Mental health treatment has evolved from the point where certain conditions were thought of as something to do with poor moral fiber to things that could be treated but were typically done so in private with next to no discussion in the public sphere. Today modern mental health treatment has done away with all of those concepts, providing opportunities for profound social discussions of what good mental health means alongside revolutionary research to find groundbreaking treatment.
One such treatment is esketamine therapy. This article will answer questions like “What is Esketamine?” and “Are there any esketamine side effects?”
What is Esketamine?
A prescription version of ketamine called esketamine is now available for use in depression treatment. Ketamine is a derivative of angel dust, or PCP, and the esketamine version goes by the brand name Spravato. It is administered via a nasal spray, approved in 2019 by the FDA for use in patients with treatment-resistant depression and major depressive disorder in adults presenting with suicidal ideations. This therapy is used alongside an antidepressant medication.

Intranasal esketamine has a chemical name of (S)-2-(o-chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride. This means it has one part ketamine and is a water-soluble powder that can be administered by mixing it with a liquid nasal spray or a liquid IV bag.
How Esketamine Therapy Works
Traditional antidepressants change levels in the brain of things like serotonin, but esketamine treatment changes the development and growth of synapses in your brain, helping to improve neural communication by regrowing dead glutamate receptors or restoring malfunctioning glutamate receptors located on the ends of your neurotransmitters. Exposure to regular depression or stress causes these neurotransmitters to stop working because of glutamate malfunction. Esketamine therapy is able to improve brain function and communication, which, by extension, alleviates anxiety and depression symptoms and changes mood.
Administration methods
As of late, there are two administration methods for esketamine:
- Nasal spray
- Intravenous
Benefits of Esketamine Therapy
Patients can enjoy a wide range of benefits, the most important of which include the rapid onset and the efficacy.
Rapid onset of action compared to traditional antidepressants
One of the biggest benefits of esketamine therapy is that it works significantly faster compared to traditional antidepressants. Esketamine works immediately, with many seeing relief after their first session.
Now, with ketamine vs esketamine, the onset can be even faster with an IV ketamine injection over the esketamine nasal spray (within hours) but it is still a rapid onset following the first dose in either case.
By comparison, the use of traditional antidepressants on their own can take several weeks or months before results are felt. The reason for this is the mechanism of action mentioned above; esketamine treatment works differently, actually regrowing glutamate receptors on the ends of neurons and interacting directly with the brain, whereas antidepressants do things like stop the body from reabsorbing serotonin after it has been released, leaving you feeling slightly better for slightly longer.
This process of traditional antidepressants does not happen overnight (literally or figuratively), and it takes time to build in the system before you feel any differently. For this reason, many people struggle with side effects while continuing to abide by their treatment regimen because they don’t get relief right away.
Effectiveness in treatment-resistant depression
Another esketamine treatment benefit is its applicability in treatment-resistant depression.
Treatment-resistant depression can happen when individuals have tried other methods of antidepressants and therapy with no results. This must be tried for at least one year with no change. For others, they develop treatment-resistant depression after several years of taking the same medication.
In these cases, it can feel like there is no hope, no way out of the symptoms. However, the FDA has approved esketamine therapy specifically for treatment-resistant depression because it has a positive impact on:
- Reducing symptoms
- Leading to complete remission in around 30% of cases
The efficacy comes back to the mechanism of action; by working to regrow parts of the brain that have previously been damaged by depression and stress, the brain physically functions better. Those with treatment-resistant depression cannot get relief from medications that are supposed to help outside of the brain, with things like stopping serotonin absorption, but they don’t do anything to actually fix communication in the brain. This is why steaming therapy is so revolutionary.
Esketamine Treatment Process
Esketamine therapy is only administered through restricted programs called Spravato REMS. You can receive treatment at certified healthcare facilities which operate in an outpatient program so you don’t have to stay overnight.
Initial consultation and evaluation
The use of esketamine therapy starts with an initial consultation and evaluation.
Before you start esketamine, you will undergo an evaluation where you work with your team to discuss any medical conditions or history of medical issues that you might have including:
- History of heart or brain problems
- History of stroke or heart attacks
- Hypertension
- Liver problems
- History of psychosis
- Whether or not you are pregnant, nursing, or plan to become pregnant
There are certain conditions that may disqualify you but in most cases your medical history will simply help inform the team as to what potential side effects to look out for or what medications need to be moderated before or after your esketamine therapy.
For example, if you are using decongestant medicine or nasal corticosteroids, you’ll be informed to take them at least one hour before the nasal spray version of esketamine. If you are on central nervous system depressants or psychostimulants this can have potentially serious contraindications so it’s something your medical team will want to discuss.
In addition to your medical history your evaluation will include an opportunity to let your team know about any medication you are on including over the counter medication, vitamins, or herbal supplements. Adjustments might have to be made immediately surrounding your treatment sessions to things like herbal supplements that increase blood pressure.
Treatment sessions and frequency
The treatment sessions and frequency will be decided upon during your evaluation and it is a similar process depending on how you receive your dose.
IV
If you opt for the IV treatment, you will come to the qualified facilities each time, be placed in a comfortable chair and be set up with your IV bag. This process takes an average of 45 minutes to 1 hour, during which time you are free to do approved activities like reading or watching videos on your phone.
Following the IV process you will likely remain at the facility for an average of 2 hours so that you can be under supervision to monitor for any potentially serious esketamine side effects that would manifest very early.
After that you will be given your schedule to follow in terms of when to come back to the facility for subsequent treatment and what other signs to look out for which indicate a serious side effect developing after you leave.
Nasal Spray
While it is only a nasal spray, esketamine is something that has to be taken under supervision. This means you come to the treatment facility, and a healthcare provider or other licensed professional will show you how to use the nasal spray and watch you as you self-administer a specific dose.
You will receive a treatment schedule which tells you when to come to the facility for regular administration of your individual doses and it’s important that you follow that schedule. If for any reason you cannot make a specific session you’ll have to reschedule.
Not only will you remain under supervision while you are self-administering your nasal spray but you are required by law to remain at certified facilities for an average of 2 hours during which time you will be monitored for any potential side effects, particularly serious side effects.
Following that you will be given the prescription for the required antidepressant that you take alongside your nasal spray as well as a schedule to follow for that.
Esketamine Side Effects
Are there esketamine side effects? Yes, there are some common side effects, many of which are short lived, as well some potential serious side effects which are rare.
Common side effects
Common esketamine side effects include the following:
- Feeling intoxicated or high
- Lack of energy
- Headache
- Dissociation
- Sedation
- Drowsiness
- Insomnia
- Dizziness
- Nausea
Due to these common side effects, many of which will dissipate within a few hours or at least one day after your session, you will need to arrange a ride from your appointments.
Rare but serious side effects
During your consultation, it’s important that you talk about pre-existing conditions so that any additional serious side effects like depression of your respiratory system or dangerously high blood pressure can be monitored.

More serious esketamine side effects can include:
- Abuse
- Respiratory system depression
- Dangerously high blood pressure
Because esketamine is ketamine based, some of the most significant side effects include the risk of abuse which is why it is only administered in legitimate facilities under supervision and not done at home.
To help monitor all of your side effects including the rare but serious ones and the common ones, you remain at your treatment center for 2 hours after each dose. The serious side effects will manifest almost immediately if they happen. Remaining at the facility means that you are under the safety and supervision of medical staff, who can intervene if that takes place.
Managing and mitigating side effects
There are things that you can do at home to help manage and mitigate the side effects, particularly the common esketamine side effects like nausea and dizziness.
In many cases, you will be advised not to eat or drink several hours prior to your sessions, which can help with nausea and potential vomiting. Herbal remedies that have been approved like peppermint tea can help with things like nausea as well.
Things like headaches, dizziness, or lack of energy can be managed and mitigated by staying hydrated and getting sleep after your sessions rather than trying to resume normal activities. You can also take approved over-the-counter medications or herbal supplements to help with these common symptoms.
Immediately after the 2 hours of supervision, you’ll need to avoid certain activities like driving or operating heavy equipment. Any activity which would require you to be alert is something that you should avoid for at least 24 hours after each session.
Esketamine Cost and Accessibility
So what is the esketamine cost?
There are several insurance companies that apply benefits to esketamine treatment costs including:
- Medicaid
- United Healthcare
- Anthem /BCBS
- Aetna
- Cigna
- Medicare
If these are your insurance providers, you can reach out to them to see what your benefits will cover for this type of treatment. The coverage is contingent upon your provider and the plan.
For example:
With Medicare, the cost for 56 mg is $951, but 84 mg is $1,353. The majority of people with treatment resistant depression or major depressive disorder will require 84 mg.
If you have Medicare, you typically have to pay 20% of the total cost, which for the 84 mg dose would be a few hundred dollars per session.
If you have private insurance you might get higher coverage but you might also get lower coverage. If you do not have a provider that covers the cost, you will likely have to pay out of pocket which, at different facilities can be less than what is charged to an insurance company and equal to what you might have to cover with a copay.
To determine your esketamine cost it is important to reach out to a facility after your consultation and inquire as to what the cost would be both with and without insurance.
Future of Esketamine Therapy in Mental Health
Continuing research will investigate potential new applications for esketamine therapy, not just for treatment resistant depression, but for FDA approval for other conditions as well, including anxiety, PTSD, and bipolar disorder.
Moreover, continued research can examine innovative and improved delivery methods, with more offers for those who might need oral supplements or patches. Right now, the nasal spray must be administered with an antidepressant by law, but over time, this may no longer be necessary, or the medication requirement might extend to other options.
As research moves forward, and approval for different methods and uses continue, there is great potential for esketamine therapy to be integrated with other mental health treatments. Doing so would increase the efficacy and management of treatments long term.
Conclusion
What is esketamine? It is a revolutionary new treatment for major depressive disorder, treatment-resistant depression, and, at some facilities, related disorders like anxiety or PTSD. It is important to stay informed about new treatment options so that you can find a solution for your symptoms. Always seek professional advice for personalized mental health care and to see if esketamine therapy can work for you.