Esketamine (Spravato)

Section: Injections
Effective Date: July 15, 2019
Revised Date: July 05, 2019


Esketamine (SpravatoTM) is the S-isomer of racemic ketamine and is an antidepressant which is a non-selective, non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor (an ionotropic glutamate receptor). Due to adverse events (sedation, dissociation, etc.) an individual must be monitored by a healthcare provider while administering the medication and for at least two hours after administration is complete. Due to the risk of increased blood pressure with administration, the healthcare provider should monitor the individual’s blood pressure before and after treatment.


Coverage is subject to the specific terms of the member’s benefit plan.

Federal Employee Program members (FEP) should check with their Retail Pharmacy Program to determine if prior approval is required by calling the Retail Pharmacy Program at 1-800-624-5060 (TTY:1-800-624-5077). FEP members can also obtain the list through the website.

Esketamine (Spravato) may be considered medically necessary for the treatment of individuals 18 years of age and older when ALL of the following criteria are met:

  • Prescribed by or in consultation with a licensed mental health professional with prescriptive authority (e.g., psychiatrist, psychiatric or mental health nurse practitioner, etc.); and
  • Diagnosis of treatment resistant major depressive disorder (MDD) based on the current DSM by a mental health professional; and
  • Individual has failed to adequately respond to at least three (3) different antidepressants which may be defined as:
    • Individual has had no response at minimal therapeutic dose for four (4) weeks of therapy resulting in therapy change; or
    • Individual has had no response or a partial response with dose limiting side effects resulting in therapy change; or
    • Individual has had a partial response at or above maximum therapeutic dose for a treatment duration of at least eight (8) weeks resulting in therapy change; and
  • At least one of these antidepressant trials must be in the current episode of depression; and
  • Individual has failed to adequately respond to at least one (1) trial of augmentation with a second agent along with one of the antidepressant trials; and
  • Esketamine (Spravato) is not to be used as monotherapy and is being prescribed in conjunction with least one oral antidepressant; and
  • Healthcare setting and pharmacy are certified by and individual will be enrolled in the Spravato Risk Evaluation and Mitigation Strategy (REMS) program, providing the appropriate monitoring to include at least two (2) hours of observation by the healthcare provider after administration of esketamine (Spravato) by the individual in the healthcare setting.

Esketamine (Spravato) for any other indication is considered experimental/investigational and, therefore, non-covered. Scientific evidence does not support the use of esketamine (Spravato) for any other indication.

Procedure Codes


NOTE: In addition to the above criteria, product specific dosage and/or frequency limits may apply in accordance with the U.S. Food and Drug Administration (FDA)-approved product prescribing information, national compendia, Centers for Medicare and Medicaid Services (CMS) and other peer reviewed resources or evidence-based guidelines. Blue Cross Blue Shield of North Dakota may deny, in full or in part, reimbursement for utilization that does not fall within the applicable dosage and/or frequency limits.

Diagnosis Codes

F32.0  F32.1  F32.2  F32.3  F32.4  F32.8  F32.9 
F33.0  F33.1  F33.2  F33.3  F33.41  F33.8  F33.9