What Is Esketamine? A Complete Guide to Spravato Treatment
Esketamine is an FDA-approved nasal spray for adults with depression that hasnât responded to other treatments. It comes from the same family as ketamine, though it isnât the same as the ketamine infusions you might have seen advertised elsewhere â a difference worth understanding before you go any further.
It exists because standard antidepressants donât work for everyone. Around one in three people with depression donât get real relief from the usual medications, and waiting weeks to find out if yet another pill will help isnât just discouraging â for some people, itâs genuinely risky. Esketamine works through a different pathway in the brain, and as of January 2025, it can be used on its own or alongside an antidepressant youâre already taking. Thatâs new flexibility that didnât exist before.
Hereâs everything worth knowing: who itâs actually for, what happens during treatment, what the research and the doctors who prescribe it are saying, how it stacks up against other options, and the side effects worth being aware of.
Who Is Eligible for Esketamine Treatment?
Esketamine isnât usually a first step, and it isnât for everyone with depression. Itâs approved for two specific situations.
The first is treatment-resistant depression â meaning youâve genuinely tried at least two different antidepressants, at a real dose, for a real stretch of time, and neither one helped enough. If thatâs your story, esketamine may be worth a serious conversation with a psychiatrist. Since 2025, you can take it either alone or alongside your current antidepressant, whichever fits your situation better.
The second is depression that comes with suicidal thoughts. This is one of the reasons esketamine matters so much to the people who prescribe it â it can work within a day or two, which is a meaningful difference when someone is in real distress and every week of waiting counts.
Beyond diagnosis, your doctor will also want to know a few other things before moving forward. Blood pressure thatâs hard to control matters, since esketamine can raise it temporarily. So does a history of aneurysms or certain heart and blood vessel conditions. If substance use involving ketamine or similar drugs has ever been part of your history, thatâs worth an honest conversation too, and the same goes for pregnancy or breastfeeding.
None of this is meant to be a checklist that disqualifies you on the spot â itâs simply what a good doctor needs to know to make this decision safely, together with you.
Know More About:
Is Esketamine Right for You? A Guide to Treatment-Resistant Depression
Why you should consider TMS & Esketamine Therapy for Depression
What to Expect: Your First Session to Ongoing Treatment
Esketamine isnât a prescription you pick up and take at home. Every dose happens inside a certified clinic, under supervision â thatâs a federal requirement, not just how one clinic chooses to do things.
Before your first session, your provider will go over your medical history, check your current medications and blood pressure, and make sure you have a ride home, since you wonât be allowed to drive yourself afterward. During the session, youâll spray the medication yourself while a healthcare provider watches over you â usually two doses a few minutes apart. Including the time youâre monitored afterward, the whole appointment takes around two hours.
That monitoring period matters. Youâll stay at the clinic for at least two hours after your dose while staff check your blood pressure and make sure any sedation or dissociation has worn off before you leave.
In terms of how often, treatment starts intensively and then eases off. For the first four weeks, sessions happen twice a week. From weeks five through eight, that drops to once a week, and after that, most people move to a session every one to two weeks, depending on how theyâre doing. Whether you keep taking an oral antidepressant alongside this depends on which approach you and your doctor choose.
How Esketamine Actually Works
Esketamine is essentially one half of the ketamine molecule â the S-enantiomer, if you want the technical term â purified and turned into a nasal spray. Thatâs what âintranasal esketamineâ means, and itâs what allows for precise, repeatable dosing without an IV.
Most antidepressants, like SSRIs and SNRIs, work by adjusting serotonin and norepinephrine, and they typically take four to eight weeks to show their full effect. Esketamine takes a completely different route. It blocks a receptor called NMDA, which plays a role in glutamate signaling in the brain. Researchers believe this encourages the brain to build new connections between neurons, which may be why so many patients notice a shift in mood within 24 hours instead of weeks.
That different mechanism is also why people notice something happening during the session itself â a temporary sense of detachment from their surroundings, drowsiness, or changes in perception. These effects are expected and short-lived, which is exactly why the two-hour monitoring window exists.
What Experts and Clinical Trials Say
None of this is based on marketing claims â esketamineâs approval came from FDA-reviewed trials, and researchers have kept studying it since it first came to market in 2019.
A 2025 review that looked across several major trials â TRANSFORM-2, SUSTAIN-1, and ASPIRE I and II â found that esketamine tends to work quickly, often within hours, and improves both remission and response rates for people with treatment-resistant depression. The trial that supported the 2025 monotherapy approval backed this up: esketamine alone showed a statistically significant improvement over placebo at four weeks, and in a separate look at the same data, 22.5% of patients reached remission by that point, compared with 7.6% on placebo.
The doctors who actually prescribe esketamine have been fairly candid about it, too â both the good and the complicated parts. Dr. Gregory Mattingly, President of Midwest Research Group, said the 2025 monotherapy approval gives providers âthe freedom to further personalize treatment plansâ for their patients. But itâs not all upside from a clinical standpoint. A review of how mental healthcare providers talk about esketamine found real enthusiasm for how fast it works, alongside genuine concerns â the monitoring requirements, the cost (which can run into the thousands of dollars in the first month), and the extra staff and space clinics need to offer it responsibly.
Guideline groups have echoed a similar, balanced message. The American Psychological Associationâs 2025 guidance on treatment-resistant depression recommends a careful, step-by-step approach â reassessing the diagnosis and making sure prior antidepressants were given a fair shot before moving on to something like esketamine.In plain terms: this is a strong option for the right person, at the right point in their treatment journey, not something meant to replace everything that came before it.
Esketamine vs. Your Other Options
Itâs natural to wonder how this compares with what youâve already tried, or with other treatments youâve heard about. Every option trades off speed, how invasive it is, how easy it is to access, and how much evidence backs it up. Hereâs how the main ones stack up, side by side:
A few things genuinely set esketamine apart. It tends to work faster than any oral medication, often in days rather than weeks. Itâs also far more standardized than off-label IV ketamine â the dosing, the safety checks, and the monitoring are all set by the FDA, not left up to whichever clinic you walk into. And since 2025, it offers something none of the others do quite the same way: the choice to use it alone or alongside your current antidepressant. Compared with ECT, it also asks much less of you physically â no general anesthesia, no induced seizure, and far less disruption to memory and daily life for most people.
That said, esketamine isnât automatically the âbestâ choice in every case. ECT still has some of the highest remission rates for the most severe depression, and TMS skips sedation and monitoring requirements altogether. The honest answer is that esketamine is a strong fit for a specific group of people â not a blanket upgrade over everything else.
Benefits of Esketamine Treatment
Put simply, for the people itâs approved for, esketamine tends to offer:
Faster relief than most oral antidepressants, often within a day or two
A different way of working in the brain, useful when serotonin-based medicine hasnât helped
A structured, supervised process, so thereâs less guesswork around dosing
Flexibility to use it alone or with your current antidepressant
A meaningful option when suicidal thoughts make speed genuinely matter
Not everyone responds the same way, and it isnât a guaranteed fix â but for people whoâve run out of other options, it can genuinely change how quickly relief arrives.
Esketamine Side Effects & Safety
Esketamine, like any psychiatric medication, has real side effects, and it carries the FDAâs most serious safety label â a boxed warning â covering sedation, dissociation, and the potential for misuse.
The most common things people notice during and shortly after a session include feeling disconnected from reality, drowsiness, dizziness or vertigo, a temporary rise in blood pressure, nausea, anxiety, and a general feeling of intoxication. These usually fade fairly quickly, which is exactly why the two-hour monitoring window is built into every session at Ohio Psychiatric Services.
Itâs also worth knowing that cost can be a real barrier â sometimes running into the thousands of dollars for the first month â and that long-term safety data is still limited for people who may need this treatment indefinitely. Both are worth raising directly with your provider and your insurance plan before you begin. For more information on what to expect or to discuss whether esketamine treatment is right for you,Â
If youâve tried multiple antidepressants and still donât feel like yourself, it can be discouraging and exhausting. Treatmentâresistant depression (TRD) is more common than many people realize, and it does not mean you have run out of options or it is a sign that you are not trying hard enough. Advances in depression treatment, including Spravato (esketamine), are offering renewed hope to individuals who have struggled to find relief through traditional approaches.
If youâve tried multiple antidepressants and still donât feel like yourself, it can be discouraging and exhausting. Treatmentâresistant depression (TRD) is more common than many people realize, and it does not mean you have run out of options or it is a sign that you are not trying hard enough. Advances in depression treatment, including Spravato (esketamine), are offering renewed hope to individuals who have struggled to find relief through traditional approaches.
If youâve tried multiple antidepressants and still donât feel like yourself, it can be discouraging and exhausting. Treatmentâresistant depression (TRD) is more common than many people realize, and it does not mean you have run out of options or it is a sign that you are not trying hard enough. Advances in depression treatment, including Spravato (esketamine), are offering renewed hope to individuals who have struggled to find relief through traditional approaches.
Spravato (esketamine) nasal spray was developed specifically for adults in this situation. It is the only FDAâapproved nasal spray for treatmentâresistant depression and can be used on its own or alongside an oral antidepressant. For people seeking advanced depression treatment or alternatives to antidepressants in Columbus, Ohio area, understanding how Spravato works and what the research shows can make next steps feel clearer and more hopeful.
How Spravato Works in the Brain
Most antidepressants gradually change serotonin or norepinephrine levels and often take several weeks to work. Spravato targets a different system: the glutamate pathway.
Esketamine briefly blocks NMDA receptors, triggering a surge of glutamate and activating AMPA receptors. This increases a growth factor (BDNF) that supports neuroplasticity, the brainâs ability to form new, healthier connections. In depression, brain pathways can become rigid and locked into negative patterns. Spravato helps interrupt those patterns and gives your brain a chance to âresetâ and build new routes instead of staying stuck in the same loop.
Because it acts directly on these circuits, some patients notice a shift in symptoms within hours to days, rather than waiting weeks as with standard antidepressants alone.
How Quickly Spravato Starts to Work
A key difference between Spravato and many oral antidepressants is speed. While typical medications may take four to six weeks to show full effect, Spravato often acts sooner.
Many people experience a pattern like this:
Within 24 hours: Some patients report subtle improvements, such as feeling less overwhelmed or experiencing a much lower intensity of their symptoms or reduced suicidal thinking.
First 1â2 weeks: Improvements become more consistent as the brain responds to repeated doses.
By about 4 weeks: During the induction phase, many patients see more stable and significant relief.
Each personâs course is unique. How long you have been depressed, what you have already tried, other medical conditions, and whether you are also in therapy or TMS will all influence how quickly and how strongly you respond.
What the Evidence Shows
Clinical trials and realâworld data show that Spravato can bring meaningful relief to adults with treatmentâresistant depression who have not improved enough with at least two antidepressants. These results are especially important because they come from a group that is often hardest to treat.
Studies have found:
Rapid symptom reduction for many patients within the first month.
Some individuals notice benefit within 24 hours of the first dose.
Patients who continue Spravato as maintenance treatment are less likely to relapse than those who stop after an initial response.
People who respond often describe clearer thinking, better energy, renewed interest in activities, and a stronger ability to connect with others, not just a small lift in mood.
What Spravato Treatment Looks Like at OPS
Esketamine is an FDA-approved nasal spray for adults with depression that hasnât responded to other treatments. It comes from the same family as ketamine, though it isnât the same as the ketamine infusions you might have seen advertised elsewhere â a difference worth understanding before you go any further.
It exists because standard antidepressants donât work for everyone. Around one in three people with depression donât get real relief from the usual medications, and waiting weeks to find out if yet another pill will help isnât just discouraging â for some people, itâs genuinely risky. Esketamine works through a different pathway in the brain, and as of January 2025, it can be used on its own or alongside an antidepressant youâre already taking. Thatâs new flexibility that didnât exist before.
Hereâs everything worth knowing: who itâs actually for, what happens during treatment, what the research and the doctors who prescribe it are saying, how it stacks up against other options, and the side effects worth being aware of.
Who Is Eligible for Esketamine Treatment?
Esketamine isnât usually a first step, and it isnât for everyone with depression. Itâs approved for two specific situations.
The first is treatment-resistant depression â meaning youâve genuinely tried at least two different antidepressants, at a real dose, for a real stretch of time, and neither one helped enough. If thatâs your story, esketamine may be worth a serious conversation with a psychiatrist. Since 2025, you can take it either alone or alongside your current antidepressant, whichever fits your situation better.
The second is depression that comes with suicidal thoughts. This is one of the reasons esketamine matters so much to the people who prescribe it â it can work within a day or two, which is a meaningful difference when someone is in real distress and every week of waiting counts.
Beyond diagnosis, your doctor will also want to know a few other things before moving forward. Blood pressure thatâs hard to control matters, since esketamine can raise it temporarily. So does a history of aneurysms or certain heart and blood vessel conditions. If substance use involving ketamine or similar drugs has ever been part of your history, thatâs worth an honest conversation too, and the same goes for pregnancy or breastfeeding.
None of this is meant to be a checklist that disqualifies you on the spot â itâs simply what a good doctor needs to know to make this decision safely, together with you.
Know More About:
Is Esketamine Right for You? A Guide to Treatment-Resistant Depression
Why you should consider TMS & Esketamine Therapy for Depression
What to Expect: Your First Session to Ongoing Treatment
Esketamine isnât a prescription you pick up and take at home. Every dose happens inside a certified clinic, under supervision â thatâs a federal requirement, not just how one clinic chooses to do things.
Before your first session, your provider will go over your medical history, check your current medications and blood pressure, and make sure you have a ride home, since you wonât be allowed to drive yourself afterward. During the session, youâll spray the medication yourself while a healthcare provider watches over you â usually two doses a few minutes apart. Including the time youâre monitored afterward, the whole appointment takes around two hours.
That monitoring period matters. Youâll stay at the clinic for at least two hours after your dose while staff check your blood pressure and make sure any sedation or dissociation has worn off before you leave.
In terms of how often, treatment starts intensively and then eases off. For the first four weeks, sessions happen twice a week. From weeks five through eight, that drops to once a week, and after that, most people move to a session every one to two weeks, depending on how theyâre doing. Whether you keep taking an oral antidepressant alongside this depends on which approach you and your doctor choose.
How Esketamine Actually Works
Esketamine is essentially one half of the ketamine molecule â the S-enantiomer, if you want the technical term â purified and turned into a nasal spray. Thatâs what âintranasal esketamineâ means, and itâs what allows for precise, repeatable dosing without an IV.
Most antidepressants, like SSRIs and SNRIs, work by adjusting serotonin and norepinephrine, and they typically take four to eight weeks to show their full effect. Esketamine takes a completely different route. It blocks a receptor called NMDA, which plays a role in glutamate signaling in the brain. Researchers believe this encourages the brain to build new connections between neurons, which may be why so many patients notice a shift in mood within 24 hours instead of weeks.
That different mechanism is also why people notice something happening during the session itself â a temporary sense of detachment from their surroundings, drowsiness, or changes in perception. These effects are expected and short-lived, which is exactly why the two-hour monitoring window exists.
What Experts and Clinical Trials Say
None of this is based on marketing claims â esketamineâs approval came from FDA-reviewed trials, and researchers have kept studying it since it first came to market in 2019.
A 2025 review that looked across several major trials â TRANSFORM-2, SUSTAIN-1, and ASPIRE I and II â found that esketamine tends to work quickly, often within hours, and improves both remission and response rates for people with treatment-resistant depression. The trial that supported the 2025 monotherapy approval backed this up: esketamine alone showed a statistically significant improvement over placebo at four weeks, and in a separate look at the same data, 22.5% of patients reached remission by that point, compared with 7.6% on placebo.
The doctors who actually prescribe esketamine have been fairly candid about it, too â both the good and the complicated parts. Dr. Gregory Mattingly, President of Midwest Research Group, said the 2025 monotherapy approval gives providers âthe freedom to further personalize treatment plansâ for their patients. But itâs not all upside from a clinical standpoint. A review of how mental healthcare providers talk about esketamine found real enthusiasm for how fast it works, alongside genuine concerns â the monitoring requirements, the cost (which can run into the thousands of dollars in the first month), and the extra staff and space clinics need to offer it responsibly.
Guideline groups have echoed a similar, balanced message. The American Psychological Associationâs 2025 guidance on treatment-resistant depression recommends a careful, step-by-step approach â reassessing the diagnosis and making sure prior antidepressants were given a fair shot before moving on to something like esketamine.In plain terms: this is a strong option for the right person, at the right point in their treatment journey, not something meant to replace everything that came before it.
Esketamine vs. Your Other Options
Itâs natural to wonder how this compares with what youâve already tried, or with other treatments youâve heard about. Every option trades off speed, how invasive it is, how easy it is to access, and how much evidence backs it up. Hereâs how the main ones stack up, side by side:
A few things genuinely set esketamine apart. It tends to work faster than any oral medication, often in days rather than weeks. Itâs also far more standardized than off-label IV ketamine â the dosing, the safety checks, and the monitoring are all set by the FDA, not left up to whichever clinic you walk into. And since 2025, it offers something none of the others do quite the same way: the choice to use it alone or alongside your current antidepressant. Compared with ECT, it also asks much less of you physically â no general anesthesia, no induced seizure, and far less disruption to memory and daily life for most people.
That said, esketamine isnât automatically the âbestâ choice in every case. ECT still has some of the highest remission rates for the most severe depression, and TMS skips sedation and monitoring requirements altogether. The honest answer is that esketamine is a strong fit for a specific group of people â not a blanket upgrade over everything else.
Benefits of Esketamine Treatment
Put simply, for the people itâs approved for, esketamine tends to offer:
Faster relief than most oral antidepressants, often within a day or two
A different way of working in the brain, useful when serotonin-based medicine hasnât helped
A structured, supervised process, so thereâs less guesswork around dosing
Flexibility to use it alone or with your current antidepressant
A meaningful option when suicidal thoughts make speed genuinely matter
Not everyone responds the same way, and it isnât a guaranteed fix â but for people whoâve run out of other options, it can genuinely change how quickly relief arrives.
Esketamine Side Effects & Safety
Esketamine, like any psychiatric medication, has real side effects, and it carries the FDAâs most serious safety label â a boxed warning â covering sedation, dissociation, and the potential for misuse.
The most common things people notice during and shortly after a session include feeling disconnected from reality, drowsiness, dizziness or vertigo, a temporary rise in blood pressure, nausea, anxiety, and a general feeling of intoxication. These usually fade fairly quickly, which is exactly why the two-hour monitoring window is built into every session at Ohio Psychiatric Services.
Itâs also worth knowing that cost can be a real barrier â sometimes running into the thousands of dollars for the first month â and that long-term safety data is still limited for people who may need this treatment indefinitely. Both are worth raising directly with your provider and your insurance plan before you begin. For more information on what to expect or to discuss whether esketamine treatment is right for you,Â
Step 1: Comprehensive evaluation
Your care starts with a psychiatric evaluation. A psychiatrist reviews your depression history, previous medications, current symptoms, and medical background to confirm whether Spravato is appropriate and safe. This visit is also a time to discuss your goals and concerns.
Step 2: Insurance review and approval
If Spravato appears to be a good fit, the OPS team helps with insurance verification and prior authorization. Many major insurance plans now provide coverage for Spravato for treatmentâresistant depression, when medical necessity criteria are met, although prior authorization is typically required. Trained staff will explain the expected costs and scheduling so you know what to expect.
Step 3: Induction phase (first month)
Once approved, you start the induction phase:
Treatments typically occur twice a week for four weeks.
You selfâadminister the nasal spray in a private room under direct clinical supervision.
Doses are given in a sequence of sprays spaced a few minutes apart.
After dosing, you stay for at least two hours while staff monitor your blood pressure, level of alertness, and side effects.
Because Spravato can cause temporary sedation or dissociation, you will need a ride home and should not drive or operate machinery for the rest of the day. Spravato cannot be taken at home; all doses are given in a certified clinic under a REMS safety program.
Step 4: Maintenance phase
If you respond to Spravato, your psychiatrist will transition you to a maintenance schedule. Many people start with weekly sessions and then move to every one to two weeks as symptoms stabilize. The goal is to maintain progress with the lowest effective treatment frequency.
Spravato may be used on its own or combined with an oral antidepressant, allowing your provider to tailor your plan to your history, preferences, and sideâeffect profile.
Side Effects and Safety
Most Spravato side effects are shortâlived and occur around the time of each treatment. Many people find side effects lessen as they continue treatment and become more familiar with the process. Common experiences include:
Feeling detached or floaty (dissociation)
Dizziness or unsteadiness
Nausea
Temporary rises in blood pressure
Sleepiness or fatigue
These are the main reasons treatment happens in a clinic with monitoring instead of at home. Some patients also describe the treatment experience as calming or reflective. Having a dedicated team present throughout the monitoring period often helps patients feel reassured and supported.
Spravato may not be right for everyone. Aneurysmal vascular disease, a history of brain hemorrhage (stroke), severe or uncontrolled hypertension or pregnancy may make other treatment options more suitable. Your OPS psychiatrist will review your medical history and current medications carefully before starting.
Why Consider Spravato at Ohio Psychiatric Services?
At OPS, Spravato is one part of a broader, personalized approach to depression care in Central Ohio. In addition to esketamine therapy, we also offer:
TMS therapy in Columbus and Hilliard, Ohio
Comprehensive medication management
Counseling and psychotherapy
Psychiatric evaluations
Genetic testing and other advanced options
This allows your treatmentâresistant depression plan in Columbus, Ohio to be built around you, not just a single medication or procedure. For some people, Spravato is the missing piece that finally moves the needle after years of trial and error. For others, it becomes a key part of a combined strategy that includes TMS, medication adjustments, and therapy.
If you have tried multiple medications and continue to struggle with depression, you do not have to navigate the next steps alone. The team at Ohio Psychiatric Services can help you determine whether Spravato, TMS, or another advanced treatment option may be right for you and create a personalized plan designed to help you regain hope and improve your quality of life.