For many people living with depression, traditional antidepressants can be life-changing. But for others, symptoms persist despite trying multiple medications, therapy, lifestyle changes, and other treatment approaches. This experience can feel exhausting, discouraging, and isolating. If you’ve been told you have treatment-resistant depression (TRD), it’s important to know that there are still effective options available.
One of the most significant advances in depression treatment in recent years has been Spravato (esketamine nasal spray), the first FDA-approved nasal spray specifically indicated for adults with treatment-resistant depression.
At Innerbloom Ketamine Therapy, we believe education is one of the most important parts of mental health care. Starting a treatment like SPRAVATO® can feel intimidating at first, especially if you are unfamiliar with ketamine-based therapies. This article is designed to help explain what SPRAVATO® is, how it works, what treatment looks like, and what patients can realistically expect throughout the process.
What Is Treatment-Resistant Depression?
Treatment-resistant depression generally refers to depression that has not adequately improved despite trying at least two different oral antidepressants at appropriate doses and durations.
Unfortunately, this is more common than many people realize. Approximately 1 in 3 people do not experience sufficient symptom relief from oral antidepressants alone.
Traditional antidepressants typically work by affecting neurotransmitters such as serotonin, norepinephrine, and dopamine. While these medications can be very helpful for many individuals, depression is an incredibly complex condition involving far more than a single chemical imbalance. This is one reason why some people continue to struggle despite multiple medication trials.
For patients who feel stuck, hopeless, or discouraged after years of trying different medications, SPRAVATO® represents a fundamentally different approach.
How SPRAVATO® Works Differently
SPRAVATO® contains esketamine, a molecule derived from ketamine. Unlike traditional antidepressants, SPRAVATO® primarily acts through the glutamate system and NMDA receptor pathways in the brain.
Glutamate is the brain’s primary excitatory neurotransmitter and plays a major role in neuroplasticity — the brain’s ability to adapt, reorganize, and form new connections. Researchers believe impaired neuroplasticity may contribute to depression, especially chronic or treatment-resistant forms.
While scientists are still learning exactly how ketamine and esketamine produce antidepressant effects, the medication appears to work differently than conventional antidepressants, which is part of why it can sometimes help patients who have not responded to standard treatments.
Another important distinction is that SPRAVATO® is not a daily pill. Treatment occurs in a certified medical setting under supervision, using a structured dosing schedule tailored to the patient’s response and progress.
How Quickly Does SPRAVATO® Work?
One reason ketamine-based therapies have received so much attention is their potential for relatively rapid symptom improvement compared to traditional antidepressants, which can sometimes take many weeks to show benefit.
Clinical studies demonstrated a reduction in depression symptoms as early as 24 hours in some patients.
This does not mean every patient experiences overnight relief, nor does it mean SPRAVATO® is a “magic cure.” Mental health recovery is rarely linear. However, for individuals who have spent years feeling emotionally numb, chronically depressed, or trapped in cycles of hopelessness, even subtle shifts can be profoundly meaningful.
At Innerbloom, we often remind patients that improvement may initially appear in small ways:
- Feeling slightly more motivated
- Having more emotional flexibility
- Sleeping better
- Feeling less overwhelmed
- Becoming more engaged with loved ones
- Regaining interest in activities
- Experiencing moments of hope again
These changes can gradually build over time.
What Happens During SPRAVATO® Treatment?
One of the most common questions patients ask is: “What does treatment day actually look like?”
SPRAVATO® is only administered in certified healthcare settings through a restricted safety program called the SPRAVATO® REMS Program.
During treatment, patients self-administer the nasal spray under medical supervision. After administration, patients remain in the clinic for at least two hours for observation and monitoring.
This monitoring period is important because SPRAVATO® can cause side effects such as:
- Sedation
- Dizziness
- Dissociation
- Increased blood pressure
- Nausea
- Anxiety
- Feeling disconnected from oneself or surroundings
Most side effects occur shortly after administration and usually resolve the same day.
Many patients spend their observation time quietly resting, listening to music, meditating, journaling, or simply relaxing.
Patients are also instructed not to drive or operate machinery until the following day after a restful sleep. Because of this, transportation arrangements are necessary for every treatment session.
The Typical SPRAVATO® Schedule
Treatment begins with what is often called the induction phase.
The standard schedule generally includes:
- Weeks 1–4: treatments occur twice weekly
- Weeks 5–8: treatments occur once weekly
- Ongoing maintenance: treatment may continue weekly or every other week depending on clinical response
Consistency matters. Some patients feel eager to stop treatment early once they begin feeling better, but completing the initial series often provides the best opportunity for stabilization and sustained improvement.
Depression recovery is not simply about temporarily reducing symptoms. The goal is creating longer-lasting emotional resilience, improved functioning, and meaningful quality-of-life changes.
SPRAVATO® and Long-Term Outcomes
One of the more encouraging aspects of SPRAVATO® is the growing body of long-term data supporting its use.
Research has demonstrated long-term safety and outcomes data extending out to five years when SPRAVATO® is used alongside an oral antidepressant.
Studies also suggest that patients who continue treatment are less likely to experience relapse of depressive symptoms compared to those who discontinue therapy.
This highlights an important reality about depression: for many people, it is a chronic condition requiring ongoing maintenance and support, much like diabetes or hypertension. Continuing treatment is not a sign of weakness. It is part of long-term care and stability.
Safety and Important Considerations
SPRAVATO® is not appropriate for everyone. Before starting treatment, patients undergo medical and psychiatric evaluation to determine whether the treatment is safe and clinically appropriate.
There are several important safety considerations, including certain vascular conditions, uncontrolled hypertension, history of brain bleeding, pregnancy considerations, and substance use history.
Additionally, because ketamine-based therapies can sometimes temporarily increase blood pressure and alter perception, careful monitoring is essential.
At Innerbloom, patient safety is always the priority. This includes:
- Thorough psychiatric and medical screening
- Careful monitoring during treatment
- Collaboration with existing healthcare providers when appropriate
- Education about realistic expectations
- Integration of psychotherapy and lifestyle support whenever possible
We strongly believe ketamine therapies work best when viewed as part of a broader mental health strategy rather than a stand-alone intervention.
SPRAVATO® and Suicidal Depression
SPRAVATO® is also FDA-approved, in combination with an oral antidepressant, for depressive symptoms in adults with major depressive disorder and suicidal thoughts or behaviors.
Clinical studies showed greater reduction in depressive symptoms at 24 hours compared to placebo plus an oral antidepressant.
However, SPRAVATO® is not a replacement for hospitalization when hospitalization is clinically necessary. If someone is in immediate crisis or danger, emergency psychiatric care remains essential.
Learn what the latest research reveals about ketamine therapy for suicidal ideation.
Cost and Insurance Coverage
One barrier many patients worry about is affordability.
Fortunately, most insurance plans now cover SPRAVATO®, and coverage continues to expand across the country. There are also manufacturer assistance programs available for eligible patients that may significantly reduce out-of-pocket costs.
At Innerbloom, our team helps patients navigate insurance verification, prior authorizations, and affordability programs whenever possible because accessing mental health treatment should not feel impossible.
Final Thoughts
Living with treatment-resistant depression can make people feel as though they have run out of options. Many patients who come through our doors have spent years trying medication after medication while silently carrying exhaustion, shame, hopelessness, or emotional numbness.
SPRAVATO® is not a miracle cure, and it is not appropriate for every person. But for many individuals, it represents a meaningful new pathway toward healing — one grounded in modern neuroscience, neuroplasticity, and a more comprehensive understanding of depression.
Most importantly, patients deserve to know they are not failing because traditional antidepressants did not work well enough. Depression is complex, and sometimes healing requires a different approach.
If you are struggling with persistent depression despite previous treatment attempts, our team at Innerbloom Ketamine Therapy is here to help educate, guide, and support you in exploring whether SPRAVATO® may be an appropriate option for your care.
Medical Disclaimer
All content on this website, including but not limited to this article, blog posts, testimonials, and FAQs, is not medical advice and should not be considered as such. This website cannot diagnose or treat any medical condition. Only a licensed medical professional who is familiar with you and your medical history can provide medical advice, diagnosis, or treatment.
The information provided here is for educational and informational purposes only. It is not intended to replace a consultation with a qualified healthcare provider. If you are experiencing symptoms of depression or any mental health condition, please consult with a licensed mental health professional or your primary care physician.
If you are in crisis or experiencing suicidal thoughts, please call the 988 Suicide and Crisis Lifeline (call or text 988) or go to your nearest emergency room immediately.
Innerbloom Ketamine Therapy cannot be held responsible or liable for any actions taken by those who access our website or rely on its content. Please refer to our Terms & Conditions for more information.
Has your antidepressant stopped working? Contact Innerbloom Ketamine Therapy at (805) 321-8471 or visit us at 100 Casa Street, Suite D3, San Luis Obispo, CA 93405.