CurrentAnthemPolicy CC-0140

Zulresso (brexanolone) intravenous for postpartum depression — Medical necessity and prior authorization criteria

Medical necessity and prior authorization criteria for brexanolone (Zulresso) infusion for treatment of moderate-to-severe postpartum depression in eligible members under the medical benefit.

Policy Summary

PayerAnthem

PolicyZulresso (brexanolone) intravenous for postpartum depression

Policy CodePolicy CC-0140

Change TypeNo material change

Effective DateMar 26, 2026

Next Review Date

Key ActionObtain prior authorization and documentation confirming age ≥15 years, ≤6 months postpartum, qualifying standardized depression score, and REMS monitoring capability.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

60 hoursinfusion duration

15minimum age

6 monthspostpartum window

J1632HCPCS

F53.0ICD-10 example

Coverage Criteria for Brexanolone (Zulresso)

inv-01: Approval Criteria

Requests for Zulresso (brexanolone) may be approved if ALL of the following are met:

Initial approval criteria: I. Individual is 15 years of age or older; AND II. Individual is 6 months postpartum or less; AND III. Individual has a diagnosis of moderate to severe postpartum depression consistent with a qualifying score using a standardized screening tool for depression (examples: HAM-D, PHQ-9, BDI, MADRS, EPDS).

Per Meltzer-Brody 2018; single 60-hour continuous infusion per label and REMS requirements.

inv-02: Non-approval / Exclusions

Requests for Zulresso (brexanolone) will not be approved when ANY of the following apply:

Exclusion criteria: I. Individual has end stage renal disease (ESRD) with eGFR < 15 mL/min/1.73 m2; OR II. When the above criteria are not met and for all other indications.

Exclusion — End-stage renal disease (ESRD): Zulresso (brexanolone) is not approved for individuals with ESRD with eGFR < 15 mL/min/1.73 m2. This exclusion applies even if other criteria might be present.

Policy Summary

PayerAnthem

PolicyZulresso (brexanolone) intravenous for postpartum depression

Policy CodePolicy CC-0140

Change TypeNo material change

Effective DateMar 26, 2026

Next Review Date

Key ActionObtain prior authorization and documentation confirming age ≥15 years, ≤6 months postpartum, qualifying standardized depression score, and REMS monitoring capability.

SourceLink

On This Page

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Provider Requirements and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization required for Zulresso (brexanolone) infusion (HCPCS J1632). Requests will be considered only when the clinical criteria for age, postpartum timing, and severity of postpartum depression are met and required documentation of monitoring capability is provided.

HCPCS: J1632
Drug: Zulresso (brexanolone)
Prior authorization required

Note

Therapy Sequencing Context

ACOG guidance recommends psychotherapy as standard therapy for mild-to-moderate postpartum depression; for moderate-to-severe PPD, oral antidepressants plus psychotherapy may be an option. Brexanolone administration may be considered for moderate-to-severe perinatal depression with onset in the third trimester or within 4 weeks postpartum. Provide documentation of prior or concurrent psychotherapy and rationale for selecting brexanolone (e.g., inadequate response or contraindication to standard oral antidepressant therapy) when applicable.

Psychotherapy recommended for mild-to-moderate PPD
Oral antidepressants + psychotherapy option for moderate-to-severe PPD
Document prior/concurrent psychotherapy and rationale for brexanolone

Documentation Required

Required Clinical and Safety Monitoring Documentation

Documentation must support age (>= 15 years), postpartum timing (<= 6 months), and a diagnosis of moderate-to-severe postpartum depression confirmed by a standardized screening tool (e.g., HAM-D, PHQ-9, BDI, MADRS, EPDS). Because of the risk of excessive sedation and sudden loss of consciousness, include documentation that the facility and clinical team can provide continuous pulse oximetry monitoring, trained staff for continuous monitoring during the ~60-hour infusion, and procedures to ensure the individual is accompanied during interactions with their child(ren). Also document exclusion criteria (e.g., history of bipolar disorder, schizophrenia, or schizoaffective disorder) and renal function if relevant (ESRD with eGFR < 15 mL/min/1.73 m2 is a denial trigger).

Age >= 15 years
<= 6 months postpartum
Moderate-to-severe PPD documented with standardized scale (e.g., HAM-D, PHQ-9, BDI, MADRS, EPDS)
Facility can provide continuous pulse oximetry monitoring for duration of infusion
Staffing plan for continuous observation during ~60-hour infusion
Plan to ensure individual is accompanied during interactions with child(ren)
Document absence of exclusionary psychiatric diagnoses (bipolar disorder, schizophrenia, schizoaffective disorder)
Report renal function; eGFR < 15 mL/min/1.73 m2 = not approved

Denial Risk

Denial Triggers

Requests may be denied if the individual has ESRD with eGFR < 15 mL/min/1.73 m2, if required age/postpartum/severity criteria are not met, or if monitoring/capability documentation is insufficient. Zulresso is only available through the REMS program; lack of REMS-compliant facility or inability to meet REMS requirements may result in denial. Note: Zulresso commercial availability discontinued in the U.S. as of 2025; coverage criteria remain until obsolete in pharmacy files.

Denial triggers: eGFR < 15 mL/min/1.73 m2 (ESRD)
Denial triggers: age < 15 years, > 6 months postpartum, or not moderate-to-severe PPD
Denial triggers: inadequate documentation of continuous monitoring capability or REMS noncompliance

Definitions and Program Requirements

Qualifying standardized screening tool — examples and use (inv-14)

DefinitionAny validated depression rating scale demonstrating moderate-to-severe postpartum depression (examples include HAM-D, PHQ-9, BDI, MADRS, EPDS)

Examples listedHamilton Rating Scale for Depression (HAM-D); Patient Health Questionnaire (PHQ-9); Beck Depression Inventory (BDI); Montgomery-Åsberg Depression Rating Scale (MADRS); Edinburgh Postnatal Depression Scale (EPDS)

Use requirementA qualifying score on one of these instruments is required to document moderate-to-severe postpartum depression for authorization

ContextPart of the coverage criteria for Zulresso; used alongside age and postpartum timing criteria

Zulresso REMS — safety monitoring and mitigation (inv-15)

REMS requirementZulresso is available only through the Zulresso REMS program due to risk of excessive sedation and sudden loss of consciousness

Monitoring requirementsContinuous pulse oximetry monitoring is required during administration

Supervision requirementIndividuals must be accompanied during interactions with their child(ren) while receiving the infusion

Setting implicationAdministration must occur in a supervised setting with capability to monitor for sedation and loss of consciousness

F32.0-F32.9	Major depressive disorder
F53.0	Postpartum depression

OpenPayer

Zulresso (brexanolone) intravenous for postpartum depression — Medical necessity and prior authorization criteria

Coverage Criteria for Brexanolone (Zulresso)

Billing and Diagnosis Codes

Provider Requirements and Documentation

Definitions and Program Requirements

Brexanolone (Zulresso) Infusion

Background