When considering Spravato® vs. Ketamine to treat depression, they both are effective, but they have some critical differences. Spravato® (esketamine) is the S-enantiomer of ketamine, essentially one specific form of the ketamine molecule. Ketamine typically refers to racemic ketamine, which contains both S and R forms of the molecule. Spravato® is FDA-approved specifically for treatment-resistant depression and for depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior. Ketamine is FDA-approved as an anesthetic, but is used off-label for depression treatment.
Spravato® treatment is administered as a nasal spray in a certified medical setting, where you must be monitored for at least two hours after each dose. Ketamine for depression is typically given as an IV infusion, though some clinics offer other forms through intranasal or oral. Spravato® may be covered by insurance since it’s FDA-approved for depression, though it’s expensive. Ketamine infusions are usually not covered by insurance for depression since it’s an off-label use, and can cost $400 to over $800 per session.
Spravato® is considered about twice as potent as racemic ketamine at the same dose. Both work relatively quickly compared to traditional antidepressants and affect similar brain pathways, but the choice between them often depends on insurance coverage, availability, and individual response to treatment.
Which Is More Effective: Spravato® or Ketamine Infusion Therapy?
The effectiveness comparison between Spravato® vs. ketamine infusion therapy is actually quite complex, and there’s no clear consensus that one is definitively better than the other. There have been few direct head-to-head studies comparing Spravato to racemic ketamine infusions, making it difficult to determine which is more effective definitively. Most of the evidence comes from separate clinical trials using different methodologies.
Spravato®:
- Has robust FDA approval based on multiple controlled trials
- Studies show significant improvement in treatment-resistant depression compared to a placebo
- Response rates typically range from 40-70% depending on the research and how response is measured
Ketamine Infusions:
- Extensive real-world clinical experience and research dating back further
- Many studies show rapid antidepressant effects, often within hours to days
- Response rates are similarly around 50-70% in many studies
- Some clinicians report strong anecdotal success with their patient populations
Factors That May Influence Effectiveness
- Individual variation matters tremendously—some people respond better to one approach than to another, and we can’t always predict who will respond to which.
- Dosing and frequency differ between the two treatments, which makes comparison difficult.
- Duration of effect – both typically require ongoing maintenance treatments, though protocols vary.
Many psychiatrists and researchers consider them roughly equivalent in effectiveness, with the choice often coming down to:
- Access and availability
- Cost and insurance coverage
- Patient preference for delivery method (nasal spray vs. IV)
- Individual response and tolerability
- Clinic protocols and expertise
If you’re considering the benefits of ketamine-assisted treatment or Spravato®, it’s worth discussing both options with a psychiatrist who specializes in these therapies, as they can help determine which might be more appropriate for your specific situation.
Should I Choose Spravato® or Ketamine for Depression Treatment?
Choosing between Spravato® vs. ketamine is a very personal decision that should ultimately be made with a qualified psychiatrist who specializes in these treatments. Here are some key factors and essential questions to consider:
- Have you tried other antidepressants? Spravato® is specifically approved for treatment-resistant depression, so insurance typically won’t cover it unless you meet this criteria.
- What does your insurance cover? This is often the most significant practical factor. Spravato® may be covered if you qualify, while ketamine infusions are usually out-of-pocket.
- What are your thoughts on the delivery method? Some people prefer the nasal spray of Spravato®, while others prefer the controlled IV infusion. The IV also allows for more precise dosing adjustments.
- What’s your schedule like? Spravato® requires at least two hours of monitored observation at each appointment. Ketamine infusions typically take 40 minutes to an hour for the injection itself, plus some observation time.
- What providers are available near you? Spravato® requires a certified treatment center. Ketamine clinics are becoming more common, but may not be available everywhere.
Since neither treatment works for everyone, and it’s difficult to predict who will respond to which, sometimes the right choice is simply whichever one patients can access and afford to try first, as both have helped many people with treatment-resistant depression.
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How Is Spravato® Administered Compared to Ketamine Infusions?
Spravato® is administered as a nasal spray in a certified healthcare facility under strict medical supervision. Patients self-administer the spray under direct observation of a healthcare provider, with the medication delivered in two or three devices, depending on the prescribed dose. After administration, patients must remain at the facility for at least two hours to be monitored for potential side effects such as dissociation, sedation, changes in blood pressure, and other adverse reactions.
Ketamine infusions are administered intravenously through an IV line, typically over 40 minutes to an hour, with the patient seated in a comfortable chair or lying in a reclining position. The dosing can be precisely controlled and adjusted during the infusion based on the patient’s response and tolerability. Most ketamine infusions for mental health begin with an induction phase of six infusions over two to three weeks, followed by maintenance infusions that may occur monthly or as needed, depending on symptom return.
Which Conditions Are Treated with Spravato® vs. Ketamine?
Spravato® has specific FDA-approved indications for mental health treatment, making it a targeted therapeutic option. It is approved for treatment-resistant depression in adults, defined as major depressive disorder that has not adequately responded to at least two different antidepressant treatments, and must be used in conjunction with an oral antidepressant. Spravato® is approved for treating depressive symptoms in adults with major depressive disorder who are experiencing acute suicidal ideation or behavior.
Ketamine infusions, while FDA-approved only as an anesthetic, are used off-label to treat a broader range of psychiatric and pain conditions based on clinical experience and research. The primary off-label use is for treatment-resistant depression. Still, many clinics also treat other forms of depression, bipolar depression, post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), and anxiety disorders with ketamine therapy.
Key Takeaways on Spravato® vs. Ketamine
- Spravato® is the S-enantiomer of ketamine and is approximately twice as potent as racemic ketamine.
- Spravato® is FDA-approved specifically for treatment-resistant depression and acute suicidal ideation in major depressive disorder, which means it may be covered by insurance if you meet the criteria.
- Spravato® is a nasal spray self-administered under supervision with mandatory two-hour monitoring periods at certified treatment centers.
- Ketamine is delivered via IV infusion over 40-60 minutes with shorter post-treatment observation, and can be administered at various types of facilities, including specialized ketamine clinics.
- Spravato® is limited to its specific FDA-approved indications for depression, while ketamine infusions are used off-label for a broader range of conditions, including various forms of depression, PTSD, OCD, anxiety disorders, and chronic pain conditions.
Knowing the differences between Spravato® vs. Ketamine therapies can help patients gain a deeper understanding of how each treatment works to address mental health conditions. If you’re considering these innovative treatment options, reach out to Moment of Clarity in Southern California. Our team of mental health experts at our network of outpatient facilities is dedicated to providing personalized outpatient care tailored to your needs. Call 949-625-0564 today to learn more about how they can support your mental health journey.
Resources
- NPR –FDA allows standalone use of nasal spray antidepressant Spravato (esketamine)
- National Library of Medicine –Ketamine and Esketamine in Clinical Trials: FDA‐Approved and Emerging Indications, Trial Trends With Putative Mechanistic Explanations
- GoodRx –Top 5 Differences for Hard-to-Treat Depression
