More than 140,000 patients worldwide have used SPRAVATO® (esketamine) nasal spray for difficult-to-treat depression. SPRAVATO® is an FDA-approved nasal spray that works differently than traditional antidepressants by targeting the NMDA receptor in the brain, offering a treatment option for people who haven’t achieved adequate improvement with oral medications alone.
How SPRAVATO® Works in the Brain
SPRAVATO® contains esketamine, the S-enantiomer of ketamine, which has 2–4 times higher affinity for NMDA receptors than ketamine itself. NMDA receptors play a critical role in glutamate signaling—the brain’s primary excitatory neurotransmitter system. While most antidepressants work on serotonin, norepinephrine, or dopamine, esketamine takes a different approach by modulating glutamate activity.
When esketamine blocks NMDA receptors, it triggers a cascade of neurobiological changes. The medication increases release of brain-derived neurotrophic factor, a protein that supports neuron health and promotes formation of new neural connections. This process, called synaptogenesis, may help repair disrupted brain circuits associated with depression. Unlike oral antidepressants that can take weeks to show effects, some people notice improvement in depressive symptoms within 24 hours of their first SPRAVATO® treatment (Johnson & Johnson/FDA, 2025).
The exact mechanism behind SPRAVATO®’s rapid action remains under investigation, but current research suggests it works by temporarily lifting the chronic stress-related suppression of glutamate activity. This temporary boost may allow the brain to restore healthier communication patterns between regions involved in mood regulation.
Catalyst Psychiatry offers SPRAVATO® treatment as part of comprehensive psychiatric care for adults with difficult-to-treat depression. The practice’s board-certified psychiatrists have extensive experience managing this specialized treatment, ensuring appropriate patient selection and careful monitoring throughout the process.
Who Qualifies for SPRAVATO® Treatment
SPRAVATO® received FDA approval for three specific uses. The medication treats major depressive disorder in adults who have not achieved adequate response to at least two different oral antidepressants. It’s also approved for adults with major depressive disorder and acute suicidal ideation or behavior, and as a monotherapy for major depressive disorder with inadequate response to at least two oral antidepressants (Johnson & Johnson/FDA, 2025). If you are acutely suicidal, this medication may not be your best option and further stabilization before using SPRAVATO® may be needed.
The term “inadequate response” generally means you’ve taken an antidepressant at an appropriate dose for an adequate duration without sufficient improvement in your symptoms. Your psychiatrist will evaluate your complete medication history to determine whether SPRAVATO® represents an appropriate next step. For a deeper look at what qualifies as difficult-to-treat depression, see our post on what difficult-to-treat depression means and how it differs from standard treatment-resistant cases.
SPRAVATO® isn’t appropriate for everyone. The medication carries a Risk Evaluation and Mitigation Strategy due to potential for serious adverse outcomes including sedation, dissociation, and abuse potential. As a Schedule III controlled substance, esketamine requires careful oversight and monitoring. Treatment must occur in a certified healthcare setting where you’ll be observed for at least two hours after each dose.
People with certain medical conditions may not be candidates for SPRAVATO®. Your psychiatrist will review your complete health history, including cardiovascular status, history of substance use, and current medications, to determine if SPRAVATO® treatment aligns with your needs and safety profile.
What to Expect During Treatment
SPRAVATO® treatment occurs only in certified healthcare facilities under medical supervision. Before each session, your vital signs will be measured, as the medication can temporarily increase blood pressure and decrease oxygen saturation. You’ll be asked not to eat for at least two hours before treatment and to avoid liquids for 30 minutes prior to your appointment.
You’ll self-administer the nasal spray device under direct observation from your healthcare team. There are two doses available—either 56 mg or 84 mg depending on your treatment plan. You’ll wait five minutes between devices to allow the previous dose to absorb.
During and after administration, you’ll rest in a comfortable setting. Many people experience temporary side effects including dissociation (feeling detached or experiencing distorted perception of time), dizziness, nausea, or sedation. These effects typically resolve within 40 minutes, but may continue longer, which is why you must remain at the facility for two hours after dosing. Your vital signs will be checked about 40 minutes after your first dose and then again before you leave.
You cannot drive yourself home after SPRAVATO® treatment. You’ll need to arrange transportation for every appointment. The monitoring period and transportation requirement mean each treatment session takes about 2–3 hours total. It is recommended that you do not work, drive, or make any important decisions the day after treatment until you have had a full night’s sleep.
Treatment Schedule and Duration
The initial treatment phase includes twice-weekly sessions for four weeks, after which insurance requires a transition to weekly sessions. At Catalyst Psychiatry, we don’t automatically discontinue treatment if you haven’t responded within the first four weeks. Some patients respond later, and as long as your prior authorization supports continued treatment, we’ll work with that timeline. Most patients remain on weekly treatment for months or longer, while others are eventually able to taper to less frequent sessions or stop altogether. Your psychiatrist will adjust your schedule based on your individual response and symptom patterns.
In clinical trials, 22.5% of people taking SPRAVATO® with an oral antidepressant achieved remission at week 4, compared to 7.6% taking an oral antidepressant alone (Johnson & Johnson/FDA, 2025). Results vary by individual, and not everyone experiences significant improvement. Your psychiatrist will regularly assess whether SPRAVATO® provides meaningful benefit for your specific situation.
The duration of SPRAVATO® treatment depends on your response and treatment goals. Some people continue maintenance treatment for months or years, while others may transition back to oral antidepressants after achieving improvement. Treatment decisions should be made collaboratively with your psychiatrist based on symptom monitoring and quality of life measures.
Catalyst Psychiatry provides comprehensive follow-up care throughout your SPRAVATO® treatment, monitoring your response and adjusting your treatment plan as needed. The practice serves patients throughout Corvallis and the mid-Willamette Valley who need advanced treatment options for difficult-to-treat depression.
Side Effects and Safety Considerations
Common side effects during treatment include dissociation, dizziness, nausea, sedation, and headache. Dissociative effects—feeling disconnected from your thoughts, feelings, or surroundings—occur in about 60% of patients but typically resolve quickly. Your treatment team can adjust dosing or provide supportive measures if side effects become problematic.
Some people experience increased blood pressure or heart rate during treatment. Your treatment team monitors these vital signs throughout each session. If you have cardiovascular concerns, your psychiatrist will carefully weigh the risks and benefits of SPRAVATO® treatment.
Because esketamine has abuse potential, it’s classified as a controlled substance. All SPRAVATO® treatment occurs under the Risk Evaluation and Mitigation Strategy program, which requires certification of treatment centers and tracking of patient outcomes. You’ll be monitored for signs of substance misuse throughout treatment.
Long-term effects of extended SPRAVATO® use are still being studied. Current evidence from clinical trials and post-marketing surveillance suggests the medication can be used safely over time with appropriate monitoring, but research on very long-term outcomes continues.
Cost and Insurance Coverage
SPRAVATO® treatment costs vary based on dosing and insurance coverage. Many insurance plans cover the medication when it’s used for FDA-approved indications, though prior authorization is typically required. Your treatment team can work with your insurance company to determine coverage and out-of-pocket costs before you begin treatment.
The cost includes both the medication itself and the required monitoring time. Some insurance plans cover one component but not the other, so clarifying coverage details before you begin treatment helps you understand your financial commitment. Catalyst Psychiatry can help you navigate insurance authorization and work through coverage questions ahead of your first appointment. You can also review the full scope of our medication management services to understand how SPRAVATO® fits within a broader treatment plan.
FAQ Section
Q: How quickly does SPRAVATO® work?
A: Some people notice improvement in depressive symptoms within 24 hours after their first treatment, though this varies by individual. Clinical trials measured outcomes at four weeks, when differences between SPRAVATO® and placebo became statistically significant.
Q: Can I take SPRAVATO® at home?
A: No, all SPRAVATO® administration must occur in a certified healthcare setting with direct observation. The medication’s dissociative and sedative effects, plus the need for blood pressure monitoring, require in-person medical supervision.
Q: Will I feel “high” during SPRAVATO® treatment?
A: SPRAVATO® can cause dissociative effects, which some people describe as feeling detached or dreamlike. These sensations differ from recreational drug effects and typically resolve within an hour or two. Your treatment team monitors you throughout this period.
Q: Can I stop my other antidepressants when starting SPRAVATO®?
A: SPRAVATO® can be used alongside an oral antidepressant or, in some cases, as a standalone treatment. Some patients do taper off antidepressants during SPRAVATO® treatment. If your antidepressants are prescribed by another provider, any changes to those medications need to be coordinated with them directly. Never adjust or stop psychiatric medications without first consulting the provider who prescribed them.
Q: How long will I need SPRAVATO® treatment?
A: Treatment duration varies by individual. Initial treatment lasts at least four weeks, with maintenance treatment continuing as long as it provides benefit. Your psychiatrist will regularly assess whether ongoing treatment remains appropriate for your situation.
Conclusion
SPRAVATO® offers a scientifically distinct treatment approach for adults whose depression hasn’t responded adequately to oral antidepressants. The medication works through glutamate modulation rather than traditional neurotransmitter systems, with some people experiencing rapid symptom improvement. Treatment requires medical supervision, regular monitoring, and commitment to the treatment schedule.
If standard antidepressants haven’t provided adequate improvement for your depression, the board-certified psychiatrists at Catalyst Psychiatry can evaluate whether SPRAVATO® treatment might be appropriate for your situation. Call 541-730-4400 or contact us online to schedule a consultation.
References
- Johnson & Johnson/FDA. (2025). SPRAVATO® (esketamine) CIII nasal spray prescribing information. https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/SPRAVATO-pi.pdf
- Pérez-Esparza, R., Ramos-Zavala, M. G., González-Olvera, J. J., Barajas, A., Tovilla-Zárate, C. A., & López-Narváez, M. L. (2021). Esketamine for treatment-resistant depression. PubMed Central. https://pmc.ncbi.nlm.nih.gov/articles/PMC8542453/
- FDA Prescribing Information. (2019, with subsequent updates). SPRAVATO® (esketamine) nasal spray — Full prescribing information. U.S. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211243lbl.pdf