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Over the last decade, the field of psychiatry has witnessed a quiet but powerful shift in how we approach treatment-resistant major depressive disorder (MDD). Among the most significant developments is the introduction of Spravato — a brand-name medication derived from esketamine. Spravato is called the “s-enantiomer” of ketamine — ketamine, as a drug, is composed of two molecules that are identical but for their orientation. Much like our hands are identical except that they are mirror images of each other, ketamine molecules are identical except for the fact that they exist as mirror images of each other. The molecule that is oriented to the left is called the “s-enantiomer” and is esketamine. This innovation has offered new hope to those whom traditional antidepressants have fallen short of treating mental health conditions.
But what is Spravato (esketamine)? How does it work — and for whom it is prescribed? This post seeks to demystify this novel therapy, offering clarity for patients, families, and clinicians navigating complex mental health journeys.
What Is Esketamine?
Esketamine, as above, is a chemical mirror image of ketamine, known as the s-enantiomer. While ketamine has been used for decades as an anesthetic — and more recently, in off-label psychiatric contexts — esketamine was developed and studied specifically for major depressive disorder and treatment-resistant depression. Its greater potency at the NMDA receptor compared with ketamine makes it especially promising in lower doses for psychiatric use.
In 2019, the FDA approved Spravato, the first esketamine nasal spray intended for adults with treatment-resistant depression. Unlike traditional antidepressants, which often take weeks to work, Spravato (esketamine) can create rapid improvement in mood — sometimes within hours. Importantly, esketamine was recently approved for “monotherapy,” meaning that patients no longer need to take an antidepressant medication to participate in esketamine. Generally, it is approved for treatment refractory MDD (depression that fails to respond to 2-4 traditional antidepressant medications) or Major Depressive Disorder that coincides with suicidal thoughts. The depression also needs to be of a certain severity which is measured using validated depression rating scales (at Lumin Health, we use the MADRS rating scale).
Spravato is the brand name for esketamine nasal spray, developed by Janssen Pharmaceuticals, Spravato is administered in a medical setting where proper monitoring and assistance is available, and delivered intranasally under clinician supervision. The typical course is twice a week for the first month, once weekly for 4 weeks, then weekly or every other week thereafter (so long as it remains effective). Some people are able to stretch out treatments to every 4 weeks later in the course and some only come in as needed after they have completed the initial 2-3 month long initiation course. At Lumin Health, as no two recoveries are the same, every person finds his/her/their own particular path forward with information and guidance from our clinical team.
Unlike oral antidepressants that modulate serotonin, norepinephrine, or dopamine, Spravato (esketamine) acts primarily on the brain’s glutamate system. This glutamatergic modulation is thought to promote neuroplasticity — helping the brain forge new, healthier patterns of thought and emotion. There are a host of other places in the brain the medication impacts, such as opioid receptors (delta and kappa), the default mode network, and astrocytes that may also play a role in recovery and symptom relief.
Because of its dissociative and potential psychedelic effects, the medication must be administered in certified clinics, with patients monitored on-site for at least two hours post-dose. This structure offers not only safety, but also the chance to begin emotional integration immediately after each session.
Esketamine Treatment: Who Is It For?
Esketamine treatment is currently approved for individuals with treatment-resistant MDD — defined as a lack of adequate response to at least two prior antidepressants. It may also be used for patients with major depressive disorder who have suicidal thoughts,.
So, who might benefit? At Lumin Health, we see esketamine treatment as a potential turning point for patients who feel stuck — those who’ve tried multiple therapies, but whose lives remain constrained by depression’s grip. For them, the arrival of ketamine nasal spray (esketamine) isn’t just a new medication; it’s a reframing of what recovery might look like. It offers the people we see hope and a way to affirm their own agency.
Still, Spravato is not for everyone. Patients with a history of substance use disorder, uncontrolled hypertension, certain psychiatric conditions, recent stroke, vascular disorders, pregnancy, and other disorders may not be good candidates. That’s why every course of esketamine treatment begins with a thorough diagnostic and medical evaluation to make sure the treatment is safe and advised
Ketamine vs. Esketamine: What’s the Difference?
Both ketamine and esketamine are dissociative anesthetics that influence how a chemical in the brain called “glutamate” is sent from one brain cell to another. However, there are important distinctions. Other routes of ketamine dosing – i.e. nasal spray, IV infusions, and intramuscular injections – are used off-label, meaning they haven’t gone through the FDA’s formal approval process for psychiatric use.
By contrast, Spravato is FDA-approved and covered by many insurance plans. It is also dosed and delivered in a more standardized format. While both options can be effective, Spravato (esketamine) nasal spray offers the benefit of a predictable protocol and extensive clinical trial data. It is overseen by clinical staff and has a government required oversight committee to make sure it is safe. Coupled with the accessibility provided by the insurance coverage, this makes Spravato (esketamine) a popular, safe, and accessible method of ketamine administration at Lumin Health.
That said, some patients respond better to one approach over the other. Choosing between ketamine nasal spray and Spravato isn’t simply a medical decision — it’s a collaborative one, guided by patient preference, treatment history, and clinical expertise.
How to Tell if Ketamine or Spravato (Esketamine) is Right For Me
Spravato (esketamine) represents a convergence of neuroscience, pharmacology, and compassion. It’s not just about managing symptoms — it’s about restoring the capacity for connection, creativity, and presence. While not a magic bullet, esketamine therapy opens a door for patients long trapped by the limits of conventional treatment.
If you’re wondering whether esketamine treatment could be right for you or someone you care about, the first step is a conversation. Not just about the science, but about the experience. Because when it comes to healing, how a treatment feels matters just as much as how it works. So don't hesitate to get in touch with Lumin Health to explore your options and see if ketamine therapy might be right for you.
