), prescriber specialty, age, severity criteria or failed antidepressant trial, and that no more than 12 months have passed since delivery. Approval is for a single 14‑day treatment course (50 mg/day, 2 capsules/day) with a 30‑day authorization duration.

One 14‑day treatment course per pregnancy
Dose limit: 50 mg per day; 2 capsules per day
Approval duration: 30 days

Prior Authorization

Prescriber, Assessment, and Dosing Requirements

Prescriber must be a psychiatrist or obstetrician-gynecologist (prescribed by or in consultation with). Clinical interview to confirm severe depression may be performed by a psychiatrist or an obstetrician-gynecologist. Acceptable validated depression severity scales include HAMD, MADRS, PHQ‑9, EPDS, and BDI per thresholds in Appendix D. If scales do not demonstrate severe depression, documentation of severe depression from a qualifying clinical interview is required. Appendix B contains updated oral antidepressant dosing regimens referenced for step-therapy failures.

Drug-Specific Treatment Details

inv-19: Zuranolone (oral neuroactive steroid)

Zuranolone dosing: 50 mg orally once daily in the evening for 14 days; maximum 50 mg/day.

inv-20: Pharmacotherapy (zuranolone)

Assessment tools and references: BDI and EPDS are acceptable validated scales to identify severe depression and may be used in addition to HAM-D, MADRS, and PHQ-9 per policy updates; references include APA and ACOG guidance.

Pharmacotherapy guidance: Zuranolone (Zurzuvae) is the oral neuroactive steroid indicated for postpartum depression; dosing and administration per prescribing information and policy appendices apply.

Terms and Assessment Tools

Postpartum Depression (as used in this policy)

DefinitionPostpartum depression (PPD) is defined as a major depressive episode that began no earlier than the third trimester and no later than the first 4 weeks following delivery, diagnosed by Structured Clinical Interview for DSM-5.

Required diagnostic methodDiagnosis documented using Structured Clinical Interview for DSM-5

Timing restrictionOnset must occur between third trimester and within 4 weeks postpartum

Depression rating scales (policy usage)

Standardized scales listedHAM-D, MADRS, PHQ-9, EPDS, and BDI are recognized depression rating scales used in the policy to assess severity.

PurposeThese instruments are used to identify severe depression thresholds that inform coverage eligibility

Clinical Background

Zuranolone (Zurzuvae) is an oral neuroactive steroid and GABA‑A receptor positive modulator approved for the treatment of postpartum depression (PPD) in adults. This policy defines PPD as a major depressive episode with onset no earlier than the third trimester and no later than 4 weeks postpartum, and links coverage to specified clinical criteria including age, timing since delivery, prescriber type, severity or prior antidepressant therapy, and dosing limits.

Coverage is limited to adults aged ≥ 18 years, within ≤ 12 months of delivery, prescribed by or in consultation with a psychiatrist or obstetrician‑gynecologist, and when the requested treatment does not exceed a 14‑day course with a maximum daily dose of 50 mg/day (2 capsules daily).

Severity for initial approval may be documented by one of the listed standardized rating scales meeting the severe thresholds (for example, HAM‑D ≥ 24; MADRS ≥ 35; PHQ‑9 ≥ 20; EPDS ≥ 20; BDI ≥ 29), or by a documented clinical interview confirming severe depression performed by a psychiatrist or obstetrician‑gynecologist. Alternatively, if severity thresholds are not met, coverage may be authorized when there is documentation of failure of a 4‑week trial of one oral antidepressant at an adequate dose, unless contraindicated.

Prior authorization is required and re‑authorization is not permitted; each request must demonstrate that all initial approval criteria are met. Providers must submit supporting documentation such as office chart notes, assessment scores, or other clinical information demonstrating diagnosis, timing, severity or prior treatment history, prescriber specialty, and dosing consistent with policy limits.

Policy updates noted in the most recent review added obstetrician‑gynecologist as an acceptable prescriber/specialist to perform the clinical interview and added the Beck Depression Inventory (BDI) and Edinburgh Postnatal Depression Scale (EPDS) to the list of validated assessment tools used to identify severe depression; dosing regimens were also updated in the appendices and remain limited to a maximum of 50 mg/day for up to 14 days.

Policy Summary

PayerCentene

PolicyZuranolone (Zurzuvae) for Postpartum Depression

Policy CodePolicy CP.PHAR.650

Change TypeAdded prescriber specialtyupdated assessment tools and dosing

Effective DateDec 1, 2023

Next Review Date

Key ActionSubmit prior authorization with documentation that initial approval criteria for postpartum depression are met, including timing of onset, prescriber type, age, severity, and dosing limits.

SourceLink

On This Page

Prescriber specialty: psychiatrist or obstetrician-gynecologist
Accepted scales and severe thresholds: HAMD ≥24; MADRS ≥35; PHQ‑9 ≥20; EPDS ≥20; BDI ≥29
If no severe score, require documented clinical interview by psychiatrist or obstetrician-gynecologist
Step-therapy options reference Appendix B for dosing

Documentation Required

Required Documentation

Provider must submit supporting documentation such as office chart notes, clinical assessment results, laboratory data (if relevant), and any consultation notes that verify the diagnosis, timing relative to delivery, prescriber specialty involvement, severity assessment (scale scores or clinical interview), prior antidepressant trials (agent, dose, duration, and reason for discontinuation), and statement that member has not received prior Zulresso™ or Zurzuvae for the current pregnancy.

Office chart notes and clinical interview documentation
Depression scale scores with dates (HAMD, MADRS, PHQ‑9, EPDS, BDI) or psychiatrist/OB‑GYN interview note
Documentation of a 4‑week trial of one oral antidepressant including agent, dose, duration, and intolerance or contraindication if applicable
Confirmation member has not received Zulresso™ or Zurzuvae for the current pregnancy

Denial Risk

Triggers for Denial

Requests will be denied if documentation is incomplete or does not demonstrate that ALL approval criteria are met. Examples of denial triggers include: lack of prescriber specialty evidence (psychiatrist or obstetrician-gynecologist), absent or non‑qualifying severity assessment (no scale meeting thresholds and no qualifying clinical interview), failure to document prior antidepressant trial when required by step‑therapy, dosing requests exceeding a 14‑day course or the specified dose limits, and requests for non‑FDA‑approved indications without appropriate off‑label justification per plan off‑label policies.

Missing or incomplete clinical documentation supporting criteria
No qualifying severity score and no documented clinical interview by psychiatrist/OB‑GYN
No documented 4‑week oral antidepressant trial when step therapy applies
Request exceeds 14‑day treatment course or dose limits
Non‑FDA approved indications without off‑label policy justification

Step Therapy

Step Therapy / Severity or Antidepressant Trial

Step therapy / severity requirements: Member must meet ONE of the severity criteria (HAMD ≥24; MADRS ≥35; PHQ‑9 ≥20; EPDS ≥20; BDI ≥29) OR have documented severe depression from a psychiatrist or obstetrician‑gynecologist clinical interview. Alternatively, proof of failure of a 4‑week trial of one oral antidepressant at an adequate dose (SSRI, SNRI, TCA, bupropion, or mirtazapine) is acceptable unless contraindicated or not tolerated. Dose requirements and alternative agent availability are reflected in Appendix B.

Severity thresholds: HAMD ≥24; MADRS ≥35; PHQ‑9 ≥20; EPDS ≥20; BDI ≥29
Clinical interview by psychiatrist or OB‑GYN may substitute if scales are not severe
Step‑therapy trial: 4 weeks of one oral antidepressant at no less than commonly recognized minimum therapeutic dose
See Appendix B for acceptable agents and updated dosing regimens

Reference to appendicesSee Appendix D for scale descriptions and score interpretation

Edinburgh Postnatal Depression Scale (EPDS)

EPDS inclusionEdinburgh Postnatal Depression Scale (EPDS), a 10-item questionnaire for postnatal depression screening, is accepted as an assessment tool to identify severe depression (score > 19 considered severe per Appendix D).

Role in criteriaEPDS score ≥ 20 is one of the qualifying severity thresholds for coverage consideration

Appendix referenceEPDS defined in Appendix A and described in Appendix D for score interpretation

Beck Depression Inventory (BDI)

BDI inclusionBeck Depression Inventory (BDI), a 21-item self-reported inventory, is accepted as an assessment tool to identify severe depression (score > 28 considered severe per Appendix D).

Role in criteriaBDI score ≥ 29 is one of the qualifying severity thresholds for coverage consideration

Appendix referenceBDI listed in Appendix A and described in Appendix D for scoring categories