ModifiedmhnPolicy CP.PMN.199

Esketamine (Spravato) coverage criteria

Defines medical necessity, prior authorization, and coverage criteria for esketamine (Spravato) for treatment-resistant depression and MDD with suicidal ideation/behavior for affected Centene-affiliated lines of business.

Policy Summary

Payermhn

PolicyEsketamine (Spravato) coverage criteria

Policy CodePolicy CP.PMN.199

Change TypeMaterial revisions (step therapy, authorization durations, coding)

Effective DateJun 1, 2019

Next Review Date

Key ActionObtain prior authorization and submit documentation demonstrating diagnosis, psychiatrist involvement, baseline severity score, and required prior treatment trials or augmentation.

SourceLink

POLICY UPDATE CHANGES

Revised TRD requirement for failure of antidepressant augmentation therapies from two to one; revised continued approval duration from 6 months to 12 months; updated HCPCS code; references reviewed and updated.

Initial authorization for TRD revised to 4 weeks to align with induction dosing time; revised MDD with suicidal ideation initial authorization to allow for 24 nasal spray devices.

For TRD, updated indication to include monotherapy option and removed requirement for use in combination with an oral antidepressant for continued therapy.

168 mg/weekmax induction weekly dose

24devices allowed (4 wk)

PHQ-9 ≥15baseline PHQ-9 threshold

MADRS ≥20|HAMD ≥17

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severity thresholds (suicidality)

4 weeksinduction approval length

Coverage Criteria for Esketamine (Spravato)

Initial Approval — Treatment‑Resistant Depression (TRD) - Covered when ALL of the following are met:

Covered when ALL of the following are met:

TRD initial criteria: 1. Diagnosis of treatment‑resistant depression (TRD). 2. Prescribed by or in consultation with a psychiatrist. 3. Age ≥ 18 and < 65 years. 4. Documented baseline PHQ‑9 score ≥ 15 within the previous 4 weeks. 5. Member meets one of the following (a or b): a. Request is for a member in a State with limitations on step therapy in certain mental health settings; b. For all other requests, both of the following (i and ii): i. Failure of TWO antidepressants from at least two different classes, each used ≥ 4 weeks at therapeutic doses unless contraindicated or not tolerated; ii. Failure of ONE antidepressant augmentation therapy (second‑generation antipsychotic, lithium, thyroid hormone, or buspirone) used ≥ 4 weeks unless contraindicated. 6. Member meets one of the following (a or b): a. No prior history of treatment with Spravato; b. Documentation of a prior positive response to Spravato (≥ 50% reduction in PHQ‑9). 7. Dose limits during the 4‑week induction do not exceed: a. 168 mg (6 nasal spray devices) per week; and b. 24 nasal spray devices for four weeks.

Approval duration: 4 weeks (up to 24 nasal spray devices)

Initial Approval — MDD with Suicidal Ideation or Behavior - Covered when ALL of the following are met:

Covered when ALL of the following are met:

MDD with suicidality initial criteria: 1. Diagnosis of major depressive disorder (MDD) with acute suicidal ideation or behavior. 2. Prescribed by or in consultation with a psychiatrist. 3. Age ≥ 18 years. 4. Spravato is prescribed in combination with initiation or optimization of an oral antidepressant. 5. Member is recently (within the last 5 days) discharged from or currently in acute or subacute inpatient care for suicidality. 6. Member meets one of the following (a or b): a. No prior history of treatment with Spravato; b. Documentation of a prior positive response to Spravato. 7. Severity meets one of the following: a. MADRS ≥ 20; b. HAM‑D ≥ 17; c. PHQ‑9 ≥ 15. 8. Dose limits do not exceed: a. 168 mg (6 nasal spray devices) per week; and b. 24 nasal spray devices for four weeks.

Approval duration: 4 weeks (up to 24 nasal spray devices). Re‑authorization not permitted for this indication.

Continuation / Re-authorization — TRD - Covered when ALL of the following are met:

Covered when ALL of the following are met:

TRD continuation criteria: 1. Member is currently receiving Spravato via the Centene benefit or documentation supports at least 30 days of prior Spravato for a covered indication. 2. Member is responding to therapy as evidenced by ≥ 50% reduction in PHQ‑9 score from baseline. 3. If the request is for a dose increase, the new weekly dose does not exceed 84 mg (3 nasal spray devices) per week.

Approval duration: 12 months

Coverage criteria (induction, maintenance, REMS, prior trials) - Covered when ALL of the following are met (as applicable to the indication):

Covered when ALL of the following are met (as applicable to the indication):

Dosing and administration: Induction phase (weeks 1–4): administer 56 mg or 84 mg nasally twice weekly. Maintenance phase (weeks 5–8): administer 56 mg or 84 mg nasally once weekly. Week 9 and after: administer 56 mg or 84 mg nasally every 2 weeks or once weekly. Maximum per administration: 84 mg per dose.

Applies to TRD and MDD with acute suicidal ideation/behavior.

REMS and monitoring: Patient and administering healthcare setting must be enrolled in the Spravato REMS. Spravato must be dispensed to and administered only in certified healthcare settings, under direct observation, with monitoring by a healthcare provider for at least 2 hours after administration. Pharmacies must dispense only to REMS‑certified healthcare settings.2 hours post‑administration observation

Failure to comply with REMS requirements may result in denial.

Prior treatment and step therapy for TRD:

Non‑FDA approved indications for Spravato are not authorized under this policy unless the provider supplies sufficient documentation of efficacy and safety consistent with applicable off‑label use policies. Providers should follow the referenced off‑label policies (e.g., CP.CPA.09 for commercial, HIM.PA.154 for marketplace, CP.PMN.53 for Medicaid) or other evidence-of-coverage guidance when requesting coverage for indications not explicitly addressed in this policy.

Spravato is not indicated for the treatment of bipolar depression. Contraindications include: aneurysmal vascular disease or arteriovenous malformation (including thoracic and abdominal aorta, intracranial, and peripheral arterial vessels), history of intracerebral hemorrhage, and hypersensitivity to esketamine, ketamine, or any excipients. The product carries boxed warnings for risk of sedation, dissociation, respiratory depression, and potential for abuse/misuse; patients must be monitored for at least 2 hours after each administration. Spravato is available only through the Spravato REMS, and administration/dispensing must follow REMS requirements.

Spravato is not approved for pediatric use. The labeling warns of an increased risk of suicidal thoughts and behaviors in pediatric and young adult patients treated with antidepressants; therefore Spravato is not authorized for pediatric patients under this policy. Providers should closely monitor younger patients for clinical worsening or emergence of suicidal ideation when treating with antidepressants (per REMS and boxed warning guidance).

Coding and Clinical Thresholds

Referenced HCPCS/CPT/NDC codesmixed

G2082	Office or other outpatient visit for the evaluation and management of an established patient that requires the supervision of a physician or other qualified health care professional and provision of up to 56 mg of esketamine nasal self-administration, includes 2 hours post administration observation
G2083	Office or other outpatient visit for the evaluation and management of an established patient that requires the supervision of a physician or other qualified health care professional and provision of greater than 56 mg esketamine nasal self-administration, includes 2 hours post administration observation.
S0013	Esketamine, nasal spray, 1 mg

PHQ-9 continuation threshold

PHQ-9 response requirement for continuationAt least a 50% reduction in PHQ-9 score from baseline for continued (re-authorization) approval

Timing of documented responseMember must have received Spravato for at least 30 days or be currently receiving via Centene benefit with documentation showing the >=50% reduction

Source scale for response assessmentPHQ-9 used to compare baseline and follow-up scores to determine response

Baseline PHQ-9 for TRD

Baseline PHQ-9 threshold for TRDPHQ-9 score ≥ 15 documented within the previous 4 weeks

InterpretationScore of ≥15 indicates moderately severe major depression per policy Appendix D

Provider Requirements and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for Spravato (esketamine) per policy CP.PMN.199. Providers must document that all approval criteria are met before requesting authorization; incomplete requests may be denied. Initial authorizations for TRD and for MDD with suicidal ideation/behavior are time‑limited (typically 4 weeks for induction — see policy for current durations) and renewals/updates must demonstrate ongoing eligibility.

Policy: CP.PMN.199
Effective Date: 2019-06-01
Prior authorization required for both TRD and MDD with suicidality indications

Denial Risk

REMS Noncompliance Will Risk Denial

Requests that do not demonstrate compliance with the Spravato REMS requirements will be considered noncompliant and may be denied. REMS requirements include facility and pharmacy certification, patient enrollment in the REMS program, administration only in certified healthcare settings, direct observation of administration, and monitoring of the patient for at least 2 hours after each dose.

Clinical Background

Esketamine nasal spray (Spravato) is a non‑competitive NMDA receptor antagonist indicated for adult patients with treatment‑resistant depression (TRD) and for adults with major depressive disorder (MDD) and acute suicidal ideation or behavior. It is intended for use under the supervision of a qualified healthcare professional in REMS‑certified settings and is not an anesthetic agent.

Dosing uses intranasal devices that deliver 28 mg per device, with induction and maintenance regimens varying by indication; per dosing guidance the maximum per administration is 84 mg and patients must be monitored for at least 2 hours after each dose. Spravato is available only through the Spravato REMS because of risks for sedation, dissociation, respiratory depression, and potential for abuse or misuse.

Definitions and Rating Scales

Treatment‑Resistant Depression (TRD) definition

Definition of TRD per policyTreatment‑resistant depression (TRD) requires a documented diagnosis of TRD and prior failures of required antidepressant trials/augmentation as specified in the initial approval criteria

Prescriber requirementMust be prescribed by or in consultation with a psychiatrist

Age and severity requirementsAge ≥18 and <65 and baseline PHQ-9 ≥15 within previous 4 weeks required for TRD initial approval

PHQ-9: description and policy use

PHQ-9 descriptionThe PHQ-9 is a 9-item questionnaire used for diagnosis, screening, monitoring and measuring severity of depression

Policy usePHQ-9 is required as the baseline and follow-up response measure for TRD (baseline ≥15) and may be used to document ≥50% response for continuation

Level of Care — Outpatient

Esketamine Formulation and Administration

Esketamine (intranasal) — formulation criteria

Esketamine (intranasal) formulation and prescribing: Esketamine must be prescribed by or in consultation with a psychiatrist and may be used as monotherapy or in conjunction with an oral antidepressant per FDA indication and policy updates; Spravato is not an anesthetic and safety for prevention of suicide has not been established.

Follow dosing schedule and REMS requirements.

Esketamine nasal spray (Spravato) — product-specific criteria

Spravato product‑specific requirements: Dosing regimens for Spravato follow the policy dosing table (56 mg or 84 mg per administration with maximum 84 mg/dose); positive response criteria include documented improvement on PHQ‑9, MADRS, or HAM‑D17. REMS enrollment and monitoring for at least 2 hours post‑administration are required.

Refer to dosing and REMS sections for administration details.

Authorization Lengths and Visit Limits

Esketamine administration — initial authorization and device limits

Initial authorization period for TRD inductionInitial authorization aligned to a 4-week induction period (approval duration: 4 weeks)

Induction dosing alignmentInduction weeks 1-4 with twice-weekly dosing (56 mg or 84 mg twice weekly) — initial approval matches this induction schedule

MDD with suicidality device limitsInitial authorization for MDD with suicidal ideation updated to permit up to 24 nasal spray devices for the 4-week induction

Policy Revision History

2025-02-24Annual review — material clinical changeLatest

Revised TRD requirement for failure of antidepressant augmentation therapies from two to one; revised continued approval duration from 6 months to 12 months; updated HCPCS code and references.

2025-02-13RT4 update

Updated TRD indication to include a monotherapy option; revised initial approval maximum to allow 24 nasal spray devices and removed requirement for future combination with an oral antidepressant for initial and continued therapy.

2024-02-27

Policy Summary

Payermhn

PolicyEsketamine (Spravato) coverage criteria

Policy CodePolicy CP.PMN.199

Change TypeMaterial revisions (step therapy, authorization durations, coding)

Effective DateJun 1, 2019

Next Review Date

Key ActionObtain prior authorization and submit documentation demonstrating diagnosis, psychiatrist involvement, baseline severity score, and required prior treatment trials or augmentation.

SourceLink

On This Page

Per recent updates, TRD requirement is failure of one antidepressant augmentation therapy (used ≥ 4 weeks) unless contraindicated; prior authorization durations and device allowances adjusted to align initial TRD authorization with the 4‑week induction. State‑specific redirection or step therapy limitations may supersede (see Appendix F).

>= 4 weeks for augmentation trial

Policy revised TRD augmentation requirement and initial authorization timing in 2Q2024–2Q2025 updates.

Timing requirementBaseline score must be within the 4 weeks prior to request

MADRS / HAM-D severity thresholds

MADRS severity thresholdMADRS score ≥ 20 (moderate depression)

HAM-D17 severity thresholdHAMD (HAM-D17) score ≥ 17 (moderate depression)

Severity used for eligibilityEither MADRS ≥20 or HAM-D17 ≥17 may satisfy the policy severity requirement for initial approval

Device content and per-dose maximum

Esketamine per deviceEach nasal spray device delivers a total of 28 mg esketamine (two sprays per device)

Per-dose maximumMaximum esketamine per administration (dose) is 84 mg

Dose relation to devices84 mg corresponds to 3 nasal spray devices per dose

REMS enrollment required for patient and administering facility
Patients must be monitored ≥ 2 hours after each administration
Pharmacies must dispense only to REMS-certified healthcare settings

Documentation Required

Required Documentation

Submit supporting clinical documentation with the prior authorization request. Acceptable documentation includes office chart notes, psychiatric consultation notes, baseline and follow-up rating scales, medication histories, and relevant lab results or other clinical information that verify the criteria below.

Office chart notes and psychiatric documentation
Baseline and follow-up PHQ-9, MADRS, or HAM-D17 scores (see Appendix D)
Medication history with dates, doses, and reasons for discontinuation or intolerance

Documentation Required

Depression Severity and Prior Treatment Documentation

Document baseline depression severity using a validated scale and prior treatment response/failure. For TRD initial requests, a baseline PHQ-9 ≥ 15 within the previous 4 weeks is required; alternative acceptable scales include MADRS (≥ 20) or HAMD (≥ 17) where specified. For MDD with suicidality, document recent inpatient/subacute care for suicidality when applicable and baseline severity per the criteria. Follow-up scores and objective evidence of clinical response or lack thereof must be provided for renewals.

Baseline PHQ-9 ≥ 15 for TRD (within 4 weeks) or MADRS ≥ 20 or HAM-D ≥ 17 where specified
Document recent discharge or current inpatient/subacute care for suicidality when claiming MDD with suicidality
Provide follow-up rating scale scores to support ongoing benefit

Step Therapy

Step Therapy Prior Failures (TRD)

Step therapy requirements and prior-failure documentation must be met for TRD requests unless a permitted exception applies. For most TRD requests (outside states with redirection limits), document failure of TWO antidepressants from at least two different classes, each at adequate dose and duration (≥ 4 weeks at minimally therapeutic dose), AND failure of ONE antidepressant augmentation therapy used ≥ 4 weeks (e.g., second‑generation antipsychotic, lithium, thyroid hormone, or buspirone), unless contraindicated or intolerable.

Failure of ≥2 antidepressants from different classes, each ≥4 weeks at adequate dose (SSRI, SNRI, TCA, bupropion, mirtazapine, etc.)
Failure of ≥1 augmentation therapy for ≥4 weeks (second‑generation antipsychotic, lithium, thyroid hormone, buspirone)
Document clinical reasons if trials were shorter, not tolerated, or contraindicated

Step Therapy

Step Therapy Revisions and Redirection Bypass

States with limitations on step therapy redirections (see Appendix F) may allow a single‑drug redirection or modified step requirements. If the member resides in or the request is for a setting covered by such state restrictions (e.g., Texas per Appendix F for HIM requests), indicate this on the request and provide documentation supporting eligibility for the redirection bypass. Do not apply standard step requirements when the redirection exception explicitly applies.

Appendix F lists states with limitations against redirections in certain mental health settings
If applicable, note state redirection restriction (e.g., TX) and supply supporting documentation
When redirection bypass applies, only the modified single‑drug requirement (per Appendix F) is needed for HIM requests

Score interpretation referenceAppendix D provides PHQ-9 score ranges (e.g., 15-19 = moderately severe)

REMS (Spravato REMS)

REMS program referencedSpravato is available only through the Spravato REMS (restricted program)

Facility and patient enrollmentBoth the patient and the administering healthcare setting must be enrolled/certified in the REMS

Monitoring and dispensing requirementsPharmacies must be REMS-certified and only dispense to certified healthcare settings; patients must be monitored for at least 2 hours post-administration

Depression rating scales used in policy

Accepted rating scalesPolicy uses PHQ-9, MADRS, and HAM-D17 for baseline assessment and monitoring response

PHQ-9 roleSelf- or clinician-rated 9-item scale used for diagnosis, monitoring, and response criteria (baseline ≥15 for TRD)

MADRS and HAM-D17 roleMADRS (≥20) or HAM-D17 (≥17) may satisfy severity criteria for eligibility

Initial authorization for TRD revised to 4 weeks to align with induction dosing time; revised MDD with suicidal ideation initial authorization to allow up to 24 nasal spray devices; references reviewed and updated.

2021-02-01Annual review

Corrected upper age limit to less than 65 years and updated references.