Spravato

Spravato® (esketamine) is a prescription nasal spray used to treat severe depression when other antidepressants have not worked. This is called treatment-resistant depression (TRD). It is also approved for adults with major depression who have active suicidal thoughts or behaviors.

Spravato is FDA-approved and is usually used along with an oral antidepressant, although in some cases it may be used on its own.

How Is Spravato Different From Regular Antidepressants?

Most antidepressants (like SSRIs and SNRIs) work by changing levels of chemicals such as serotonin or norepinephrine, and they can take weeks to start helping.

Spravato works completely differently.

It targets a brain pathway involving glutamate, which plays a key role in mood, learning, and brain connections. By doing this, Spravato helps the brain:

• Form new, healthier connections
• Improve communication between brain cells
• Restore areas of the brain affected by chronic depression

Because of this, many patients feel improvement within hours to days, not weeks.

• Spravato is taken as a nasal spray in the clinic
• It is not taken at home
• You use the spray under medical supervision

After treatment, patients must stay in the clinic for at least 2 hours so the care team can monitor for side effects and ensure safety.

What Does a Typical Treatment Schedule Look Like?

For treatment-resistant depression:

• Weeks 1–4 (Induction Phase):
  Treatment twice weekly
• After that (Maintenance Phase):
  Treatment once weekly or every other week, depending on response

The dose is typically 56 mg or 84 mg, adjusted by your provider.

Most side effects are temporary and happen on treatment days only.

Common effects include:

• Feeling disconnected or “floaty”
• Dizziness
• Sleepiness
• Mild nausea
• Temporary increase in blood pressure

These effects usually peak within the first hour and wear off by the end of monitoring. This is why patients cannot drive the same day and must have a ride home.

Importantly, Spravato has a very low risk of sexual side effects, unlike many traditional antidepressants.

Yes, when used as directed.

Spravato is only available through a special FDA safety program (REMS), which means:

• It can only be given in certified clinics

• Patients are carefully monitored

• Providers are specially trained

Large clinical trials have shown Spravato to be effective and safe for long-term use when properly supervised.

Patients often choose Spravato because:

• Other antidepressants did not work
• They need faster relief
• They want an option with fewer sexual side effects
• They feel “stuck” despite years of treatment

Many patients report improvements in mood, motivation, clarity, and hope, sometimes after just a few treatments.

Insurance companies want to be sure that Spravato is being used for patients who truly need it. Most payors require three main things

1. A Diagnosis of Major Depression

You must have a diagnosis of major depressive disorder (MDD) or treatment-resistant depression, meaning your depression has been ongoing and significantly affecting your daily life.

2. Proof That Other Antidepressants Didn’t Work

Most insurance plans require that you have tried at least two different antidepressant medications in the past, taken:

• At an appropriate dose

• For long enough (usually 6–8 weeks each)

These medications did not provide enough relief, or caused side effects that made them unsafe or intolerable.

This helps insurance confirm that Spravato is being used after standard treatments were unsuccessful.

3. Ongoing Mental Health Monitoring

Insurance companies also typically require that:

• You are actively followed by a qualified mental health provider

• Your symptoms are tracked using standardized depression questionnaires

• Spravato is given in a certified medical clinic with appropriate monitoring

This ensures the treatment is safe, medically necessary, and effective.

Important Things Patients Should Know

• Approval is not instant. Insurance authorization can take days to a few weeks.

• Denials are common at first, but many are overturned with additional documentation.

• Your care team handles the paperwork and appeals on your behalf.

• Approval requirements vary slightly between insurance plans.

Why Is There a Waiting Period?

Spravato is a powerful, specialized treatment. Insurance companies require extra steps to make sure it is:

• Medically appropriate

• Used safely

• Provided in the correct clinical setting

Spravato® Used With an Oral Antidepressant

In a 4-week clinical study, patients received either:

• Spravato® plus an oral antidepressant, or
• A placebo nasal spray plus an oral antidepressant

Results showed that patients treated with Spravato® and an oral antidepressant experienced a faster and greater reduction in depression symptoms compared to those receiving placebo with an oral antidepressant.

Key findings included:

• Significant improvement in symptoms as early as 24 hours
• Continued improvement throughout the 4-week study period
• Most symptom relief occurred early, with sustained benefit over time

Spravato® Used Alone

In a separate clinical study, patients were randomly assigned to receive either:

• Spravato® alone, or
• A placebo nasal spray

Patients treated with Spravato® alone experienced significantly greater improvement in depression symptoms at both 24 hours and 4 weeks compared to placebo.

Improvements were measured using standardized clinical depression rating scales.

Long-Term Effectiveness and Relapse Prevention

Spravato® has also been evaluated in a long-term maintenance study to determine whether benefits are sustained over time.

In this trial:

• Patients who continued Spravato® treatment were significantly less likely to experience a return of depressive symptoms (relapse)
• Outcomes were compared between patients who remained on Spravato® plus an oral antidepressant and those who transitioned to a placebo nasal spray with an oral antidepressant

These results suggest that ongoing Spravato® treatment can help maintain symptom improvement and reduce relapse risk in appropriate patients.

Below is a clear, patient-friendly explanation you can use for a blog, FAQ, or consultation discussion. It is written to be neutral, accurate, and easy to understand.

How Is Ketamine Different From Spravato®?

Ketamine and Spravato® are related treatments, but they are not the same. While both can help with depression, they differ in form, approval status, how they’re given, and how insurance covers them.

The Key Difference: How Much Reaches the Brain

• Spravato® (esketamine) is a nasal spray
  • Only about 40–50% of the medication is absorbed
  • It delivers a controlled, targeted effect
  • Designed to minimize sedation while still treating depression
• Ketamine (IV or IM) enters the bloodstream directly
  • Nearly 100% bioavailability
  • Produces a stronger and more immediate effect
  • Often results in deeper dissociation and sedation

Important Clarification for Patients

Stronger does not mean better.

• Some patients respond very well to Spravato® and prefer the gentler experience
• Others need the intensity of ketamine to achieve symptom relief
• The goal is effectiveness and safety, not intensity

Both treatments can be highly effective when matched to the right patient.

Which One Is Better?

Neither is universally “better.” The right option depends on:

• Insurance coverage
• Severity and urgency of symptoms
• Prior treatment response
• Medical history
• Patient preference
• Provider Recommendations

Some patients respond better to one than the other. Others may try both at different points in their care.

The Bottom Line

If you have:

• Long-standing depression
• Tried multiple antidepressants without success
• Are working with a qualified provider

You may be a strong candidate for insurance-approved Spravato treatment.

Our team will guide you through every step and advocate for you with your insurance company.

Take the following Surveys to better determine if you are a candidate for Spravato Treatment!