Depression can make the mind feel fixed in place. Thoughts repeat, energy contracts, sleep changes, and even the possibility of relief can begin to feel abstract. For people who have tried more than one conventional approach without adequate improvement, it is reasonable to ask whether a medication working through a different pathway might matter.
SPRAVATO® is the brand name for esketamine, a prescription nasal spray administered in a certified healthcare setting. It is FDA-approved for adults with treatment-resistant depression, where it may be used alone or with an oral antidepressant. It is also FDA-approved, with an oral antidepressant, for depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior. It is not a take-home medication, and that distinction is important.
At Minnesota Ketamine & Wellness Institute, we believe you deserve a clear explanation before deciding whether to pursue care. That includes what is known about brain signaling, what clinical evidence can and cannot tell us, and why observation after each treatment is part of safe administration.
This article is for educational purposes only. It is not medical advice and does not replace an evaluation or treatment recommendations from a qualified clinician who understands your health history.
Depression involves more than low serotonin
For decades, public conversations about depression centered heavily on serotonin. Serotonin remains relevant, and many antidepressants work through serotonin-related pathways. But depression is not a single-chemical condition, nor does every person experience it in the same way.
Researchers have increasingly examined glutamate, the brain’s primary excitatory neurotransmitter, as another important part of the picture. Glutamate participates in communication between neurons, learning, memory, and the brain’s ability to adapt in response to experience. A review of glutamatergic approaches to major depression describes why this system has become clinically important in depression research (McIntyre et al., 2024).
This does not mean we can point to one brain circuit and call it the cause of depression. We cannot. Brain science is more complex than that. Still, it gives us a useful framework for understanding why some treatments may feel different from traditional daily antidepressants.
For those considering a broader plan of care, our depression treatment options begin with the person in front of us, including your history, symptoms, current medications, medical considerations, and goals.
Esketamine and the brain’s signaling systems
Esketamine is one component, or enantiomer, of ketamine. It acts primarily on the NMDA receptor, which is involved in glutamate signaling. You can learn more about the NMDA receptor and why it appears so often in discussions of ketamine-related care.
The simplest explanation is that SPRAVATO® temporarily changes aspects of glutamate signaling. This change may set off downstream processes associated with synaptic communication and neuroplasticity, meaning the brain’s capacity to form, strengthen, or revise connections. These proposed effects are biologically plausible and supported by a growing body of research, but they should not be presented as a complete explanation for why any individual person improves.
That uncertainty matters. A mechanism is not a promise. Depression has psychological, social, biological, relational, and environmental dimensions, and medication is often one part of a larger treatment plan rather than the whole plan.
Ketamine and esketamine are related, but they are not interchangeable in regulatory terms. SPRAVATO® is FDA-approved for its specific labeled depression indications. Ketamine is not FDA-approved for psychiatric conditions, and when ketamine is used for depression, that use is off-label. The clinical literature on both options emphasizes careful patient selection, dosing, monitoring, and follow-up. An international review of evidence and implementation considerations highlights both the potential value and practical responsibilities involved in this area of care (McIntyre et al., 2021).
What treatment-resistant depression means in practice
The phrase treatment-resistant depression can sound discouraging, as though you have failed treatment or are beyond help. We do not see it that way. Usually, the term describes depression that has not responded adequately to multiple appropriate antidepressant treatments.
There is no single life story behind that definition. You may have tried medications with partial benefit but difficult side effects. An antidepressant may have helped for years before symptoms returned. Or you may have had careful therapy, medication management, and strong support, yet still feel burdened by persistent depression.
Researchers have worked to create more consistent definitions because the phrase is used differently across studies and settings. A consensus definition of treatment-resistant depression emphasizes the need to account for adequate treatment trials rather than reducing a complex history to a simple label (Sforzini et al., 2022).
Before considering SPRAVATO®, we review the details. We want to understand what you have tried, how long you tried it, what changed, what did not, and what may need more attention now. This is where thoughtful integrative treatment matters. A medication decision should fit the larger clinical picture.
Why clinical monitoring is built into SPRAVATO® care
SPRAVATO® is administered as a nasal spray in a certified clinical setting, followed by required observation. Monitoring is not an administrative formality. It is a central part of treatment.
During the observation period, we monitor how you are feeling and assess for effects that can occur after dosing, including sedation, dissociation, changes in perception, dizziness, nausea, and increases in blood pressure. You remain with our clinical team for at least two hours after administration, and you need a responsible adult to drive you home. You should not drive or operate machinery until the next day after a restful sleep.
Dissociation deserves a direct explanation. Some people describe feeling detached from their body, surroundings, time, or ordinary thought patterns. For some, this is brief and manageable. For others, it can feel unfamiliar or unsettling. We prepare you for that possibility, check in throughout the visit, and create a calm, structured setting for the experience.
This is different from home use of a nasal medication. The setting, pre-treatment assessment, vital-sign checks, observation, and safe discharge planning are all part of responsible SPRAVATO® administration.
What the evidence can and cannot establish
Clinical studies can tell us whether a treatment performed better than a comparison condition for groups of participants under specific circumstances. They can identify common adverse effects and help guide dosing and maintenance decisions. They cannot predict with certainty what one person’s experience will be.
A Cochrane review of ketamine and glutamate receptor modulators found evidence of antidepressant effects while also noting limitations in the available research, including the need for clearer long-term evidence (Dean et al., 2021). That is the honest middle ground. The evidence is meaningful, but it does not erase uncertainty.
Maintenance also requires attention. Depression can be recurrent, and the question is not only whether symptoms shift after an initial phase of care, but what helps sustain stability over time. A systematic review of maintenance ketamine research found encouraging but still limited evidence regarding longer-term efficacy, safety, and tolerability (Smith-Apeldoorn et al., 2022).
We use those limits to guide a thoughtful conversation, not to make a decision for you. We discuss benefits, risks, alternatives, ongoing medications, psychotherapy, sleep, substance use, medical history, and the practical reality of attending monitored appointments.
Frequently asked questions about SPRAVATO®
Is SPRAVATO® the same as ketamine?
Not exactly. SPRAVATO® contains esketamine, one component of ketamine, and it is a nasal spray with specific FDA-approved indications and required monitoring. Ketamine is not FDA-approved for psychiatric conditions. Its use for depression is off-label. Our introduction to ketamine can help clarify the broader terminology.
Will SPRAVATO® replace my current antidepressant?
Not necessarily. For adult treatment-resistant depression, SPRAVATO® may be used alone or with an oral antidepressant. For depressive symptoms associated with major depressive disorder with acute suicidal ideation or behavior, SPRAVATO® is used with an oral antidepressant. Any medication changes should be made carefully with a qualified prescriber who understands your full history.
How quickly will I know whether it helps?
Responses vary. Some people notice changes sooner than they have with prior medications, while others need time, adjustment, or a different plan. We do not promise a particular timeline or outcome. Research on personalized ketamine and esketamine care also underscores the importance of individual clinical factors when considering these treatments (Medeiros et al., 2024).
What if I am having thoughts of suicide right now?
If you are in immediate danger, call 911 or go to the nearest emergency department. You can also call or text 988 for the 988 Suicide and Crisis Lifeline at any time. SPRAVATO® care is not a substitute for emergency intervention when your safety is at risk.
A measured next step
SPRAVATO® is neither a simple answer nor an option that should be approached casually. It is a carefully regulated medication that may be worth discussing when depression has remained present despite prior care. The question is not whether it is universally right. The question is whether it fits your circumstances, health history, and treatment goals.
If you are considering SPRAVATO® for depression, we can help you think through that question with care. We begin by listening, reviewing your history, and discussing what a monitored treatment plan would realistically involve. You can also explore our approach to care before reaching out to our Maple Grove team.
Key takeaways
SPRAVATO® is esketamine nasal spray, administered in a certified healthcare setting with required monitoring.
For adult treatment-resistant depression, SPRAVATO® may be used alone or with an oral antidepressant.
For depressive symptoms associated with major depressive disorder with acute suicidal ideation or behavior, SPRAVATO® is used with an oral antidepressant.
It works through glutamate-related signaling, including NMDA receptor activity, though no single mechanism fully explains depression or individual response.
Ketamine is not FDA-approved for psychiatric conditions. Ketamine treatment for depression is off-label.
Monitoring addresses possible short-term effects such as sedation, dissociation, dizziness, nausea, and blood pressure changes.
A thorough evaluation should include your treatment history, current medications, safety needs, and the supports that help you stay well.
Works Cited
1. McIntyre RS, et al. Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation. https://pubmed.ncbi.nlm.nih.gov/33726522/
2. McIntyre RS, et al. Glutamatergic Modulators for Major Depression from Theory to Clinical Use. https://pubmed.ncbi.nlm.nih.gov/39150594/
3. Smith-Apeldoorn SY, et al. Maintenance ketamine treatment for depression: a systematic review of efficacy, safety, and tolerability. https://pubmed.ncbi.nlm.nih.gov/36244360/
4. Sforzini L, et al. A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials. https://pubmed.ncbi.nlm.nih.gov/34907394/
5. Dean RL, et al. Ketamine and other glutamate receptor modulators for depression in adults with unipolar major depressive disorder. https://pubmed.ncbi.nlm.nih.gov/34510411/
6. Medeiros GC, et al. Personalized use of ketamine and esketamine for treatment-resistant depression. https://pubmed.ncbi.nlm.nih.gov/39613748/
Disclaimer
This article is for educational purposes only and is not a substitute for individualized evaluation, diagnosis, or treatment from a qualified healthcare professional.