Esketamine Nasal Spray

What to know about esketamine nasal spray

Esketamine nasal spray is a new medication that has been approved by the Food and Drug Administration (FDA) for those suffering from severe treatment-resistant major depression.  What sets this medication apart is that it begins working within hours of application.  Esketamine is a more potent form of ketamine- a known treatment for major depression for many years. Ketamine is an anesthetic, and esketamine is its FDA-approved version as a nasal spray. Because the medication is more potent, less medication is needed, so there are fewer side effects.

How is esketamine administered?

Esketamine is administered on an outpatient basis under close observation of healthcare providers through a restricted distribution system- known as a Risk Evaluation and Mitigation Strategy (REMS). This is because there are some potential severe adverse effects associated with this medication, and it has the potential to be abused.  One concern is regarding the occurrence of altered perceptions, so it must be closely monitored until a certain time frame has passed.  

The medication is usually administered in the clinic setting.  Three sprays are administered by the patient five minutes apart under physician supervision.  Esketamine can not be taken home by the patient.  The patient must be monitored for two hours before they may be discharged home.  They are informed not to drive or use heavy machinery for the rest of the day after receiving the medication.  Esketamine is not used alone and must be used in addition to traditional antidepressant medications.  Esketamine is believed to take effect faster than the traditional antidepressant.

Who should use esketamine?

Currently, esketamine is only approved for individuals that traditional antidepressant medication has not been effective for.  This usually means failed use of at least two traditional medications for six weeks each during the current episode of depression.  There must be evidence of no improvement in mood by at least 50%.  This gives hope to the 33% of people who have not responded to traditional antidepressant therapy.  There is currently only one other approved medication for treatment-resistant depression. However, that medication has an extensive array of potentially severe and permanent side effects.

Who should avoid using esketamine?

Esketamine has many benefits but may not work best in the following patients:

  • Patients with unstable or poorly controlled hypertension. 
  • Patients with pre-existing aneurysmal vascular disorders. 
  • Patients who may be preganant or want to become pregnant in the near future.
  • Women who are breastfeeding.

How does esketamine work against depression?

Esketamine works similarly to traditional antidepressants except it increases glutamate versus the typical serotonin, norepinephrine and dopamine levels seen with other antidepressants.  It also immediately impacts the brain cells providing rapid relief of depression symptoms.  This is different from traditional medications that take several weeks to provide relief of symptoms. Additionally, it has been shown to reduce suicidal thoughts, whereas traditional antidepressants can increase this risk. Lastly, research shows esketamine helps counteract any changes in brain structure due to untreated depression.  This helps reduce the potential for brain damage and future problems with dementia.

Potential side effects

There are a variety of symptoms associated with the use of esketamine.  Some include:

  • Nausea
  • Drowsiness
  • Increased blood pressure
  • Vertigo
  • Lethargy
  • Vomiting
  • Anxiety
  • Feeling drunk
  • Headache
  • Hallucinations
  • Sedation
  • Dissociation
  • Suicidal thoughts

It is important to note that symptoms seem to peak at the 40-minute mark after administration and appear to subside within two hours of treatment.  The most prominent symptoms usually occur during the first two treatments and seem to become less severe after that.


Have you or someone you know tried and failed with traditional approaches for treating your major depression symptoms?  If traditional antidepressant medications and psychotherapy treatment modalities have failed, you may be a great candidate for esketamine nasal spray therapy.  The benefits of starting this medication include rapid relief of symptoms while giving your traditional medications more time to take effect.  Speaking with a healthcare provider at the Speciality Clinic of Austin may provide you with more insight on if this medication may be the right fit for you.


Kaplan, A. (n.d.). Esketamine for Treatment-Resistant Depression.  John Hopkins Medicine. 

U.S. Food & Drug Association.  (2019, March). FDA approves new nasal spray medication for treatment-resistant depression. 

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