Ketamine vs. Spravato®: Which Is Best for Me?

At Holistic Behavioral & TMS Therapy, we meet many people who have “tried everything” — multiple antidepressants, therapy, lifestyle changes — and still feel stuck. For some, ketamine-based treatments like ketamine therapy and Spravato® (esketamine nasal spray) offer new hope when standard medications fall short.

Both options act quickly compared with traditional antidepressants and can help ease symptoms of treatment-resistant depression. They’re not identical, though, and understanding the differences can help you feel more confident as you explore your choices.

How Spravato works

Spravato is a nasal spray form of esketamine, a chemical cousin of ketamine. It’s FDA-approved for adults with treatment-resistant depression and is administered only in certified clinics under a special safety program.

During a Spravato session, you self-administer the nasal spray under supervision, then remain in our office for at least two hours while we monitor your blood pressure, mood, and side effects. Common short-term effects can include dizziness, feeling “spacey,” changes in perception, or nausea, which usually fade the same day.

You take Spravato on a set schedule — more frequently at the beginning, then less often for maintenance — and many insurance plans cover it, recognizing its FDA-approved status for treatment-resistant depression.

How ketamine therapy works

Ketamine therapy uses racemic ketamine, the original medication long used as an anesthetic that was later found to have rapid antidepressant effects. 

It’s usually delivered in a medical setting by infusion or injection and is considered “off-label” when used for depression, even though research shows it can be highly effective for many people with treatment-resistant symptoms.

Studies and reviews suggest that intravenous ketamine may, in some cases, produce stronger or faster antidepressant responses than intranasal esketamine, although both treatments have demonstrated meaningful benefits.

Because ketamine therapy is off-label for depression, insurance coverage can be more variable, and treatment plans are often more flexible and individualized in terms of dose and schedule.

What Spravato and ketamine have in common

Despite their differences, Spravato and ketamine share several key features:

They both act on the brain’s glutamate system, which is different from standard antidepressants that primarily target serotonin or related chemicals.

They both tend to work quickly, sometimes easing symptoms within hours or days rather than weeks.

They both require careful monitoring for blood pressure changes, dissociation, and other short-term side effects, and they must be provided in a controlled, professional setting, not at home or recreationally.

Most importantly, both are usually part of a broader plan that can include talk therapy, lifestyle changes, and ongoing support, rather than stand-alone cures.

How to think about which option may be best for you

Choosing between Spravato and ketamine therapy is not something you have to do alone. Still, it helps to know what factors your clinician will consider.

Your diagnosis and treatment history

Your provider will look at which medications you have tried, how long you used them, what helped, and what caused side effects. For many people with clear treatment-resistant depression, either option may be considered.

Your medical conditions and current medications

Blood pressure, heart health, substance use history, and other medical factors all matter. These details can make one option safer or more appropriate than the other.

Your comfort with the treatment experience

Some people prefer the structure of a nasal-spray session in a clinic. Others are more comfortable with an infusion-style approach. How far you can travel, how often you can come in, and how you feel about the experience itself all play a role.

Insurance coverage and budget

Because Spravato is FDA-approved for treatment-resistant depression, insurance may cover more of the cost in some cases. Off-label ketamine coverage varies widely. We can help you explore what your plan may support.

How Holistic Behavioral & TMS Therapy helps you decide

At Holistic Behavioral & TMS Therapy, we don’t believe there is a “one-size-fits-all” answer. 

Our team takes time to understand your history, symptoms, medical background, goals, and concerns. We explain how Spravato and ketamine work, review the latest evidence, and talk honestly about benefits and risks so you can make an informed decision together with your clinician.

If neither option is right for you now, we may discuss other services such as medication management, psychotherapy, or transcranial magnetic stimulation (TMS) as part of a comprehensive plan.

Moving forward with clarity and support

If you’re living with depression that hasn’t responded to standard treatment, you’re not out of options, and you don’t need to navigate these decisions alone.

To learn whether Spravato, ketamine therapy, or another treatment path might be right for you, call Holistic Behavioral & TMS Therapy or book an appointment online today at our locations in Chicago or Aurora, Illinois, or Las Vegas, Nevada. Together, we can explore the choices that give you the best chance at relief and renewed hope.