If you have been researching advanced treatments for depression, you have probably come across both Spravato and ketamine infusions. They sound similar, they are chemically related, and they are often mentioned in the same breath. But they are not the same treatment, and the differences between them matter a great deal when it comes to choosing what is right for your situation. This post breaks down exactly how Spravato and ketamine infusions compare, where each one has the advantage, and how to think through the decision. What They Have in Common Both Spravato and ketamine infusions work through the same basic mechanism. They both target NMDA receptors in the brain and trigger a rapid increase in glutamate signaling, which promotes the growth of new synaptic connections in areas of the brain associated with mood and emotional regulation. This is why both treatments can produce antidepressant effects far faster than traditional medications, sometimes within hours of the first session. Both are administered in a supervised clinical setting. Neither is a take-home medication. Both are primarily used for patients who have not responded adequately to standard antidepressants. And both are available at NeuPath Mind Wellness across our South Florida locations. That is largely where the similarities end. What Is Spravato? Spravato is the brand name for esketamine, a nasal spray form of ketamine that was developed specifically for depression and received FDA approval in 2019. It is the first genuinely new class of antidepressant the FDA has approved in decades. Spravato is administered as a nasal spray in a clinical setting. You self-administer the spray under the supervision of a healthcare provider, then remain in the clinic for a two-hour observation period. You cannot drive yourself home afterward. Sessions are typically twice weekly for the first month, then weekly, then every one to two weeks as a maintenance dose. Because Spravato is FDA-approved specifically for treatment-resistant depression and, more recently, for major depressive disorder with acute suicidal ideation, it has a well-established insurance coverage pathway. Most major insurers cover it under similar criteria to TMS. What Are Ketamine Infusions? IV ketamine infusions use the full racemic form of ketamine, delivered directly into the bloodstream through an intravenous line over approximately 40 to 60 minutes. Ketamine has been used as an anesthetic for decades and is used off-label for depression, meaning its use for mood disorders is not FDA-approved for that specific indication, even though the clinical evidence supporting it is extensive. During an infusion, most patients experience a dissociative state, a dreamlike, floaty feeling that typically lasts for the duration of the session and resolves shortly after. The infusion is monitored closely by clinical staff throughout. Afterward, patients need a recovery period and cannot drive themselves home. A standard course for depression is typically six infusions over two to three weeks, followed by maintenance infusions as needed. How They Compare: The Key Differences This is the most practically significant difference for most patients. Does Insurance Cover Spravato? Spravato is covered by insurance. Because it is FDA-approved for treatment-resistant depression, most major insurers including Aetna, Blue Cross Blue Shield, Cigna, UnitedHealthcare, and Medicare have established coverage policies for it. The standard requirement is a diagnosis of treatment-resistant depression and a documented history of failed antidepressant trials, criteria most patients seeking this level of treatment already meet. Does Insurance Cover Ketamine Infusions? IV ketamine is generally not covered by insurance. Because it is used off-label, insurers do not have formal coverage policies for it. A full course of six infusions typically costs several thousand dollars out of pocket. Which Is More Cost-Effective? If cost and insurance coverage are significant factors in your decision, Spravato has a clear and meaningful advantage. The Molecule Spravato uses esketamine, which is one half of the ketamine molecule, specifically the S-enantiomer. IV ketamine uses the full racemic mixture, meaning it contains both the S and R forms of the molecule. The R-enantiomer in racemic ketamine may contribute additional antidepressant effects that esketamine alone does not produce, which is one reason some clinicians believe IV ketamine may have a clinical edge in certain patient populations. The research on this is still evolving. The Experience Spravato is a nasal spray. The dissociative experience it produces is generally milder than that of IV ketamine, though it varies by patient. The two-hour observation window is required regardless of how you feel. IV ketamine produces a more pronounced dissociative effect for most patients. Some find this deeply therapeutic. Others find it uncomfortable. Because the drug is delivered directly into the bloodstream, the onset is faster and the peak experience more intense than with Spravato. Speed of Onset Both treatments are fast-acting compared to oral antidepressants. IV ketamine may produce a slightly faster and more intense initial response due to the direct intravenous delivery and the full racemic formulation. Spravato’s effects are meaningful but the onset curve is somewhat gentler for most patients. Dosing Flexibility IV ketamine allows for more precise, individualized dosing. Because the infusion rate and concentration can be adjusted in real time, clinicians can titrate the dose based on the patient’s response, weight, and tolerance. Spravato comes in fixed doses of 56mg and 84mg, which limits that level of personalization. The Clinical Setting Both require clinical supervision and a period of observation. Spravato’s two-hour window is longer than a typical ketamine infusion visit when you factor in recovery time, though the total time commitment across a treatment course is comparable. What the Research Says Both treatments have solid clinical evidence behind them. Spravato’s approval was based on pivotal trials demonstrating significant reduction in depressive symptoms in treatment-resistant patients within 24 hours of the first dose. IV ketamine’s evidence base is even longer-standing, with dozens of well-designed studies consistently showing rapid antidepressant effects. Head-to-head comparisons between the two are limited, and the existing research does not definitively establish one as superior to the other for all patients. The practical differences, particularly around insurance coverage, dosing flexibility, and the in-session experience, tend to