Spravato vs. Ketamine: Understanding the Differences

Ketamine therapy and Spravato have transformed the landscape of mental health care, offering hope for individuals who have not found relief with standard medications. While related, these treatments have distinct features. In this article, we’ll break down their key differences, so you can make an informed decision about which one is right for you.

What is Ketamine?

Ketamine is a dissociative anesthetic that has been safely used in medicine since the 1960s. While initially developed for surgical anesthesia, it has since emerged as a promising therapy for various mental health disorders, including:

• Depression
• Anxiety
• Post-traumatic stress disorder (PTSD)
• Suicidal thoughts
• Obsessive-compulsive disorder (OCD)
• Addiction 

Unlike traditional antidepressants, which often take weeks to show effects, ketamine can reduce symptoms within hours. This rapid response makes it a valuable option for individuals in or at risk of a mental health crisis.

Ketamine can be administered in several forms, including intravenous (IV) infusions, intramuscular (IM) injections, nasal sprays, and oral tablets. At ReYou, we deliver ketamine intravenously, as this method has been well-researched and gives the fastest-acting benefits.

What is Spravato?

Spravato is the brand name for Esketamine, one of the two enantiomers (mirror-image molecules) that make up ketamine.

Unlike ketamine, which is often prescribed “off-label” for psychiatric use, Spravato was developed specifically for depression. In 2019, the FDA approved Spravato for treatment-resistant depression (TRD), and in 2020, approval was expanded to include major depressive disorder with suicidal ideation (MDSI).

Spravato is a nasal spray that patients administer while under the guidance of a medical professional. Because of its approval, it can only be administered in registered clinics in accordance with specific guidelines.

How Do They Work?

Both ketamine and Spravato work differently from standard antidepressants. They interact with proteins called NMDA receptors, which increase activity in brain areas associated with mood regulation. They also increase neuroplasticity, which is the ability of neural pathways to grow and reorganize. This mechanism potentially helps “re-wire” nerve circuits associated with negative thinking and habits.

Ketamine and Spravato work the same, but Spravato interacts more strongly with NMDA receptors. Ketamine can also have psychedelic effects when provided at high doses, which can help facilitate personal insights and emotional release.

Administration and Dosing

Ketamine Infusions

Ketamine infusions take place in a comfortable treatment room. For the session, you’ll have an IV line placed by a trained medical professional. The infusion itself usually lasts about 40 minutes, during which time you’ll have an eye mask on while listening to a carefully curated playlist. Many patients describe the experience as calming or dreamlike, and our staff remains by your side to ensure your safety and comfort. Once over, you’ll chat with an integrator to discuss your experience, then be monitored to ensure you’re safe to leave.

Most patients require multiple sessions over several weeks to get the full benefits, and we’ll work with you to design a treatment plan that fits your needs. Doses will vary depending on how you respond.

Spravato

Spravato sessions at Reyou follow a similarly structured and supportive process. After checking in, you’ll be shown how to self-administer the nasal spray under the guidance of our clinical team. The treatment is completed in just a few minutes, but you’ll remain in our care for about two hours afterward so we can monitor you as the medicine takes effect.

Spravato is typically taken twice a week during the first month. As your symptoms improve, treatments are gradually reduced to once a week or every other week. Doses are set within FDA guidelines, either 56 mg or 84 mg.

Effectiveness

Clinical studies and real-world evidence show that both IV ketamine and Spravato are highly effective for treatment-resistant depression.

• A Cambridge University study found both treatments produced significant symptom improvements, with IV ketamine showing slightly higher remission rates.
• A Mayo Clinic study reported no significant difference in overall response between the two therapies.

Effectiveness may vary by individual, but both are considered strong options when standard treatments have failed.

Safety and Side Effects

Common side effects of ketamine and Spravato may include:

• Dissociation (feeling “detached”)
• Dizziness
• Nausea
• Temporary increases in blood pressure

Ketamine often produces stronger psychoactive effects than Spravato. While more intense, many patients find these experiences therapeutic, especially when they have support in processing them afterward.

Both treatments also have side effects related to their administration. For instance, some people may have pain at the injection site following ketamine infusions. Nasal congestion and irritation can happen after Spravato.

Cost and Insurance Considerations

Because ketamine is prescribed “off-label” for mental health conditions, it is rarely covered by insurance. This means patients are usually responsible for the full cost of treatment, though some plans offer partial reimbursement for things like evaluation costs.

Spravato is more expensive than ketamine, but, because it is FDA-approved, the medication cost is covered through most insurance plans. However, you must have a diagnosis of TRD or MDSI to receive treatment. Out-of-pocket costs will vary depending on the individual plan, copays, and deductibles.

At Reyou, we’re here to help you navigate expenses and insurance coverage. Our team can break down costs and guide you in getting the right financial support.

Which Treatment is Right for You?

Both ketamine and Spravato offer rapid, life-changing relief for individuals who have struggled with depression.

Ketamine therapy may be right for you if:

• You are seeking treatment for a broader range of conditions than just depression
• You prefer a personalized dosing plan that can be adjusted to your unique response
• You are open to a deeper therapeutic experience, as ketamine often produces stronger psychoactive effects that can be processed with support
• You value the flexibility of a therapy that can be tailored to your individual goals and progress

Spravato may be right for you if:

• You have TRD or MSDI
• You would benefit from insurance coverage
• You prefer a nasal spray administration rather than an IV infusion.
• You want the reassurance of a standardized treatment plan with fixed dosing and a structured schedule

If you’re unsure which option is right for you, our clinical team at Reyou will guide you through the decision-making process. We’ll review your medical history, treatment goals, and insurance benefits to help you determine the best fit. Get in touch today to find out more.