For many people living with depression, antidepressant medications provide meaningful relief. But for others, improvement is partial, short-lived, or doesn’t come at all. If you’ve tried multiple medications and still feel stuck, you may have been told you have treatment-resistant depression—or you may simply feel frustrated that nothing seems to work.
SPRAVATO® (esketamine) represents a fundamentally different approach to treating depression. It works through a different mechanism in the brain, offers faster symptom relief for some patients, and has become an important option for adults who haven’t responded to traditional antidepressants.
At EverHope Wellness Clinic in Columbus, Ohio, SPRAVATO treatments are offered to individuals seeking evidence-based alternatives when standard approaches haven’t been enough.
Why Traditional Antidepressants Don’t Work for Everyone
Most commonly prescribed antidepressants—such as SSRIs and SNRIs—work by adjusting levels of neurotransmitters like serotonin, norepinephrine, and dopamine. These chemicals help regulate mood, sleep, appetite, and emotional balance.
While these medications are effective for many people, they also share limitations:
- They work indirectly, influencing mood over time rather than immediately
- They often take 4–8 weeks to show noticeable effects
- They primarily affect chemical signaling, not brain connectivity
- For some individuals, benefits plateau or fade
Modern research shows depression is not simply a “chemical imbalance.” It also involves changes in brain circuitry, stress-response systems, inflammation, and reduced neuroplasticity—the brain’s ability to adapt and form new connections (Duman & Aghajanian, 2012).
This understanding helps explain why ketamine treatment and SPRAVATO® therapy can be effective when traditional medications are not.
What Is SPRAVATO®?
SPRAVATO® is an FDA-approved nasal spray derived from ketamine that is often used alongside an oral antidepressant for adults whose depression has not adequately responded to traditional treatments. It is specifically approved for individuals with treatment-resistant depression, as well as for certain patients experiencing depressive symptoms alongside suicidal thoughts or behaviors, when clinically appropriate.
Unlike some oral or IV ketamine therapy programs that can vary widely in structure and oversight, SPRAVATO® is delivered under a strict Risk Evaluation and Mitigation Strategy (REMS). This means treatment must take place in a certified medical clinic with trained providers, where patients are closely monitored to ensure safety and support throughout each session.
The Key Difference: Glutamate, Not Serotonin.
To understand how SPRAVATO® works, it helps to understand glutamate. Glutamate is the brain’s primary excitatory neurotransmitter and plays a crucial role in learning and memory, long-term emotional regulation, and communication pathways between brain cells.
Chronic stress and depression are often associated with disrupted glutamate signaling, particularly in brain regions responsible for mood and motivation. So, traditional antidepressants primarily work by influencing (boosting or extending) serotonin creation, a neurotransmitter that affects emotional regulation and balance.
SPRAVATO®, however, targets glutamate, the brain’s most abundant neurotransmitter and a key driver of neural connection—allowing it to support the brain in forming lasting healthier communication pathways rather than simply adjusting mood chemicals regularly. This makes it a fundamentally different form of ketamine therapy for depression.
How SPRAVATO® Affects the Brain
SPRAVATO® works by influencing the brain’s glutamate system, which plays a key role in how brain cells communicate, adapt, and recover from stress. Esketamine, the active ingredient in SPRAVATO®, temporarily blocks NMDA receptors—a specific type of glutamate receptor. This brief blockage shifts how glutamate signals through the brain, increasing activity at AMPA receptors instead.
That shift sets off a cascade of biological processes linked to brain growth and repair. These processes involve pathways such as BDNF (brain-derived neurotrophic factor) and mTOR, which support the formation of new synapses, strengthen existing neural connections, and improve overall communication between brain cells. Rather than simply adjusting neurotransmitter levels, SPRAVATO® helps the brain rebuild connectivity that can be weakened by chronic depression (Daly et al., 2018).
This mechanism helps explain why some patients notice improvement more quickly with SPRAVATO®—sometimes within days rather than weeks—compared to traditional antidepressants.
Why SPRAVATO® Can Work When Other Treatments Haven’t
SPRAVATO addresses biological factors of depression that traditional antidepressants may not fully target: stress-related synaptic loss, neural rigidity (the brain becoming “stuck” in depressive patterns) or reduced plasticity in mood-regulating regions.
Because it works through a different pathway, ketamine-based treatments can benefit individuals who have tried multiple antidepressants without adequate relief (Zarate et al., 2006).
What Research Shows
Multiple clinical trials support the effectiveness of SPRAVATO® for individuals with treatment-resistant depression. Research has shown that many patients experience a more rapid reduction in depressive symptoms compared to traditional treatments, particularly when SPRAVATO® is used alongside an oral antidepressant. For some individuals, continued treatment may also help sustain improvements over time, offering longer-term symptom relief with appropriate maintenance care.
Importantly, treatment-resistant does not mean untreatable. It often means a different approach is needed.
What a SPRAVATO® Treatment Session Looks Like
At EverHope Wellness Clinic in Columbus, Ohio, SPRAVATO® is administered in a certified medical setting with close clinical supervision. Each treatment session is designed to prioritize safety, comfort, and support throughout the process.
A typical SPRAVATO® visit follows a clear structure. First, patients self-administer the nasal spray under medical guidance. After dosing, they rest in a calm, monitored environment while our clinical team observes for at least two hours. Because of the short-term effects of the medication, patients are required to arrange transportation home and are not permitted to drive the same day.
Some individuals experience temporary side effects during or shortly after treatment, such as:
- Dissociation or altered perception
- Drowsiness
- Lightheadedness
These effects are expected, closely monitored, and generally resolve on the same day before patients leave the clinic.
Comprehensive Care Plans
SPRAVATO® is most effective when it is part of a comprehensive, personalized treatment plan. It is used alongside an oral antidepressant and supported by ongoing psychiatric care and, when appropriate, therapy or other supportive interventions.
At EverHope, treatment decisions are collaborative and tailored to each person’s history and needs—ensuring advanced options like SPRAVATO® are integrated thoughtfully, safely, and with long-term well-being in mind.
Who Might Consider SPRAVATO® or Ketamine Therapy?
SPRAVATO® may be appropriate for adults who:
- Have tried two or more antidepressants without sufficient improvement
- Continue to experience significant depressive symptoms
- Feel emotionally numb, hopeless, or stuck
- Are seeking advanced depression treatment in Columbus, Ohio
A comprehensive psychiatric evaluation is an essential first step to determine whether SPRAVATO® is appropriate, safe, and aligned with an individual’s medical history, symptoms, and overall treatment goals. For individuals who are seeking advanced, evidence-based options beyond traditional antidepressants, SPRAVATO® may offer a new path forward.
A Different Kind of Hope
Depression can feel especially heavy when you’ve tried multiple treatments without relief. SPRAVATO® offers a science-backed alternative—rooted in modern neuroscience and a deeper understanding of how depression affects the brain.
If you’ve been told you’re out of options, that may not be true. Sometimes, it simply means it’s time for a different treatment.
Considering SPRAVATO® in Columbus, Ohio?
At EverHope Wellness Clinic, we specialize in advanced treatments for depression, including SPRAVATO® and other evidence-based approaches. Our team takes the time to listen, evaluate your history, and determine whether this treatment may be right for you.
If you’re ready to explore your options—or simply want more information—we’re here to help.
Schedule a consultation with EverHope Wellness Clinic today.
There is still hope, and you don’t have to navigate this alone.
References
Esketamine efficacy and rapid antidepressant effects
Daly, E. J., et al. (2018). Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in treatment-resistant depression. American Journal of Psychiatry, 175(2), 139–148.
https://pubmed.ncbi.nlm.nih.gov/29282469/
Ketamine’s impact on treatment-resistant depression
Zarate, C. A., et al. (2006). A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Archives of General Psychiatry, 63(8), 856–864.
https://pubmed.ncbi.nlm.nih.gov/16894061/
Synaptic dysfunction and neuroplasticity in depression
Duman, R. S., & Aghajanian, G. K. (2012). Synaptic dysfunction in depression: Potential therapeutic targets. Science, 338(6103), 68–72.
https://www.science.org/doi/10.1126/science.1222939
FDA safety and prescribing guidance
U.S. Food and Drug Administration. (2019). SPRAVATO® (esketamine) prescribing information.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211243lbl.pdf
