CurrentCignaPolicy IP0270

Psychiatry - Zulresso

This policy governs prior authorization, coverage criteria, dosing, and coding for Zulresso (brexanolone) intravenous infusion for treatment of postpartum depression for Cigna-administered health benefit plans.

Policy Summary

PayerCigna

PolicyPsychiatry - Zulresso

Policy CodePolicy IP0270

Change TypeRevised dosing, added pregnancy requirement, and documentation clarifications

Effective DateAug 1, 2025

Next Review Date

Key ActionSubmit prior authorization with documentation confirming diagnosis of postpartum depression, symptom onset timing, and pregnancy status to request approval for a one-time 60-hour Zulresso infusion.

SourceLink

POLICY UPDATE CHANGES

Added requirement that the patient is not currently pregnant to the coverage criteria for postpartum depression.

Added dosing to the medical necessity criteria stem specifying approval up to 90 mcg/kg/hour as a one-time 60-hour infusion.

Documentation requirement added for diagnosis of postpartum depression.

Updated policy title from Brexanolone to Psychiatry - Zulresso.

60 hoursduration of single Zulresso infusion

90 mcg/kg/hrmax infusion rate

≥15minimum patient age

≤6 months

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Coverage Criteria for Zulresso (brexanolone)

inv-02: Dosing

Dosing requirement:

Dosing: Approve up to 90 mcg/kg/hour given intravenously as a one-time, 60-hour continuous infusion once per postpartum period.max 90 mcg/kg/hour; total duration 60 hours

If excessive sedation occurs, stop infusion until symptoms resolve; after resolution, infusion may be restarted at same or lower dose. Dose titration schedule provided in policy (see Table 1).

Zulresso (brexanolone) is not medically necessary for uses other than treatment of postpartum depression as defined in this policy. This includes, but is not limited to, previous treatment with Zulresso during the current episode of postpartum depression.

Use of Zulresso for indications other than postpartum depression (as defined in this policy) or for repeat treatment during the same episode of postpartum depression is considered not medically necessary and is excluded from coverage.

Billing and Coding

Considered Medically Necessary CodesHCPCSCovered

J1632

Injection, brexanolone, 1 mg

Postpartum timing (allowable window and symptom onset)

Allowable postpartum windowPatient is ≤ 6 months postpartum

Symptom onset timingOnset during third trimester of pregnancy or up to 4 weeks post-delivery

Approval durationApproval provided for 1 month (30 days) to allow scheduling and administration of the one-time 60-hour infusion

Provider Actions and Prior Authorization

Prior Authorization

Prior Authorization Required

Prior Authorization is required for benefit coverage of Zulresso. Approval is recommended for those who meet the clinical criteria and dosing for the FDA‑approved indication. All approvals are provided for the duration noted in the policy; when duration is specified in months, 1 month = 30 days. Because of the specialized skills required for evaluation, diagnosis, and monitoring of patients receiving Zulresso, approval requires the drug to be prescribed by or in consultation with a psychiatrist or obstetrician‑gynecologist.

Prior authorization required prior to benefit coverage
Approvals are issued for the duration specified (1 month = 30 days)
Prescriber requirement: psychiatrist or obstetrician‑gynecologist (prescribed by or in consultation with)

Note

A 1‑month (30 days) approval duration is applied to allow for scheduling and administration of the onetime, 60‑hour infusion (single administration per postpartum period). Dosing: up to 90 mcg/kg/hour IV as a onetime, 60‑hour infusion once per postpartum period.

Definitions

Postpartum (peripartum) depression — definition and clinical notes

DefinitionA major depressive episode with onset during pregnancy or within 4 weeks of delivery (peripartum/postpartum depression)

Typical severity and timingMany cases are moderate to severe; may begin as late as the third trimester or within 4 weeks postpartum

FDA-approved indication for ZulressoTreatment of postpartum depression in patients aged ≥ 15 years with symptom onset during the third trimester up to 4 weeks post-delivery and within 6 months postpartum

Clinical considerationsCan adversely affect maternal–infant bonding and infant development; efficacy demonstrated in trials initiated within 6 months of delivery

Safety/monitoring noteZulresso administration requires continuous pulse oximetry and sedation checks every 2 hours during planned nonsleep periods due to risk of excessive sedation and sudden loss of consciousness (REMS)

Monitored Infusion Setting Requirements

inv-13: Monitored infusion setting (inpatient or suitably equipped outpatient infusion center)

Covered when ALL of the following are met:

Monitored infusion setting (inpatient or suitably equipped outpatient infusion center): Patient meets FDA-approved indication criteria and is prescribed by/with a psychiatrist or OB-GYN, and the infusion will be administered in a monitored inpatient setting or a suitably equipped outpatient infusion center with continuous pulse oximetry and sedation monitoring.REMS monitoring required; continuous pulse oximetry; sedation checks every 2 hours during planned nonsleep periods

Patients must be accompanied during interactions with their children. If excessive sedation or loss of consciousness occurs, stop infusion until resolution; may restart at same or lower dose.

Treatment Modalities — IV Infusion

inv-14: IV continuous infusion (brexanolone)

Modality - IV continuous infusion: Zulresso administered as a continuous IV infusion over 60 hours with the specified titration schedule; monitoring for excessive sedation and sudden loss of consciousness required per REMS.60 hours total; titration per Table 1

One-time infusion per postpartum period; follow dose hold and restart guidance if excessive sedation occurs.

Background

Postpartum (peripartum) depression is a major depressive episode with onset during pregnancy or within 4 weeks of delivery and can adversely affect maternal–infant bonding and infant development. Many cases are moderate to severe and some begin as late as the third trimester or within the early postpartum period. Clinical trials demonstrating efficacy of Zulresso targeted moderate to severe cases initiated within 6 months of delivery.

Zulresso (brexanolone) is a GABA-A positive modulator indicated for postpartum depression in patients aged ≥ 15 years. Administration is by a one-time, continuous intravenous infusion over 60 hours with a titration schedule up to a maximum of 90 mcg/kg/hour. Because of risks for excessive sedation and sudden loss of consciousness, administration requires continuous monitoring and is available only through a REMS-compliant program.

Infusion with Zulresso must occur in a monitored setting (inpatient or suitably equipped outpatient infusion center) with continuous pulse oximetry and sedation checks every 2 hours during planned nonsleep periods; patients should be accompanied during interactions with their children. If excessive sedation or loss of consciousness occurs, the infusion must be stopped until resolution and may be restarted at the same or a lower dose.

For administrative purposes, prior authorization is required. Approval is recommended for patients who meet the specified FDA‑approved indication criteria and dosing requirements and is provided for 1 month (30 days) to allow scheduling and administration of the single 60‑hour infusion.