Ketamine vs esketamine: the difference in one page

The chemistry

Ketamine is a racemic mixture of two mirror-image molecules, S-ketamine (esketamine) and R-ketamine. Esketamine binds the NMDA receptor more strongly, so a lower dose produces a similar effect. Spravato is esketamine formulated as a nasal spray and approved for depression; generic ketamine is the racemic mixture approved as an anesthetic and used off label. See the coverage hub, the Spravato hub, and the coverage checker.

What differs in practice

| | Esketamine (Spravato) | Racemic ketamine | |---|---|---| | Route | Nasal spray | IV, IM, oral, nasal (compounded) | | Dose | 56 or 84 mg fixed | Weight based, adjustable | | Where | REMS certified clinic, 2-hour observation | Any clinic, clinic policy | | Evidence | Large placebo-controlled trials | Many smaller controlled trials, mostly IV | | Head-to-head | Small trials find comparable response; IV ketamine may act slightly faster | | | Insurance | Covered with prior authorization | Not covered | | Cash price | 50 to ,500 per session | 50 to 50 per infusion | | Oral antidepressant | Required by most plans | Optional |

Which works better?

The few direct comparisons show similar response rates. IV ketamine may produce a faster initial response; esketamine has the larger evidence base and regulatory backing. For most people the deciding factors are coverage, cost and logistics, not efficacy.

Which to choose?

If your plan covers Spravato and you meet its criteria, it costs a fraction of ketamine out of pocket. If you do not qualify (bipolar depression, no oral antidepressant, prior authorization denied), or a ketamine clinic is far cheaper for you, racemic ketamine is a reasonable alternative offered by many of the same clinics.

See Spravato, ketamine therapy, and the coverage checker.