Q: What is the difference between ketamine and esketamine for depression?
A: Spravato (esketamine) is an FDA-approved nasal-spray product with specific adult depression indications. FDA-approved ketamine injection is an anesthetic; using an approved injectable product for a psychiatric condition is an off-label use. Compounded oral, nasal or other ketamine products are different: the compounded product itself is not FDA-approved and has no FDA-approved indication or route. These are related drugs and ingredients, not interchangeable labels for the same product or treatment.¹ ² ³ ⁴
The practical comparison
| Question | Spravato (esketamine nasal spray) | FDA-approved ketamine injection | Compounded ketamine product |
|---|---|---|---|
| What FDA approved | Specific adult depression indications | Injection for anesthesia—not a psychiatric indication | No FDA-approved product, indication or route |
| Psychiatric-use category | FDA-approved only for the label's named uses | Off-label use of an approved injectable drug | Use of a product that is not FDA-approved |
| Route and setting | Nasal spray in a certified health-care setting under the Spravato REMS | IV or IM injection under the approved label; psychiatric protocols use the injection off-label | The prescription may name an oral, nasal or other compounded form; ask exactly what is being made and by whom |
| Observation | At least two hours after each treatment | Ask the practice; do not assume the Spravato protocol applies | Ask the practice; FDA has warned about at-home psychiatric use without onsite monitoring |
| Insurance | May be covered when plan criteria are met | Coverage varies for off-label psychiatric use | Ask the plan and pharmacy; do not assume coverage means FDA approval |
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. FDA does not review a compounded product for safety, effectiveness or quality before marketing and has warned specifically about at-home psychiatric use without onsite monitoring.³ ⁴ This is not the same regulatory category as a clinician using an FDA-approved ketamine injection off-label. In either setting, the exact product, route and medical standards belong in the decision—not in the fine print.
Do this: ask the clinic, in writing: “Which exact product, route and indication are you treating? Is this an FDA-approved use, off-label psychiatric use of FDA-approved ketamine injection, or a compounded product that is not FDA-approved? 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—or an approved injection and a compounded product—into one word, keep looking.
Comparing a Bay Area offer? Print the San Francisco ketamine-clinic checklist →
Sources:
- FDA-approved Spravato prescribing information, revised 2025 — FDA label (PDF).
- FDA-approved Ketalar prescribing information, revised October 2025 — FDA label (PDF).
- FDA warning on compounded ketamine products for psychiatric disorders — FDA compounding risk alerts.
- FDA, Compounding and the FDA: Questions and Answers.