Spravato vs. Ketamine Therapy – What Is the Difference and Which Is Right for You?

Why Rapid-Acting Treatments Matter for Depression and PTSD

For patients living with treatment-resistant depression (TRD) or post-traumatic stress disorder (PTSD), traditional antidepressants can take weeks or months to show results—if they work at all. That is why rapid-acting treatments like Spravato in Weston, FL and IV ketamine therapy have become some of the most promising breakthroughs in modern psychiatry. Both target the brain’s glutamate system rather than the serotonin pathways conventional antidepressants use, producing noticeable mood improvements in hours or days instead of weeks.

At Refresh TMS in Weston, FL, board-certified psychiatrist Dr. Paula-Ann Francis, MD—with over 13 years of clinical experience—offers both Spravato esketamine therapy and IV ketamine infusion therapy to help patients find relief when other treatments have failed. In this article, we break down the key differences between these two options so you can make an informed decision about your care.

What Is Spravato (Esketamine)?

Spravato is the brand name for esketamine, an FDA-approved nasal spray developed specifically for treatment-resistant depression. Approved by the U.S. Food and Drug Administration in 2019, Spravato represented a landmark moment in psychiatry—it was the first truly novel mechanism for depression treatment in decades.

How Esketamine Works

Esketamine is the S-enantiomer of ketamine, meaning it is a more targeted molecular form of the same compound. It works by blocking NMDA receptors in the brain, triggering a cascade of neuroplasticity—essentially helping the brain form new neural connections that support healthier mood regulation. Unlike traditional SSRIs that modulate serotonin over weeks, esketamine acts on the glutamate system and can produce measurable improvements after just one or two sessions.

How It Is Administered

The nasal spray is self-administered under medical supervision. At Refresh TMS, each session follows a structured protocol:

• You arrive at our Weston, FL clinic and self-administer the spray under the guidance of our clinical team.
• You remain in our monitored observation area for a minimum of two hours after administration.
• Sessions are typically scheduled twice weekly for the first month, then weekly or biweekly as maintenance.
• Because of its Risk Evaluation and Mitigation Strategy (REMS), esketamine can only be administered in a certified healthcare setting—never at home.

What Is IV Ketamine Therapy?

IV ketamine infusion therapy uses the same base compound but delivers the full racemic molecule (both S- and R-enantiomers) directly into the bloodstream through an intravenous drip. While ketamine has been FDA-approved as an anesthetic since 1970, its use for depression and PTSD is considered “off-label”—meaning physicians prescribe it based on clinical evidence even though the FDA has not specifically approved it for those conditions.

How IV Ketamine Works

IV ketamine targets the same NMDA receptors but includes both enantiomers of the molecule. Some researchers believe the R-enantiomer may contribute additional therapeutic benefits, including anti-inflammatory effects. The intravenous route allows for precise dose control, and many patients report mood improvement within hours of their first session.

How IV Ketamine Is Administered

During an IV ketamine session at Refresh TMS:

• A low-dose solution is delivered intravenously over approximately 40 to 60 minutes.
• Dr. Francis and her team monitor your vital signs throughout the infusion.
• A typical initial protocol involves six infusions over two to three weeks, followed by periodic boosters.
• You will need someone to drive you home, as mild dissociative effects may persist briefly.

Spravato vs. IV Ketamine: Key Differences at a Glance

This table summarizes the key differences between Spravato and IV ketamine:

Category	Spravato (Esketamine)	IV Ketamine
Administration	Self-administered nasal spray under medical supervision	Intravenous infusion administered by clinical staff
FDA Approval	FDA-approved for treatment-resistant depression (2019) and major depressive disorder with suicidal ideation (2020)	FDA-approved as an anesthetic; off-label for depression and PTSD
Clinical Setting	REMS-certified clinic only (required by FDA)	Medical office or infusion clinic
Speed of Results	Many patients notice improvement within 24–72 hours	Some patients report improvement within hours of first infusion
Insurance Coverage	Covered by most major insurance plans (including Medicare)	Typically not covered by insurance; paid out of pocket
Duration of Effects	Maintenance sessions needed; effects sustained with ongoing treatment	Effects may last days to weeks; periodic boosters recommended
Monitoring Period	Minimum 2-hour observation after each session	Brief recovery period (30–60 minutes post-infusion)

Which Conditions Benefit Most from Each Treatment?

Both Spravato and IV ketamine are effective for mood disorders that have not responded to conventional treatment, but each has areas of particular strength.

Esketamine Nasal Spray May Be Especially Beneficial For

• Treatment-resistant depression (TRD): Patients who have not responded to at least two adequate trials of antidepressants are the primary candidates.
• Major depressive disorder with suicidal ideation: Esketamine received a specific FDA indication for this population in 2020, making it one of the only treatments directly approved for acute suicidality.
• Patients who prefer a non-IV option: The nasal spray delivery may be less intimidating for individuals uncomfortable with needles or infusions.

IV Ketamine May Be Especially Beneficial For

• PTSD and complex trauma: A growing body of evidence supports IV ketamine for PTSD, and many clinicians consider it a first-line rapid-acting option for trauma-related conditions.
• Severe or acute depressive episodes: The rapid onset of IV ketamine—sometimes within hours—makes it valuable during psychiatric crises.
• Chronic pain with co-occurring depression: Ketamine’s analgesic properties may provide dual benefits for patients dealing with both pain and mood disorders.
• Patients who have not responded to esketamine: Because IV ketamine delivers both enantiomers, some patients who do not respond to the nasal spray alone may benefit from the full racemic molecule.

Insurance and Cost Considerations

One of the most significant practical differences between Spravato and IV ketamine is insurance coverage.

Esketamine nasal spray is covered by most major commercial insurance plans, Medicare, and many Medicaid programs. Because it is FDA-approved with a specific indication for TRD, insurance companies generally cover it after prior authorization. At Refresh TMS, our team handles insurance verification and prior authorization to minimize out-of-pocket costs for patients in Weston, FL.

IV ketamine, on the other hand, is typically an out-of-pocket expense. Because its psychiatric use is off-label, most insurers do not cover infusion sessions. The cost per infusion generally ranges from $400 to $800, and a full initial course of six infusions can represent a significant investment. However, for patients who specifically need IV ketamine—particularly for PTSD or when esketamine has not been effective—the clinical benefits can outweigh the cost difference.

How Dr. Francis Determines the Right Treatment for You

At Refresh TMS, the process always begins with a comprehensive psychiatric evaluation. Dr. Paula-Ann Francis takes a thorough approach to understanding each patient’s history, including:

• Previous medication trials and their outcomes
• Current diagnosis and symptom severity
• Medical history, including any contraindications to ketamine-based treatments
• Insurance coverage and financial considerations
• Patient preferences regarding administration method

For many patients with treatment-resistant depression, esketamine nasal spray is an excellent starting point because of its FDA approval and insurance coverage. For those with PTSD, complex trauma, or cases where esketamine alone has not provided sufficient relief, IV ketamine may be the more appropriate option. In some cases, Dr. Francis may also recommend TMS as a non-infusion alternative that can complement ketamine-based treatments.

The goal is never a one-size-fits-all approach. Dr. Francis’s extensive experience as a board-certified psychiatrist allows her to craft individualized treatment plans that address each patient’s unique needs.

Frequently Asked Questions

Is Spravato the same as ketamine?

Not exactly. Spravato contains esketamine, which is one of two mirror-image molecules (enantiomers) that make up ketamine. Think of it as a more targeted version. While both act on the same brain receptors, the nasal spray is FDA-approved, whereas IV ketamine uses the full racemic compound delivered intravenously.

Is Spravato covered by insurance?

Yes, in most cases. Because it is FDA-approved for treatment-resistant depression and major depressive disorder with suicidal ideation, most commercial insurance plans, Medicare, and some Medicaid programs cover it. Prior authorization is typically required, and our team at Refresh TMS assists with this process.

How quickly does ketamine work?

Many patients experience noticeable mood improvement within hours to days of their first IV ketamine infusion. The nasal spray may take one to two sessions before patients notice a difference. Both work significantly faster than traditional antidepressants, which typically require four to six weeks.

Take the Next Step Toward Relief

If you have been struggling with depression or PTSD that has not responded to traditional treatments, you do not have to keep waiting. Both options offer evidence-based, rapid-acting pathways to recovery—and the right choice depends on your unique clinical profile.

Not sure which treatment is right for you? Call Refresh TMS at (754) 216-0840 for a free consultation. Dr. Paula-Ann Francis and our team in Weston, FL are ready to help you find the treatment that fits your needs.

References

1. Daly EJ, et al. "Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression: A Randomized Clinical Trial." JAMA Psychiatry. 2019;76(9):893–903. PMID: 31166571.
2. Popova V, et al. "Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study." American Journal of Psychiatry. 2019;176(6):428–438. American Journal of Psychiatry. PMID: 31109201.
3. Feder A, et al. "Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder: A Randomized Clinical Trial." JAMA Psychiatry. 2014;71(6):681–688. PMID: 24740528.
4. Murrough JW, et al. "Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial." American Journal of Psychiatry. 2013;170(10):1134–1142. PMID: 23982301.
5. Bahji A, Vazquez GH, Zarate CA Jr. "Comparative Efficacy of Racemic Ketamine and Esketamine for Depression: A Systematic Review and Meta-Analysis." Journal of Affective Disorders. 2021;278:542–555. PMID: 33022440.