Esketamine Nasal Spray for Treatment-Resistant Depression

Our Mood Disorders Consultation Clinic provides expert consultation for patients with treatment-resistant depression.

We now offer a nasal spray medication for treatment-resistant depression called Spravato® (intranasal esketamine).

What is esketamine nasal spray?

Esketamine nasal spray is administered through the nose and only under the supervision of medical staff in the clinic, due to potential side effects.

The nasal spray medication is:

  • FDA-approved for adults with treatment-resistant major depressive disorder (MDD) or depressive symptoms in MDD associated with suicidal thoughts or actions
  • Taken in addition to an oral antidepressant medication
  • Helpful to patients who have tried multiple, conventional antidepressants and are still depressed
  • A medication that may work faster than conventional antidepressants

What are some considerations before starting esketamine treatment?

You will need a driver to take you home after treatment. Each treatment takes at least 2 hours.

Because of the importance of close follow-up with this treatment, you must have an established psychiatric provider who you will see regularly throughout your esketamine treatments.

Esketamine has higher risks if you have any of the following conditions, but may still be an option with careful medical evaluation:

  • Bladder inflammation
  • Frequent falls
  • Heart disease
  • High blood pressure
  • History of alcohol or drug abuse or addiction
  • Kidney disease
  • Liver disease
  • Memory problems
  • Psychosis

What is the treatment schedule?

Phase Treatments per week
Induction 2 treatments per week for 4 weeks
Taper (if esketamine works well during the first month) 1 treatment per week for 4 weeks
Maintenance (if esketamine continues to work well for you) 1 treatment per week or every other week, (long term treatment)

Important: Each treatment requires a minimum of 2 hours of observation. Because of the side effects of esketamine, you will need a driver to take you home after treatment.

Common side effects

The common side effects may include:

  • Dissociation or confusion
  • High blood pressure that comes and goes or an elevated heart rate
  • Nausea or vomiting
  • Sedation or dizziness

You cannot use esketamine if you have:

  • An allergy or adverse reaction to esketamine or any of its ingredients, or to ketamine
  • Aneurysmal vascular disease, including arteriovenous malformation
  • History of bleeding in the brain

Refer to the Spravato website for more information.

Insurance guidelines

Esketamine is considered medically necessary in adults who:

  • Have a diagnosis of major depressive disorder (MDD) in a single or recurrent episode
  • Are resistant to treatment due to the lack of response or inability to tolerate 2 trials of antidepressant medications in the current depressive episode

Different insurance companies may have different requirements before covering esketamine. We encourage you to call your insurance company.

For referring providers

For our providers: When referring a patient, place the referral in eD-H and indicate the following:

  • Refer to the department: "LEB PSYCH MED MOOD DO"
  • Refer to provider: David Eiler, MD
  • In the comments field: “referring for IN esketamine”

For outside providers: To refer a patient for consultation, contact our Physician Connection Center. Please use our Outpatient Referral Form (PDF).

Interventional Psychiatry and Mood Disorders Consultation Clinic team

Paul E. Holtzheimer, MD



  • Lebanon

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Julia C. Knight, MD, PhD



  • Lebanon

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