The long-term benefits of Spravato® (esketamine) have become a central question for many patients considering this treatment for lasting relief. Since it was first approved for clinical use in 2019, Spravato has brought hope and promise to patients suffering from treatment-resistant depression (TRD).
Spravato is a form of ketamine, a medicine originally used as an anesthetic and pain reliever. It works by quickly changing how certain brain chemicals communicate. These effects may play a role in the long-term benefits of Spravato by helping to strengthen and repair neural connections damaged by depression or stress.
Typically used in conjunction with antidepressant medication, studies show that Spravato decreased the risk of relapse by 51% in patients who achieved stable remission.¹ It is approved for adults with TRD or major depressive disorder who have suicidal thoughts or actions.
For patients who have seemingly tried everything, Spravato offers hope for relief from treatment-resistant symptoms. But many may wonder what happens after treatment ends. Do the long-term benefits of Spravato extend beyond symptom relief, and what are its lasting effects on mental health?
What is Spravato and how does it improve brain health?
Administered as a prescription nasal spray, Spravato is a fast-acting medicine that can provide rapid relief from symptoms as early as four hours after the first dose.2
Spravato targets glutamate, a chemical in the brain that functions as a messenger and helps cells talk to each other.
The medicine works by blocking certain receptors on brain cells, which causes a surge in glutamate. This in turn activates the AMPA receptor, which is responsible for Spravato’s rapid antidepressant effects.
Long-term benefits of Spravato include:
- Repairs damaged connections Helps strengthen and regrow parts of the brain, such as the hippocampus, which controls memory and mood. These areas can become weak or damaged due to chronic stress, repeated bouts of depression, and early-life trauma.
- Boosts communication Improves how brain cells transmit messages, which can lead to better mood, memory, and learning.
- Fast relief Can start to relieve symptoms of depression much faster than most other medications.
- May reduce inflammation Some studies suggest Spravato might also help lower inflammation in the brain, which is linked to depression.
Spravato is noted for quickly boosting neuroplasticity, the brain’s ability to heal, adapt, and “rewire” itself. This is one of the reasons why people tend to notice mood improvements within hours or days.
Exploring the long-term benefits of Spravato
Research has shown that Spravato can cause rapid and continued improvement from symptoms of depression, especially when used alongside an oral antidepressant.
- Sustained symptom relief According to long-term studies, Spravato’s antidepressant effects can be maintained for up to 4.5 years with ongoing, intermittent treatment.3
- Reduced risk of relapse Patients who continued Spravato after remission typically went up to nearly two years before experiencing a relapse of their depression.4
- Higher remission and response rates Patients treated with Spravato were 1.54 times as likely to reach remission after eight weeks than those taking an antipsychotic used to treat depression.5
- Quality of life In addition to reduced symptoms of depression, many patients reported improvements in daily function, sleep, concentration, and overall well-being.5
Side effects are generally mild, including headache, dizziness, and nausea, with dissociation — a temporary feeling of detachment — being the most common. These short-term effects usually resolve within hours. Serious risks (increased blood pressure, sedation, or potential for misuse,) are rare and are typically managed by in-clinic administration and monitoring. Long-term use of Spravato has not revealed any additional safety concerns.
What to expect during Spravato treatment?
Spravato is administered as a nasal spray in a medical clinic under close supervision to ensure your safety and comfort.
Treatments typically start with two sessions per week for the first month, gradually reducing in frequency depending on your progress and your clinician’s recommendation.
Many patients describe their Spravato experience as surreal, peaceful, or introspective. They may also experience dissociation, a temporary sense of “stepping outside” of themselves, as if they were observing their life rather than living it directly.
Some people feel a wave of relaxation or a dreamlike sensation. Others find that the problems they found quite challenging before are now easier to handle.
During a Spravato session, a technician or nurse is always on hand to:
- Check your vitals and monitor your safety
- Create a calm, quiet, and safe environment
- Provide comfort and reassurance as needed
- Listen when you want to talk and answer any questions
Patients are not allowed to drive or operate heavy machinery for the rest of the day after treatment, as they may experience some fatigue.
Many patients notice mood improvements within the first few weeks, some as early as 24 to 72 hours — an early sign of the benefits of Spravato when used consistently. Common feelings include a sense of a mental “reset,” less emotional numbness, and increased motivation.
Your care team will check in regularly, track your progress, and adjust your treatment plan as needed.
Preventing relapse: Spravato maintenance and booster sessions
Maintenance treatments are key to a long-term plan to prevent relapse and keep the benefits of Spravato from fading. A typical treatment plan may include:
- Induction phase Treatment starts with two sessions a week for four weeks.
- Optimization phase Treatment frequency is reduced to once a week for four weeks.
- Maintenance phase Frequency is reduced further, typically once every one to two weeks, depending on need.
- Booster sessions These can be scheduled if symptoms return or during particularly stressful times.
Tips for maintaining long-term benefits of Spravato
Staying well after Spravato therapy involves building healthy habits and practicing self care.
- Stick to your maintenance schedule
- Attend regular follow-ups with your clinician
- Continue oral antidepressant therapy as prescribed
- Prioritize healthy lifestyle habits
- Engage in therapy or counseling as needed
- Monitor and communicate about side effects
- Rest and recover after each session
- Talk with your care team about how to extend the long-term benefits of Spravato.
Key Takeaways
For many patients, Spravato offers renewed hope and a promising path forward.
- Spravato provides rapid and effective relief for adults with TRD, especially those who haven’t found success with traditional medications.
- It works by repairing and strengthening brain connections, leading to improvements in mood, daily functioning, and overall quality of life.
- Ongoing maintenance therapy helps sustain the long-term benefits of Spravato and significantly reduce the risk of relapse.
- A strong partnership with your care team and healthy lifestyle habits are essential for maintaining progress and supporting lasting recovery.
With growing evidence and real-world success stories, Spravato offers new hope for those who have struggled to find lasting relief. With proper support, ongoing care, and a commitment to wellness, patients can experience not only symptom improvement but meaningful, sustained change in their mental health and quality of life.
References
1Daly, E. J., Trivedi, M. H., Janik, A., Li, H., Zhang, Y., Li, X., … & Singh, J. B. (2019). Efficacy of esketamine nasal spray plus oral antidepressant treatment for relapse prevention in patients with treatment-resistant depression: A randomized clinical trial. JAMA Psychiatry, 76(9), 893–903. https://doi.org/10.1001/jamapsychiatry.2019.1189
2Gastaldon, C., Papola, D., Ostuzzi, G., Barbui, C., & Cipriani, A. (2021). Esketamine for treatment-resistant depression: A rapid review. CNS Drugs, 35(2), 165–173. https://doi.org/10.1007/s40263-020-00772-y
3Janssen Pharmaceuticals, Inc. (n.d.). SPRAVATO® (esketamine) CIII nasal spray: Efficacy & safety for treatment-resistant depression (TRD). Retrieved May 21, 2025, from https://www.spravatohcp.com/trd-efficacy-safety/
4Wagner, G. R., & Zuardi, A. W. (2021). Ketamine and esketamine in treatment-resistant depression. In StatPearls. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK572271/
5Ochs-Ross, R., Daly, E. J., Zhang, Y., Lane, R., Lim, P., Morrison, R. L., … & Singh, J. B. (2023). Esketamine nasal spray for treatment-resistant depression: A randomized, double-blind, active-controlled study. The New England Journal of Medicine, 389(5), 410–420. https://doi.org/10.1056/NEJMoa2304145
Medically reviewed by Joshua Flatow, MD.
