Spravato vs. Ketamine Infusion Therapy: Which Treatment Is Right for Treatment-Resistant Depression?

For people living with treatment-resistant depression, the hardest part is often not the diagnosis — it is the cycle of trying medication after medication and still not feeling better.

Traditional antidepressants can be helpful for many patients, but they do not work for everyone. Some people experience partial relief. Others feel emotionally flat. Some never get meaningful improvement at all.

That is why ketamine-based treatments have become such an important part of the mental health conversation.

Two options often come up:

Spravato, also known as esketamine nasal spray, and IV ketamine infusion therapy.

Both are used in medically supervised settings. Both affect glutamate pathways in the brain. Both may help patients who have not responded to standard antidepressants.

But they are not the same treatment.

Understanding the difference can help patients make a more informed decision with their clinician.

What Is Spravato?

Spravato is the brand name for esketamine, a nasal spray approved by the FDA for treatment-resistant depression and certain cases of depression with suicidal thoughts or actions.

Because Spravato is FDA-approved, it may be covered by insurance when patients meet criteria. It must be administered in a certified medical office under a safety monitoring program.

Patients do not take Spravato at home. They self-administer the nasal spray in the office and remain under observation afterward, typically for about two hours.

What Is IV Ketamine Therapy?

IV ketamine therapy uses ketamine delivered through an intravenous infusion. It is often used off-label for treatment-resistant depression, anxiety, PTSD symptoms, and certain pain-related conditions.

Because IV ketamine is not FDA-approved specifically for depression, insurance coverage may be more limited. However, it allows clinicians more flexibility in dosing and treatment adjustment.

For some patients, that flexibility matters.

How the Treatments Differ

The biggest differences are:

• Delivery method

• Insurance coverage

• Dosing flexibility

• Treatment protocol

• Patient preference

Spravato is delivered through a nasal spray. IV ketamine is delivered directly into the bloodstream.

Spravato follows a standardized dosing model. IV ketamine allows more precise titration based on patient response.

Spravato may be more accessible for patients with insurance coverage. IV ketamine may be preferred when customized dosing is clinically important.

Which One Works Faster?

Both treatments can work faster than traditional antidepressants.

Some patients notice improvement within hours or days. Others require multiple treatments before changes become clear.

Response varies based on diagnosis, medication history, biology, sleep, stress levels, and the presence of anxiety, trauma, or chronic pain.

No responsible clinic should promise a specific result.

Who Might Be a Better Fit for Spravato?

Spravato may be a good option for patients who:

• Have treatment-resistant depression

• Want an FDA-approved option

• Prefer potential insurance coverage

• Can commit to in-office monitoring

• Meet medical and psychiatric screening criteria

Who Might Be a Better Fit for IV Ketamine?

IV ketamine may be considered for patients who:

• Need more individualized dosing

• Have anxiety, trauma symptoms, or pain overlap

• Have not responded well to standard protocols

• Prefer infusion-based treatment

• Are appropriate candidates after screening

The Bottom Line

Spravato and IV ketamine therapy are both meaningful options for patients who feel stuck after traditional depression treatments.

The right choice depends on medical history, insurance, symptoms, goals, and clinician judgment.

At KetaRevive, the first step is not choosing a treatment from a headline. It is getting a careful evaluation so the treatment fits the patient — not the other way around.