When depression has not improved after several well-chosen medications, hearing about a treatment that may work differently can bring real hope – and a lot of questions. The conversation about Spravato versus ketamine therapy is not simply about choosing one medication over another. It is about understanding your diagnosis, treatment history, health needs, support system, and the level of clinical structure that will help you feel safe and supported.
Both options are related to ketamine and may be considered for certain adults with difficult-to-treat depression. They are not interchangeable, and neither is a quick fix for the underlying experiences that can contribute to depression. A thoughtful psychiatric evaluation can help clarify whether either approach belongs in your personalized treatment plan.
What Is Spravato?
Spravato is the brand name for esketamine, a form of ketamine delivered as a nasal spray. It is FDA-approved for adults with treatment-resistant depression when used along with an oral antidepressant. It is also approved, in combination with an oral antidepressant, for depressive symptoms in adults with major depressive disorder who have acute suicidal thoughts or behaviors.
Treatment-resistant depression generally means that symptoms have continued despite trials of more than one antidepressant at an adequate dose and duration. That definition is clinically useful, but the decision to consider Spravato should remain personal. A psychiatrist will look closely at prior medication trials, current symptoms, co-occurring anxiety or trauma symptoms, substance use history, medical conditions, and whether your depression has affected safety or daily functioning.
Spravato is administered in a certified health care setting under a federal safety program known as REMS. Patients self-administer the nasal spray while clinical staff supervise, then remain at the site for monitoring for at least two hours. Because temporary sedation, dissociation, and increases in blood pressure can occur, patients should not drive or operate machinery until the next day after a restful sleep.
For many people, that built-in monitoring is reassuring. It creates space to receive treatment with trained staff nearby and to discuss how symptoms are changing over time.
What Does Ketamine Therapy Mean?
“Ketamine therapy” can refer to several different approaches. Ketamine itself is an anesthetic that has been used in medicine for decades. For depression, the most researched non-Spravato approach is typically intravenous, or IV, racemic ketamine. It may be provided off-label, meaning clinicians use an approved medication for a purpose that is not specifically listed in its FDA approval.
Some settings may also offer ketamine by injection, lozenge, tablet, or nasal spray. The research, dosing consistency, clinical supervision, and regulatory framework can vary substantially between these approaches. For that reason, the phrase “ketamine therapy” does not tell you enough on its own. It is reasonable to ask exactly which form is being offered, who will assess you, how you will be monitored, and how progress will be measured.
Like Spravato, ketamine-based treatment may produce altered perception, a sense of disconnection from one’s surroundings, sleepiness, nausea, dizziness, or a temporary rise in blood pressure. Experiences differ from person to person. A responsible program should prepare you for these possibilities, review your medical history carefully, and have a clear plan for monitoring and follow-up.
Spravato Versus Ketamine Therapy: The Main Differences
The most visible difference is the medication and method of delivery. Spravato contains esketamine and is administered as a nasal spray in a certified treatment setting. Ketamine therapy often refers to racemic ketamine, frequently delivered by IV infusion, although other formats exist.
The second difference is FDA approval and care requirements. Spravato has specific FDA-approved uses for certain forms of major depression and is subject to the REMS program. Its administration and observation process are standardized. IV ketamine for depression is commonly an off-label treatment. Off-label prescribing can be medically appropriate, but protocols may differ across practices, so the quality and consistency of clinical oversight deserve careful attention.
Insurance coverage can also shape the decision. Because Spravato is FDA-approved for qualifying depression-related indications, some insurance plans may cover it when clinical criteria and prior authorization requirements are met. Coverage is never guaranteed. IV ketamine and other non-Spravato ketamine treatments are less likely to be covered by insurance, which can create significant out-of-pocket costs. Before beginning care, ask for a clear explanation of expected treatment frequency, medical visits, monitoring charges, and potential insurance responsibilities.
Finally, the practical schedule may differ. Spravato is often administered twice weekly during the early phase of treatment, followed by a gradual reduction in frequency based on response and clinical judgment. Ketamine infusion programs may begin with a series of treatments over several weeks, with later maintenance sessions considered for some patients. The right schedule depends on the treatment, your response, and your broader care plan.
Which Option May Be a Better Fit?
There is no universal winner. Spravato may be a meaningful option for an adult with treatment-resistant depression who values an FDA-approved treatment pathway, structured on-site monitoring, and the possibility of insurance coverage. It can also fit well within a coordinated psychiatric plan that includes medication management and psychotherapy.
Ketamine therapy may be considered when a patient and clinician determine that an off-label approach is appropriate, available, and clinically sound. In those situations, the experience and credentials of the treating team matter greatly. Look for clear medical screening, monitoring during treatment, emergency procedures, communication with your existing mental health providers, and a plan for what happens between sessions.
Neither treatment is appropriate for everyone. A clinician may need to explore concerns such as uncontrolled high blood pressure, certain vascular conditions, a history of psychosis, mania or bipolar-spectrum symptoms, substance use concerns, pregnancy, or medications that could affect safety. These are not automatic exclusions in every circumstance, but they require careful discussion rather than a one-size-fits-all decision.
Treatment Works Best as Part of a Larger Plan
Rapid improvement in depressive symptoms can be meaningful, especially for someone who has felt stuck for months or years. Still, medication treatment alone may not address the thought patterns, grief, relationship stress, trauma responses, executive functioning difficulties, or daily routines that influence recovery.
Therapy can help a person make sense of changes in mood and build practical skills for difficult moments. Medication management supports thoughtful adjustments when benefits, side effects, or new symptoms emerge. For some people, diagnostic clarification is also essential. What appears to be treatment-resistant depression may coexist with anxiety, OCD, ADHD, trauma, sleep disruption, bipolar-spectrum symptoms, or medical factors that deserve attention.
At LumiClinics, this kind of coordinated care begins with listening. A psychiatric evaluation can examine the full picture rather than treating a diagnosis in isolation. Together, you and your care team can consider evidence-based options while also strengthening coping tools, routines, relationships, and supports that help sustain progress.
Questions Worth Asking Before You Decide
A consultation should leave you with more clarity, not more pressure. Ask whether you meet the criteria for treatment-resistant depression, what alternative treatments have been considered, and why a clinician believes Spravato or ketamine may help in your specific situation.
You can also ask how treatment response will be tracked, what side effects require a call to the office, whether you will need someone to take you home, and how the treatment will coordinate with therapy and current medications. If cost is a concern, ask for an honest overview before starting. Good care includes helping you understand the practical commitments as well as the potential benefits.
Feeling discouraged after unsuccessful treatments is understandable. It does not mean you have run out of options, and it does not mean you need to make a rushed choice. With an individualized evaluation and a care team that helps you feel seen and heard, the next step can be a more informed one – toward relief, resilience, and a healthier you.
