The short version
- Treatment-resistant depression means inadequate response to two or more oral antidepressants in the current episode.
- SPRAVATO® (esketamine) is the only FDA-approved ketamine-based medicine for depression, with a labeled boxed warning for sedation, dissociation, respiratory depression, abuse and misuse, and suicidal thoughts and behaviors.
- IV racemic ketamine has the largest evidence base among the off-label routes, based on randomized trials and systematic reviews in treatment-resistant depression.
- Effects, when they occur, often appear within hours to days rather than the weeks typical of oral antidepressants.
- SPRAVATO® is dosed only in a REMS-certified setting, and reputable IV and IM programs dose in the clinic with monitoring and a ride home arranged after each session.
What treatment-resistant depression means
Clinicians generally describe depression as treatment-resistant when two or more adequate trials of oral antidepressants have not produced sufficient improvement. It is common: a large share of people with major depressive disorder eventually reach this point, and it is the point where ketamine-based options are most often considered.
The FDA-approved option: esketamine nasal spray
SPRAVATO® (esketamine) is approved in the United States for adults with treatment-resistant depression, used together with an oral antidepressant or as monotherapy under the 2025 label update. It is self-administered under direct observation in a certified healthcare setting, and patients are monitored for at least two hours after each dose because of the risk of sedation, dissociation, and elevated blood pressure. It is available only through the SPRAVATO® REMS program.
Off-label routes: IV, IM, and oral ketamine
Intravenous racemic ketamine has been studied the most, with randomized trials and systematic reviews reporting rapid antidepressant effects in many patients with treatment-resistant depression. Intramuscular injection and oral ketamine (tablets or lozenges) are also offered by clinics, often for maintenance between IV courses or where IV access is impractical. None of these routes is FDA-approved for depression, so insurers generally do not cover them, and protocols vary considerably between clinics.
What a course looks like
An induction phase — commonly six IV infusions over two to three weeks, or twice-weekly esketamine sessions for the first month — is followed by a maintenance phase whose frequency is set by response. Your prescriber should reassess benefit at each visit and stop treatment that is not helping.
Safety
Ketamine-based treatment can raise blood pressure and heart rate and can cause dissociation, a temporary detached feeling, during and shortly after dosing. Long-term heavy misuse carries bladder and dependency risks, which is why supervised clinical use with screening is important. If you are in crisis, call or text 988 for the Suicide & Crisis Lifeline.
What a course of treatment looks like
- 1
Consultation and eligibility
A qualified healthcare professional reviews your diagnosis, treatment history, medicines, and safety risks before determining which treatment approach, if any, is appropriate.
- 2
Pricing, and coverage if it applies
IV, IM, and oral ketamine are off-label and usually self-pay, so ask for a written price for the full course. Only SPRAVATO® (esketamine) is commonly insurance-covered, typically after prior authorization.
- 3
A monitored treatment visit
Depending on the route, you receive an IV infusion, an IM injection, or a supervised oral dose — or, for SPRAVATO®, self-administer the nasal spray — while staff monitor your vital signs.
- 4
Recovery and a ride home
You rest until the effects wear off (at least two hours after SPRAVATO®). Arrange a ride home and do not drive until the next day after restful sleep.
- 5
Individualized follow-up
The prescriber assesses benefit, tolerability, and ongoing need, including whether maintenance sessions make sense for you.
Eligibility
Could ketamine treatment be an option to discuss?
A clinic confirms all of this at your consultation. Use it to see whether a consultation is worth booking.
- A diagnosis of major depressive disorder confirmed by a qualified clinician
- Inadequate response to at least two oral antidepressants in the current depressive episode
- Adult, age 18 or older, for the FDA-approved esketamine uses
- Blood pressure, heart, liver, and bladder conditions reviewed before treatment
- No current psychosis or unstable substance use disorder
- Ability to attend repeated sessions and arrange transportation home
Questions people ask
Is ketamine approved for treatment-resistant depression?
Esketamine nasal spray (SPRAVATO®) is FDA-approved for adults with treatment-resistant depression, with an oral antidepressant or as monotherapy. Racemic ketamine given by IV, IM, or mouth is not FDA-approved for any psychiatric condition; those uses are off-label.
How fast does ketamine-based treatment work?
In studies, some patients showed improvement within hours to days of the first doses. Response varies from person to person, and a course of treatment is used to judge whether it helps you.
Will my insurance cover it?
Coverage for SPRAVATO® is common for its approved uses but always depends on your plan and prior authorization. IV, IM, and oral ketamine for depression are usually paid out of pocket; clinics can confirm costs before you commit.
What are the main risks?
The FDA label for esketamine carries a boxed warning for sedation, dissociation, respiratory depression, abuse and misuse, and suicidal thoughts and behaviors. Off-label IV, IM, and oral ketamine share related risks, including raised blood pressure. This is why dosing happens under clinical monitoring, never alone.
Other conditions we cover
Depression (major depressive disorder)
Ketamine-based treatments act on glutamate, a different pathway from traditional antidepressants, and can work within hours to days for some patients. Only esketamine is FDA-approved, and only for specific depression populations; other routes are off-label.
Anxiety disorders
Early evidence from randomized trials and meta-analyses suggests ketamine can reduce anxiety symptoms short-term, including in people whose anxiety has resisted other treatments. All such use is off-label — no ketamine-based medicine is FDA-approved for anxiety.
PTSD
Ketamine is being studied and used off-label for post-traumatic stress disorder, with early trials suggesting rapid but temporary symptom reduction. Esketamine is not approved for PTSD, and treatment should be coordinated with trauma-focused therapy.
Chronic pain
Ketamine is an FDA-approved anesthetic, but its use for chronic pain conditions — neuropathic pain, complex regional pain syndrome, fibromyalgia — is off-label. Evidence is mixed, with some support for neuropathic and CRPS pain.
OCD
Early research on ketamine for obsessive-compulsive disorder shows mixed and short-lived results in small trials. It remains off-label and experimental — standard care is still exposure-based therapy with SSRIs.
Ketamine treatment centers near you
Browse clinics by town or county, or read more about treatment in United States.
This guide is general information, not medical advice. Only a prescriber who knows your history can say whether ketamine treatment, including SPRAVATO® (esketamine), is right for you. If you are in crisis, call or text 988.