ModifiedPremera BluecrossPolicy 5.01.33

Pharmacologic Treatment of Postpartum Depression

Defines medical necessity criteria, dosing/administration, and coverage stance for Zurzuvae (zuranolone) for treatment of postpartum depression in adults, and documents required clinical information for coverage decisions. Affects providers prescribing or requesting pharmacy benefit coverage for Zurzuvae.

Policy Summary

PayerPremera Bluecross

PolicyPharmacologic Treatment of Postpartum Depression

Policy CodePolicy 5.01.33

Change TypeRemoved brexanolone criteriaclarified authorization durationsother minor revisions

Effective DateMay 1, 2026

Next Review DateMay 1, 2026

Key ActionObtain prior authorization for Zurzuvae and submit medical records documenting DSM-5 peripartum MDD criteria, moderate-to-severe severity, age and postpartum timing.

SourceLink

POLICY UPDATE CHANGES

Removed coverage criteria for Zulresso (brexanolone) as product has been removed from the market.

Non-formulary exception review authorizations for all drugs listed in this policy may be approved up to 12 months.

Age criteria were updated from 18+ to 15+ for use of Zulresso (brexanolone) in 2022 (note: later removed from market).

14 daysmax course per pregnancy

≥18HAMD-17 threshold

50 mgrecommended dose

Zurzuvae

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Removedbrexanolone status

Coverage Criteria for Zurzuvae (zuranolone)

Policy-level coverage statements

Policy updates and coverage stance for pharmacologic treatment of postpartum depression:

Brexanolone (Zulresso): Coverage criteria for brexanolone (Zulresso) were removed because the product was removed from the market.

removed 2026

Zuranolone (Zurzuvae): Zurzuvae (zuranolone) is included in the policy; prescribing information was reviewed and no new evidence was found that would change the policy in the 2024–2026 updates.

see 2024 and 2026 updates

Use of Zurzuvae (zuranolone) is covered only when all listed medical necessity criteria are met. Specifically, the individual must be aged 18 years or older, have medical record documentation meeting DSM-5 diagnostic criteria for Major Depressive Disorder with peripartum onset, have a current episode of depression that is moderate to severe as demonstrated by symptom documentation or one or more standardized depression rating scales, be within 12 months or less postpartum, and the treatment course must be limited to 14 days. All other uses of Zurzuvae (zuranolone) for conditions not outlined in this policy are considered not medically necessary.

Brexanolone (Zulresso) coverage criteria have been removed from this policy because the product was removed from the market. Requests referencing brexanolone (Zulresso) and the previously associated HCPCS code J1632 are no longer approvable under this policy.

Re-authorization of Zurzuvae (zuranolone) beyond a single 14-day treatment course per pregnancy is considered not medically necessary and will not be approved.

There are no additional explicit not-medically-necessary statements in this policy beyond the removal of coverage for a product no longer available. The primary policy change associated with market removal is the elimination of brexanolone (Zulresso) criteria and its former HCPCS code; other NMN determinations remain tied to the specific coverage criteria for each drug.

Coding and Diagnostic Thresholds

Previously listed HCPCS codes (removed)HCPCSNot Covered

J1632

HCPCS code previously listed for brexanolone (removed)

PHQ-9 and other depression scale thresholds

PHQ-9 thresholdPHQ-9 score ≥10 indicates likely major depression (scores: 5–9 mild; 10–14 moderate; 15–19 moderately severe; ≥20 severe)

HAMD-17 (HAM-D) thresholdHAM-D-17 score ≥18 indicates moderate to severe depression

MADRS thresholdMADRS: 20–34 = moderate; ≥35 = severe

QIDS-SR thresholdQIDS-SR: 11–15 = moderate; 16–20 = severe; ≥21 = very severe

Minimum age for certain medications

Minimum age (policy note)Documented minimum age updated from 18 years to 15 years for certain treatments (noting this applied to brexanolone in 2022)

Provider Actions, Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for Zurzuvae (zuranolone) when requested through the pharmacy benefit. Submit requests to the pharmacy prior authorization process before dispensing.

Medication managed under pharmacy benefit: Zurzuvae (zuranolone)
Initial treatment course limited to 14 days per pregnancy

Prior Authorization

Authorization Duration and Prescribing

Authorizations granted via non-formulary exception review may be approved for up to 12 months when clinically appropriate; however, the single treatment course for Zurzuvae is limited to 14 days per pregnancy. Prescriptions should follow the product's FDA dosing and administration information.

Non-formulary exception approvals: up to 12 months (operational)
Clinical limit: single treatment course limited to 14 days per pregnancy

Background

Postpartum depression (PPD) affects a substantial proportion of women after childbirth; estimates commonly cited include approximately 10–20% affected and a significant fraction of episodes being moderate to severe. Zuranolone is a neuroactive steroid GABA-A receptor positive modulator developed for treatment of PPD. Clinical guidance for PPD generally follows major depressive disorder principles: antidepressant medications and psychotherapy are commonly used, and psychotherapeutic or nonmedication options may be considered first for some pregnant or postpartum individuals. The policy requires documentation of DSM-5 criteria for a major depressive episode with peripartum onset and demonstration of moderate-to-severe symptoms when considering Zurzuvae.

Definitions

DSM-5 Major Depressive Episode (with peripartum onset)

Core diagnostic requirementPresence of five (or more) symptoms during the same two‑week period representing a change from previous functioning, with at least one being depressed mood or loss of interest/pleasure

Key symptom examplesDepressed mood, markedly diminished interest/pleasure, weight/appetite changes, insomnia/hypersomnia, psychomotor changes, fatigue, feelings of worthlessness, impaired concentration, recurrent thoughts of death or suicidal ideation

Functional impact and exclusionsSymptoms must cause clinically significant distress or impairment and not be attributable to substance use or another medical condition; no history of a manic or hypomanic episode

Definition — Postpartum Depression

Definition of postpartum depressionDepression occurring in the first year after childbirth; often managed with antidepressants and psychotherapy following major depressive disorder principles

Policy Summary

PayerPremera Bluecross

PolicyPharmacologic Treatment of Postpartum Depression

Policy CodePolicy 5.01.33

Change TypeRemoved brexanolone criteriaclarified authorization durationsother minor revisions

Effective DateMay 1, 2026

Next Review DateMay 1, 2026

Key ActionObtain prior authorization for Zurzuvae and submit medical records documenting DSM-5 peripartum MDD criteria, moderate-to-severe severity, age and postpartum timing.

SourceLink

On This Page

Age group supported by evidenceUse in individuals 15–17 years supported by adult efficacy studies, pharmacokinetic data, and safety data (per 2022 update)

Implication for documentationWhen age <18 is relevant, cite supporting prescribing information and study/safety data as applicable

Documentation Required

Nonpharmacologic First-line Consideration

Consider nonpharmacologic therapies as first-line for some pregnant or postpartum individuals. Psychotherapy (including interpersonal therapy), counseling interventions, and electroconvulsive therapy (when indicated) should be part of the treatment plan whenever possible and appropriate.

Psychotherapy and counseling interventions should be considered and documented when used or recommended
Electroconvulsive therapy is an option for major depressive disorder during pregnancy when clinically appropriate

Documentation Required

Depression Severity Documentation

Document depression severity with either detailed symptom documentation in the medical record or by using one or more standardized depression rating scales (for example, PHQ-9, HAM-D, or other validated instruments). The current episode must be moderate to severe to meet medical necessity criteria.

Acceptable documentation: office notes detailing symptoms and severity or results of standardized depression rating scales (e.g., PHQ-9, HAM-D)
Required clinical finding: current episode assessed as moderate to severe

Documentation Required

Required Clinical Documentation

Clinical documentation submitted for prior authorization must include office visit notes with history and physical evaluation that support diagnosis and severity, evidence of DSM-5 criteria for Major Depressive Disorder with peripartum onset, postpartum timing (≤ 12 months), and planned treatment course duration.

Include DSM-5 diagnostic documentation for Major Depressive Disorder with peripartum onset
Document postpartum status: within 12 months
Provide planned treatment duration (limit 14 days)

Denial Risk

Indication Mismatch — Not Medically Necessary for Other Indications

Zurzuvae (zuranolone) is considered medically necessary only for postpartum depression meeting the specific criteria in this policy. Requests for use in indications not described here are considered not medically necessary and will be denied.

Not medically necessary for indications other than postpartum depression as defined in policy

Note

Brexanolone (Zulresso) Removal — Operational Impact

Brexanolone (Zulresso) coverage criteria and codes have been removed from this policy following product withdrawal from the market. Do not submit requests referencing Zulresso; such requests will be denied as product is no longer available.

Zulresso (brexanolone) removed — references to Zulresso should not be submitted

Screening recommendationsUSPSTF recommends screening pregnant and postpartum persons (within 1 year) who are at increased risk and referral to counseling interventions as indicated (category B)

Treatment considerationsPsychotherapy and other nonmedication therapies may be considered first for some pregnant women; antidepressants are often prescribed per MDD guidance

Definition — pregnant persons and persons <1 year postpartum at increased risk (screening population)

Screening population (USPSTF)Pregnant persons and persons <1 year postpartum without current depression but at increased risk are the USPSTF-recommended screening population

Age range for adolescent screeningUSPSTF recommends screening adolescents aged 12–18 years; insufficient evidence to recommend for children ≤11 years

Clinical action for at‑risk individualsProvide or refer pregnant/postpartum persons at increased risk to counseling interventions (category B recommendation)