Intravenous (IV) infusion of lidocaine or ketamine has been used for the treatment of chronic neuropathic pain. Chronic neuropathic pain disorders include phantom limb pain, post-herpetic neuralgia, complex regional pain syndromes, diabetic neuropathy, and pain related to stroke or spinal cord injuries. For this application, one or more courses of IV infusion would be administered over a period of several hours or several days.

Lidocaine, which prevents neural depolarization through effects on voltage-dependent sodium channels, is also used systemically for the treatment of arrhythmias. Lidocaine should only be given intravenously to patients with normal conduction on electrocardiography and normal serum electrolyte concentrations to minimize the risk of cardiac arrhythmias. IV lidocaine is approved by the U.S. Food and Drug Administration for systemic use in the acute treatment of arrhythmias and locally as an anesthetic; IV lidocaine for the treatment of chronic pain is an off-label use.

Ketamine is an antagonist of the N-methyl-_-aspartate receptor and a dissociative anesthetic. It is the sole anesthetic agent approved for diagnostic and surgical procedures that do not require skeletal muscle relaxation. Respiratory depression may occur with overdosage or too rapid a rate of administration of ketamine; it should be used by or under the direction of physicians experienced in administering general anesthetics. The potential benefits of pain control must be carefully weighed against the potential for serious, harmful adverse events. Ketamine hydrochloride injection is approved for diagnostic and surgical procedures that do not require skeletal muscle relaxation, for the induction of anesthesia before the administration of other general anesthetic agents, and to supplement low-potency agents, such as nitrous oxide. IV ketamine for the treatment of chronic pain is an off-label use.

Intravenous infusion of anesthetics (e.g., Ketamine hydrochloride, or lidocaine) for the management of chronic pain, chronic neuropathic pain, chronic daily headache, and fibromyalgia is considered experimental/investigational, and therefore, not covered. Scientific evidence does not support the use of intravenous infusion of anesthetics for chronic pain.

Ketamine (Ketalar) may be considered medically necessary for the treatment of individuals 18 years of age and older when 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 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
• Ketamine (Ketalar) is not to be used as monotherapy and is being prescribed in conjunction with least one oral antidepressant; and
• Individual does not have substance abuse or alcohol use disorder or be at risk for substance abuse or alcohol use disorder; and
• Provider attestation that individual will receive the appropriate monitoring including at least two (2) hours of observation by the healthcare provider after administration of ketamine (Ketalar) by the individual in the healthcare setting.

Ketamine (Ketalar) 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 ketamine (Ketalar) 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.