For people with depression, especially treatment-resistant depression, this is the practical branch point: what is legal, what insurance may cover, what evidence supports, and what to ask before the first appointment.
| Option | Best fit | Insurance | First move |
|---|---|---|---|
| Spravato (esketamine) | Treatment-resistant depression when coverage and regulatory guardrails matter. | Most likely of the options here; prior authorization is common. | Ask your psychiatrist or insurer for REMS-certified sites and TRD criteria. |
| IV/IM ketamine clinic | Patients who can self-pay and want the most studied ketamine administration model. | Rare for depression; sometimes partial superbill reimbursement. | Vet medical leadership, dose protocol, monitoring, and maintenance plan. |
| At-home oral ketamine | Lower-cost access where telehealth is allowed and risk profile is low. | Usually no; HSA/FSA may apply. | Confirm real psychiatric evaluation, state licensure, and session support. |
| Psilocybin trial or regulated service | People seeking a classic psychedelic model and able to travel or enroll in research. | No coverage for state service programs; trials may cover study costs. | Search clinical trials, then compare Oregon/Colorado licensed services. |
Start with Spravato. It is the only ketamine-family depression treatment here with FDA approval and broad payer pathways.
Compare in-clinic IV/IM ketamine against at-home oral programs by supervision, not just price.
Psilocybin is promising for depression, but access is very different from ketamine.
Do the clinician conversation before booking anything.
Ketamine-family treatment is usually fast-acting but not one-and-done. Some people notice mood shifts within hours or days; durability often depends on repeated dosing, psychotherapy, medication management, and a maintenance plan. Psilocybin trials sometimes report longer follow-up effects after one or two dosing sessions, but access is narrower and the blinding problem makes headline effect sizes hard to interpret.
For most US patients, the practical first branch is ketamine-family care: Spravato if insurance coverage matters, or clinic-based IV/IM ketamine if paying out of pocket is possible. Psilocybin is not FDA-approved and is legally accessible mainly through clinical trials or regulated Oregon and Colorado service programs.
No. Spravato is esketamine nasal spray, FDA-approved for treatment-resistant depression and administered only in certified offices under a REMS program. IV ketamine usually means racemic ketamine infusion used off-label for depression; it is commonly self-pay and not governed by the Spravato REMS.
Do not stop or taper psychiatric medication without the prescriber who manages it. Ketamine is often used while patients remain on antidepressants. Psilocybin effects can be reduced by SSRIs/SNRIs, but any taper decision requires medical supervision.
Ask who performs the medical evaluation, whether they screen cardiovascular and psychosis/mania risk, what route and dose protocol they use, how blood pressure and distress are handled during sessions, whether integration support is included, and what maintenance or exit plan they recommend after the initial series.