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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Spravato (esketamine) is a groundbreaking treatment for individuals with treatment-resistant depression (TRD) and major depressive disorder with suicidal ideation (MDSI). Unlike traditional antidepressants, Spravato works rapidly, often providing symptom relief within hours. In this article, we’ll introduce Spravato, discuss how long it takes to work, and explore its short- and long-term effects. What is Spravato and How Does It Work? Spravato (esketamine) is an FDA-approved nasal spray derived from ketamine, specifically designed to treat individuals with TRD and MDSI. Like ketamine, Spravato works by inhibiting NMDA receptors —proteins involved in learning and memory. This inhibition leads to the release of glutamate, a key neurotransmitter, triggering several downstream effects in brain cells. Unlike standard antidepressants, Spravato has rapid-acting effects, sometimes appearing almost immediately after use. 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In a study of adults with TRD, those who took Spravato along with an antidepressant experienced noticeable symptom relief within 24 hours—an improvement greater than those who took a placebo with an antidepressant. Both groups continued improving over the next 28 days, but the difference between them remained significant. For people with MDSI, clinical studies have shown that Spravato, combined with an antidepressant, significantly reduces symptoms within 24 hours compared to placebo groups. The greatest differences are seen within four hours of taking the medication. Factors That Affect How Long Spravato Takes to Work The time it takes for Spravato to start working varies from person to person. Some may feel relief within hours, while others may require several treatments over days or weeks to notice significant changes. Factors that influence how quickly Spravato works include: Severity of Depression – Those with more severe symptoms may take longer to notice improvement. Individual Brain Chemistry – Differences in neurotransmitter activity can affect response time. Previous Treatments – If someone has had multiple unsuccessful treatments, their response may be slower. Overall Health – Chronic illnesses or nutritional deficiencies may impact treatment effectiveness. Psychological and Environmental Factors – Stress levels, support systems, and therapy participation can all play a role. How Long Do the Effects of Spravato Last? A single dose of Spravato provides relief for up to 24 hours, but for sustained benefits, treatment follows a structured regimen: Induction Phase Twice-weekly doses for the first four weeks. Maintenance Phase Begins after Week 4, with dosing frequency gradually reduced based on clinical response—typically shifting to once weekly or every two weeks. A long-term study found that 35.6% of patients achieved remission after the induction phase , and 46.1% remained in remission during the maintenance phase . On average, patients in the maintenance phase had used Spravato for just over three years, indicating its continued benefits with long-term use. Spravato Short-Term Side Effects While Spravato is generally well tolerated, mild side effects are common, including: Dizziness Nausea Sedation or drowsiness Dissociation (feeling detached from one’s body or reality) Increased blood pressure Anxiety or restlessness Elevated mood or euphoria These side effects typically wear off within a few hours but can linger for up to 24 hours. Safety Considerations Monitoring : Spravato is administered in a certified healthcare setting under medical supervision. Patients are monitored for at least two hours post-dose for potential side effects. Driving Restrictions : Due to possible sedation and dissociation, patients should not drive or operate heavy machinery until the following day after a full night’s rest. Potential Long-Term Risks of Spravato Ketamine is a drug of abuse with addictive properties. Chronic misuse has been linked to long-term effects such as cognitive impairment and damage to the bladder, liver, and kidneys. However, Spravato is administered in a controlled clinical environment, significantly reducing the risk of misuse . While it has not been extensively studied in patients with pre-existing substance abuse disorders, those with addiction histories may be at higher risk. Physically, Spravato appears safe for long-term use , though some evidence suggests users may experience bladder-related symptoms. However, clinical trials have found no significant difference in bladder infections between Spravato and non-Spravato patients. Spravato Treatment at SW Florida TMS & Ketamine Clinic At Southwest Florida TMS & Ketamine Clinic , we specialize in innovative depression treatments , including Spravato therapy for individuals with TRD. If you’re struggling with depression and haven’t found relief from conventional therapy, our services, based in Fort Myers, could have the solution you need. Spravato is a fast-acting medication with sustained benefits, and our team is highly experienced in delivering this medicine with expert care. If you choose to have treatment at our service, we will closely monitor you during and after administration and will be here to provide support after and between doses. For more information on Spravato treatment and to schedule a consultation, visit our Spravato Clinic page . Key Takeaways Rapid Relief: Many patients experience symptom improvement within hours or days of starting Spravato. Mechanism of Action: Spravato enhances mood-regulating brain activity and promotes neuroplasticity. Individual Variability: Factors like depression severity, brain chemistry, and past treatments influence response time. Sustained Benefits: With continued treatment, Spravato strengthens neural connections, supporting long-term depression relief. Safety Considerations: While generally well-tolerated, Spravato requires medical supervision due to potential side effects and driving restrictions. Expert Care at SW Florida TMS & Ketamine Clinic: Offering specialized Spravato therapy with close monitoring and personalized treatment plans for patients with TRD.
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