For decades, the treatment of depression has largely revolved around medications that work on serotonin and other monoamine neurotransmitters. These medications such as SSRIs or SNRIs can be effective for many people, but they often take weeks to work and may come with unwanted side effects. In recent years, a newer treatment has emerged that works through an entirely different pathway in the brain: Spravato (esketamine).
Because many patients notice improvement relatively quickly and continue to feel benefits long after a treatment session ends, a common question arises:
Is Spravato simply a long-lasting antidepressant?
At first glance, it might seem that way. But the reality is more nuanced. While Spravato certainly has antidepressant effects, the way it works in the brain suggests that it is doing much more than simply prolonging the action of a typical medication.
What Is Spravato?
Spravato is a prescription nasal spray derived from ketamine, a medication that has been used safely in medicine for decades as an anesthetic and pain medication. The active ingredient, esketamine, is one of the two mirror-image molecules that make up ketamine and has been specifically developed for the treatment of depression.
The medication is approved by the FDA for:
- Treatment-resistant depression
- Major depressive disorder with suicidal thoughts or behaviors
Unlike most antidepressants, Spravato is not taken daily at home. Instead, it is administered in a medical setting under supervision as part of the SPRAVATO REMS Program, a safety program required by the FDA.
During treatment, patients self-administer the nasal spray under medical guidance and remain in the clinic for monitoring. Because temporary side effects such as sedation or dissociation may occur, patients are observed for at least two hours before going home.
This supervised model allows the treatment to be delivered safely while also creating an environment where patients can relax and focus on their experience.
How Spravato Works in the Brain
Traditional antidepressants typically work by increasing levels of serotonin, norepinephrine, or dopamine. These medications gradually change neurotransmitter signaling over time, which is why they often require weeks before patients notice improvement.
Spravato works through a very different mechanism.
Rather than targeting serotonin directly, Spravato primarily influences the brain’s glutamate system, which plays a major role in learning, memory, and neural communication. By modulating glutamate signaling, the medication triggers a cascade of events that promote neuroplasticity—the brain’s ability to form new connections and reorganize itself.
Researchers believe Spravato helps stimulate several important processes in the brain, including:
- Increased glutamate release
- Activation of AMPA receptors
- Increased production of brain-derived neurotrophic factor (BDNF)
- Strengthening of synaptic connections between neurons
These changes may help repair circuits in the brain that have become disrupted in depression.
Many people living with depression experience persistent negative thinking patterns and emotional rigidity. By promoting neuroplasticity, Spravato appears to help the brain break out of those rigid patterns, allowing new and healthier pathways to form.
How Spravato Differs from Traditional Antidepressants
One of the most striking differences between Spravato and traditional antidepressants is how long its effects last relative to how long the drug remains in the body.
Most SSRIs require continuous daily dosing because their effects are tied closely to the presence of the medication in the bloodstream. If the medication is stopped, neurotransmitter levels typically return to baseline relatively quickly.
Spravato behaves differently.
The medication itself is cleared from the body within hours, but the changes it initiates in the brain may last much longer. In other words, Spravato acts more like a trigger for biological change rather than a substance that must be constantly present to maintain its effects.
This is one reason many patients experience meaningful improvements within hours or days, rather than the weeks typically required for traditional antidepressants.
How Long Do the Effects Last?
During a Spravato treatment session, patients may experience temporary effects such as mild dissociation, relaxation, or altered perception. These acute effects generally occur within the first hour and gradually fade during the observation period.
Patients remain in the clinic for two hours of monitoring, allowing time for these sensations to resolve before leaving.
However, the antidepressant benefits extend well beyond the treatment session. Many patients notice improvements in mood, motivation, and emotional resilience that persist for days or even weeks after treatment.
Because of this prolonged benefit, Spravato is not administered daily. Instead, it follows a structured schedule that typically includes:
- An induction phase during the first month with treatments twice per week
- A maintenance phase where treatments gradually become less frequent
Over time, many patients transition to treatments every two weeks or longer depending on their individual response.
Advantages Compared With Conventional Antidepressants
Another reason patients are interested in Spravato is that it may avoid some of the persistent side effects associated with conventional antidepressants.
Many people taking SSRIs report long-term issues such as:
- Weight gain
- Reduced libido or sexual dysfunction
- Emotional blunting
- Cognitive fog or fatigue
Spravato’s side effects tend to be temporary and occur primarily during the treatment session itself. These may include dizziness, mild dissociation, nausea, or temporary increases in blood pressure. In most cases, these effects resolve during the observation period at the clinic.
Because Spravato is administered intermittently rather than daily, it generally does not produce the same long-term metabolic or sexual side effects that can occur with traditional antidepressants.
Starting Spravato Treatment
Beginning Spravato therapy involves a careful evaluation to ensure the treatment is appropriate.
The process includes a comprehensive consultation where the clinician reviews a patient’s mental health history, prior treatments, and overall medical status. Patients who are good candidates can then be enrolled in the required REMS safety program before beginning treatment. Patients are required to have a referral from their psychiatrist or physician stating they have a diagnosis of treatment-resistant depression, having failed a trial of at least two antidepressants.
Each visit usually lasts about two hours and includes:
- Administration of the nasal spray
- Monitoring of vital signs and symptoms
- Observation until the medication’s acute effects resolve
Patients must arrange transportation home after treatment, as driving is not permitted the same day.
The Importance of Set and Setting
Although Spravato is a medication, the environment in which it is administered matters greatly.
At Innerbloom Ketamine Therapy in San Luis Obispo, we believe the treatment experience should feel calm, supportive, and comfortable. We place special emphasis on creating a therapeutic atmosphere that promotes relaxation and safety.
Patients at Innerbloom receive care in a warm and thoughtfully designed environment where:
- Each patient has their own private treatment room
- The clinic environment is quiet, comfortable, and welcoming
- Patients are monitored at all times by an onsite physician.
- Care is personalized to support both safety and emotional well-being
This attention to environment and support helps patients feel secure during treatment and allows them to focus fully on the healing process.
So… Is Spravato Just a Long-Lasting Antidepressant?
In one sense, yes. Spravato is an antidepressant treatment that can provide lasting relief from symptoms of depression.
But when we look more closely at how it works, it becomes clear that Spravato is much more than that.
Rather than simply maintaining neurotransmitter levels, Spravato appears to help the brain create new neural pathways and restore flexibility to circuits affected by depression. By promoting neuroplasticity, it may open a window of opportunity for meaningful emotional and psychological change.
For many patients, this means not just temporary symptom relief, but a chance to reset patterns of thinking and feeling that have been stuck for years.
So is Spravato just a long-lasting antidepressant?
Well—yes, but it’s so much more.
It represents a fundamentally different approach to treating depression—one that works with the brain’s natural ability to heal, adapt, and grow. And for many people who have struggled to find relief with conventional treatments, that difference can be life-changing.
About the Author
Dr. Rivas is a ketamine specialist and board-certified acute care and trauma surgeon with over 12 years of experience in ketamine administration. Before founding Innerbloom Ketamine Therapy in 2022, Dr. Rivas served on the frontlines of emergency and trauma medicine in Santa Maria, CA, and Austin, TX. Dr. Rivas applies his extensive medical expertise to provide safe, evidence-based ketamine treatments for mood disorders, including depression, anxiety, PTSD, and chronic pain. His passion lies in helping patients find relief and rediscover hope through personalized, compassionate care.
Newy: Bridging the Gap Between Ketamine Treatment and Everyday Wellness
A supplement formulated by Dr. Rivas for enhanced brain and mood support. The formula pairs especially well with ketamine therapy by helping extend and enhance the neuroplasticity effects. That said, the ingredients are equally effective on their own, so it’s a supportive option whether or not someone is undergoing ketamine treatment. Learn more about how Newy supports cognitive function detoxification and cellular repair.
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.
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Struggling with depression that won’t respond to traditional treatments? Contact Innerbloom Ketamine Therapy at (805) 592-5085 or visit us at 100 Casa Street, Suite D3, San Luis Obispo, CA 93405. We offer complimentary consultations to discuss whether ketamine therapy might be right for you.