CurrentmhnPolicy CP.PMN.199

Esketamine (Spravato) coverage and prior authorization criteria

This clinical policy defines medical necessity criteria, initial and continuation approval requirements, dosing limits, excluded indications, REMS requirements, coding guidance, and approval durations for esketamine (Spravato) across Commercial, HIM, and Medicaid lines of business.

Policy Summary

Payermhn

PolicyEsketamine (Spravato) coverage and prior authorization criteria

Policy CodePolicy CP.PMN.199

Change TypeMultiple material revisions (age limit, trials, dosing, HCPCS updates)

Effective DateJun 1, 2019

Next Review Date

Key ActionProvider must submit documentation (office notes, lab results, rating scales) supporting that the member meets all approval criteria including baseline PHQ-9, prior antidepressant and augmentation trials, and psychiatrist involvement.

POLICY UPDATE CHANGES

Corrected upper age limit to less than 65 years (02.01.21).

Reduced trial duration of antidepressants for TRD from at least 8 weeks to 4 weeks (06.07.22).

For TRD added clarification that Spravato be used in combination with oral antidepressant (02.07.23).

Added redirection bypass for members in States with limitations on step therapy and Appendix F listing (07.11.23).

Initial authorization for TRD revised to 4 weeks to align with induction dosing; revised MDD with suicidal ideation initial authorization to allow for 24 nasal spray devices (02.27.24, P&T 05.24).

RT4 updates (02.13.25): TRD indication updated to include monotherapy option; initial approval maximum to allow for 24 nasal spray devices; removed requirement for stabilization and future combination use with an oral antidepressant; removed requirement for combination use in continued therapy.

2Q 2025 annual review: 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 (02.24.25, P&T 05.25).

HCPCS codes updates: added J0013 and removed S0013 (01.06.26).

2FDA Approved Indications

Coverage Summary

Coverage stance: covered_with_criteria for esketamine (Spravato) with specific prior authorization criteria. Scope: policy applies across Commercial, HIM, and Medicaid lines of business and defines medical necessity criteria, dosing limits, REMS requirements, coding guidance, and approval durations. FDA approved indications: 2 (treatment‑resistant depression [TRD] in adults, as monotherapy or with an oral antidepressant; and depressive symptoms in adults with MDD with acute suicidal ideation or behavior in conjunction with an oral antidepressant). Age ranges and limits: TRD initial approval requires age ≥ 18 and < 65 years; the suicidal‑ideation indication requires age ≥ 18 years. Approval durations and key thresholds: initial/induction authorization is 4 weeks (up to 24 nasal spray devices); continuation for TRD requires ≥ 50% PHQ‑9 reduction and may be approved for up to 12 months; MADRS ≥ 20, HAM‑D17 ≥ 17, and baseline PHQ‑9 ≥ 15 are the score thresholds used in the criteria. Effective date: 06.01.19. Last review: 05.25.

Thresholds / Key Limits

PHQ-9 baseline>= 15 (within previous 4 weeks)

PHQ-9 response (for continuation)>= 50% reduction from baseline

MADRS threshold>= 20 (for MDD with suicidal ideation/behavior)

HAM-D17 threshold>= 17 (for MDD with suicidal ideation/behavior)

Age for TRD initial approval>= 18 and < 65 years

Max devices for induction (4 weeks)24 nasal spray devices (max 168 mg/week; 6 devices/week)

Initial approval duration4 weeks (up to 24 nasal spray devices)

Continuation approval duration (TRD)12 months (requires documented >=50% PHQ-9 reduction and >=30 days on therapy)

Initial Approval Criteria — Treatment-Resistant Depression (TRD)

Initial Approval Criteria - Treatment-Resistant Depression (TRD)

Covered when ALL of the following are met:

ALL of the following

Diagnosis of TRD
Prescribed by or in consultation with a psychiatrist
Age ≥ 18 and < 65 years (see Appendix E)
Documented baseline PHQ-9 score ≥ 15 within the previous four weeksPHQ-9 >= 15 (within previous 4 weeks)
ONE of

Initial Approval Criteria — Major Depressive Disorder (MDD) with Suicidal Ideation or Behavior

Initial Approval Criteria - Major Depressive Disorder (MDD) with Suicidal Ideation or Behavior

Covered when ALL of the following are met:

ALL of the following

Diagnosis of MDD
Prescribed by or in consultation with a psychiatrist
Age ≥ 18 years
Spravato is prescribed in combination with initiation or optimization of oral antidepressant therapy

Initial Approval Limits

ALL of the following

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

Continuation / Reauthorization Criteria — Treatment-Resistant Depression (TRD)

Continuation/Reauthorization Criteria - Treatment-Resistant Depression (TRD)

Covered when ALL of the following are met:

ALL of the following

Member is currently receiving Spravato via Centene benefit or documentation supports member has received Spravato for at least 30 days>=30 days on therapy
Member is responding positively to therapy evidenced by ≥ 50% reduction in PHQ-9 score compared to baseline>=50% PHQ-9 reduction
If request is for a dose increase, new dose does not exceed 84 mg (3 nasal spray devices) per week<=84 mg/week

Continuation — MDD with Suicidal Ideation or Behavior

Continuation - MDD with Suicidal Ideation or Behavior

ALL of the following

Re-authorization is not permitted; members must meet the initial approval criteria
Approval duration: Not applicable

Other Diagnoses, Off-Label Use, and Exclusions

Other Diagnoses/Off-Label Use

If not listed above:

ANY of the following

If drug label changed within last 6 months and policy not updated, refer to formulary/no-coverage or non-formulary policies listed (CP.CPA.190, HIM.PA.33, CP.PMN.255, HIM.PA.103, CP.PMN.16)
If requested use is not listed under section III and above does not apply, refer to off-label use policy for relevant line of business (CP.CPA.09, HIM.PA.154, CP.PMN.53)

Not Authorized Indications

Coverage is NOT authorized when:

ALL of the following

Non-FDA approved indications that are not addressed in this policy (unless sufficient documentation per off-label use policies or evidence of coverage documents)

Applicable Codes

HCPCS/Drug J-codeHCPCSCovered

J0013

Esketamine, nasal spray, 1 mg

G-codes for supervised administration and observationHCPCSCovered

G2082	Office/outpatient visit for established patient requiring supervision and provision of up to 56 mg of esketamine nasal self-administration, includes 2 hours post administration observation
G2083	Office/outpatient visit for established patient requiring supervision and provision of greater than 56 mg esketamine nasal self-administration, includes 2 hours post administration observation

Provider Actions and Billing Notes

Prior Authorization

Documentation submission required

Provider must submit documentation supporting that member meets all approval criteria. Consolidated required items: baseline PHQ-9 (≥15 within previous 4 weeks), documentation of prior antidepressant trials (failures as specified), documentation of prior antidepressant augmentation trial (failure of one augmentation therapy used ≥4 weeks unless contraindicated), evidence of psychiatrist prescribing or consultation, office chart notes, and rating scales (PHQ-9, MADRS, HAM-D17 as applicable).

Baseline PHQ-9 (≥15 within previous 4 weeks)
Prior antidepressant trials (per criteria)
Prior antidepressant augmentation trial (per criteria)
Evidence of psychiatrist prescribing or consultation
Office chart notes
Relevant rating scales (PHQ-9, MADRS, HAM-D17)

Clinical Evidence and References

References: Prescribing Information (Janssen, January 2025) and multiple clinical guidelines and trials, including TRANSFORM‑3 (Ochs‑Ross et al., TRANSFORM‑3 cited in references). The REMS requirement is described in the product labeling and policy references; the REMS exists because of risks of sedation, dissociation, respiratory depression, and potential for abuse/misuse and mandates administration and dispensing only in certified healthcare settings with direct observation and at least 2 hours of monitoring post‑administration.

Background

Esketamine (Spravato) is a non‑competitive NMDA receptor antagonist administered as an intranasal spray indicated for TRD and for depressive symptoms in MDD with acute suicidal ideation or behavior. Spravato is available only through the Spravato REMS; healthcare settings and pharmacies must be REMS‑certified, patients must be enrolled, doses must be administered under direct observation, and patients must be monitored for at least 2 hours after each administration because of risks including sedation, dissociation, respiratory depression and the potential for abuse. The policy covers Commercial, HIM, and Medicaid lines of business and specifies required documentation, dosing limits, and monitoring to support medical necessity.

Definitions / Quick Reference

TRD (term)Treatment-resistant depression

PHQ-9Patient Health Questionnaire-9; baseline threshold >= 15 for policy; used for diagnosis and monitoring

MADRSMontgomery-Åsberg Depression Rating Scale; threshold >= 20 for suicidal indication

HAM-D17Hamilton Rating Scale for Depression 17-item; threshold >= 17 for suicidal indication

Revision History

02.01.21annual_review

Corrected upper age limit to less than 65 years (2Q 2021 annual review); references reviewed and updated.

06.07.22revised

Reduced trial duration of antidepressants for TRD from at least 8 weeks to 4 weeks (06.07.22).

02.07.23revised

For TRD added clarification that Spravato be used in combination with oral antidepressant (2Q 2023 annual review).

Policy Summary

Payermhn

PolicyEsketamine (Spravato) coverage and prior authorization criteria

Policy CodePolicy CP.PMN.199

Change TypeMultiple material revisions (age limit, trials, dosing, HCPCS updates)

Effective DateJun 1, 2019

Next Review Date

On This Page

Request is for the treatment of a member in a State with limitations on step therapy in certain mental health settings (see Appendix F)
Otherwise
- Failure of TWO antidepressants from at least two different classes at up to maximally indicated doses but no less than commonly recognized minimum therapeutic doses, each used for ≥ 4 weeks, unless clinically significant adverse effects or contraindicatedtwo antidepressant trials >=4 weeks
- Failure of ONE antidepressant augmentation therapy (second-generation antipsychotic, lithium, thyroid hormone, buspirone) used for ≥ 4 weeks, unless clinically significant adverse effects or contraindicatedone augmentation trial >=4 weeks

Prior Authorization

Documentation submission required

Provider must submit documentation supporting that member meets all approval criteria. Required items include office chart notes, rating scales, baseline PHQ-9 (≥15 within previous 4 weeks), documentation of prior antidepressant trials (failure of two antidepressants from at least two different classes each used ≥4 weeks unless contraindicated or adverse effects), documentation of prior antidepressant augmentation trial (failure of one augmentation therapy used ≥4 weeks unless contraindicated), and evidence that the drug was prescribed by or in consultation with a psychiatrist (psychiatrist involvement).

Office chart notes
Baseline PHQ-9 (≥15 within previous 4 weeks)
Rating scales (PHQ-9, MADRS, HAM-D17 as applicable)
Documentation of prior antidepressant trials (see criteria)
Documentation of prior antidepressant augmentation trial (see criteria)
Evidence of psychiatrist prescribing or consultation

Documentation Required

Monitoring and REMS compliance

Administration must occur in a REMS-certified healthcare setting. Patients must be directly observed during administration and monitored by a healthcare provider for at least 2 hours after administration. Pharmacies must be certified in the Spravato REMS and may only dispense Spravato to REMS-certified healthcare settings.

REMS-certified setting required
Direct observation during administration
At least 2 hours post-administration monitoring
Pharmacies may only dispense to certified healthcare settings

Billing Rule

Dose limits during induction

HCPCS J0013 is the drug code for esketamine (nasal spray, 1 mg). Dose limits during the four-week induction phase: do not exceed 168 mg per week (6 nasal spray devices) and do not exceed 24 nasal spray devices for four weeks. Initial approval duration for induction is limited to 4 weeks (up to 24 devices).

HCPCS: J0013 (Esketamine, nasal spray, 1 mg)
Max 168 mg/week (6 devices) during 4-week induction
Max 24 nasal spray devices for 4 weeks
Initial approval duration: 4 weeks (up to 24 devices)

Prior Authorization

Continuation criteria for TRD

For continuation/reauthorization for TRD, provider must document that the member has received Spravato for at least 30 days and is responding positively with ≥50% reduction in PHQ-9 score from baseline. If request is for a dose increase, the new dose must not exceed 84 mg (3 nasal spray devices) per week. Approval duration for continued therapy is up to 12 months.

Member has received Spravato for ≥30 days
Documented ≥50% reduction in PHQ-9 vs baseline
If dose increase requested, new dose ≤84 mg/week (3 devices)
Approval duration: 12 months

Documentation Required

Monitoring and REMS compliance

Administration must occur in a REMS-certified healthcare setting with direct observation and at least 2 hours post-administration monitoring. Pharmacies must be certified in the Spravato REMS and may only dispense to REMS-certified healthcare settings.

REMS-certified healthcare setting required
Direct observation during administration
At least 2 hours post-administration monitoring
Pharmacies may only dispense to certified settings

Billing Rule

Dose limits and HCPCS coding

HCPCS J0013 is the current drug J-code for esketamine (nasal spray, 1 mg). Dose/device limits during induction: do not exceed 168 mg per week (6 nasal spray devices) and do not exceed 24 nasal spray devices for the four-week induction phase. Initial approvals align with a 4-week induction period.

HCPCS: J0013 (Esketamine, nasal spray, 1 mg)
Max 168 mg/week (6 devices) during induction
Max 24 nasal spray devices for 4-week induction
Initial approval duration aligns to 4 weeks