Esketamine Therapy

Esketamine Therapy

At Principium Psychiatry, we offer a form of ketamine therapy known as esketamine therapy. Our esketamine patients self-administer SPRAVATO™, an FDA-approved type of esketamine, in our office during their treatment appointments. This medicine serves as a new option for patients who have treatment-resistant depression.

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What Is Esketamine?

Esketamine is a version of the ketamine molecule used to address treatment-resistant depression. It stimulates the production of glutamate, a neurotransmitter that creates new neural connections and influences many brain functions. Compared to ketamine, esketamine targets more brain connections and needs a lower dose to relieve depression symptoms. Scientists developed esketamine after finding that the anesthetic ketamine triggered glutamate production.

Is Esketamine FDA-Approved?

SPRAVATO™, a branded version of esketamine, has FDA approval. It comes in the form of a nasal spray that the patient takes under a doctor’s direct supervision.

Johnson & Johnson submitted five Phase 3 studies on the drug: three-short term studies, one maintenance study, and a long-term safety study. Two of those turned up positive results. One was a randomized trial in adults under age 65 with treatment-resistant depression who were started on an oral antidepressant and intranasal esketamine. After a month, roughly 70% of patients who received the treatment responded compared to just over half in a placebo group. The researchers considered an improvement of 50% or more on a common depression rating scale as a successful response.

As a result of findings like these, the FDA approved SPRAVATO™ for supervised use in March 2019. Because of esketamine’s potential side effects, the FDA requires doctors to distribute SPRAVATO™ under the Risk Evaluation and Mitigation Strategy (REMS).

The SPRAVATO™ REMS (Risk Evaluation and Mitigation Strategy)

To protect patients, SPRAVATO™ treatment has the following measures in place:

  • Patients may only receive and take SPRAVATO™ in a medically supervised setting
  • Pharmacies and health care organizations that distribute SPRAVATO™ must have special certification
  • Each patient receives detailed information on the potential severe side effects of SPRAVATO™
  • Every SPRAVATO™ patient must enroll in a registry

During a SPRAVATO™ treatment session, the doctor monitors the patient for side effects after administration. These symptoms vary in severity, depending on the patient. An esketamine treatment like SPRAVATO™ includes potential side effects.

What Are the Treatment Protocol and Dosage Recommendation for Esketamine?

A SPRAVATO™ treatment plan involves ongoing appointments where the patient self-administers the medicine. SPRAVATO™ comes in the form of a 28-milligram nasal spray device. Depending on how the patient reacts to the medication, they may take 56-milligram doses (two devices) or 84-milligram doses (three devices). For the first four weeks of treatment, the patient will visit twice a week for the induction phase, then once a week for the fifth to eighth weeks. After those first two phases, the doctor will recommend treatment once or twice a week.

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Ketamine FAQs

Because Ketamine is an off-label treatment, insurance companies do not cover Ketamine infusions for depression treatment. This means that medical appointments for SPRAVATO™ are not covered in-network.

In recent years, there has been a surge of information on the uses of ketamine for the treatment of depression. Ketamine is an anesthetic which has been on the market since the 1960s. Ketamine was introduced into clinical practice as an anesthetic that reliably brought about sedation for surgical purposes with little effect on respiration or the circulatory system. The name “ketamine” derives from two of the molecules found in ketamine’s molecular structure: a ketone and an amine.


It was first suggested in 2000 that ketamine may have antidepressant effects in humans. The suggestion was based on animal studies of depression showing that a neurotransmitter called glutamate was dysfunctional in depression. Other studies showed that NMDA, a drug that binds to glutamate receptors, relieved depression in humans. This led to the “glutamate hypothesis” about the origins of depression. Ketamine was known to bind to glutamate receptors.


A number of clinical trials support the use of ketamine for depression. These randomized, controlled clinical trials, have compared Ketamine to a placebo. Studies have shown that even one infusion of Ketamine is superior to placebo and achieves clinically meaningful reductions in depression rating scores. Other studies have shown that serial treatments with Ketamine (i.e. more than one infusion) can increase the response rate to the treatment. On the basis of this evidence, the American Psychiatric Association released a consensus statement on the use of Ketamine to treat depression:

Ketamine treatment for depression is an off-label treatment. This means that although Ketamine is an FDA approved drug for anesthesia, and has passed the FDA’s rigorous safety testing process for this purpose, the FDA has not approved the use of ketamine for depression. Physicians, however, are authorized to prescribe a medicine to treat other conditions based on clinical judgment and professional evidence.


The website of the FDA ( explains off-label medication use:

“From the FDA perspective, once the FDA approves a drug, healthcare providers generally may prescribe the drug for an unapproved use when they judge that it is medically appropriate for their patient. You may be asking yourself why your healthcare provider would want to prescribe a drug to treat a disease or medical condition that the drug is not approved for. One reason is that there might not be an approved drug to treat your disease or medical condition. Another is that you may have tried all approved treatments without seeing any benefits. In situations like these, you and your healthcare provider may talk about using an approved drug for an unapproved use to treat your disease or medical condition.”

Of note, Ketamine is given in smaller doses for the treatment of depression than are typically used in anesthesia.

Studies show that approximately 3 out of 4 patients will have a positive response to ketamine treatment for depression.

Simply call our office at 917-993-5018. Alternatively, you can book an appointment online at ZocDoc: You do not need a referral from a psychiatrist, since Principium Psychiatry is psychiatrist led by our medical director, Ziv Cohen, MD, a Fellow of the American Psychiatric Association. Dr. Cohen will do a comprehensive assessment and provide you with a diagnosis and recommendations, including whether you are appropriate for Ketamine treatment.

Ketamine is given in small doses for the treatment of depression. As such, a typical side effect is mild sedation. Some patients complain of mild nausea, which is easily treated with anti-anxiety medication. Some patients have mild elevations or reductions in blood pressure. Dr. Cohen will discuss with you side effects in detail during your consultation.

The typical treatment course involves 6 infusions, which are given 2 to 3 times per week (for a period of 2-3 weeks). In some cases, further infusions are given during the initial course.

At Principium Psychiatry, we offer Ketamine infusions in our private, comfortably appointed office located off Columbus Circle and Central Park South in the heart of New York City. We are located directly across the street from Carnegie Hall.

During the infusion, a multidisciplinary team will be present, including a registered nurse and a psychiatrist or psychiatric nurse practitioner. Your blood pressure, heart rate, and blood oxygen levels will be measured continuously during the infusion. The team will be closely monitoring you. You will be free to engage in conversation, close your eyes and relax, or listen to calming music. You will not fall asleep during the treatment.

Ketamine is rapidly metabolized. Within ten to fifteen minutes after the infusion you will feel substantially more alert. Patients generally report that a full recovery to normal activities takes about 1 hour. There is some individual variation in responses to ketamine.

After you finish your initial course of 6 or more infusions, you and the treatment team will make a plan for follow up care. Some patients will return for further infusions on an as needed basis (typically several months or more after the initial course), while other patients with particularly severe symptoms will be placed on a regular maintenance treatment schedule (typically monthly infusions).

Yes, Ketamine is safe to administer with most medications.

No, administered at small doses in a medical setting, there is no evidence that Ketamine is addictive. In contrast, those who abuse ketamine recreationally do so at very high doses to induce psycho-active affects.

Yes, clinical experience supports that Ketamine can be effective for patients with treatment resistant depression, including those who have already tried ECT and TMS without benefit.

At Principium Psychiatry, we offer both TMS and Ketamine treatment.

We offer a detailed comparison of the two treatments in our blog: Ketamine vs TMS – Which Treatment is Best for me. You will also find additional useful information about ketamine and TMS on our blog.

In general, ketamine is safe for patients with a variety of health conditions. If there is a concern about your cardiovascular health, we may refer you for a check up to make sure you are able to receive ketamine treatments.

While still in preliminary studies, there has been scientific evidence showing that IV infusions of ketamine can be effective in treating generalized anxiety disorder and social anxiety disorder. Our team at Principium Psychiatry has treated many patients who, in addition to having depression, also have varying degrees of anxiety. Throughout their infusion protocols, we have found that not only do their depressive symptoms improve, but so does their anxiety.

Some patients ask, “Why does it have to be IV? I don’t like needles!”

IV is the best route for your brain to receive ketamine because of something called bioavailability. In addition, it is also more effective, more precise, and safer for you.

Receiving a medication intravenously is the only way to have 100% bioavailability. Let’s take a look at the different bioavailability percentages based on what route you receive ketamine:

Intravenous: 100%
Intranasal: 25-50%
Sublingual (under the tongue): 30%
Orally (by mouth): 16-24%

When we give ketamine intravenously, we know exactly where your entire dose is going: straight to your brain. The same cannot be said for other forms of ketamine.

IV ketamine is by far the safest and most effective approach in using ketamine to treat depression. You are in a comfortable setting with healthcare providers with you the whole time, the potential for side effects is low, and you are certain that the dose you receive is the dose that is going to your brain, maximizing the benefits of this cutting-edge treatment.

Why Do Patients Choose Principium Psychiatry for Esketamine Treatment?

Patients with depression and other mental health conditions come to Principium Psychiatry for treatment because of our:

  • Expertise: Dr. Cohen and the Principium team have experience in a broad range of psychiatric specialties. They will work with you to create a personalized treatment plan based on the best approaches for you.
  • Innovative approaches: Principium offers the latest evidence-based treatments in psychiatry. These services include esketamine therapy and TMS.
  • Convenient, beautiful locations: Four office locations, one in Midtown Manhattan near Grand Central Station, one in Lower Manhattan located along Wall Street, a location in Greenwich Connecticut and our newest location in Santa Monica California.

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