When Depression Won't Budge: What Spravato Means for Treatment-Resistant Depression
I want to be honest: one of the hardest moments in psychiatric care is hearing someone say, “I’ve tried everything, and nothing is changing.”
I’ve sat with young adults who are doing all they can: taking medication consistently, showing up for therapy, trying to sleep, exercise, eat well, and stay connected: while depression still feels like wet cement around their ankles. The brain fog remains. Motivation stays out of reach. Even hopeful moments can feel muted by an invisible gray sea.
When treatment does not bring meaningful relief, it can be tempting to believe you are the problem.
You are not.
Depression can be persistent, biologically complex, and deeply personal. That is why Inside and Out Psychiatry will begin offering Spravato® (esketamine) treatment in September 2026 as part of our integrated psychiatric care for eligible young adults. Spravato is not a magic wand, and it is not a first-line treatment. But for people living with treatment-resistant depression, it may offer another carefully monitored, evidence-based path forward.
What Is Spravato?
Spravato is the brand name for esketamine nasal spray, a medication that works differently from traditional antidepressants. It affects the brain’s glutamate system, including NMDA receptors, rather than primarily targeting serotonin, norepinephrine, or dopamine.
In the United States, Spravato is approved for adults with:
Treatment-resistant depression, generally meaning major depressive disorder that has not responded adequately to at least two oral antidepressant treatments.
Major depressive disorder with acute suicidal ideation or behavior, under a separate indication and in conjunction with appropriate clinical care.
The FDA prescribing information provides the official details about approved uses, risks, dosing, and monitoring requirements.
Spravato is related to ketamine, but it is not the same as receiving ketamine in an unsupervised setting. It is a prescription medication delivered through a structured clinical program with safety safeguards.
Why Consider It for Treatment-Resistant Depression?
When depression has not improved after multiple adequate treatment trials, continuing to repeat the same approach can feel demoralizing. Spravato may create an additional option to discuss with a qualified psychiatric clinician.
Research suggests that esketamine combined with an oral antidepressant can improve outcomes compared with an oral antidepressant alone. Across analyses, the estimated relative risk is approximately:
1.44 for response
1.52 for remission
In everyday language, this means that people receiving esketamine plus an oral antidepressant were about 44% more likely to respond and 52% more likely to reach remission than those receiving antidepressant treatment alone in the analyzed studies.
A clinical response commonly means a reduction of at least 50% in depressive symptoms. Remission means symptoms have decreased to a much lower level, although definitions can vary by study.
These numbers do not promise a specific result for any individual. They do offer something vital: evidence that a different treatment mechanism may help some people when conventional approaches have not provided enough relief.
Improvement May Begin Quickly
Traditional antidepressants often require several weeks before their full effects become clear. One of the distinctive features of esketamine is its potential for a more rapid response.
Research has found that symptom improvements can appear within 24 hours of the first dose for some patients.
That does not mean complete remission occurs overnight. It means the emotional weather may begin to shift sooner than expected. A person may notice slightly more energy, less emotional heaviness, reduced suicidal thinking, or a small return of interest in daily life.
Sometimes a small opening is enough to begin doing the work that depression made impossible.
Maintenance Treatment and Relapse Prevention
Depression is not only about getting better. It is also about protecting the progress you make.
In the SUSTAIN-1 relapse-prevention study, people who had achieved stable remission and continued esketamine treatment had a relapse hazard ratio of approximately 0.49, or about a 51% lower risk of relapse, compared with those who stopped esketamine and continued with an oral antidepressant alone.
For stable responders who had improved but had not reached full remission, the relapse hazard ratio was approximately 0.30.
Maintenance treatment is individualized. Some people may eventually space sessions farther apart, while others may need continued support at a different frequency. The goal is not to keep you in treatment indefinitely without reflection. The goal is to build a sustainable plan based on your symptoms, response, safety, preferences, and life circumstances.
Who Might Be a Candidate?
Spravato is not appropriate for everyone, and careful screening is essential. You may be considered if:
You have a qualifying depressive diagnosis.
You have tried at least two oral antidepressants at adequate doses and for an adequate duration without sufficient improvement.
Your medical and psychiatric history supports safe treatment.
You can participate in monitored clinic-based sessions.
You are willing to continue coordinated psychiatric care, which may include medication management and psychotherapy.
Your clinician will also review blood pressure, cardiovascular and neurological history, current medications, substance-use history, and other safety considerations.
Spravato may not be appropriate for people with certain vascular conditions, a history of intracerebral hemorrhage, or an allergy to esketamine or ketamine. Because it is a Schedule III controlled substance, screening for misuse risk is also part of responsible care.
Most importantly, Spravato is not a first-line treatment for depression. It is designed for people who have experienced inadequate relief from prior treatments or who meet another qualifying indication.
If you are experiencing an immediate mental health emergency or may act on thoughts of suicide, call or text 988 in the United States or go to the nearest emergency department. Spravato treatment is not a substitute for emergency support.
What Happens During a Spravato Session?
At Inside and Out Psychiatry, your treatment plan will begin with a thorough psychiatric evaluation. If Spravato is clinically appropriate, we will explain the process, expected benefits, potential risks, and alternatives.
A typical session includes:
You receive the nasal spray in a supervised clinical setting.
The medication is self-administered under direct clinician guidance.
Your blood pressure and other vital signs are checked.
You remain in the clinic for observation, generally for at least two hours.
Your clinician monitors your mood, alertness, breathing, coordination, and overall safety.
You leave only when you are clinically stable and safe to do so.
Temporary side effects can include:
Dissociation or a feeling of being detached from yourself or your surroundings
Dizziness or vertigo
Sleepiness or sedation
Nausea
Temporary increases in blood pressure
Changes in perception or a “dreamlike” feeling
These experiences can feel unfamiliar, but monitoring is there so you do not have to navigate them alone. Many side effects lessen during the observation period.
You will need to arrange transportation and should not drive, operate machinery, or make important decisions until the next day after a restful sleep, according to prescribing guidance.
How Spravato Fits Into Whole-Person Care
Spravato is one tool: not the entire toolbox.
Our approach at Inside and Out Psychiatry is rooted in integrative medication management. We consider how your symptoms connect with your body, relationships, sleep, nutrition, stress, identity, and daily environment.
That may include:
Medication management: Reviewing your oral antidepressant and other medications while monitoring effectiveness, side effects, and interactions.
Psychotherapy: Creating space to process grief, trauma, identity questions, relationship patterns, and the practical challenges of rebuilding a life after depression.
Body-based therapies: Using somatic awareness and movement-based approaches to help you reconnect with your body and recognize signs of stress.
Nutrition counseling: Exploring practical nourishment and routines that support energy, cognition, and overall wellness.
Integrative supports: Incorporating complementary practices, when appropriate, alongside: not instead of: evidence-based psychiatric care.
A Spravato session may help shift the biology of depression. Therapy can help you understand what you are experiencing and make meaning from it. Body-based work can help your nervous system feel safer. Lifestyle support can help strengthen the foundation beneath your recovery.
This is the “inside and out” difference: we are not only asking whether your symptoms have decreased. We are also asking whether you feel more present, connected, capable, and able to participate in your own life.
What You Can Do Now
If depression has remained stubborn despite multiple treatments, you do not have to make a decision today. Start by gathering your treatment history, including:
Medications you have tried
Approximate doses and duration
Benefits or side effects
Previous therapy approaches
Hospitalizations or higher levels of care
Current medical conditions and medications
Your goals for treatment
Then reach out through our services page or book a session to begin a conversation about whether Spravato may be appropriate for you.
Our Spravato program is scheduled to begin in September 2026. Evaluation, preparation, and ongoing psychiatric follow-up may be integrated with our telehealth services, while each dose must be administered in a certified clinical setting with required monitoring.
You are not failing because your depression needs another approach.
Sometimes healing requires a new doorway: not because you did anything wrong, but because your brain and body need a different kind of support. Spravato may be that doorway for some people. With careful evaluation, compassionate monitoring, psychotherapy, and whole-person care, it can become part of a transformative plan for moving from merely surviving toward feeling present in your life again.
If you have tried multiple treatments without meaningful relief, reach out. A new possibility may be closer than you think.
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