Major depressive disorder is one of the most common mental illnesses, affecting more than 21 million American adults each year.¹ Depression causes people to lose pleasure in daily life, can often complicate medical conditions and negatively impacts work performance. While mental health awareness campaigns have brought to light the need for emotional treatment, one-third of people with depression are considered treatment-resistant and are not able to find relief from symptoms even after trying several medications or other treatments.²

In recent years, there has been growing interest in psychedelics* as a treatment for certain mental health conditions, particularly depression, anxiety and posttraumatic stress disorder (PTSD).³ Psychedelic experiences can provide individuals with unique insight, emotions or experiences that can help explain who they are and how they think.⁴ Though ketamine, one of the wellknown psychedelics, is primarily used in medical settings for anesthesia and pain management, there has been research into ketamine as a treatment for mental illness. Psychiatrists have implemented the use of ketamine in treatment-resistant depression when other medications are not found to be of clinical benefit.

One notable characteristic of Ketamine treatment is its rapid onset to treat depression combined with acute suicidal feelings, often occurring within hours to days compared to traditional antidepressants, which may take weeks to show efficacy. It is important to note that while ketamine has shown promise in treating certain mental health conditions, long-term safety and effectiveness are still areas of active research. Ketamine is typically administered through intravenous infusion in a closely monitored setting. Esketamine (Spravato®), the chemical cousin of ketamine, is available as a prescription nasal spray and is administered in a controlled medical setting under the supervision of healthcare professionals.⁵

There are critical differences between ketamine and esketamine. While they are chemically related, they are very distinct in terms of chemical compositions, dosing, administration and studies supporting their safe and effective use. Most importantly, ketamine is not FDA-approved for treatment-resistant depression (TRD) or major depressive disorder (MDD). Esketamine is FDA-approved for adults with TRD and MDD with suicidal thoughts or actions in combination with an oral antidepressant with enforced guidelines that a physician must follow. By contrast, there is no drug safety program for ketamine, and physicians continue to have flexibility in off-label prescribing.

When employers think about providing coverage for ketamine treatment, they must navigate various considerations and guardrails to ensure a balanced and responsible approach. Here are key factors for employers to keep in mind:

• Provide educational resources about mental health, treatment options and the effects of treatments like ketamine. This can help reduce stigma and encourage proactive mental health engagement.
• Consult with medical providers and health plan carriers on the clinical appropriateness and/or the medical necessity of ketamine treatment. This involves consulting with licensed healthcare professionals and promoting established clinical guidelines, weighing benefits, risks and potential side effects.
• Evaluate the financial aspects of providing ketamine coverage. Ketamine infusion treatments are often considered elective and may not be covered by insurance in all cases. On average, the cost of a single ketamine infusion can range from several hundred to over one thousand dollars.
• Seek legal advice to ensure that the provision of ketamine coverage aligns with employment laws, health insurance regulations and other relevant legal considerations as appropriate.
• If an employee’s job involves safety-sensitive tasks, consider performing evaluations to assess safety risks for those thinking about treatment.

Ketamine holds great potential, but employers need to carefully weigh both risks and opportunities before including it in their employee health benefit programs.

*Psychedelics are defined as drugs that can produce hallucinations, perceptual distortions, or intense sensory experiences. (Source: Psychedelics – PMC (nih.gov))

1. https://www.mhanational.org/conditions/depression
2. https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2799488
3. https://www.psychiatry.org/News-room/News-Releases/study-supports-effectiveness-of-new-fast-acting-an
4. Reiff, CM, et al. Psychedelics and Psychedelic-Assisted Psychotherapy. American Journal of Psychiatry. Published online Feb. 2020.
5. Ketamine vs Esketamine: Critical Differences Explained (medscape.com)

Dr. Joel Axler, MD

National Behavior Health Leader

Andrea Grande

Principal

Liz Reed

Analyst