Ketamine non-responders / relapse: when to give up?


My boyfriend (late thirties) has had MDD for some 20 years, worsened over the last 5 years. He has tried all the drugs, TMS, ECT, all failed. Therapy has been only marginally useful.

It seemed like Ketamine infusions were working. After the first 7 infusions he had about 5 days being depression-free. However, he soon relapsed, with an apparently worse crash episode than is typical. 3 additional infusions over the course of a week had no effect in lifting his mood. He stayed in bed and was not functional for 10 days.

He has now had 14 infusions in total over 8 weeks. We are wondering whether and when to call it quits. His parents are paying for the treatments, and it is so damn expensive, especially to continue without seeing any results in the hopes that the ketamine could be having some long term benefits which are not at all apparent right now…

Since there is so little evidence, we are looking for anecdotal experiences, if you have anything to share about Ketamine ultimately appearing to fail.

Thank you for your help.


Infusions can definitely have their ups and downs, but that sounds particularly rough. Does he have insight as to why he’s depressed? Is doing any integration therapy, practicing self care, or making positive changes after infusions? In my experience, ketamine works best when it’s treated like psychedelic therapy rather than just medication. Is it possible that the infusions brought up a lot of bad memories or feelings that he’s not processing?


I hope he is under the care of a mental health professional (psychiatrist) while undergoing IV infusions. They should consider all possible diagnosis in differential and why he is treatment refractory. He may also be a ketamine non responder, there may be drug-drug interactions, as well as dosing to consider.


Thanks for your response.
The clinic psychiatrist checks in with him for about 60 seconds when we go in for the treatment…it is very frustrating how busy doc is and unable to give treatment planning a moment of his time…
My bf is on no other drugs of any kind.
Ketamine dosing started at 1mg/kg and was steadily raised to 1.5mg/kg in the hope of better response. This increased dose actually lead to a harrowing experience of depersonalization during infusions, which left him weeping afterwards. We question how the quality of the infusion experience impacts its efficacy - another area of research that just doesn’t exist yet.
Thank you for your thoughts.

Thank you for your response.
His depression, like so many others with MDD, has no known cause, and he has no significant trauma history he is aware of.
He does all the self care that his level of depression allows for each day.
He is a smart, insightful, and honest person, and infusions were not raising memories he cannot or will not process - I’m a counselor myself, and I wish that a therapy fix were possible, but in his case it seems this is not the solution.
Thank you for your thoughts. I like the ethos of the psychedelic model, and believe it can be so powerful for some people.


That’s so tough. I’m sorry. The benefits for me were with the psychedelic model. Ketamine enabled me to access and process trauma that I wasn’t otherwise able to. But if trauma isn’t the issue, I don’t have any insight to offer. Best of luck finding something that helps him.

I wouldn’t give up on it just yet. Ketamine is the drug of choice simply because it’s already FDA approved, so low-dose infusions simply constitute an off label application, which is as American as apple pie. But it doesn’t mean that ketamine is the best option for him. I’d look into psilocybin assisted therapy.

If it helps, 0.5mg/kg is a standard starting dose. My clinic liked to increase slowly because a dose that’s “too high” can create anxiety. My CRNA felt that people did better on “comfortable” doses. There’s a lot of debate as to whether or not higher doses are more effective. Anecdotally, I’ve heard a number of other patients say no. It might be worth experimenting with a lower dose to see if that provides more relief.

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