If you’re living with severe depression that hasn’t improved despite trying multiple medications, you’re not alone—and there is hope. Treatment-resistant depression can feel overwhelming and isolating, especially when traditional antidepressants fail to bring relief. But innovative therapies are changing the landscape of mental health treatment. One such breakthrough is Spravato® (esketamine)—an FDA-approved nasal spray designed specifically for people struggling with hard-to-treat depression. In this blog, we’ll explore how Spravato works, who it’s for, and what you can expect from this potentially life-changing therapy.
In This Blog:
- What is Spravato (Esketamine)?
- Who is a Candidate for Spravato Therapy?
- How Spravato Works
- The Treatment Process
- Benefits of Spravato Therapy
- Considerations and Risks
What Is Spravato (Esketamine)?
Spravato is the brand name for esketamine, a fast-acting antidepressant that is chemically related to ketamine. Unlike traditional antidepressants that work by increasing levels of serotonin, dopamine, or norepinephrine, esketamine works by targeting the glutamate pathway. This payway plays a key role in mood regulation and brain plasticity.
Approved by the U.S. Food and Drug Administration (FDA) in 2019, Spravato is specifically indicated for adults with treatment-resistant depression (TRD) and for those experiencing major depressive disorder with acute suicidal thoughts or behaviors. Unlike other medications, Spravato is not prescribed for use at home. Instead, Spravato is administered as a nasal spray under direct medical supervision in a certified treatment center, where patients are monitored for at least two hours after each dose to ensure safety.
It is important to note that Spravato is not the same as recreational or anesthetic ketamine. It is a purified, more targeted form, designed for therapeutic use and rigorously studied in clinical trials. For many individuals who haven’t found relief through traditional treatments, Spravato offers a new path forward—one that can work more rapidly and effectively than standard antidepressants.
Who Is a Candidate for Spravato Therapy?
Spravato is intended for individuals diagnosed with treatment-resistant depression (TRD)—a form of major depressive disorder that does not respond to at least two different antidepressant medications taken at adequate doses and durations. If you’ve tried multiple treatments without significant relief, you may be a candidate for this therapy.
In addition to TRD, Spravato is also approved for adults experiencing major depressive disorder with acute suicidal thoughts or behaviors, offering a rapid-acting option when time is critical. However, it’s important to note that Spravato is not used as a standalone treatment. It is always prescribed in combination with an oral antidepressant, helping to support long-term mood stabilization.
Before starting Spravato, patients undergo a comprehensive psychiatric evaluation. This ensures the therapy is appropriate and safe based on their medical history, current medications, and mental health status. Individuals with certain conditions—such as a history of substance abuse, uncontrolled hypertension, or aneurysms—may not be eligible for Spravato and should discuss these concerns with their mental health provider.
How Spravato Works
Spravato (esketamine) works differently from traditional antidepressants, offering a unique mechanism of action that targets the brain in a new way. While most antidepressants focus on increasing levels of serotonin, dopamine, or norepinephrine, Spravato acts on the glutamate system, specifically targeting N-methyl-D-aspartate (NMDA) receptors.
By modulating these receptors, Spravato helps to increase the availability of glutamate, a key neurotransmitter involved in brain plasticity, learning, and memory. This action promotes the formation of new neural connections, which may be impaired in individuals with severe depression. The result is a rapid and noticeable improvement in mood and cognitive function, often within hours to a few days, much faster than the weeks or months traditional antidepressants typically require.
This fast-acting effect is especially important for individuals in crisis or those experiencing intense depressive symptoms. In clinical studies, many patients reported a reduction in depressive symptoms after just one or two doses. While the exact mechanism behind esketamine’s antidepressant effects is still being studied, its ability to work through a different chemical pathway offers hope for those who haven’t benefited from other treatments.
By helping to reset and rewire key brain circuits involved in mood regulation, Spravato offers a new direction in the treatment of severe depression, particularly for those who have been left frustrated by conventional options.
The Treatment Process
Spravato therapy is designed to be both effective and safe, which is why it’s administered in a controlled medical setting. Unlike traditional antidepressants that are taken at home, Spravato is delivered as a nasal spray at a certified treatment center under the supervision of a healthcare professional. Here’s what the treatment process typically looks like:
Initial Evaluation:
Before starting, patients undergo a thorough mental health assessment to determine if Spravato is appropriate for their condition. This includes a review of medical history, current medications, and mental health status.
Induction Phase:
Treatment begins with twice-weekly sessions for the first four weeks. During each session, patients self-administer the nasal spray under medical supervision.
Monitoring:
After taking the dose, patients are closely monitored for at least two hours. During this time, staff check vital signs and observe for any side effects such as dissociation (a sense of detachment from reality), dizziness, nausea, or sedation.
Maintenance Phase:
After the initial month, sessions typically decrease in frequency—first to once a week, then possibly to once every two weeks—based on how well the patient is responding.
Ongoing Support:
Since Spravato is always used alongside an oral antidepressant, patients continue to work closely with their psychiatrist or mental health provider to monitor progress, adjust medications, and manage overall wellness.
Most patients describe the experience as manageable, though it’s not uncommon to feel a bit groggy or disconnected during and shortly after the session. That’s why patients must arrange for transportation home and are not allowed to drive until the next day.
Benefits of Spravato Therapy
Spravato offers several important benefits for individuals struggling with treatment-resistant depression, especially those who have found little to no relief from traditional medications. Its unique mechanism and rapid onset of action make it a game-changer in the field of psychiatry.
Rapid Relief of Symptoms
One of the most significant advantages of Spravato is how quickly it can begin to work. Many patients experience a noticeable improvement in mood within hours to days—a stark contrast to the weeks or months it can take for conventional antidepressants to take effect. This is particularly critical for individuals experiencing acute suicidal thoughts or overwhelming depressive symptoms, where time is of the essence.
Effective for Treatment-Resistant Depression
Spravato has shown success in patients who haven’t responded to two or more antidepressants. For many, it offers a renewed sense of hope after years of struggling with limited treatment options.
Enhances Brain Plasticity
By acting on the glutamate system and promoting the formation of new neural connections, Spravato may help repair and strengthen key brain pathways involved in mood regulation supporting not just symptom relief, but also long-term emotional resilience.
Reduced Suicidal Ideation
Studies have shown that Spravato can significantly reduce suicidal thoughts in patients with major depressive disorder. While it’s not a standalone treatment for suicidal behavior, it can be a vital part of a crisis intervention plan when used alongside psychotherapy and oral antidepressants.
Improved Quality of Life
For many patients, Spravato therapy leads to improved day-to-day functioning, better sleep, more energy, and the ability to re-engage with relationships and activities they had once withdrawn from. The relief it brings can pave the way for a more fulfilling and hopeful life.
In short, Spravato represents a new era of depression treatment, especially for those who’ve felt stuck or hopeless in the past. While it may not be right for everyone, for the right patient, it can be a transformative step toward healing.
Considerations and Risks
While Spravato offers hope for many with treatment-resistant depression, it’s important to be aware of the potential risks and considerations before starting therapy. Like all medications, Spravato may not be suitable for everyone, and understanding the full picture helps patients make informed decisions.
Side Effects
Common side effects of Spravato include:
- Dissociation (feeling disconnected from self or surroundings)
- Dizziness
- Nausea and vomiting
- Sedation or drowsiness
- Increased blood pressure
These effects typically occur shortly after administration and are the reason patients must remain under observation for at least two hours post-dose. Most side effects are temporary and resolve on their own within the monitoring period.
Risk of Abuse or Dependence
Because esketamine is related to ketamine, a drug known for its dissociative and euphoric effects, there is a controlled risk of misuse or dependence. However, this risk is minimized due to Spravato’s highly regulated, in-clinic administration and limited availability outside of certified treatment centers.
Medical and Psychiatric Screening Is Essential
Not everyone is a candidate for Spravato therapy. Therefore, a thorough psychiatric and medical evaluation is mandatory before beginning treatment. Individuals with a history of the following may be advised against using Spravato due to safety concerns:
- Substance use disorders
- Uncontrolled high blood pressure
- Certain aneurysms
- Psychotic disorders (such as schizophrenia)
Not a Cure or Standalone Treatment
Spravato is not a cure for depression. It should always be used in combination with an oral antidepressant and as part of a comprehensive treatment plan that may include therapy, lifestyle changes, and ongoing mental health support.
Transportation Restrictions
Because of the temporary effects on coordination, cognition, and alertness, patients cannot drive or operate machinery until the day after their treatment session. It’s necessary to arrange for transportation home after each appointment.
By understanding the risks and responsibilities involved, patients and providers can work together to ensure that Spravato therapy is both safe and effective, helping more individuals find relief from the heavy burden of severe depression.
Conclusion
For those battling treatment-resistant depression, Spravato (esketamine) offers a new sense of hope when it feels like all other options have been exhausted. With its unique mechanism of action, rapid symptom relief, and growing success stories, this innovative therapy is changing the way we approach severe depression. While it’s not without risks and requires careful monitoring, Spravato has the potential to bring meaningful, life-changing results for many.
If you or a loved one is struggling with depression that hasn’t responded to traditional treatments, talk to a mental health professional at Whole Mind to see if Spravato might be the right next step on the path to healing. Whole Mind has locations in the following Utah cities: Brigham City, Draper, Ogden, Pleasant Grove, Provo, and Tooele, as well as Novato, CA.
