Esketamine (Spravato^TM) 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. Individuals with acute suicidal ideation may benefit from hospitalization.

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

Treatment Resistant Major Depressive Disorder (MDD)

• 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 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
• Individual is not receiving esketamine (Spravato) in conjunction with transcranial magnetic stimulation (TMS); 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

Continuation of Therapy

• Individual has demonstrated sustained improvement from baseline in depressive symptoms as documented by standardized rating scales that reliably measure depressive symptoms; and
• Individual will continue to receive esketamine (Spravato) in conjunction with an oral antidepressant; and
• Dosing is in accordance with the FDA approved labeling and does not exceed 84 mg per week.

Esketamine (Spravato) not meeting the criteria as indicated in this policy is considered not medically necessary.

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

MDD with Acute Suicidal Ideation

• 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 MDD based on the current DSM by a mental health professional; and
• Individual has suicidal ideation with intent, confirmed by individual, and may warrant potential hospitalization; and
• Individual may not have a current DSM-5 diagnosis of bipolar (or related) disorder, obsessive-compulsive disorder (OCD), antisocial personality disorder or borderline personality disorder; and.
• Individual may not have a current or prior DSM-5 diagnosis of a psychotic disorder or MDD with psychosis; and
• Individual may not have a history of moderate to severe substance or alcohol use disorder within 6 months of screening; and.
• Individual may not have a positive urine test result for phencyclidine, cocaine or amphetamines; and
• Esketamine (Spravato) is not to be used as monotherapy and is being prescribed in conjunction with least one oral antidepressant; and
• Individual is not receiving esketamine (Spravato) in conjunction with transcranial magnetic stimulation (TMS); 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; and
• Treatment with esketamine (Spravato) does not exceed four (4) weeks.

Esketamine (Spravato) not meeting the criteria as indicated in this policy is considered not medically necessary.

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. Highmark may deny, in full or in part, reimbursement for utilization that does not fall within the applicable dosage and/or frequency limits.

The use of esketamine (Spravato) is typically an outpatient procedure which is only eligible for coverage as an inpatient procedure in special circumstances, including, but not limited to, the presence of a co-morbid condition that would require monitoring in a more controlled environment such as the inpatient setting.