What you need to know about Ketamine and Esketamine

Recently, the U.S. Food and Drug Administration approved the nasal spray Esketamine for the management of treatment-resistant depression and major depression with imminent risk of suicide. Esketamine is a drug developed by Janssen Pharmaceutical Companies of Johnson & Johnson under the name Spravato. It is a glutamate receptor modulator, which aids in restoring synaptic connections in the brain in patients with chronic depression.

Esketamine is getting a lot of media attention because like its parent compound, Ketamine, it has a different mechanism of action to treat depression which is different from Prozac and other SSRIs, which was introduced over 30 years ago.


Ketamine, given intravenously, has been shown to provide a robust and rapid antidepressant effect within hours of treatment. Ketamine is an NMDA receptor antagonist that works via the glutaminergic system of the brain by initiating a cascade of events leading to synaptogenesis and neuroplasticity. It allows lost nerve connections in the brain due to chronic depression to regenerate.

Ketamine is a racemic mixture consisting of 2 molecular forms, R- and S-ketamine. Esketamine, which has the S- form of ketamine, is proposed to have the same antidepressant effects of ketamine.


Ketamine is an older medication that has been used as an anesthetic for over 40 years. It is only fairly recently that it has been shown to be extremely effective in the treatment of depression and other mood disorders. Because, however, it is generic and has limited profit potential, none of the pharmaceutical companies are going to spend millions of dollars to perform clinical trials and promote its psychiatric indications. Esketamine, however, is a newly developed medication and is patented; It, therefore, has more profit potential for the pharmaceutical company to promote its efficacy against depression.


Esketamine is an intranasal spray, packaged in a delivery device that would contain two doses of 14 mg each. Initial adult dose will be 28 mg to 56 mg per administration.

It will be administered twice a week for 4 weeks, along with an oral antidepressant. This will be followed by once a week or every other week as an ongoing maintenance.

The main concern about administering Esketamine is its side effects. Like its parent compound Ketamine, Esketamine causes dissociation, dizziness, sedation, and increased blood pressure.

The following is part of a list of recommendations for the safe administration of Esketamine, once approved by the FDA:

Prescriber training on the risks of esketamine and importance of monitoring patients after their dose is administered and the need to register patients

Administration of esketamine only in certain health care settings that ensure patient monitoring by a healthcare provider for two hours after administration

Pharmacies, practitioners, or healthcare settings that dispense the drug are specially certified to ensure that esketamine is not dispensed directly to patients and that patients are monitored

Enrollment of patients who are treated with esketamine in a registry to better characterize the risks associated with esketamine administration and inform risk mitigation strategies


There has been no studies to directly compare the efficacy of Ketamine vs Esketamine; and, there may never be one due to the off-patent status of Ketamine. Studies have shown that both are effective in treating depression. Intravenous Ketamine has been shown to have over 70% success rate in the treatment of major depression. Factors to consider would be:

Bioavailability: IV infusion is 100% bioavailable and the nasal route ranges from 25-50%.

Absorption rate: IV infusion is more predictably and evenly absorbed into the blood system since the infusion rate is set. Intranasal administration will not be evenly absorbed, and will depend on the nasal passage conditions, such as mucus, congestion, and proper self-administration.

Ease of administration: IV infusion has to be administered by a trained provider while the intranasal route is self-administered by the patient in front of the provider.

Regardless of route of delivery, patients would still need to to be monitored for side effects after administration of both form of medications.


Most mental health providers, however, are out-of-network. Although you would have to pay for treatments upfront, you can get reimbursed by your insurance company with your out-of-network benefits. This would be the case for both Ketamine and Esketamine. You need to check with your insurance company regarding your coverage for these treatments.


MindBody Therapeutics is committed to the treatment of mental health conditions, and will offer treatments which are accessible to patients.

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