Nasal Esketamine vs. Intravenous (IV) Ketamine

Esketamine and Ketamine are both used to treat individuals diagnosed with depression who have shown to be treatment-resistant when it comes to the usual prescription medications. Ketamine can be delivered intravenously or intramuscularly, while esketamine is taken intranasally via a nasal spray. Intravenous delivery is the most effective when it comes to the absorption, accuracy, and efficacy of the dose. 

What Is IV Esketamine?

In March 2019, esketamine (also known as S-ketamine) received Food and Drug Administration (FDA) approval in the form of a nasal spray when used in conjunction with an oral antidepressant. Esketamine is used for patients with treatment-resistant depression (TRD) who have failed two antidepressant medications from two different pharmacological classes. 

Esketamine is a molecule taken from ketamine’s racemic mixture (two mirror-image molecules which spin in different directions). As it is an altered form of ketamine, esketamine could be newly patented. As a result, corporate dollars were invested in clinical trials that led to the current FDA’s indicated use of nasal esketamine for TRD. 

FDA approval is a precursor for an insurance company to offer coverage. However, FDA approval and insurance coverage are not simultaneously guaranteed, or guaranteed with the same clinical guidelines. For instance, transcranial magnetic stimulation (TMS) was FDA-indicated for TRD as early as 2008. It was not until seven years later that TMS became a covered benefit on most insurance plans. TMS being a covered benefit does not equate with insurance authorization for coverage or authorization with the same FDA indication. TMS is FDA-indicated for depressed patients who have failed one antidepressant medication of adequate dose and duration. Most insurance companies, however, require that patients have failed multiple antidepressant trials, with augmentation strategies and therapy, before they will authorize payment.

The recent FDA approval of nasal esketamine is only available at preapproved healthcare facilities per FDA regulations. This is being done as an effort to reduce abuse and misuse of the drug. The currently recommended doses are either 56 mg or 84 mg. The recommended treatment course is for administration twice weekly for the first four weeks, weekly for the next four weeks, and then weekly or bi-weekly thereafter. A trained professional must supervise the patient while they self-administer the nasal spray to each nostril. Following the dose, the patient must remain at the facility for two hours of observation and must have transportation arrangements.

Perhaps the most significant aspect of the recent FDA approval for esketamine is that it is the first antidepressant approved with a novel mechanism of action since the introduction of Prozac in 1987. Most antidepressants operate via modulating serotonin, norepinephrine, and dopamine. In contrast, ketamine/esketamine modulates glutamate NMDA receptors resulting in an increased production of neurotrophic factors (particularly BDNF) that repair damaged neurons and improve neuronal connectivity within the brain. It is very exciting for psychiatry to have a novel treatment to offer patients suffering from TRD. As well, according to John Hopkins Medicine, esketamine is the only drug other than lithium that has been proven in studies to decrease suicidal thoughts. 

What Is Ketamine?

Ketamine is an FDA-approved anesthetic used for decades. Research demonstrates that ketamine is also an effective treatment for TRD when used intravenously (IV) in low doses (approximately 1/10th of anesthetic doses). More recently, research also demonstrates efficacy for anxiety, post-traumatic stress disorder (PTSD), chronic pain, fibromyalgia, and more. However, IV ketamine remains “off label” for these purposes because it is not FDA-indicated for use in treating these diagnoses. In fact, the FDA will most likely never approve ketamine for indications other than anesthesia because the patent for ketamine expired long ago. Without a patent, pharmaceutical companies are unlikely to invest in the costly clinical trials necessary to meet the FDA’s requirements for approval, simply because they cannot monetize the drug.

IV ketamine is administered at a slow, controlled rate throughout a typical 40-minute treatment. The dose is calculated according to a patient’s weight and individually adjusted according to the patient’s tolerability. A course of treatment includes 6-8 infusions over a 3-4 week period, and the patient must have transportation arrangements. Most patients will achieve response or remission after 3-4 weeks and will remain healthy and not needing any IV ketamine boosters for 3-4 months.

IV ketamine has a 70-80% success rate in treating TRD and has been used in the clinical psychiatric community since 2010, providing over a decade of real-world experience. Ketamine is the anesthesia of choice for children because of its excellent safety profile; it has no respiratory effects.

Side Effects of Esketamine and Ketamine

Side effects experienced tend to peak at around 40 minutes and wear off within two hours after a treatment session ends. The most intense side effects typically occur during the first two treatments and lessen after that. 

Side effects for esketamine may include: 

  • Nausea
  • Headache
  • Drowsiness
  • Increased blood pressure
  • Feeling drunk
  • Blurred vision
  • Feeling of lightness
  • Mild disassociation
  • Nausea, which can be prevented by including an IV anti-nausea medication with the infusion
  • Vertigo
  • Decreased sensitivity
  • Anxiety
  • Hallucinations, in rare occurrences

Side effects for ketamine may include:

  • Rapid heartbeat
  • Headache
  • Nausea, which can be prevented by including an IV anti-nausea medication with the infusion  
  • High blood pressure
  • Blurred vision
  • Feeling of lightness
  • Spontaneously making sounds or speaking
  • Drowsiness
  • Mild disassociation
  • Delirium
  • Hallucinations

Will Ketamine or Esketamine Be Covered by Insurance? 

Ketamine and Esketamine treatments are covered by many insurance plans. Currently cited costs of esketamine are $590 for the 56 mg dose and $885 for the 84 mg dose. Schedule a free consultation with at Neuro Wellness Spa to find out about possible insurance coverage and payment options.

3 responses to “Nasal Esketamine vs. Intravenous (IV) Ketamine

  • Sofro de depressão seria onde encontrar como faço poderiam me ajudar Não aguento mais ficar deste jeito

  • Greg McCracken

    1 year ago

    The only advantage to esketamine is that it does not require an IV. That’s it. You still have to go to a clinic to get it, it costs a lot of money, and you can’t tailor the dosage to what the patient needs. You only have 2 dosage choices, high and low.

  • IV esketamine has a 70-80 % success rate

    What is the success rate with 1 nasal esketamine treatment. Or series of
    nasal treatments?

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