Over the last several years, several new therapies have been clinically approved for people living with depression that hasn’t responded to standard treatments. If you’re exploring, or are already familiar with these approaches, you may have heard both ketamine and esketamine (Spravato®) discussed, sometimes interchangeably.
While related, ketamine and Spravato® are not the same treatment. Understanding the differences can help you make a more informed decision about your care, and understand why many clinics, like Being Health, exclusively offer Spravato®.
What do ketamine and Spravato® have in common?
Both ketamine and esketamine work differently from traditional antidepressants.
Rather than targeting serotonin or norepinephrine, they act on the glutamate system, which plays a key role in mood regulation, neuroplasticity, and how the brain adapts to stress. This unique mechanism is why ketamine-based treatments may help some people who haven’t found relief with standard medications.
At the core, both treatments support neuroplasticity, or the brain's remarkable ability to reorganize its structure, functions, and neural connections throughout life in response to learning, experience, or injury. Depression can make the brain feel rigid or “stuck,” reinforcing patterns of low mood and negative thinking. By helping the brain become more flexible and adaptable, ketamine-based treatments may create an opportunity for meaningful change, especially when paired with ongoing therapy and comprehensive psychiatric care.
Key differences between ketamine and Spravato®
1. FDA approval & clinical oversight
Spravato® (esketamine) is FDA-approved for:
- Adults with treatment-resistant depression (TRD), or clinically diagnosed depression that has not improved with standard treatments
- Adults with major depressive disorder (MDD) experiencing an active mental health crisis with acute suicidal ideation or behavior
It is delivered under a strict, federally-regulated program, with required monitoring and safety protocols.
The main difference between esketamine and ketamine is reflected in their chemical composition: esketamine is a racemic mixture containing two molecules, S-ketamine (esketamine) and R-ketamine. Unlike esketamine, ketamine is not FDA-approved for the treatment of depression. Its use in mental health settings is considered off-label, meaning protocols, dosing, and monitoring can vary significantly from clinic to clinic.
Why this matters: FDA approval means Spravato® has undergone large-scale clinical trials, standardized dosing, and ongoing safety review, providing patients with a higher level of consistency and regulatory oversight.
2. Formulation & delivery
Spravato® is self-administered as a nasal spray under medical supervision, while IV/IM (intravenous/intramuscular) ketamine is delivered intravenously or via injection, typically requiring higher peak doses and more intensive administration and monitoring.
Many patients find intranasal delivery to be less invasive, more approachable, and more comfortable, while still clinically effective.
3. Safety, monitoring & standardization
Spravato® treatment includes:
- Required pre-treatment evaluation
- On-site monitoring for at least 2 hours after each session
- Clear clinical guidelines for frequency, dosing, and continuation
- Integration with an ongoing psychiatric care plan
While some IV ketamine clinics provide excellent care, the lack of national standards can result in:
- Variable dosing practices
- Inconsistent monitoring
- Limited integration with long-term psychiatric treatment
4. Long-term care model
Spravato® is designed to be part of a comprehensive treatment plan, often alongside:
- Ongoing psychiatric care
- Medication management
- Psychotherapy
- Whole-person support
Rather than acting as a standalone or episodic intervention, Spravato® fits into a structured, longitudinal care approach, which many patients find more sustainable and effective in treating their depression over time.
5. Cost and coverage
Because Spravato® (esketamine) is FDA-approved, it is covered by many major insurance plans when clinical criteria are met. For eligible patients, this can significantly reduce out-of-pocket costs over time.
IV/IM ketamine is rarely covered by insurance because of its “off-label” use. Most patients pay fully out of pocket, and costs can add up quickly, especially with ongoing or maintenance treatment.
Is Spravato® right for everyone?
Not necessarily. Eligibility is typically based on insurance and medical guidelines, but Spravato® is typically considered for adults 18 and over who:
- Have moderate to severe major depressive disorder confirmed by a standardized scale such as a PHQ-9, or have major depressive disorder (MDD) with current suicidal thoughts or behaviors
- Have tried at least two antidepressants (at adequate dose and duration) without meaningful improvement
- Are appropriate candidates following a comprehensive psychiatric evaluation
- Do not have medical, psychiatric, or substance use conditions that are contraindicated for the use of Spravato®*
A thorough assessment with an experienced clinician is essential to determine whether Spravato® is the right fit. At Being Health, we complete a comprehensive initial consultation with every patient to determine whether patients are a good fit for treatment.
Deciding what's right for you
Ketamine and esketamine share the same scientific foundation, but Spravato® treatment offers a more regulated, research-backed approach to care. With FDA approval, standardized protocols, and broader insurance coverage, it offers a treatment path that many patients find safer, more comfortable, more accessible, and easier to sustain over time.
At Being Health, Spravato® is just one part of a comprehensive, whole-person care model. Our team specializes in interventional psychiatry and takes a thoughtful, personalized approach: every patient’s treatment decision is based on your clinical history, goals, and ongoing needs. If Spravato® is a fit for you, it’s delivered within a broader plan designed to support meaningful, lasting improvement.
Next Steps
For more personalized answers and to learn if Spravato® is right for you, schedule a consultation with Being Health today or give us a call at 888-668-7600.
*Please note: Individuals with a history of drug abuse or dependence may be at greater risk for abuse and misuse of Spravato®. Careful consideration is advised prior to treatment of individuals with a history of substance use disorder, including alcohol. Monitoring for signs of abuse or dependence is recommended.
