Spravato® vs. Ketamine: Understanding the Key Differences in Treatment
The main difference between Spravato® and ketamine is that Spravato® (which is a specific molecule called esketamine) is an FDA-approved nasal spray for treatment-resistant depression. In contrast, intravenous (IV) ketamine treatment is considered an evidence-informed, off-label option administered via infusion, with a different molecular composition.
Navigating advanced options for depression can feel overwhelming. At Lumin Health, we understand this challenge. When traditional antidepressants haven’t provided the relief you need, you may encounter two closely related terms: Spravato and ketamine therapy. While they share a common origin, they are distinct treatments with different methods of administration, regulatory statuses, and applications. Understanding these differences is a critical step in making an informed decision about your mental health care.
This guide aims to provide a clear, medically-grounded comparison to help you understand the unique properties of each option, empowering you to have a more productive conversation with a qualified medical professional.
First, What is Foundational Ketamine?
Ketamine has been used for decades as a safe and effective anesthetic in medical settings worldwide. It is a dissociative anesthetic that, at sub-anesthetic doses, has been observed to have rapid and potent antidepressant effects. This discovery has led to its use as an off-label ketamine treatment and broader ketamine therapy for various mental health conditions, particularly severe depression. The growing body of evidence supporting ketamine for depression highlights its potential as a transformative option.
The foundational form of ketamine used in mental health, often referred to as ketamine therapy, is typically a racemic mixture, meaning it contains two mirror-image molecules: S-ketamine and R-ketamine. When administered, usually through an IV infusion, this mixture works on the brain’s glutamate system, a major departure from traditional antidepressants that primarily target serotonin or norepinephrine. This mechanism is believed to trigger a cascade of events that can lead to rapid synaptogenesis—the formation of new connections between brain cells. This innovative approach to ketamine treatment, particularly as a solution for ketamine for depression, represents a significant shift in psychiatric care.
What is Spravato® (Esketamine)? A Specific, FDA-Approved Formulation
Spravato® is the brand name for esketamine, which is the "S" molecule isolated from the racemic ketamine mixture used in broader ketamine therapy. By isolating this specific molecule, Janssen Pharmaceuticals developed a medication that could be standardized, studied in large-scale clinical trials, and ultimately submitted for regulatory approval.
In 2019, this effort was successful. The U.S. Food and Drug Administration (FDA) approved Spravato® nasal spray, taken in conjunction with an oral antidepressant, for a specific and important purpose: for adults with treatment-resistant depression (TRD) and for adults with major depressive disorder with acute suicidal ideation or behavior (MDSI). This FDA approval is a crucial distinction, as it provides a clear regulatory pathway for both physicians and insurance providers when considering this particular treatment. The development of Spravato marks a significant milestone in modern psychiatry.
At a Glance: Comparing Spravato® and IV Ketamine Therapy
To provide maximum clarity, this table breaks down the essential differences between Spravato and IV ketamine treatment options. It is important to remember that the right choice is highly individual and depends on a thorough psychiatric evaluation.
FeatureSpravato® (Esketamine)IV Ketamine TherapyFDA Approval StatusFDA-approved for specific conditions (TRD and MDSI).Used "off-label" for depression and other conditions based on extensive clinical evidence.Route of AdministrationSelf-administered nasal spray under the supervision of a healthcare provider.Administered intravenously (IV infusion) by a medical professional.Chemical CompositionContains only the S-ketamine molecule.Racemic mixture containing both S-ketamine and R-ketamine molecules.Insurance CoverageOften covered by insurance, including Medicare, due to its FDA-approved status (subject to plan specifics and prior authorization).Generally not covered by insurance, often requiring out-of-pocket payment.Clinical SettingMust be administered in a certified medical practice where the patient is monitored for at least two hours.Administered in a medical setting with continuous vital sign monitoring during the infusion.
The Neurological Goal: Unsticking Rigid Brain Patterns
Your brain isn't broken—it may be stuck. Chronic depression is often associated with rigid, negative thought patterns and a reduction in neural connectivity, particularly in an area known as the Default Mode Network (DMN). The DMN is active when we are at rest or introspecting and can become overactive in depression, leading to rumination.
Both IV ketamine and Spravato® aim to disrupt these rigid patterns. By modulating the glutamate system, they foster neuroplasticity—the brain's ability to reorganize itself by forming new neural connections. This process, which can be supported by subsequent psychotherapy, may help the brain exit persistent depressive states. The overall goal of ketamine therapy, particularly ketamine treatment for chronic conditions, is to foster this change. As noted in a pivotal study published in The American Journal of Psychiatry, the rapid antidepressant effects are linked to this ability to quickly restore synaptic function. The goal of using ketamine for depression is to create a biologically receptive window for profound and lasting change.
“We often see that depression can create deep grooves in a person's neural pathways, making it difficult to find a way out. The value of a powerful tool like IV
– Dr. Ben Yudkoff, Chief Medical Officer at Lumin Health
Frequently Asked Questions About Esketamine and Ketamine
Which treatment is "better" for me?
There is no single "better" option; the most appropriate ketamine treatment, whether Spravato or broader ketamine therapy, is entirely dependent on your individual clinical situation. Factors include your specific diagnosis, treatment history, medical comorbidities, and insurance coverage. The FDA-approved status of Spravato makes it a primary choice for individuals who meet the specific criteria for treatment-resistant depression. A comprehensive psychiatric assessment is required to determine suitability.
Is a "bad trip" a common concern?
The term "bad trip" is often associated with recreational, unsupervised use of ketamine. In a controlled, medical environment, the experience is very different. You will be in a comfortable, monitored setting with medical professionals present at all times. The dissociative effects are expected and managed as part of the therapeutic process. The focus is on safety, comfort, and clinical outcomes, not a recreational experience.
Why is medical supervision so important?
Both esketamine and IV ketamine can cause temporary increases in blood pressure and heart rate, as well as dissociative or psychotomimetic effects. For this reason, administration of both esketamine and any form of ketamine therapy is strictly limited to certified medical sites where you can be monitored by trained personnel. As established by FDA guidelines, and detailed by the National Institute of Health, safety protocols are non-negotiable for ensuring your well-being during and after administration.
Finding a Path Forward with Expert Guidance
Choosing between advanced psychiatric treatments can feel like a significant decision, because it is. It represents a step towards reclaiming your well-being. At large, impersonal health systems, it can be easy to feel like just another number. A psychiatrist-led practice like Lumin Health is designed differently, prioritizing personalized, attentive care where you are seen and heard as an individual, especially when considering complex options like ketamine for depression.
A comprehensive evaluation is the first and most important step to determine if a ketamine treatment, such as ketamine therapy, may be an appropriate part of your care plan. Lumin Health is dedicated to guiding you through this process. While our physical locations serve patients in Massachusetts, we hope this guide serves as a valuable educational resource for anyone exploring advanced options like ketamine for depression. If you are ready to see whether this approach may be a fit, we would be grateful to walk with you towards relief.
