Introduction
Ketamine, once known primarily as an anesthetic and sometimes misused recreationally, has undergone a renaissance in mental health care. Its transformation into a controlled, medically supervised treatment—particularly in the form of Spravato® (esketamine) nasal spray—marks a breakthrough for patients with treatment-resistant depression (TRD) and major depressive disorder (MDD) with suicidal ideation or behavior.
Spravato is FDA-approved for both conditions and is administered intranasally under clinical supervision, offering a fast-acting alternative for those who haven’t found relief with oral antidepressants. Unlike traditional medications that may take weeks to begin working, Spravato acts on different brain pathways and often produces symptom relief within hours or days.
As interest in this novel treatment grows, many patients want to know what to expect—not just during the session but after. How long do the effects of ketamine nasal spray last? That question is essential for both understanding its impact and making informed decisions about long-term care.
Understanding Ketamine Nasal Spray and How It Works
Esketamine is a derivative of ketamine, with a slightly different chemical structure that allows it to be administered via intranasal spray. Unlike SSRIs or SNRIs, which may take weeks to show effects, esketamine works through a different pathway in the brain.
How It Works:
- Esketamine acts as an NMDA receptor antagonist, influencing glutamate, the most abundant neurotransmitter in the brain.
- This mechanism helps restore synaptic connections, which are often impaired in people with depression.
- Most patients begin to feel relief within hours, making it one of the fastest-acting antidepressant options available today.
- The FDA approved Spravato in 2019 for adults with TRD and, later, for MDD with acute suicidal ideation or behavior.
For a deeper dive into the science behind Spravato®, how it’s administered, and what sets it apart from traditional antidepressants, visit our Spravato® page.
How Spravato® Compares to Other Ketamine Treatments
While Spravato® is the only FDA-approved ketamine nasal spray for depression, other forms of ketamine treatment—like intravenous (IV) infusions, intramuscular injections, and oral lozenges—are also offered in various clinics. These off-label treatments may provide similar biochemical effects, but they are not standardized or regulated in the same way.
Spravato’s REMS (Risk Evaluation and Mitigation Strategy) certification ensures a higher level of safety, requiring patients to be monitored on-site for at least two hours post-dose. Its approval for treatment-resistant depression (TRD) and major depressive disorder (MDD) with suicidal ideation adds additional credibility and makes it more likely to be covered by insurance.
While IV ketamine may be effective in some cases, it often involves greater out-of-pocket costs and less oversight. For patients seeking an evidence-based, insurance-supported option, Spravato is often considered the gold standard.
Who Is (and Isn’t) a Good Fit for Spravato®?
Spravato is designed specifically for individuals diagnosed with treatment-resistant depression or major depressive disorder with suicidal ideation. However, it’s not right for everyone.
Candidates who may be a good fit:
- Adults who have tried two or more antidepressants without success.
- Individuals needing a fast-acting solution during a crisis period.
- Patients able to commit to in-clinic monitoring and follow-up care.
Spravato may not be appropriate for:
- People with uncontrolled high blood pressure or cardiovascular issues.
- Individuals with a history of substance abuse or dissociative disorders, depending on case severity.
- Patients unable to commit to in-clinic observation periods or lacking reliable transportation.
The best way to know if Spravato is a fit is through a comprehensive consultation, which includes medical history, current symptoms, and mental health goals. At Psyche Denver, consultations are always free and supportive.
Duration of Effects After a Single Dose
The duration of symptom relief after a single esketamine treatment can vary depending on the individual.
What to Expect:
- Initial relief can be felt within hours and typically lasts several days.
- Clinical studies have shown that peak antidepressant effects often occur between 24 and 48 hours post-treatment.
- For many patients, the benefits taper off after a few days—making ongoing treatment essential.
Factors That Influence Duration:
- Severity of depression
- Individual metabolism
- Other medications
- Coexisting mental or physical conditions
Recommended Treatment Schedule and Maintenance
Each Spravato treatment plan begins with a structured induction phase followed by a personalized maintenance plan. The induction phase typically includes two treatments per week for four weeks, allowing clinicians to assess both response and tolerability.
After this, patients who benefit from Spravato typically move into weekly or biweekly maintenance dosing. This schedule can vary based on individual symptoms, lifestyle, and long-term treatment goals. Some patients eventually taper to less frequent sessions, while others remain on a steady schedule to maintain progress.
It’s important to view Spravato not as a one-time fix, but as part of a comprehensive mental health strategy that may include therapy, lifestyle changes, and other medications.
A study published in JAMA Psychiatry found that consistent esketamine use led to sustained symptom reduction over months.
What Patients Should Expect Between Treatments
The time between Spravato treatments can vary significantly from patient to patient. Some individuals report feeling stable and energized for several days or even a week after each dose, while others notice their symptoms begin to return sooner.
In either case, how patients manage their time between sessions is often just as important as the treatment itself. Engaging in therapy, exercise, mindfulness practices, and healthy sleep habits can extend the benefits of each dose.
Your provider may also make recommendations about adjusting oral medications, exploring TMS therapy, or integrating support groups as part of your broader plan.
Spravato Treatment Experience at Psyche Denver
Spravato is administered under medical supervision in a calm, supportive environment. At Psyche Denver, each session includes careful observation before and after dosing to ensure your safety and comfort. Patients often report the treatment space feels welcoming and low-pressure—an important factor when navigating mental health care.
Curious about the full process? Learn what to expect during a Spravato® session: https://psychedenver.com/spravato/
Frequently Asked Questions
How soon will I feel better after my first dose?
Many patients begin to notice improvements in mood within 24 to 48 hours after their first treatment. While individual response varies, this rapid relief can be life-changing for those in crisis or experiencing severe depressive episodes.
What does a treatment session feel like?
Patients often describe the experience as mildly dissociative or dreamlike. You may feel relaxed, floaty, or mentally distant during the session. These effects are temporary and closely monitored by clinical staff.
Can I go back to work afterward?
No. Because of the potential for sedation, dizziness, or cognitive changes, you will need to rest and arrange a ride home. Most patients take the remainder of the day to relax and recover before resuming regular activities the following day.
Is Spravato safe for long-term use?
Clinical research and real-world patient outcomes suggest that Spravato is safe when administered as prescribed over months or even years. Ongoing monitoring by your care team ensures your treatment remains appropriate and effective.
Over time, many patients stabilize on a schedule that includes treatment once every one to two weeks. Some may eventually space treatments out to once per month under clinical guidance. The ideal frequency is determined by your symptom patterns, how well you’re tolerating the treatment, and what your mental health goals are.
As of 2025, the FDA has approved Spravato for use with or without an oral antidepressant, giving patients and providers more flexibility in how it’s integrated into a broader treatment plan.
Further Reading
To learn more about how Spravato® works, who it may help, how it compares to traditional antidepressants, and what to expect with insurance, check out our companion blog:
Unpacking Spravato: What You Need to Know About This Novel Depression Treatment
Ready to Explore Spravato®?
If you or a loved one is struggling with treatment-resistant depression and want to learn if Spravato® may be a good fit, Psyche Denver offers free pretreatment consultations. Our team will walk you through your options and help determine whether esketamine nasal spray is right for you.
Schedule your free consultation today: https://psychedenver.com/contact-us/
Or download our Spravato® Info Guide (PDF): https://psychedenver.com/spravato/
REFERENCES
- Johnson & Johnson. (Jan 21, 2025). SPRAVATO® approved as first and only monotherapy for major depressive disorder; patients may experience symptom improvements as early as 24 hours. https://www.jnj.com/media-center/press-releases/spravato-esketamine-approved-in-the-u-s-as-the-first-and-only-monotherapy-for-adults-with-treatment-resistant-depression jamanetwork.com
- JAMA Psychiatry. (28 Sep 2019). Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With TRD: A Randomized Clinical Trial. https://pubmed.ncbi.nlm.nih.gov/31166571/
- UTHealth Houston Psychiatry. (Jan 22, 2025). FDA expands approval of intranasal esketamine therapy (Spravato). https://med.uth.edu/psychiatry/2025/01/22/fda-expands-approval-of-intranasal-esketamine-therapy-spravato/
- JAMA Network. (2017). Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant in Treatment-Resistant Depression. https://pubmed.ncbi.nlm.nih.gov/29282469/
- Reuters. (Jan 21, 2025). FDA approves standalone use of J&J’s ketamine derived depression treatment. https://www.reuters.com/business/healthcare-pharmaceuticals/us-fda-approves-jjs-ketamine-based-therapy-treat-depression-2025-01-21/
- National Institute of Mental Health. (2023). Cracking the Ketamine Code: How the “club drug” is leading to rapid-acting treatments for depression.
https://www.nimh.nih.gov/news/science-updates/2023/cracking-the-ketamine-code
