CurrentPremera BluecrossPolicy 5.01.609

Spravato (esketamine) Nasal Spray

Policy governs medical-benefit coverage, criteria, documentation, dosing limits, approval duration, investigational uses, coding, and monitoring requirements for Spravato (esketamine) nasal spray for treatment of major depressive disorder (including treatment-resistant depression and MDD with acute suicidal ideation/behavior) for adults.

Policy Summary

PayerPremera Bluecross

PolicySpravato (esketamine) Nasal Spray

Policy CodePolicy 5.01.609

Change TypeMultiple annual and interim updates (coding, dosing, coverage criteria)

Effective DateJun 1, 2026

Next Review Date

Key ActionDocument DSM-5 diagnosis and severity, prior failed medication trials and induction/maintenance dosing in the medical record per policy before authorizing Spravato.

SourceLink

POLICY UPDATE CHANGES

2025 Update removed separate coverage criteria for MDD with acute suicidal ideation or behavior; criteria for MDD now apply to individuals with or without acute suicidal ideation or behavior.

2024 Update clarified investigational/not medically necessary distinctions and removed stipulation regarding second antidepressant as augmenting agent.

2023 Update clarified DSM-5 documentation, substance use abstinence/remission timelines, and concurrent substance restrictions; required naming of oral antidepressant used in conjunction.

2022 Update added criteria for a 'new course' and expanded substance restrictions (no concurrent mind-altering substances) and re-authorization clarifications.

2021 Update added that Spravato must continue to be used in conjunction with an oral antidepressant and added dosage limits per FDA prescribing information.

2020 Update added new indication and evidence summary for MDD with acute suicidal ideation or behavior (ASPIRE trials).

Reviewed prescribing information for Spravato and literature; no changes to policy statements (06/01/26 Annual Review).

HCPCS code J0013 added and S0013 termed effective January 1, 2026 (01/01/26 history).

Clarified maintenance dose limit: week 5 and after limited to 84 mg once weekly for the rest of the first 12 months and for re-authorization (12/01/25).

Removed requirement that an oral antidepressant must be used in conjunction with Spravato consistent with FDA Jan 21, 2025 approval of monotherapy (03/01/25 history).

Documentation requirement for prior failed therapies.

Substance use disorder remission definitions clarified several times (dates through 06/01/25).

Adult (>=18)Age group

12 monthsMax approval duration

84 mgMaintenance dose (weekly)

84 mg twice weeklyTemporary increased frequency

3 or 2+augmentRequired failed trials

MultipleHCPCS coding

Coverage Summary

This policy governs medical-benefit coverage for Spravato (esketamine) nasal spray in adults with major depressive disorder, specifying medical necessity criteria and required documentation, dosing limits (induction and maintenance), approval duration (initial and re-authorization up to 12 months), investigational or not medically necessary uses, applicable coding, and monitoring/administration requirements including supervised administration with approximately 2 hours post-administration observation.

Key thresholds

Age>= 18 years

Induction dosing84 mg twice weekly for weeks 1-4 OR 56 mg on day 1 then up to 84 mg twice weekly for 4 weeks

Maintenance dosing84 mg once weekly for the remainder of the first 12 months

Temporary increased maintenance dosing84 mg twice weekly for up to 8 weeks (then return to 84 mg once weekly)

Prior antidepressant trialsFailure of 3 antidepressants from >=2 classes OR 2 antidepressants from 2 classes plus an augmenting agent

Substance use remission definitionComplete abstinence for >=3 months (preferred) OR >=1 month with agreement to remain abstinent

Maintenance dose limit (week 5+)84 mg once weekly for the rest of the first 12 months of treatment

Max approval duration / Authorization periodInitial and re-authorization approvals up to 12 months

Initial Therapy Criteria (Medical Necessity) & Ongoing Use

Medical Necessity - Initial or Ongoing Treatment for Depression

Spravato may be considered medically necessary when ALL of the following are met:

ALL of the following

The individual is aged 18 years or older
Medical record documentation of DSM-5 diagnostic criteria for major depressive disorder without psychotic features (unipolar, not bipolar)
No present or past diagnosis of a bipolar disorder, and no history of any manic or hypomanic episodes
Current episode of depression is moderate to severe as demonstrated by documentation of individual's symptoms and their severity or by one or more standardized depression rating scales

Investigational / Not Medically Necessary

Uses considered investigational or not medically necessary:

ALL of the following

All other uses of Spravato for conditions not outlined in this policy are investigational (including treatment for chronic pain and bipolar depression)
Use in conjunction with any modality of neuromodulation (e.g., TMS, ECT, VNS) is investigational
Use in conjunction with any other formulation of ketamine or with any psychedelic drug is investigational
Spravato with more than one provider/group/clinic at the same time is considered not medically necessary

Provider Actions & Authorization Rules

Prior Authorization

Prior authorization required

Prior authorization is required before initiating Spravato (esketamine). Authorizations may be issued for up to 12 months. For individuals who started Spravato under a prior (non-Company) plan, the original medical necessity criteria must have been met at that time for coverage to continue under this policy.

Initial authorization: up to 12 months
Re-authorization: up to 12 months when clinical benefit is documented
If Spravato was started under a non-Company plan, prior-plan start must have met medical necessity criteria

Documentation Required

Document DSM-5 diagnosis and severity

Document DSM-5 diagnostic criteria and severity for major depressive disorder (unipolar, not bipolar). Records should show the current episode is moderate to severe using clinical notes or one or more standardized depression rating scales.

Applicable Codes

HCPCS / Drug / Administration codes listedmixed

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.
J0013	Esketamine, nasal spray (Spravato), 1 mg (new code effective 01/01/26).
S0013	Esketamine, nasal spray (Spravato), 1 mg (code termed effective 01/01/26).

HCPCS / J codes mentioned in historyHCPCS|CPT|mixed

G2082	HCPCS code added June 01, 2020 (coding update)
G2083	HCPCS code added June 01, 2020 (coding update)
J3490	HCPCS code removed January 01, 2021
S0013	HCPCS code added January 01, 2021; later termed
J0013	HCPCS code added (coding update) effective January 1, 2026

Clinical Evidence & Safety

-21.4 vs -17.0TRANSFORM-2 primary outcome (MADRS change), p=0.02 (N=223)

0.49SUSTAIN-1 relapse hazard ratio (95% CI 0.29-0.84)

41%,29%,28%,23%Common adverse events >=5% (placebo-adjusted): dissociation 41%, dizziness 29%, nausea 28%, sedation 23%

ASPIRE/TRANSFORM/SUSTAINKey randomized trials cited: ASPIRE I & II; TRANSFORM series; SUSTAIN series

Prescribing information referenced: Spravato Prescribing Information, Revised March 2026 (Janssen Pharmaceuticals). Key randomized trials cited in the evidence base include the ASPIRE I & II studies, the TRANSFORM series (including TRANSFORM-2), and the SUSTAIN series, with additional publications through 2025 supporting the policy.

Background and Definitions

Background: Spravato (esketamine) is the S‑isomer of ketamine approved for treatment‑resistant depression and previously indicated for MDD with acute suicidal ideation/behavior. It is available only through a REMS program and must be administered under direct supervision with monitoring for approximately 2 hours after each treatment. Significant safety concerns include sedation, dissociation, abuse/misuse potential, and an increased risk of suicidal thoughts/behavior noted in pediatric and young adults; the product has a history of indication and criteria changes reflected in the policy history.

Term	Definition
Failed trial	Not effective, partially but inadequately effective, initially effective then lost effectiveness, or intolerable side effects. Each failed medication must be identified and documented.
Remission of substance use disorder	Complete abstinence for at least 3 months (preferred) or at least 1 month with agreement to remain abstinent.
Remission of substance use disorder (historical variation)	Variously defined across policy history: complete abstinence for one month or three months, or absence of DSM criteria for at least three months. Current policy language allows remission or at least one month abstinence with agreement to remain abstinent.

Revision History

07/01/19policy_added

New policy approved June 11, 2019 establishing coverage criteria for Spravato (esketamine) nasal spray.

06/01/20coding_update

Coding update added HCPCS codes G2082 and G2083.

01/01/21coding_update

Annual review removed HCPCS code J3490 and added HCPCS code S0013; no changes to policy statements.

Policy Summary

PayerPremera Bluecross

PolicySpravato (esketamine) Nasal Spray

Policy CodePolicy 5.01.609

Change TypeMultiple annual and interim updates (coding, dosing, coverage criteria)

Effective DateJun 1, 2026

Next Review Date

Key ActionDocument DSM-5 diagnosis and severity, prior failed medication trials and induction/maintenance dosing in the medical record per policy before authorizing Spravato.

SourceLink

On This Page

No current or past psychosis

Substance use condition

No current substance use disorder unless in remission (complete abstinence for at least 3 months)
Complete abstinence for at least 1 month and the individual agrees to continue to remain abstinent
Confined 24/7 in a hospital or residential treatment facility or similar facility where access to alcohol or non-prescribed drugs is not possible and the individual has agreed to not use alcohol or non-prescribed drugs after discharge while continuing treatment with Spravato

No concurrent use of any hallucinogens/psychedelics

No concurrent use of any illicit drugs

No concurrent use of any illicit or non-prescribed stimulants

No concurrent use of any prescribed stimulants in excess of prescribed doses

No concurrent use of any prescribed controlled medications that were not prescribed for the individual

Prior treatment failures (ONE of)

Tried and failed 3 antidepressants from at least 2 different classes
Tried and failed 2 antidepressants from 2 different classes plus an augmenting agent

Induction dose (weeks 1-4) limited to 84 mg twice per week, or 56 mg on day 1 followed by no more than 84 mg twice per week for 4 weeks84 mg twice weekly (or 56 mg day 1 then up to 84 mg twice weekly)

Maintenance dose (week 5 and after) limited to 84 mg once weekly for the rest of the first 12 months of treatment84 mg once weekly (week 5 and after)

Temporary Increase in Frequency During Maintenance

A temporary increase in frequency during maintenance may be considered medically necessary when:

ALL of the following

ANY of the following
- The individual's depression was mild or in remission during maintenance treatment, and depression has worsened to moderate or severe as demonstrated by documentation of symptoms or standardized rating scales
- The individual's depression was moderate during maintenance treatment, and depression has worsened to severe as demonstrated by documentation of symptoms or standardized rating scales
Dose prescribed is limited to 84 mg twice per week for no more than 8 weeks84 mg twice weekly for up to 8 weeks
Dose then returns to maintenance dose limited to 84 mg once weekly84 mg once weekly

New Course (repeat course) of Spravato

A new course starting with an induction dose may be considered medically necessary when ALL of the following are met:

ALL of the following

The individual previously met criteria for coverage for Spravato and had a course of treatment
Had a positive response to the previous course of treatment with Spravato
Previous course of treatment with Spravato was terminated, and the time since the last Spravato treatment is greater than 30 days>30 days since last treatment
Current episode of depression is moderate to severe as demonstrated by documentation of symptoms or standardized rating scales
No new or past or previously undisclosed diagnosis of a bipolar disorder and no new or past or previously undisclosed manic or hypomanic episodes
No current or past psychosis
Substance use condition (repeat course)
- No current substance use disorder unless in remission (complete abstinence for at least three months)
- Complete abstinence for at least one month and the individual agrees to continue to remain abstinent
- Confined 24/7 in a hospital or residential treatment facility or similar facility where access to alcohol or non-prescribed drugs is not possible and the individual has agreed to not use alcohol or non-prescribed drugs after discharge while continuing treatment with Spravato
No concurrent use of hallucinogens/psychedelics, illicit drugs, illicit/non-prescribed stimulants, or prescribed stimulants in excess of doses
No concurrent use of any prescribed controlled medications that were not prescribed for the individual
If the individual uses alcohol or marijuana, the individual agrees to either cease use while being treated with Spravato or to not use within 24 hours before and 24 hours after each Spravato treatment24 hours before and after each treatment
Induction and maintenance dosing limits as specified above must be followedInduction and maintenance dosing limits per policy

Use that meets age and diagnosis but does not meet other policy criteria within Medical Necessity is considered not medically necessary

Formulations other than Spravato nasal spray (e.g., IV, IM, SC, oral) are investigational for any symptom or condition

Documentation Required

Document prior medication trials

Document prior medication trials: list each antidepressant and augmenting agent tried, duration, dose, and reason for failure (ineffective, partially/inadequately effective, loss of effect, or intolerable side effects). Required failure pattern: either 3 antidepressants from at least 2 different classes, or 2 antidepressants from 2 different classes plus an augmenting agent.

Each failed medication must be identified with reason for failure
If restarting Spravato after >30 days since last treatment, this qualifies as a new course (see New course requirement)

Documentation Required

Bipolar and psychosis exclusion documentation

Provide documentation that there is no current or past diagnosis of bipolar disorder and no history of manic or hypomanic episodes. Also document absence of current or past psychosis.

If any bipolar or psychotic symptoms are identified, Spravato is not medically necessary per policy

Documentation Required

Substance use limitations and agreements

Document substance use history and agreements: no current substance use disorder unless in remission (complete abstinence ≥3 months) or abstinence ≥1 month with agreement to remain abstinent. If confined in a facility where access is impossible, document the confinement and agreement not to use post-discharge while continuing Spravato. If alcohol or marijuana use occurs, individual must agree to cease use during treatment or abstain for 24 hours before and 24 hours after each treatment.

Specify remission duration or abstinence agreement
Document facility confinement when applicable

Documentation Required

Record details required

Record details required in the medical record: induction and maintenance dosing, dates of each treatment, dose administered per treatment session, response assessments (standardized scales or clinical notes), adverse events, and any temporary increases in frequency with rationale and duration.

Induction dosing options and limits must be recorded (see Induction dosing option)
Maintenance dosing and any temporary frequency increase must be documented with start/stop dates and clinical justification

Documentation Required

Induction and maintenance dosing

Induction dosing options must be documented: either 84 mg twice weekly for weeks 1–4, or 56 mg on day 1 followed by up to 84 mg twice weekly for 4 weeks. Maintenance dosing (week 5 and after) is limited to 84 mg once weekly for the remainder of the first 12 months.

Induction: 84 mg twice weekly for weeks 1–4 OR 56 mg day 1 then ≤84 mg twice weekly for 4 weeks
Maintenance: 84 mg once weekly (week 5 onward) up to 12 months

Documentation Required

Temporary frequency increase allowance

A temporary increase in maintenance frequency may be allowed when the individual's depression worsens (from mild/remission to moderate/severe, or from moderate to severe) as documented by clinical assessment or standardized scales. The temporary regimen is limited to 84 mg twice per week for no more than 8 weeks, after which dosing should return to 84 mg once weekly.

Temporary increase: up to 84 mg twice weekly for ≤8 weeks with documentation of clinical worsening
Return to maintenance dosing (84 mg once weekly) after temporary period

Documentation Required

New course requirement

A new course requirement: to start a new course with induction dosing, the individual must have previously met coverage criteria for Spravato, had a prior positive response, the previous course was terminated, and >30 days have passed since the last Spravato treatment. Current episode must be moderate to severe and meet all standard exclusion and substance-use requirements.

Previous positive response to Spravato required
>30 days since last Spravato treatment to qualify as a new course

Billing Rule

Administration and monitoring required

Administration and monitoring are required: Spravato must be administered under direct supervision with appropriate monitoring for at least two hours post-dose observation as clinically indicated. Report administration/observation per applicable guidance.

2-hour observation/G2082-G2083 guidance: ensure monitoring infrastructure is available at the administering site
Spravato with more than one provider/group/clinic at the same time is considered not medically necessary

Billing Rule

Coding updates - report appropriate HCPCS

Coding updates — report the appropriate HCPCS/administration codes. Note that J0013 became effective 01/01/2026 and S0013 is retired/termed. Use current HCPCS codes for the drug and for observation/administration as applicable.

J0013 effective 01/01/2026
S0013 is termed — do not use
Report observation/administration codes (e.g., G2082/G2083) where applicable

Denial Risk

Not medically necessary or investigational scenarios

Not medically necessary or investigational scenarios that commonly result in denials include: use for bipolar depression or any bipolar diagnosis, use in patients with current psychosis, use when policy-specified age or diagnostic criteria are not met, use with other ketamine formulations or with psychedelics, and use without required prior medication failures or documentation. Also not medically necessary: concurrent treatment by more than one provider/group/clinic.

Use in bipolar depression, chronic pain, or other indications not listed in policy — investigational
Concurrent use with IV/IM/oral ketamine or any psychedelic — investigational
Missing documentation of required failed medication trials or DSM-5 diagnosis — denial risk
Concurrent care by multiple providers/groups — not medically necessary

01/01/22coverage_expansion

Added coverage for treatment of MDD with acute suicidal ideation or behavior when criteria are met; re-authorization required continued use with an oral antidepressant; dosing limits aligned with FDA prescribing information.

06/01/22criteria_added

Added criteria for a 'new course' of Spravato and prohibited concurrent use of mind-altering/mood-altering substances (including alcohol, marijuana, stimulants, hallucinogens/psychedelics).

11/01/22criteria_redefinition

Interim review updated prior treatment failure definition to require three antidepressants from at least two classes or two antidepressants from two classes plus augmenting agent and defined remission as complete abstinence for three months; added investigational listing for use with other ketamine formulations or psychedelics.

05/01/23documentation_requirement_added

Added requirement that each failed medication must be individually identified with reasons for failure and documentation of at least 30 continuous days for each failed trial; clarified DSM-5 documentation and named oral antidepressant when used in conjunction.

08/01/23new_course_requirement

Interim review added requirement that individuals must have had a positive response to the previous course of Spravato to qualify for a new course.

08/01/24criteria_clarified

Removed stipulation that addition of a second antidepressant constitutes an augmenting agent rather than a separate antidepressant trial.

10/01/24dosing_option_added

Added induction option: 56 mg on first day then up to 84 mg twice weekly for first 4 weeks; reiterated that non-Spravato formulations are investigational.

03/01/25monotherapy_approval_alignment

Removed requirement that an oral antidepressant must be used with Spravato, consistent with FDA Jan 21, 2025 approval of Spravato monotherapy.

06/01/25substance_remission_clarified

Clarified substance use disorder remission definitions (complete abstinence for at least three months or verification of absence of DSM criteria for at least 3 months); added prohibition on concurrent use of prescribed controlled meds not prescribed for the individual; increased initial authorization period to 12 months; deleted separate criteria for acute suicidality indication.

12/01/25maintenance_dose_limit_clarified

Clarified maintenance dose limit: week 5 and after limited to 84 mg once weekly for the rest of the first 12 months of treatment and for re-authorization.

01/01/26coding_update

Added HCPCS J0013 and indicated S0013 termed effective January 1, 2026; modified substance use criterion to allow either remission or complete abstinence for at least one month with agreement to remain abstinent; added allowance for temporary increase in frequency during maintenance when depression worsens.

03/01/26documentation_clarified

Added criteria clarifications to explicitly require no new or past or previously undisclosed bipolar diagnosis for new episodes or re-authorization and added 'no current psychosis' for re-authorization.

03/01/25evidence_update

Following a comprehensive review (March 2025), separate coverage criteria for MDD with acute suicidal ideation/behavior were removed due to insufficient evidence; MDD criteria now apply regardless of acute suicidality.

06/01/26annual_review_noteLatest

06/01/26 Annual Review: Reviewed prescribing information and literature (Spravato PI revised March 2026); no changes to policy statements (clarification entry).