It also tends to arrive after years of being told to be patient. People reach me having done everything asked of them, several times, and having concluded the problem is them. It usually is not. It is that the first-line approach works for a lot of people and not for everyone, and the follow-on options are poorly advertised.
Here is what is worth asking about specifically.
Whether the trials actually counted
Before adding anything, it is worth auditing what came before. A medication stopped after ten days because of early side effects is not a completed trial. Neither is one taken at the starting dose for a year because nobody revisited it.
This is not a technicality. The definition of resistance depends on adequate trials, and I have met plenty of people carrying the label who had never had two.
Spravato, and why the name matters
Spravato is esketamine, delivered as a nasal spray. It is FDA-approved for treatment-resistant depression, which puts it in a different category from most of what gets discussed under the heading of ketamine.
Because it is approved for this use, insurance often covers it. Because of how it is regulated, it is administered in a certified setting with a monitoring period afterward, rather than something you take home. That is inconvenient and it is also the reason coverage exists.
Ask about it by name. Approved is a meaningful word, and it is the one that opens the insurance conversation.
Off-label ketamine, described honestly
Sublingual and intravenous ketamine are prescribed off-label for depression. Off-label prescribing is legal and common throughout medicine, and there is real clinical experience behind this use.
What off-label means practically is that the approval on file is for something else, that coverage usually does not apply, and that the quality of what you get depends heavily on who is providing it. This is a self-pay category with wide variation in care, and it deserves the same scrutiny you would give any other purchase in that range.
Both of these can be reasonable. They are not the same thing, and a clinic that blurs them is telling you something.
What else belongs in the conversation
Augmentation strategies, where a second medication is added to one that partially works, are well established and often skipped. Some are old and inexpensive.
A look at whether the diagnosis is complete also matters more than it gets credit for. Depression that will not shift sometimes turns out to be sitting on top of untreated trauma, an unrecognized bipolar pattern, a thyroid problem, sleep apnea, or a substance that is doing more work than it appears to. A treatment aimed at the wrong target fails for reasons that have nothing to do with the treatment.
What I would want you to leave an appointment with
Not a prescription necessarily. A plan you can describe to someone else.
You should be able to say what is being tried, why that one, what would count as it working, roughly when you would know, and what happens next if it does not. If you cannot answer those five questions on the walk out, the appointment was not finished.
And a word on the other thing
People with treatment-resistant depression often arrive asking about psilocybin. Oregon has a legal program, and I am licensed to facilitate in it, so I want to be careful here rather than encouraging.
That program is not a treatment for depression. It is not health care, it does not require a diagnosis, and it is not designed or regulated as a route to symptom relief. Some people find it valuable. It is not a substitute for a psychiatric evaluation you have not had yet, and several psychiatric medications interact with it, which is its own conversation.
If you are considering both, the sensible order is usually the clinical assessment first. It is cheaper, it is covered, and it frequently turns up something actionable that nobody had checked.
