sierra health and life Spravato/Ketalar Coverage Update

Coverage Criteria

Initial Therapy - TRD

Spravato (esketamine) for treatment-resistant depression (TRD) is covered when ALL of the following are met:

Diagnosis of major depressive disorder (treatment-resistant) according to the current DSM by a mental health professional

Prior treatment failures: History of failure of at least two different antidepressants or treatment regimens with documentation of medication, date, and durationeach trial ≥ 8 weeks

Acceptable regimens include SSRIs, SNRIs, bupropion, TCAs, mirtazapine, MAOIs, serotonin modulators, or augmentation strategies (antipsychotics, lithium, thyroid hormone)

REMS certification: Provider and/or the provider's healthcare setting is certified in the Spravato REMS program

Prescriber: Prescribed by or in consultation with a psychiatrist

Dosing: Spravato dosing is in accordance with United States FDA approved labeling

Authorization period: Initial authorization will be for no longer than 12 months12 months

Continuation of Therapy - TRD

Continuation (reauthorization) criteria for Spravato (TRD):

Clinical response: Documentation of remission or a positive clinical response to Spravato therapy

Must include recent assessment within the last month

Assessment scores: Submission of baseline and recent (within the last month) scores on BDI, HAMD, MADRS, PHQ-9, or QIDS demonstrating remission or score reductionrecent within last month

REMS and prescriber: Provider/setting REMS certified and prescribed by or in consultation with a psychiatrist

Dosing and authorization period: Dosing per FDA approved labeling; reauthorization will be for no longer than 12 months

Initial Therapy - MDD with acute suicidal ideation or behavior

Spravato for MDD with acute suicidal ideation or behavior is covered when ALL of the following are met:

Diagnosis of major depressive disorder according to the current DSM by a mental health professional

Acute suicidality: Patient is experiencing acute suicidal ideation or behavior

Concomitant antidepressant: Patient will receive Spravato in conjunction with a newly initiated or optimized oral antidepressant

Per trial protocols and FDA labeling

REMS and dosing: Provider/setting REMS certified and dosing per FDA approved labeling

Authorization period:

Ketamine injection - covered and investigational uses

Ketamine injection coverage stance:

Covered uses: Medically necessary for anesthesia for diagnostic and surgical procedures that do not require skeletal muscle relaxation; induction of anesthesia prior to other agents; supplemental anesthesia for low-potency agents (e.g., nitrous oxide)

Not covered uses: Investigational and not medically necessary for psychiatric disorders (including depression, bipolar disorder, PTSD), chronic pain (including fibromyalgia, neuropathic pain, CRPS), and migraine headaches

Clinical evidence and REMS-based administration constraints

Evidence summary and contexts where esketamine demonstrated benefit in trials

Esketamine demonstrated efficacy in:: Short-term trials (e.g., TRANSFORM-2) showed statistically significant improvement in MADRS versus placebo; SUSTAIN-1 randomized withdrawal showed longer time to relapse when continuing esketamine; ASPIRE I and II showed superiority on MADRS at 24 hours in adults with MDD and active suicidal ideation when added to standard of care; Popova et al showed greater MADRS improvement at day 28 when switching to esketamine plus a newly initiated antidepressant versus newly initiated antidepressant plus placebo.

Effect sizes and time-course vary by study; some short-term trials did not meet primary endpoints.

Safety and program requirements: Spravato is available only through a REMS; it must be dispensed and administered in certified healthcare settings with direct observation and at least 2 hours of post-dose monitoring due to risks including sedation, dissociation, and potential for abuse/misuse.

Spravato and ketamine are not supported for certain uses outside their approved indications. Spravato is unproven and not medically necessary when used as an anesthetic agent, for chronic pain (including fibromyalgia, neuropathic pain, complex regional pain syndrome/Reflex Sympathetic Dystrophy), and for migraine headaches. Ketamine injection is considered investigational and not medically necessary for psychiatric disorders (including but not limited to depression, bipolar disorder, and PTSD), chronic pain conditions, and migraine headaches.

Spravato is not approved as an anesthetic agent; its safety and effectiveness as an anesthetic have not been established. In addition, compounded ketamine products (including oral formulations) have been the subject of a recent FDA warning identifying potential risks when used for treatment of psychiatric disorders. Providers and payers should note the lack of approval and the FDA advisory when evaluating requests for non‑labeled uses.

The FDA has issued a public warning about potential risks associated with compounded ketamine products, including oral formulations, for treatment of psychiatric disorders. This advisory underscores safety concerns and supports caution or exclusion of such compounded formulations for psychiatric indications in coverage determinations.

Spravato is considered unproven and not medically necessary when proposed as an anesthetic agent or for chronic pain and migraine. Ketamine injection retains an approved role for anesthesia (induction and supplementation) but is investigational and not medically necessary for psychiatric disorders, chronic pain conditions, and migraine. Coverage for esketamine is limited to its labeled psychiatric indications and subject to REMS program requirements.

Evidence for ketamine use in bipolar depression and as an adjunct to electroconvulsive therapy is limited and rated as low or insufficient quality by technology assessments. Reviews conclude that single‑dose intravenous ketamine may produce a rapid but transient antidepressant effect, while repeated infusions show greater and more durable effects; overall, Hayes assigned ratings such as C (potential but unproven benefit) or D2 (insufficient evidence) for these uses, indicating the evidence does not support routine coverage.

Initial Therapy Requirements

Initial therapy - Spravato

Initial authorization requirements for Spravato

Diagnosis: Major depressive disorder (treatment-resistant) or MDD with acute suicidal ideation/behavior

Diagnosis per current DSM by a mental health professional

Prior therapy (TRD only): Failure of at least two different antidepressants or treatment regimens documented (medication, date, and duration) each ≥ 8 weeks≥ 2 trials, ≥ 8 weeks each

Includes listed classes and augmentation strategies

REMS: Provider/setting certified in Spravato REMS program

Continuation / Reauthorization

Spravato continuation therapy

Reauthorization requirements for Spravato

Clinical response evidence: Documentation of remission or positive clinical response with submission of baseline and recent assessment scores (BDI, HAMD, MADRS, PHQ-9, QIDS) demonstrating improvementrecent within last month

Reauthorization will be for no longer than 12 months

Continuation therapy evidence

Randomized withdrawal (SUSTAIN-1) findings on continuation

Continuation benefit: Patients who achieved ≥ 50% reduction in MADRS after 4 weeks of open-label esketamine plus oral antidepressant and entered optimization had statistically significant longer time to relapse if randomized to continue esketamine versus switch to placebo (both with oral antidepressant ongoing)≥ 50% MADRS reduction

Coding and Diagnosis Codes

Applicable HCPCS and ICD-10 codesmixed

J0013	Esketamine, nasal spray, 1 mg
J3490	Unclassified drugs
F33.0	Major depressive disorder, recurrent, mild
F33.1	Major depressive disorder, recurrent, moderate
F33.2	Major depressive disorder, recurrent severe without psychotic features
F33.3	Major depressive disorder, recurrent, severe with psychotic symptoms
F33.40	Major depressive disorder, recurrent, in remission, unspecified
F33.41	Major depressive disorder, recurrent, in partial remission
F33.42	Major depressive disorder, recurrent, in full remission
F33.8	Other recurrent depressive disorders

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Applicable HCPCS Codes - editsHCPCS

J0013	Added (applicable HCPCS code)
S0013	Removed (formerly applicable HCPCS code)

Antidepressant trial duration — policy vs. phase 3 trials

Policy-required trial durationEach prior antidepressant trial must be at least 8 weeks in duration per policy

Phase 3 trials definitionPhase 3 studies defined an adequate trial as ≥6 weeks for the purposes of trial inclusion

Documentation requiredDocument medication name, start/end dates, and duration for each prior trial

Provider Actions & Documentation

Prior Authorization

Prior Authorization & Documentation Required

Prior authorization is required for Spravato (esketamine) nasal spray. Submit documentation of diagnosis, prior antidepressant treatment failures (medication name, dates, duration), baseline depression assessment scores, and evidence that the prescribing provider and administration site are certified in the Spravato REMS program. Initial and reauthorization approvals are limited to no longer than 12 months.

Prior authorization required for Spravato for TRD
Document history of failure of at least two different antidepressants or regimens (each ≥ 8 weeks) including medication name, start/end dates, and duration
Provide baseline scoring on an approved depression assessment (BDI, HAMD, MADRS, PHQ-9, QIDS) prior to starting Spravato

Documentation Required

REMS Certification & Administration Requirements

Spravato must be dispensed and administered only in REMS-certified healthcare settings with patients enrolled in the Spravato REMS program. Administration must be performed under direct observation and the patient monitored for at least 2 hours after dosing. Coverage reviewers should verify REMS enrollment and that the provider/site certification is current.

Site of Care & Administration Settings

Prior Authorization

Ensure REMS certification of provider/setting

Providers and healthcare settings must be certified in the Spravato REMS program to administer Spravato; ensure site certification is current before scheduling treatment.

Certification of the administering healthcare setting in the Spravato REMS is required
Only REMS‑certified settings may dispense and administer Spravato

Documentation Required

Administer Spravato in certified setting with direct observation and ≥2‑hour monitoring

Dispense and administer Spravato only in REMS‑certified settings with direct observation of dosing and at least 2 hours of post‑dose monitoring; document these site‑of‑care processes in the patient record.

Direct observation of dosing by a healthcare provider is required
Record at least 2 hours of monitoring following each administration

Definitions

Treatment-resistant depression (TRD) — definition

Policy definition (short)Failure to have a clinically meaningful improvement after at least two different antidepressant agents prescribed at adequate dose and duration

Clinical population notePatients who have failed at least two trials generally comprise TRD; definition is not fully standardized

Phase 3 trial thresholdIn phase 3 studies, treatment resistance was defined as ≤25% improvement after ≥6 weeks on ≥2 antidepressants

Esketamine / Spravato — description and indications

Drug identity and mechanismSpravato (esketamine) is the S‑enantiomer of racemic ketamine and a non-competitive NMDA receptor antagonist

Indications

Step Therapy

Requirement	Details
Failure of prior antidepressant trials
History of failure of a trial of at least two different antidepressants or treatment regimens
Minimum duration per trial
Each trial must be for a duration of at least 8 weeks (document medication, date, and duration)
Accepted classes/regimens
Includes SSRIs, SNRIs, bupropion, tricyclics, mirtazapine, MAOIs, serotonin modulators, or augmentation strategies (antipsychotics, lithium, thyroid hormone)

Statement	Notes
No explicit step-therapy algorithm in policy excerpt
The document does not specify a mandated sequencing algorithm; trials enrolled patients with prior inadequate response (e.g., Popova et al required retrospective nonresponse to 1–5 antidepressants)
Clinical-trial contexts commonly required prior inadequate response
Meta-analysis and trials evaluated adjunctive or switched-to esketamine in patients with prior nonresponse; benefit seen as early as 2–24 hours and up to 28 days in RCTs

Background

Major depressive disorder (MDD) is common and can be severe; a substantial minority of patients—approximately 30–40%—fail first‑line treatments and may meet criteria for treatment‑resistant depression (TRD). TRD is generally defined in this policy as failure to achieve clinically meaningful improvement after at least two different antidepressant trials given at adequate dose and duration, and esketamine (Spravato) is indicated for TRD and for depressive symptoms with acute suicidal ideation or behavior when used per FDA labeling and REMS requirements.

OpenPayer

Ketalar (Ketamine) and Spravato (Esketamine) coverage