Q: What is the difference between ketamine and esketamine for depression?
A: Esketamine (Spravato) is a nasal spray with FDA-approved indications for adults with treatment-resistant depression and for depressive symptoms in adults with major depression and acute suicidal ideation or behavior. Ketamine is an injectable anesthetic; using IV, IM, nasal or oral compounded ketamine for a psychiatric condition is off-label. They are related drugs, not interchangeable labels for the same treatment.¹ ²
The practical comparison
| Question | Esketamine | Ketamine used for depression |
|---|---|---|
| FDA status | Approved for specific adult depression indications | Not FDA-approved for a psychiatric indication |
| Where given | Certified health-care setting under the Spravato REMS | Medical practice; standards vary by route and setting |
| Observation | At least two hours after each treatment | Ask the clinic; do not assume the same protocol |
| Insurance | May be covered when plan criteria are met | Coverage varies; often treated as off-label |
| Take-home product | No | Some practices prescribe compounded oral or nasal products; FDA has warned about risks without onsite monitoring |
The esketamine label carries boxed warnings for sedation, dissociation, respiratory depression, abuse and misuse, and suicidal thoughts and behaviors in pediatric and young adult patients taking antidepressants. The restricted program exists because the altered state is not the only issue; breathing, blood pressure, judgment and misuse matter too.¹
Compounded ketamine is not FDA-approved. The FDA has not reviewed a compounded product for safety, effectiveness or quality and has warned specifically about at-home psychiatric use without onsite monitoring.² That does not make every off-label ketamine clinic improper. It makes the clinic's medical standards part of the treatment—not background paperwork.
Do this: ask the clinic, in writing: “Which drug, route and indication are you treating; is it FDA-approved or off-label; who monitors me; for how long; what emergencies can you manage onsite; and what is the total induction and maintenance cost?” If the answer collapses ketamine and esketamine into one word, keep looking.
Sources:
- FDA-approved Spravato prescribing information, revised 2025 — FDA label (PDF).
- FDA warning on compounded ketamine products for psychiatric disorders — FDA compounding risk alerts.