IV Ketamine vs. Spravato: Understanding the Best Treatment for You

Kimberly Mercille • May 27, 2025

In recent years, innovative treatments like ketamine and Spravato (esketamine) have emerged as groundbreaking options for individuals struggling with severe depression. Both treatments offer rapid relief, particularly for those who have not found success with traditional therapies. While ketamine and Spravato share similarities, they also have important differences in how they are used, how they work, their safety profiles, and their costs.


At SW Florida TMS & Ketamine Clinic, we specialize in providing personalized, effective care to individuals seeking relief from mental health challenges. Understanding the differences between ketamine and Spravato can help you make an informed decision about which treatment is best suited to your needs.

What Is Intravenous (IV) Ketamine?

Ketamine is a powerful anesthetic that was developed initially for surgical procedures. However, over the past decade, its potential as a mental health treatment has garnered significant attention. Clinical research has shown that ketamine has rapid antidepressant effects, with benefits appearing hours after treatment. The treatment is particularly important for treatment-resistant mood disorders, providing relief when other treatments have failed.


Ketamine can be administered in several different ways, including intravenous (IV) infusion, intramuscular (IM) injection, and intranasal spray. In some cases, it may also be prescribed in oral form. The most common method of administration in clinics is IV ketamine, as it allows for precise dosing and fast absorption, providing quicker therapeutic effects.

What Is Spravato?


Spravato, the brand name for esketamine, is a nasal spray that was developed by Janssen Pharmaceuticals as a more targeted form of ketamine for treating depression. While ketamine contains both the R- and S-enantiomers, Spravato is composed exclusively of the S-enantiomer (S-ketamine).


Unlike ketamine, which has a broader range of uses, Spravato is specifically approved for treatment-resistant depression(TRD) and major depressive disorder with suicidality (MDSI). The nasal spray format is designed to be easier and less invasive than the IV ketamine infusions, but it still requires monitoring for side effects during and after treatment.

How Do IV Ketamine and Spravato Work?

Both ketamine and Spravato block NMDA receptors in the brain, which play a role in learning and neuroplasticity. Neuroplasticity is the brain's ability to reorganize itself, and it's an essential player in treating mood disorders. The process helps repair dysfunctional nerve circuits and supports the development of healthier thought patterns and behaviors.


While both treatments share this mechanism of action, there are some key differences in how they affect the brain. Ketamine, especially when administered intravenously, can produce psychedelic effects, including dissociation, changes in perception, and vivid emotional experiences. These experiences can be therapeutic when paired with psychotherapeutic support, similar to classical psychedelics.


Spravato, on the other hand, interacts more strongly with NMDA receptors and is less psychoactive at therapeutic doses.


Ketamine vs Spravato Treatment Protocol


Ketamine is typically delivered through IV infusions, which provide the most consistent and rapid absorption into the bloodstream. Treatment sessions generally last about 40 minutes, with the effects starting to take hold within a few minutes. Patients are closely monitored for side effects and remain in the clinic for about two hours following treatment to ensure safety. The frequency and number of sessions will depend on a patient's unique condition and how they respond to ketamine. 


Spravato is a nasal spray that patients administer themselves under medical supervision. Each session takes about two hours, including observation time, as side effects can occur soon after administration. The treatment protocol is much less flexible and follows a standard protocol of doses twice weekly for the first four weeks, with maintenance treatments occurring weekly afterward.


Is IV Ketamine or Spravato More Effective?


Both IV ketamine and Spravato have shown promise in treating treatment-resistant depression (TRD), with similar effectiveness. However, IV ketamine may give rise to quicker symptom relief, with improvements typically occurring within hours of treatment. One study found no difference in terms of overall efficacy, but IV ketamine patients required fewer treatments to reach remission.


Safety and Side Effects


Both IV ketamine and Spravato are generally safe when administered by experienced professionals in a clinical setting. However, like all medications, they come with potential side effects.


Common side effects of both treatments can include:

  • Dizziness
  • Nausea
  • Increased heart rate
  • Dissociation (feeling detached from one’s body or surroundings)
  • Temporary changes in blood pressure


For IV ketamine, the dissociative effects can sometimes be more intense. For some patients, these sensations can feel disorienting or even frightening, while for others, they can lead to valuable insights during the therapy process. Patients may also experience side effects related to the infusion, such as pain at the site of injection.


Spravato, due to its lower dosage, generally leads to milder side effects. However, it may cause nasal irritation or congestion in some individuals, as the medication is administered via a nasal spray.


Cost and Insurance Coverage


When considering treatment options, the cost is an essential factor. Spravato, being FDA-approved, is often covered by insurance, making it a more affordable option for many patients. However, coverage may depend on the specific plan, and some individuals may still need to pay a co-pay or meet other out-of-pocket expenses.


IV ketamine, on the other hand, is not FDA-approved for depression, meaning it is less likely to be covered by insurance. While the out-of-pocket cost of ketamine can be higher, many patients find it worth the investment due to the rapid and lasting relief it provides.


At SW Florida TMS & Ketamine Clinic, we work with CareCredit, a health and wellness credit card that provides flexible financing options for ketamine treatment. This allows you to pay for the care you need or desire over time.


Which Treatment Is Right for You?


Choosing between ketamine and Spravato depends on several factors, including the severity of your condition, your preferences for treatment, and cost considerations.

  • IV ketamine therapy is an off-label treatment for several different mental health disorders. It offers flexibility with various administration methods and treatment protocols. Its psychoactive effects can give rise to potential psychotherapeutic benefits.
  • Spravato is a nasal spray that is only available for people with diagnosed TRD or MDSI. The treatment protocol is more structured, and its insurance coverage makes it a financially viable option.


At our TMS and ketamine clinic in Fort Myers, we provide personalized consultations to help you decide on the best treatment for your needs. Our medication management services will also help track your progress, manage treatment doses and schedules, and explore alternative options. Contact us today to learn more about ketamine and Spravato treatment options and how they can help you achieve lasting relief from depression and other mental health challenges.


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Living with depression can be incredibly difficult, especially when traditional medications don’t bring relief. In this article, we’ll be discussing the nasal spray, Spravato, which is a breakthrough FDA-approved treatment for depression. We’ll discuss the science and safety of Spravato and what to expect during the treatment process. What Is Spravato? Spravato is a nasal spray containing esketamine , a chemical compound derived from ketamine. Ketamine is a widely recognised, effective, rapid-acting treatment for depression and other mental health disorders that was initially developed as an anesthetic. Esketamine is an enantiomer of ketamine, meaning it is one of two mirror-image molecules that make up ketamine when in its original form (“generic ketamine”). This enantiomer interacts more strongly with NMDA receptors , which are proteins thought to underlie the ketamine’s antidepressant effects. 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It targets a different brain chemical called glutamate , which is essential for overall communication in the brain and functions like learning and memory. Spravato blocks NMDA receptors in the prefrontal cortex , a part of the brain involved in regulating mood and emotions. This boosts glutamate activity in that area, which is thought to be part of the reason why Spravato can relieve depression symptoms so quickly. Spravato also increases neuroplasticity , the brain’s ability to reorganize itself. This helps with depression in three main ways: Synaptic plasticity refers to the brain's ability to reorganize the connections between nerve cells, called synapses. Strengthening these connections may help strengthen circuits involved in stress and emotional regulation. Neurogenesis is the process of creating new nerve cells. This can help repair brain areas affected by depression. Functional connectivity describes how different regions of the brain work together. Improved connectivity may help people escape negative thought patterns and develop healthier, more flexible ways of thinking. Who Is Eligible for Spravato Treatment? Spravato is approved for use in adults diagnosed with TRD. To be considered for TRD, a person must have a formal diagnosis of MDD and must have tried at least two different antidepressants , at the right doses and for a minimum of six months, without significant improvement in symptoms. In addition to TRD, Spravato is also approved for patients experiencing depression with acute suicidal ideation or behavior . The patient will have active suicidal thoughts and intend to harm themselves. To be eligible for Spravato, patients must: Be diagnosed with MDD with TRD or MDSI Be currently taking a standard oral antidepressant (Spravato is used in combination with another medication) Be evaluated and monitored in a certified Spravato treatment center Be free from contraindications such as vascular disease or hemorrhage What to Expect During a Spravato Session Spravato is not a take-home medication. Each treatment must be administered in person at an approved clinic under close medical supervision. At our TMS and Ketamine Clinic of Southwest Florida, we’re a licensed provider of Spravato, serving Fort Myers and the surrounding areas. Here’s what you can expect if you undergo Spravato treatment at our centre: Arrival and Preparation You’ll check in and be escorted to a comfortable, private treatment room. A clinician will review your health status and answer any questions. Administration You’ll use the nasal spray yourself, but under direct observation. The device is pre-measured and easy to use. Monitoring Period After administration, you’ll be monitored for at least two hours . During this time, side effects are observed and managed, and you'll be made as comfortable as possible. Post-Treatment Once cleared by medical staff, you’ll be released to a pre-arranged caregiver or driver. You must not drive or operate heavy machinery for the rest of the day. The initial treatment schedule typically includes two sessions per week for four weeks , followed by a tapering period where the frequency is reduced based on your response. How Is Spravato Different from Ketamine? Although Spravato and ketamine are chemically related and affect the brain in similar ways, there are key differences in how they’re used in clinical practice: Spravato is FDA-approved specifically for depression , while ketamine is used “off-label” for a variety of conditions, including PTSD, anxiety, and chronic pain. Spravato is administered only via nasal spray in a certified clinic, while ketamine can be delivered through IV infusion, intramuscular injection, or oral lozenge . Spravato has a standardized dosage and protocol , ensuring consistency across treatments. Ketamine doses and regimens may vary more widely depending on the provider and purpose. Some patients find ketamine’s dissociative effects more pronounced, which can lead to therapeutic insights but may also be more intense or uncomfortable for others. Both treatments can be effective. If you’re uncertain about which one best suits you, our care team at TMS and Ketamine Clinic of Southwest Florida can help determine the most appropriate option based on your symptoms, history, and goals. What Are the Side Effects of Spravato? While Spravato is generally well-tolerated, it can cause side effects, most of which occur shortly after administration and resolve within a few hours. Common side effects include: Nausea or vomiting Dizziness or lightheadedness Dissociation (feeling disconnected from oneself or surroundings) Headache Increased blood pressure Fatigue or drowsiness Because of these effects, Spravato is administered only under supervision , with patients observed until they are stable and alert. Spravato Clinical Evidence: Effectiveness of Spravato in Depression In a 2018 study , participants with moderate to severe depression symptoms were treated with Spravato. At the final follow-up, 65% of participants had a 50% or greater decrease in scores of depression symptoms . Over 30% also achieved remission , meaning their symptoms had either gone or were very mild. In a more recent study , the effects of Spravato were assessed in 68 patients with MDD at imminent risk of suicide. Spravato led to a significant decrease in suicidal ideation and depression scores compared to the placebo, with noticeable improvement as early as four hours after treatment . Take the First Step Toward Relief At the TMS and Ketamine Clinic of Southwest Florida, we specialize in cutting-edge treatments for depression, including Spravato. Our experienced psychiatrist and dedicated mental health professionals are here to provide compassionate care and support every step of the way. If traditional treatments haven’t helped, you don’t have to keep struggling. Contact us today to find out if our innovative therapies could be the right solution for you.
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