CurrentBlue Cross Blue Shield - IowaPolicy 05.05.21

Zurzuvae (zuranolone) for Postpartum Depression — Prior Authorization and Coverage Criteria

This policy governs prior authorization and medical necessity criteria for coverage of Zurzuvae (zuranolone) to treat postpartum depression in members of Wellmark Blue Cross and Blue Shield (Blue Cross Blue Shield - Iowa). It applies to patients, prescribers, and reviewers determining benefit coverage under applicable member contracts.

Policy Summary

PayerBlue Cross Blue Shield - Iowa

PolicyZurzuvae (zuranolone) for Postpartum Depression — Prior Authorization and Coverage Criteria

Policy CodePolicy 05.05.21

Change TypeNo material changes

Effective DateAug 19, 2025

Next Review DateJun 1, 2025

Key ActionObtain prior authorization; approval of one month may be granted when all listed clinical criteria and required documentation are provided.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

1 monthinitial authorization duration

≤14 dayssingle course duration

28 caps/365d20/25 mg limit

14 caps/365d30 mg limit

18+

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Coverage Criteria for Zurzuvae (zuranolone)

Initial authorization criteria

Covered when ALL of the following are met:

Main criteria: Authorization of 1 month may be granted for treatment of moderate to severe postpartum depression in members 18 years of age or older when all of the following criteria are met:

Criterion 1: Member has had a major depressive episode that began no earlier than the third trimester of pregnancy and no later than the first 4 weeks following delivery, documented by standardized rating scales that reliably measure depressive symptoms (e.g., BDI, HDRS, MADRS).onset window: third trimester to 4 weeks postpartum

Criterion 2: Member is 6 months postpartum or less.<=6 months postpartum

Criterion 3: Member is not currently pregnant.

Criterion 4: Member will not receive more than one 14-day course per 12 months.<=1 course per 12 months

Criterion 5: Member's current episode of depression is moderate to severe.

Criterion 6 - treatment history alternatives

6a: Has tried and had an inadequate response to at least one antidepressant agent (SSRIs, SNRIs, TCAs, bupropion, or mirtazapine) at a maximally tolerated therapeutic dose for a minimum duration of 2 months.>=2 months on therapeutic dose
6b: Has a documented intolerance or FDA-labeled contraindication to ALL classes of antidepressant agents.
6c: Shows a potential risk of harm to self and/or others as determined by the treating provider and supported by documentation.

The safety and effectiveness of Zurzuvae (zuranolone) beyond a single 14-day treatment course have not been evaluated. Use is therefore limited to a single treatment course of up to 14 days per authorized episode. The policy also limits members to no more than one 14-day course per 12 months, consistent with available evidence and the FDA-evaluated treatment duration.

All uses of Zurzuvae (zuranolone) that are not specifically covered under this policy—for example, indications other than postpartum depression meeting the policy criteria—are considered not medically necessary and may be denied.

Coding and Quantity Limits

Coding guidancemixed

No codes listed

Limit on treatment courses

Allowed treatment coursesNo more than one 14-day course of Zurzuvae per 12 months.

Authorization durationApproval of one month may be granted when all listed clinical criteria are met.

Quantity limits (20 mg & 25 mg)Standard limit = 28 capsules per 365 days for 20 mg and 25 mg strengths.

Quantity limit (30 mg)Standard limit = 14 capsules per 365 days for 30 mg strength.

FDA-evaluated dosing courseFDA-recommended dosing is a 14-day course (evening dosing) as specified by strength-specific guidance.

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required before Zurzuvae (zuranolone) will be approved. Authorization may be granted for a duration of one month (a single 14-day course per approval) for treatment of moderate to severe postpartum depression in members 18 years or older when clinical criteria are met. Requests must include required documentation (see Documentation callout) and approvals beyond the one-month authorization require a new prior authorization request.

Approval duration: up to 1 month (one 14-day course).
Prior authorization required before drug is furnished.

Denial Risk

Denial Risk for Non‑listed Indications

Use of Zurzuvae for any indication not specifically described in this policy (e.g., conditions other than major depression with peripartum onset as defined herein) is considered not medically necessary and will be denied.

All other uses of Zurzuvae (zuranolone) not outlined in this policy are not medically necessary.

Pharmacotherapy: Zurzuvae (zuranolone)

Pharmacotherapy (Zurzuvae)

Medication modality: Oral Zurzuvae (zuranolone) administered per FDA-recommended dosing for 14 days; dose adjustments noted for renal impairment and CNS depressant effects.14-day dosing course

Standard quantity limits apply by strength (e.g., 20 mg and 25 mg: 28 capsules/365 days; 30 mg: 14 capsules/365 days).

Definitions

Postpartum depression (PPD) onset window and definition

Definition of PPD onset windowMajor depressive episode beginning no earlier than the third trimester and no later than the first 4 weeks following delivery.

Age indicationPolicy applies to members 18 years of age or older (FDA-approved indication for PPD).

Other timing-related criteriaMember must be 6 months postpartum or less and not currently pregnant to meet authorization criteria.

Background

Zurzuvae (zuranolone) is a neuroactive steroid that acts as a positive allosteric modulator of GABA-A receptors. It is chemically identical to the endogenous neurosteroid allopregnanolone and is administered orally for the treatment of postpartum depression according to the FDA-recommended 14-day dosing course. Its mechanism—enhancement of GABAergic inhibitory neurotransmission via GABA-A receptor modulation—underlies its antidepressant effects in the peripartum setting.

Revision History

2025-08-19effective_dateLatest

Policy current effective date established for Zurzuvae (zuranolone) coverage criteria.

2025-06revision

Policy revised and reviewed in June 2025 with updates reflected in the document history.

2023-10creation

Policy Summary

PayerBlue Cross Blue Shield - Iowa

PolicyZurzuvae (zuranolone) for Postpartum Depression — Prior Authorization and Coverage Criteria

Policy CodePolicy 05.05.21

Change TypeNo material changes

Effective DateAug 19, 2025

Next Review DateJun 1, 2025

Key ActionObtain prior authorization; approval of one month may be granted when all listed clinical criteria and required documentation are provided.

SourceLink

On This Page

Billing Rule

Quantity‑Limit and Billing Rules

Requests that exceed the allowed quantity limits or frequency will be subject to denial or manual review. Ensure submitted requests do not exceed the per‑member limits or allowability described in the quantity‑limit rules.

Do not request more than one 14-day course per 12 months without justification; standard quantity limits: 20 mg = 28 capsules/365 days, 25 mg = 28 capsules/365 days, 30 mg = 14 capsules/365 days.
FDA‑recommended dosing is a 14‑day evening dosing regimen; requests for quantities exceeding the dosing course should include clinical rationale.

Documentation Required

Required Documentation for Prior Authorization

Submit the following documentation with the prior authorization request to support medical necessity: concise but complete medical records demonstrating diagnosis, treatment history, and any clinical urgency to bypass step therapy.

Medical records (office notes) documenting relevant history and physician evaluation.
Rating scale scores or diagnostic criteria supporting major depression with peripartum onset (e.g., BDI, HDRS, MADRS).
Documentation of inadequate response to at least one antidepressant trial at a maximally tolerated therapeutic dose for ≥2 months, or documentation of intolerance/FDA‑labeled contraindication to all antidepressant classes if applicable.
If applicable, documentation of urgent need for treatment that negates trialing an antidepressant agent.

Step Therapy

Step Therapy / Alternatives

Step therapy requirements apply unless there is documented intolerance, contraindication to all antidepressant classes, or urgent risk of harm documented by the treating provider.

Member must have tried and had an inadequate response to ≥1 antidepressant (SSRI, SNRI, TCA, bupropion, or mirtazapine) at therapeutic dose for ≥2 months, OR
Documented intolerance or FDA‑labeled contraindication to ALL classes of antidepressants, OR
Documented potential risk of harm to self/others that justifies immediate treatment.

Policy created (Policy #05.05.21) to define prior authorization and coverage criteria for Zurzuvae for postpartum depression.