Ketalar (ketamine) and Spravato (esketamine) medical benefit drug policy (New Jersey)

Coverage Summary

Spravato (esketamine) is covered for Treatment‑Resistant Depression (TRD) — initial and continuation therapy and for MDD with acute suicidal ideation or behavior when the policy criteria are met. Ketalar (ketamine) injection is covered as an anesthetic agent for indicated procedural uses but is investigational/not medically necessary for psychiatric disorders and chronic pain per this policy. This policy is effective June 1, 2025 and applies to New Jersey only; it summarizes initial and continuation authorization (each limited to no longer than 12 months) and REMS requirements for Spravato as noted in the policy scope summary and coverage rationale.

Initial Therapy Criteria — Spravato (Esketamine) for Treatment-Resistant Depression (TRD)

Spravato (Esketamine) Nasal Spray - Initial Therapy for Treatment-Resistant Depression (TRD)

Spravato is proven and medically necessary when ALL of the following are met:

ALL of the following

Diagnosis of major depressive disorder (treatment-resistant) according to the current DSM (i.e., DSM-5-TR); diagnosis made by a mental health professional
Baseline clinical assessment documented using ONE of the following
- BDI: Beck Depression Inventory (BDI)
- HAMD: Hamilton Rating Scale for Depression (HAMD)
- PHQ-9: 9-item Patient Health Questionnaire (PHQ-9)
- MADRS: Montgomery-Asberg Depression Rating Scale (MADRS)
- QIDS: Quick Inventory of Depressive Symptomatology (QIDS)
Antidepressant trial history: History of failure of a trial of at least two different antidepressants or treatment regimens for a duration of at least 3 weeks each (document medication, date, and duration of trial)>= 2 trials, >= 3 weeks each
Examples of antidepressant or regimen: An antidepressant or treatment regimen would include classes or combinations such as SNRIs (e.g., duloxetine, venlafaxine), SSRIs (e.g., citalopram, fluoxetine, paroxetine, sertraline), bupropion, mirtazapine, tricyclic antidepressants (e.g., amitriptyline, clomipramine, nortriptyline), or augmentation with antipsychotics, lithium, or thyroid hormone
REMS certification: Provider and/or the provider's healthcare setting is certified in the Spravato REMS program
Spravato is available only through the Spravato REMS program with monitoring requirements
Authorization length: Initial authorization will be for no longer than 12 months<= 12 months
Dosing: Spravato dosing is in accordance with the U.S. FDA approved labeling
Refer to FDA labeling for dosing details

Prior Authorization

Prior authorization requirement and authorization duration

Initial and continuation authorizations for Spravato are limited to no longer than 12 months; prior authorization is required per plan policy to document criteria are met.

Documentation Required

Medication trial documentation

Document medication name, date, and duration for at least two failed antidepressant trials of ≥3 weeks each.

Continuation Therapy Criteria — Spravato (Esketamine)

Spravato (Esketamine) Nasal Spray - Continuation Therapy for TRD

Continuation therapy is proven and medically necessary when ALL of the following are met:

ALL of the following

Response or remission documented: Documentation of remission or a positive clinical response to Spravato therapy
Provide most recent scoring (e.g., last month) on an approved assessment
Most recent scoring demonstrating remission or clinical response on ONE of the following
- HAMD: Hamilton Rating Scale for Depression (HAMD)
- BDI:

MDD with Acute Suicidal Ideation/Behavior — Spravato

Spravato - Treatment of Depressive Symptoms with Acute Suicidal Ideation or Behavior

Spravato is proven and medically necessary when ALL of the following are met:

ALL of the following

Diagnosis of major depressive disorder according to the current DSM (DSM-5-TR), by a mental health professional
Acute suicidality: Patient is experiencing an acute suicidal ideation or behavior
REMS certification: Provider and/or the provider's healthcare setting is certified in the Spravato REMS program
Oral antidepressant:

Unproven / Not Medically Necessary — Spravato

Spravato - Not Medically Necessary / Unproven Uses

Spravato is unproven and not medically necessary for the following:

ANY of the following

Chronic pain (including but not limited to nonmalignant pain, fibromyalgia, neuropathic pain, complex regional pain syndrome, and reflex sympathetic dystrophy)
Anesthetic agent
Spravato is not approved as an anesthetic agent; safety and effectiveness as an anesthetic have not been established
Migraine headaches

Note: Spravato is FDA‑approved only for TRD and for depressive symptoms in adults with MDD with acute suicidal ideation or behavior and is available only through the Spravato REMS program because of risks of sedation, dissociation, and abuse/misuse. Per the policy, Spravato is not medically necessary when used as an anesthetic agent, for chronic pain, or for migraine indications.

Ketalar (Ketamine) — Covered Indications and Investigational Uses

Ketalar (Ketamine) Injection - Indications Considered Medically Necessary

Ketamine injection is considered medically necessary/covered for:

ANY of the following

Procedures without muscle relaxation: Anesthesia for diagnostic and surgical procedures that do not require skeletal muscle relaxation
Induction of anesthesia: The induction of anesthesia to administration of other anesthesia agents prior to their use
Supplemental anesthesia for low-potency agents, such as nitrous oxide

Ketamine Injection - Investigational / Not Medically Necessary

Applicable Codes

HCPCS / Procedure Codes (listed for reference)HCPCS

S0013	Esketamine, nasal spray, mg
J3490	Unclassified drugs

ICD-10 Diagnosis Codes (listed for reference related to MDD)ICD-10

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
F33.9	Major depressive disorder; recurrent; unspecified

Billing Rule

Use of HCPCS codes for claims

Report Spravato and related drug administration using applicable HCPCS codes (e.g., S0013; J3490) as applicable and per contract; inclusion of codes is for reference and does not guarantee reimbursement.

Provider Actions — What to Do

Clinical Evidence

MultiplePhase 3 randomized controlled trials (TRANSFORM, SUSTAIN, ASPIRE) with mixed efficacy outcomes

Pooled RCTsMeta-analysis: adjunctive intranasal esketamine showed greater study-defined response and remission vs placebo (effects as early as 2 hours, peaking at 24 hours)

Background and evidence summary: Major depressive disorder (MDD) is common and a substantial portion of patients (about 30–40%) fail to respond to first‑line treatments; patients who have failed at least two antidepressant trials generally comprise the TRD population described in the policy. Spravato is the S‑enantiomer of ketamine and is a non‑competitive NMDA receptor antagonist; it is FDA‑approved for TRD and for depressive symptoms in MDD with acute suicidal ideation or behavior, and is available only through the REMS program. Phase 3 esketamine trials had mixed efficacy outcomes: some randomized controlled Phase 3 studies (for example TRANSFORM and the randomized withdrawal maintenance study) showed statistically significant improvement on MADRS or time to relapse, while other short‑term parallel studies did not all meet the primary endpoint. A pooled meta‑analysis of intranasal esketamine RCTs showed greater study‑defined response and remission versus placebo beginning as early as 2 hours and peaking at 24 hours, but esketamine was also associated with higher rates of discontinuation due to intolerability. Evidence for ketamine in psychiatric disorders and chronic pain is limited, heterogeneous, and of low quality (small trials, short follow‑up), and the policy considers these uses investigational pending further high‑quality studies.

Definitions

Definitions: Treatment‑Resistant Depression (TRD) — history of failure of at least two different antidepressant treatments or treatment regimens for a duration of at least 3 weeks each, per the policy. Spravato REMS program — a restricted program requiring healthcare settings and pharmacies to be certified; Spravato must be administered under direct observation with monitoring for at least 2 hours post‑dose and dispensed only to certified healthcare settings and pharmacies enrolled in the REMS.

Revision History

2025-06-01revisedLatest

Revised coverage criteria for Spravato (esketamine) nasal spray: Updated list of applicable clinical assessments (added BDI; removed specific number of items for several rating scales), replaced prior wording on failure definition with history of failure of at least two antidepressants ≥3 weeks each, clarified augmentation options, and removed specific dosing requirements (refer to FDA labeling).

2025-06-01revised

Continuation therapy criteria updated: removed requirement that patient previously treated with Spravato and removed requirement to receive Spravato with an oral antidepressant; authorization length remains up to 12 months; dosing per FDA labeling; REMS certification requirement retained.

2025-06-01