CurrentPremera BluecrossPolicy 5.01.609

PHARMACY / MEDICAL POLICY - 5.01.609 Spravato (esketamine) Nasal Spray

Defines medical necessity, coverage limitations, dosing limits, investigational and not medically necessary uses, documentation and coding requirements, and approval durations for Spravato (esketamine) nasal spray for treatment of depression for individuals aged ≥18. Applies to pharmacy and medical benefit; administered under supervision with observation.

Policy Summary

PayerPremera Bluecross

PolicyPHARMACY / MEDICAL POLICY - 5.01.609 Spravato (esketamine) Nasal Spray

Policy CodePolicy 5.01.609

Change TypeMultiple clarifications and dosing/authorization updates

Effective DateMar 1, 2026

Next Review Date

Key ActionInitial authorization or repeat course may be approved up to 12 months; re-authorization requires documentation of clinical benefit/response and continued meeting of policy criteria.

POLICY UPDATE CHANGES

2025 Update removed separate coverage criteria for MDD with acute suicidal ideation or behavior and applied MDD criteria to individuals with or without acute suicidal ideation or behavior.

2023 Update clarified DSM-5 documentation requirement and substance use/remission criteria and concurrent substance restrictions.

2024 Update clarified investigational vs not medically necessary classification for uses not meeting policy criteria and removed stipulation about second antidepressant vs augmenting agent.

2021 Update added dosing limits per FDA and clarified re-authorization must include continued use with an oral antidepressant.

Added criterion requiring no present or past diagnosis of bipolar disorder and no history of manic or hypomanic episodes (01/01/26).

Added more specific criteria for new episodes and re-authorization: no new or past or previously undisclosed bipolar disorder or manic/hypomanic episodes, and no current psychosis for re-authorization (03/01/26).

Changed initial authorization period to 12 months and removed separate non-formulary exception language (06/01/25).

Removed requirement that Spravato must be used with an oral antidepressant to align with FDA monotherapy approval (03/01/25).

Defined remission for substance use disorder as complete abstinence for three months and later adjusted to three months verification (06/01/25) and then to at least one month with agreement to remain abstinent (01/01/26).

Added HCPCS/J-code J0013 and indicated S0013 has been termed, effective January 1, 2026 (01/01/26 coding update).

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

>=18Minimum age (years)

84 mgMax per-dose maintenance

84 mg x2Max temporary intensified frequency

12 monthsMax approval duration

3Failed antidepressants generally required

Coverage Summary & Scope

Scope: This policy defines medical necessity, coverage limits, dosing thresholds, documentation and coding requirements, investigational and not medically necessary uses, and approval durations for Spravato (esketamine) nasal spray for the treatment of depression in individuals aged >= 18 years. Spravato is indicated for treatment-resistant depression in adults and was previously approved for MDD with acute suicidal ideation or behavior. Coverage stance: covered with criteria. The policy applies to both the pharmacy and medical benefits and requires that Spravato be administered under the direct supervision of a healthcare provider with post-administration observation.

Key thresholds

Age>= 18 years

Induction dosing limitUp to 84 mg twice weekly for weeks 1-4 (or 56 mg on day 1 then up to 84 mg twice weekly)

Maintenance dosing limit84 mg once weekly (week 5 onward for the first 12 months)

Temporary intensified dosing limit84 mg twice weekly for no more than 8 weeks, then return to maintenance

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

Initial Therapy / Medical Necessity Criteria

Medical Necessity - Initial/Current Treatment for Depression

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

ALL of the following

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

Temporary Increase During Maintenance

Temporary Increase in Frequency During Maintenance

A temporary increase may be considered medically necessary when the following are met:

ALL of the following

Worsening from baseline severity (ONE of)
- Individual's depression was mild or in remission during maintenance and has worsened to moderate or severe as documented by symptoms or standardized scales
- Individual's depression was moderate during maintenance and has worsened to severe as documented by symptoms or standardized 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

New / Repeat Course Criteria

New Course (Repeat Course) of Spravato

New course starting with an induction dose may be considered medically necessary when ALL are met:

ALL of the following

Individual previously met criteria for coverage and had a course of treatment with Spravato
Had a positive response to the previous course of treatment with Spravato
Previous course was terminated and time since 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 and/or standardized rating scales

Continuation Therapy / Re-authorization Criteria

Length of Approval / Re-authorization Criteria

Approval up to 12 months when ALL of the following at re-authorization are met:

ALL of the following

Chart notes document improvement in signs and symptoms of major depressive disorder as demonstrated by documentation of symptoms and/or standardized rating scales
No new or past or previously undisclosed diagnosis of a bipolar disorder or manic/hypomanic episodes
No current psychosis
SUBSTANCE USE requirement (ONE of)
- No current substance use disorder unless in remission (complete abstinence for at least three months)

Not Medically Necessary / Investigational

Other uses and certain scenarios are excluded:

ALL of the following

Spravato used with more than one provider/group/clinic at the same time is considered not medically necessary
Use that meets age and diagnosis but does not meet other Medical Necessity criteria is considered not medically necessary
All other uses not outlined in this policy are investigational, including but not limited to treatment for chronic pain and bipolar depression
Use in conjunction with any modality of neuromodulation (e.g., TMS, ECT, VNS) is investigational

Provider Actions & Authorization Requirements

Prior Authorization

Authorization and duration

Initial authorization or repeat course may be approved up to 12 months; re-authorization requires documentation of clinical benefit/response and continued meeting of policy criteria. Note: authorization period is 12 months regardless of formulary status.

Authorization period is 12 months regardless of formulary or non-formulary status.

Documentation Required

Documentation of diagnosis and failed trials

Medical records must document DSM-5 diagnostic criteria for major depressive disorder (unipolar) and each failed antidepressant trial with the name and reason for failure; documentation must specify the oral antidepressant to be used with Spravato when applicable (historical/brief note).

Document DSM-5 MDD diagnostic criteria (unipolar, not bipolar).

Applicable Codes

HCPCS codes for supervised administrationHCPCSCovered

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

Drug J-code / HCPCS product codesHCPCSCovered

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-code updates referenced in historyHCPCS

G2082	HCPCS code added (coding update 06/01/20)
G2083	HCPCS code added (coding update 06/01/20)
S0013	HCPCS code added 01/01/21; later termed (history)
J0013	New HCPCS/J-code added effective January 1, 2026 (coding update)

Clinical Evidence Highlights

-21.4 vs -17.0TRANSFORM-2 MADRS change at 4 weeks (p=0.02)

no sig diffTRANSFORM-1 / TRANSFORM-3 primary MADRS (p=0.088; p=0.059)

HR 0.49SUSTAIN-1 relapse risk vs placebo (95% CI 0.29-0.84); median time to relapse 273d placebo vs not estimable for esketamine

acute MADRS day2ASPIRE I/II: statistical superiority vs placebo on MADRS at 24 hours after first dose

Background evidence: Multiple Phase 3 trials (TRANSFORM programs, SUSTAIN long-term studies, and ASPIRE I/II) showed mixed efficacy for esketamine—TRANSFORM-2 showed a statistically significant MADRS advantage while TRANSFORM-1 and TRANSFORM-3 did not meet primary endpoints; SUSTAIN-1 demonstrated reduced relapse risk; ASPIRE studies showed rapid MADRS improvement in acutely suicidal patients but mixed results on suicidality-specific measures. Safety concerns include sedation, dissociation, abuse/misuse potential, and warnings for increased suicidal thoughts/behavior; these risks are reflected in boxed warnings and the product is distributed under a REMS requiring administration by a healthcare professional and monitoring (including 2-hour post-treatment observation). A comprehensive 2025 review found no significant effect on suicidality and led to removal of separate coverage criteria for MDD with acute suicidal ideation/behavior; the FDA prescribing information and key randomized trials are cited as primary sources for these findings.

Definitions & Background

Spravato (esketamine) is indicated for treatment-resistant depression in adults and was previously indicated for MDD with acute suicidal ideation or behavior. Significant safety concerns—documented boxed warnings include risks of sedation, dissociation/perceptual changes, abuse or misuse, and increased suicidal thoughts/behavior—have resulted in a REMS program and the requirement that Spravato be administered in a healthcare setting with observation and monitoring for 2 hours after each treatment session. The FDA prescribing information and the policy's cited trials support these indications and safety requirements.

Term	Definition
Failed trial	Not effective, partially but inadequately effective, initially effective but then lost effectiveness, or intolerable side effects
Augmenting agents	Second generation antipsychotics, lithium, and anticonvulsants utilized as mood stabilizers are considered augmenting agents, not antidepressants
Remission (substance use disorder)	Initially defined as complete abstinence for three months; later modified to remission or complete abstinence for at least one month with agreement to remain abstinent

Revision History

07/01/19new_policy

New policy created establishing Spravato (esketamine) nasal spray medical necessity criteria for treatment of depression.

06/01/20coding_update

Coding update added HCPCS codes G2082 and G2083 for supervised administration and observation.

01/01/21code_change

HCPCS code S0013 added (J3490 removed); no changes to policy statements.

Policy Summary

PayerPremera Bluecross

PolicyPHARMACY / MEDICAL POLICY - 5.01.609 Spravato (esketamine) Nasal Spray

Policy CodePolicy 5.01.609

Change TypeMultiple clarifications and dosing/authorization updates

Effective DateMar 1, 2026

Next Review Date

Key ActionInitial authorization or repeat course may be approved up to 12 months; re-authorization requires documentation of clinical benefit/response and continued meeting of policy criteria.

On This Page

No current or past psychosis

SUBSTANCE USE requirement (one of)

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 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

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 treatment

Prior antidepressant treatment requirement (ONE of)

Tried and failed three antidepressants from at least two different classes
Failed trial = not effective, partially effective, initially effective then lost effect, or intolerable side effects
Tried and failed two antidepressants from two 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 weeksUp to 84 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 onward for first 12 months)

Dose then returns to maintenance dose limited to 84 mg once weekly84 mg once weekly

No new or past or previously undisclosed diagnosis of a bipolar disorder or manic/hypomanic episodes

No current or past psychosis

SUBSTANCE USE requirement (ONE of)

No current substance use disorder unless in remission (complete abstinence for at least three months)complete abstinence >=3 months preferred
Complete abstinence for at least one month and the individual agrees to continue to remain abstinent>=1 month with agreement 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, prescribed stimulants in excess of doses, or prescribed controlled meds not prescribed for the individual

If the individual uses alcohol or marijuana, agrees to either cease use while treated or not use within 24 hours before and 24 hours after each treatment

Induction and maintenance dosing limits as specified for initial therapy (induction up to 84 mg twice weekly etc.)Induction: up to 84 mg twice weekly; Maintenance: 84 mg once weekly (week 5 onward for first 12 months)

complete abstinence >=3 months preferred

Complete abstinence for at least one month and the individual agrees to continue to remain abstinent>=1 month with agreement 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

If the individual uses alcohol or marijuana, agrees to either cease use while treated or not use within 24 hours before and 24 hours after each treatment

Improvement is being maintained (is not wearing-off)

Individual is not experiencing any serious or dangerous side-effects

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

Use in conjunction with any other formulation of ketamine or with any psychedelic drug is investigational

Spravato or esketamine in formulations other than Spravato nasal spray (IV, IM, SC, oral) is investigational for any symptom or condition

Use that does not meet the age or diagnosis requirements within Medical Necessity is investigational

Document each failed antidepressant trial: medication name and reason(s) for failure.

Specify the oral antidepressant that will be used with Spravato (per documentation requirement added 2023).

Documentation Required

Dosing documentation

Records should document induction and maintenance dosing frequency and the time periods specified consistent with a 12-month authorization; include induction and maintenance dosing details in the chart.

Document induction dosing frequency and time period as specified (e.g., weeks 1–4 dosing limits).
Document maintenance dosing frequency and the time period consistent with a 12-month authorization.
Record induction and maintenance dosing as clarified 08/01/25.

Billing Rule

Administration supervision and observation

Spravato must be administered under direct supervision with observation after dosing; report the appropriate supervised administration HCPCS codes.

Direct supervision and a 2-hour post-administration monitoring period are required.
Report G2082 for up to 56 mg supervised administration and G2083 for greater than 56 mg supervised administration.

Denial Risk

Concurrent substance or disallowed combinations

Claims may be denied if Spravato is used with disallowed concurrent substances, other ketamine formulations, or neuromodulation modalities.

Concurrent use with hallucinogens/psychedelics, illicit drugs, non-prescribed stimulants, or prescribed stimulants in excess of prescribed doses is disallowed.
Use with other formulations of ketamine or with neuromodulation modalities (e.g., TMS, ECT, VNS) is investigational/not allowed and may result in denial.

Documentation Required

Failed medication trial documentation; Substance use disorder remission definition; Bipolar and psychotic disorder exclusion documentation; Concurrent provider duplication; Abstinence agreement for confined individuals

Key remaining provider actions: document individual failed medication trials, define substance use remission, confirm absence of bipolar/psychotic disorder, avoid concurrent provider duplication, and document abstinence agreement for confined individuals.

Failed medication trial documentation: identify each failed medication and specify reason(s) for failure; document at least 30 continuous days unless stopped for intolerable adverse effects. (See Additional Information.)
Substance use disorder remission definition: historically defined as complete abstinence for ≥3 months and subsequently modified to allow ≥1 month with agreement to remain abstinent; policy history documents these changes.
Bipolar and psychotic disorder exclusion documentation: document no present or past bipolar disorder and no history of manic/hypomanic episodes; for re-authorization and new episodes, document no new or previously undisclosed bipolar diagnosis or manic/hypomanic episodes and no current psychosis.
Concurrent provider duplication: use with more than one provider/group/clinic at the same time is considered not medically necessary.
Abstinence agreement for confined individuals: for those confined 24/7 where access to substances is not possible, documentation that the individual has agreed to not use alcohol or non-prescribed drugs after discharge while continuing Spravato.

01/01/22coverage_update

Added coverage criteria for treatment of MDD with acute suicidal ideation or behavior and clarified re-authorization requirement that Spravato continue to be used with an oral antidepressant; added dosage limits per FDA prescribing information and investigational restriction for use with neuromodulation modalities.

06/01/22clarification

Added 'new course' coverage criteria and strengthened restrictions on concurrent use of mind-altering substances; re-authorization criteria updated to require no current substance use disorder unless in remission (complete abstinence for a month).

05/01/23clarified

Defined remission for substance use disorder as complete abstinence for three months; added not medically necessary designation for concurrent use with more than one provider; documentation requirements for failed medication trials specified (individual identification and reasons; 30-day minimum).

08/01/23clarified

New-course criteria clarified to require a positive response to a prior Spravato course; documentation requirement added to specifically name the oral antidepressant to be used with Spravato.

08/01/24revised

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

10/01/24dosing_update

Added induction option of 56 mg on first day followed by up to 84 mg twice weekly for first 4 weeks.

03/01/25revised

Removed requirement that Spravato must be used with an oral antidepressant to align with FDA monotherapy approval (FDA Jan 21, 2025); clarified medications are subject to FDA prescribing information.

06/01/25revised

Initial authorization period increased to 12 months; clarified substance use remission definition as complete abstinence for at least three months or verification none of DSM criteria met for three months; removed separate criteria for acute suicidal ideation/behavior; clarified concurrent prescribed controlled medications restriction.

08/01/25documentation_update

Documentation requirement clarified to include induction dose and maintenance dose frequency and time period.

12/01/25clarified

Clarified maintenance dose (week 5 and after) is limited to 84 mg once weekly for the rest of the first 12 months and for re-authorization the maintenance dose is limited to 84 mg once weekly for the next 12 months.

01/01/26revised

Added explicit criterion that there is no present or past diagnosis of bipolar disorder and no history of any manic or hypomanic episodes; modified substance use requirement to allow complete abstinence for at least one month with agreement to remain abstinent as an alternative; coding update added new HCPCS/J-code J0013 and indicated S0013 termed effective January 1, 2026.

03/01/26revisedLatest

Added requirement for new episodes and re-authorization that there be no new or past or previously undisclosed diagnosis of bipolar disorder or manic/hypomanic episodes and added no current psychosis for re-authorization (most recent policy effective Mar 1, 2026).