Does Spravato Work for Treatment-Resistant Depression? [2025]

For individuals who have diligently followed traditional depression treatment plans without finding relief, the path forward can seem unclear.

If you or someone you love has gone through his experience (known as treatment-resistant depression), you should know this is not a personal failing. It’s a clinical reality that calls for a different kind of therapeutic approach.

It requires a treatment that works on a different neural pathway to create new possibilities for healing.

This guide explores how Spravato (or Esketamine) offers a new path to healing by targeting a different system in the brain. We will answer the core question of how does Spravato work, explain its rapid effects compared to other treatments, and walk through the process of accessing care, from insurance verification to your first session.

Navigating a new treatment option can feel complex, but having clear information makes the journey feel more manageable. Understanding the science, the process, and what to expect helps you move forward with clarity and hope, opening the door to potential relief.

Key takeaways

• Spravato is the only FDA-approved Ketamine nasal spray for treatment-resistant depression, working through the glutamate system for rapid relief within hours instead of weeks.
• It disrupts negative brain patterns and creates new neural connections, often improving mood within 24 hours unlike traditional antidepressants.
• Treatment happens in certified facilities with a 7-step process including insurance verification, evaluation, and 2-3 hour monitoring sessions.
• Side effects like dissociation, dizziness, and nausea are temporary and resolve within hours under medical supervision.
• Marpa Minds offers treatment in a spa-like setting and handles all insurance paperwork so you can focus on healing.

What does Spravato do for treatment-resistant depression

Spravato is a form of Ketamine is an FDA-approved nasal spray that helps people with treatment-resistant depression. This means it’s designed for adults whose depression hasn’t improved after trying at least two different antidepressants.

Treatment-resistant depression happens when standard medications don’t provide relief, even after taking them at the right dose for several weeks. If you’ve tried multiple antidepressants without success, you’re not alone — and Spravato offers a completely different approach.

Unlike traditional antidepressants that work on serotonin, Spravato targets your brain’s glutamate system. This creates rapid changes in how your brain cells communicate with each other, which in turn helps alleviate depressive symptoms.

Here’s what makes Spravato different from other depression treatments:

• FDA approval: The only FDA-approved Ketamine-based treatment for depression (do keep in mind only Spravato, the nasal spray version, is approved for treatment in patients with depression, while IV Ketamine is not)
• Rapid relief: Works within hours or days instead of weeks
• Insurance coverage: Covered by most major insurance plans
• Medical supervision: Always administered in a certified healthcare facility

The medication comes as a nasal spray that you take under medical supervision. Each treatment session lasts about two hours, including observation time.

Marpa Minds specializes in providing Spravato therapy in a calm, spa-like environment. Their team handles all the insurance paperwork so you can focus on feeling better.

Wondering if Spravato can work for you? Read more on our blog: 

• Does Spravato help with anxiety?
• How long does Spravato last?
• What do you do during Spravato treatment?
• Can Spravato be taken at home?
• How does Spravato make you feel?

How does Spravato work in the brain

Spravato (esKetamine nasal spray) works by blocking NMDA receptors in your brain. These receptors control how brain cells communicate through a chemical called glutamate.

When you have depression, certain brain pathways become stuck in negative patterns. Spravato temporarily disrupts these patterns, allowing your brain to form new, healthier connections.

NMDA receptor influence

NMDA receptors (glutamate receptors) are like gates that control brain cell communication. When Spravato blocks these gates, it creates a temporary change in brain activity.

This blocking effect only lasts a few hours. But during this time, your brain starts building new pathways that can improve your mood long after the medication wears off.

Think of it like resetting a computer — the temporary disruption allows your brain to restart with healthier patterns.

Synaptic pathways and mood regulation

Synapses are the connections between brain cells. Depression often weakens these connections, especially in areas that control mood and motivation. So far, traditional antidepressant medications weren’t aiming to repair these connections, but to help the brain generate more serotonin (which may work for some, but leaves many patients behind as well).

Spravato helps your brain grow new synapses and strengthen existing ones. This process is called neuroplasticity — your brain’s ability to rewire itself.

The medication also increases a protein called BDNF that helps brain cells survive and grow. More BDNF means stronger, healthier brain connections that support better mood regulation.

Spravato effectiveness and onset of action

Spravato often starts working much faster than traditional antidepressants. Many people notice some improvement within 24 hours of their first treatment.

This quick response happens because Spravato directly changes brain activity instead of slowly building up in your system like other medications.

Immediate vs. long-term relief

You might feel different within hours of your first Spravato session. Some people describe feeling lighter, clearer, or more hopeful.

These immediate effects can come and go at first. That’s normal — your brain is adjusting to new patterns of activity (which is precisely why this treatment works so well against depressive symptoms, in fact).

Long-term relief develops over several weeks of treatment. As you continue sessions, the positive changes become more stable and lasting.

Marpa Minds monitors your progress closely to ensure you’re getting both immediate relief and building toward lasting recovery.

Measuring successful response

Although clinical studies have proven both the safety and efficiency of Spravato, success with this mental health treatment means different things for different people.

Your doctor will use standard questionnaires to track your depression symptoms, as well as what other antidepressant medications and mental health treatments you have followed so far.

But Spravato’s success also includes how you feel day-to-day. Can you enjoy activities again? Do you have more energy? Are relationships easier to maintain?

Most people who respond well to Spravato report:

• Improved mood: Feeling more stable and positive
• Better thinking: Clearer thoughts and better concentration
• More energy: Easier to get through daily tasks
• Social connection: Renewed interest in relationships and activities

How long does it take for Spravato to work?

Spravato typically begins working within the first few treatment sessions. The exact timeline varies from person to person.

Here’s what you can expect:

• First 24 hours: Many people notice initial mood changes
• First week: Most experience some symptom improvement
• First month: Significant relief often develops during this induction phase

Your response depends on several factors including how long you’ve had depression and how closely you follow the treatment schedule.

The induction phase involves twice-weekly treatments for the first month. After that, you’ll transition to weekly or biweekly sessions based on your response.

At Marpa Minds, each patient receives personalized monitoring to optimize their treatment timeline and track progress.

7 steps to begin Spravato therapy

Starting Spravato involves several important steps to ensure it’s safe and covered by insurance. The process usually takes a few weeks from initial consultation to first treatment.

Understanding each step helps you prepare and know what to expect along the way.

Step 1: Speak with a mental health professional

You’ll need to see a psychiatrist who can prescribe Spravato. They’ll review your depression history and previous treatments.

Bring a list of all antidepressants you’ve tried, including doses and how long you took them. This information helps determine if you qualify for Spravato.

Step 2: Verify insurance coverage

Most insurance plans cover Spravato, but you’ll need prior authorization. This means your doctor submits paperwork explaining why you need this treatment.

Marpa Minds handles all insurance coordination, making this step much easier. They know exactly what documentation insurers need.

Step 3: Complete medical evaluation

Your doctor will check your overall health to ensure Spravato is safe for you. This includes reviewing your medical history and current medications.

They’ll also check your blood pressure and ask about any heart conditions, as these can affect treatment safety.

Step 4: Set treatment goals

You and your care team will discuss what you hope to achieve with Spravato. Goals might include sleeping better, enjoying hobbies again, or returning to work.

Setting clear goals helps track your progress and adjust treatment as needed.

Step 5: Plan logistics and scheduling

Spravato requires regular clinic visits — twice weekly at first. Each session takes about 2-3 hours total.

You’ll need someone to drive you home after each treatment. Plan ahead for transportation and time off work if needed.

Step 6: Arrive for your first session

Your first treatment starts with a check-in about your current symptoms. The medical team will take your vital signs and answer any questions.

You’ll self-administer the nasal spray while sitting in a comfortable chair. Staff stay nearby to monitor you throughout the session.

Step 7: Monitor and follow up

Regular check-ins help track your progress and adjust treatment. Your team will ask about symptom changes and any side effects.

Marpa Minds coordinates with your other providers to ensure comprehensive care throughout your treatment journey.

Common questions about side effects and safety

Spravato can cause temporary side effects during and after treatment. These effects are well-studied and manageable with proper medical supervision.

Most side effects go away within a few hours of treatment. Understanding what to expect helps you feel more prepared and comfortable.

Potential side effects

The most common side effects happen during your treatment session and shortly after. Your body is adjusting to the medication’s effects on brain activity.

Here’s what you might experience:

• Dissociation: Feeling detached or “floaty” for 1-2 hours
• Dizziness: Mild lightheadedness that improves with rest
• Nausea: Stomach discomfort that can be managed if needed
• Blood pressure increase: Temporary rise that’s monitored throughout treatment

These effects typically become milder with repeated treatments as your body adjusts.

Safety monitoring procedures

Spravato is only given in certified healthcare facilities under the REMS safety program. This ensures proper monitoring and immediate help if needed.

During each session, medical staff check your vital signs and mental status regularly. You’ll stay at the clinic for at least two hours until any side effects resolve.

This careful monitoring makes Spravato much safer than unsupervised Ketamine treatments. You’re never alone during the process.

Open the door to hope with Marpa Minds

Living with treatment-resistant depression can feel isolating and hopeless. Marpa Minds understands this journey because we specialize in helping people who haven’t found relief with traditional treatments.

Their approach combines clinical expertise with genuine compassion. From your first call through ongoing treatment, they handle the complex parts — insurance authorizations, scheduling, and coordination with your other providers.

The treatment environment matters too. Instead of sterile medical rooms, Marpa Minds offers a serene, spa-like setting designed for healing and comfort.

Ready to explore if Spravato could help you find relief? Take the first step with a confidential assessment to learn more about your options.

About Author

Amy Della Rocca

PMHNP – Clinical Director

Meet Amy Della Rocca, a Psychiatric Nurse Practitioner with experience in innovative mental health treatments. Amy’s credentials hail from Columbia University and her previous work experience is in Behavioral Health, Public health and Primary Care Medicine. Amy’s unwavering belief in the potential of ketamine treatment for mental well-being stems from hands-on experience with her patients. Witnessing its positive impact and lasting changes drove her to specialize in this unique field. What sets Amy apart is her holistic approach. She considers medical, emotional, and psychological aspects, earning respect for her practical solutions. Operating from Marpa, Amy evaluates patients for Spravato compatibility. She provides comprehensive on-site care during their Spravato treatment journey. Amy supports patients from evaluation to treatment completion and collaborates with their existing mental and physical health care team. Amy’s contribution goes beyond caregiving; she actively advances Ketamine Therapy. Her expertise and dedication have garnered trust among colleagues and patients alike.