Ketamine vs Spravato: What Is the Difference?

If you have been exploring options for treatment-resistant depression, you may have encountered two terms that sound almost interchangeable: ketamine and Spravato. While the medications are closely related, they are not exactly the same. Understanding the differences between ketamine vs Spravato can help you feel more prepared when discussing your treatment options with a qualified healthcare provider.

Both treatments are part of a growing shift in mental health care. Unlike many traditional antidepressants, which primarily affect serotonin or other monoamine systems, ketamine-based treatments influence glutamate, an important chemical messenger involved in communication between brain cells. However, ketamine and Spravato differ in their formulation, FDA approval, administration, treatment structure, and potential insurance coverage.

What Is Ketamine Therapy?

Ketamine is a medication that has been used as an anesthetic for decades. In mental health settings, some providers prescribe lower doses of ketamine “off-label” for conditions such as treatment-resistant depression.

Off-label use means that a medication is being prescribed for a purpose other than the specific use approved by the U.S. Food and Drug Administration. This is a recognized medical practice, but patients should understand that ketamine itself is not currently FDA-approved as a psychiatric treatment.

When people talk about ketamine therapy for depression, they are often referring to intravenous, or IV, ketamine infusions. However, ketamine may also be administered through an injection, lozenge, or compounded nasal spray, depending on the provider and treatment setting.

IV ketamine is typically delivered in a medical office over a set period of time. Patients are monitored during and after treatment because temporary side effects may include dizziness, nausea, increased blood pressure, sedation, or a sense of disconnection from oneself or one’s surroundings.

Some clinics pair ketamine treatment with psychotherapy. This approach is sometimes called ketamine-assisted psychotherapy. The goal is to combine the medication experience with therapeutic preparation, support, and integration. However, not every ketamine program includes therapy, so it is important to ask what a particular clinic means when it uses the term “ketamine therapy.”

What Is Spravato?

Spravato is the brand name for esketamine, a prescription nasal spray derived from ketamine. Ketamine contains two mirror-image forms of the same molecule. Spravato contains only one of those forms, known as esketamine.

Spravato is FDA-approved for treatment-resistant depression in adults, either by itself or alongside an oral antidepressant. It is also approved, when used with an oral antidepressant, for depressive symptoms in adults with major depressive disorder who are experiencing acute suicidal thoughts or behaviors. It has not been shown to prevent suicide, and it does not replace hospitalization when hospitalization is medically necessary.

Unlike a typical nasal spray that someone might take home, Spravato must be self-administered under the direct supervision of a healthcare provider at a certified treatment center. After receiving the medication, patients are monitored for at least two hours. This observation period allows the treatment team to watch for changes in blood pressure, sedation, dissociation, breathing, or other side effects.

Patients must also arrange transportation home after each appointment. The prescribing information advises against driving or operating machinery until the following day after a restful night’s sleep.

The Main Differences Between Ketamine and Spravato

Although both medications affect similar pathways in the brain, the practical experience of receiving them can be quite different.

1. Medication formulation

Ketamine used in an IV infusion is generally racemic ketamine, meaning it contains two molecular forms called R-ketamine and S-ketamine. Spravato contains only S-ketamine, also known as esketamine.

This chemical distinction does not automatically mean that one option is better than the other. Each has its own body of research, clinical protocols, and considerations.

2. FDA approval

Ketamine is FDA-approved as an anesthetic, but its use for depression and other mental health conditions is off-label.

Spravato is specifically FDA-approved for certain forms of depression in adults. It is also regulated through a safety program called a Risk Evaluation and Mitigation Strategy, or REMS. This program requires participating patients, pharmacies, and treatment centers to follow specific safety procedures.

3. How the medication is given

Ketamine for mental health treatment is commonly delivered through an IV infusion, although other forms are also used in some practices.

Spravato is available only as a nasal spray. Patients administer the spray themselves while supervised by a healthcare professional in a certified treatment setting.

4. Treatment schedule

Ketamine schedules vary between clinics because its psychiatric use is off-label. A treatment plan may begin with several sessions over a few weeks, followed by maintenance sessions based on the patient’s response.

Spravato follows a more standardized dosing schedule. Treatment for treatment-resistant depression commonly begins twice weekly for four weeks. Sessions then typically become less frequent, with the schedule individualized according to how well the treatment is working and how well it is tolerated.

5. Insurance coverage

Because IV ketamine for depression is an off-label treatment, many insurance plans do not cover the medication or infusion. Patients may need to pay out of pocket, although coverage varies.

Spravato may be covered by insurance because it is FDA-approved for specific conditions. Coverage is not guaranteed, and patients may need prior authorization or documentation showing that other treatments have not provided enough relief. The clinic and insurance company can help clarify eligibility, copays, deductibles, and other costs.

6. Clinical experience

Both ketamine and Spravato can produce temporary changes in perception, mood, alertness, and sense of time. Some people describe feeling detached, dreamlike, or deeply relaxed during treatment. Others may experience anxiety, dizziness, nausea, headache, or increased blood pressure.

The experience can vary from person to person and even from one treatment session to another. A reputable provider should explain what to expect, review potential risks, monitor you appropriately, and create a plan for managing side effects.

Is One Treatment More Effective?

There is no universal answer. Some people respond well to IV ketamine, while others may be better candidates for Spravato. Neither treatment works for everyone, and a faster-acting option is not necessarily a permanent or stand-alone solution.

A healthcare provider may consider several factors when recommending a treatment, including:

• Your diagnosis and current symptoms

• The treatments you have already tried

• Your physical health and blood pressure

• Your medication history

• Your history of substance use

• Your comfort with IV or nasal treatment

• Insurance coverage and treatment cost

• Your ability to attend and arrange transportation for appointments

• Whether you would benefit from psychotherapy alongside treatment

Your care plan may also include ongoing medication management, therapy, lifestyle support, or other evidence-based treatments. Ketamine-based care is usually most helpful when it is thoughtfully integrated into a broader mental health plan.

What Should You Ask a Treatment Provider?

Before beginning either treatment, consider asking:

• Which medication and formulation do you provide?

• Is the treatment FDA-approved for my diagnosis or being prescribed off-label?

• Who will evaluate and monitor me?

• What side effects should I expect?

• How long will each appointment take?

• Is psychotherapy included?

• How will we measure whether treatment is helping?

• What happens if I do not respond?

• What is the expected cost?

• Will your office help with insurance authorization?

• What is the plan for maintenance care?

Clear answers can help you understand not only the medication, but also the quality and structure of the care surrounding it.

Finding the Right Treatment Path

The most important distinction in the ketamine vs Spravato conversation is not simply that one is typically given through an IV and the other as a nasal spray. Each treatment has a different formulation, regulatory status, treatment structure, and coverage pathway. The right choice depends on your symptoms, medical history, previous treatments, preferences, and the recommendation of a qualified healthcare professional.

If depression has not improved with traditional approaches, it may be time to learn about additional options. At Goodwin Health Cafe, patients can explore personalized, evidence-informed mental health care in a supportive environment.

Goodwin Health Cafe5625 N. Wall St. Suite 100Spokane, WA 99205

This article is for educational purposes only and is not a substitute for medical advice, diagnosis, or treatment.