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.

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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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I’m in the same category as your boyfriend. I took ketamine infusions in December of 2019 and January of 2020 - took a total of 12 infusions over 4 weeks. I did really well for 6 months…took a booster in March and another booster in June but at the end of July I began to crash. I went back in August and took 3 more infusions which didn’t help and went back again in September and took 6 more infusions over a 2 week period ending at the beginning of October. I’ve basically been home bound again since August…I haven’t noticed any improvement at all after the last 9 infusions I’ve taken. I feel badly for your boyfriend and can sympathize - I also am at the point of giving up. I’ve been through over 30 meds and have also had ECT which didn’t help either. This was my last shot - and it looks like it has stopped working for me. I haven’t completely given up because the CRNA that does my treatments thinks that the BuSpar I have taken for years could be causing a negative effect on the way that the treatments are working so I’m in the process of weaning off of it very slowly. I hope we can both find something that helps one day. I am talking to a counselor by phone every week and she’s encouraging - if he doesn’t have one, it at least gives me a bit of a different perspective on things to listen to her. Best wishes for you.

I had a similar experience. Boosters were more helpful to me than blasts — for a while, I got infusions once every six weeks, and I thought that was more helpful. Like a refresh button every once in a while to keep your mind and mood stimulated. About a year in, I was prescribed oral troches (once every two days as needed). I thought they worked well in tandem with infusions (once every six weeks), and they helped sustain mood lift and momentum (as well as day-to-day stability) for about a month or so. After a while, I decided infusions were too expensive to justify the added benefit. I continue to take just the troches, and I believe that has been as helpful long term compared to conjunctive infusion therapy. Moderate mood lift and significant day-to-day stability. Less side effects.

Thanks so much for writing and sharing your experience…it sounds like we have really shared the same experience with Ketamine, and my boyfriend also tried virtually every medication and ECT, like you. We are looking now at fecal transplant, which some people with bipolar depression in particular have had good results with. We also recently saw a video about deep brain stimulation, which is surgical. Always holding some hope for recovery! I’m sorry to hear of your struggle with this horrible disease, let’s keep in touch. We will share anything we find to be helpful, and please do the same.

Hi musicman, thank you very much for sharing your experience with us, glad to hear the booster approach has helped you, and now the troches…that is super interesting…may I ask how easy or difficult you found it to be to access these? Do you know if they are they widely available? Thank you again

No problem I’m always looking to share with anyone in any way that I can if it will help. I’m currently trying another route myself - I visited a functional medicine doctor a couple of weeks ago. They perform extremely extensive bloodwork in addition to other tests that most medical doctors don’t or won’t perform because they’re too time consuming. It’s definitely not a quick fix but I’m hoping that they can actually find a cause for what’s going on instead of all the band aids (or at least that’s what I’m feeling like they’ve been over all these years). The thing I’m having to keep in the front of my mind is that The Lord is going to work this out for good somehow. I can’t see how He will, but that’s what gives me hope. I can send you my email if you’d like - I didn’t know that you had replied to my post but just happened to log on and look (I’m new on this site). If your friend wants someone that’s in the same boat to correspond with, I’m here. Best wishes to you both.

Thanks for your response! That is so interesting about the bloodwork - we are also pursuing some tests, though yours sounds really extensive: would love to hear how that goes! And yes, that completely makes sense that we want to find out the cause rather than just treating the symptoms. So glad your faith gives you a sense of sustaining hope despite the suffering. And thank you for your email - we shall be in touch!

I think for me my problem is being unable to escape stressful situations and so it interferes with the progress I make on K. But it’s def not for some ppl. I’ve heard there is an 80 percent success rate but I am not sure what recourse there is for ppl who fall in that 20 percent. I’m actually interested in knowing since, while my situation is different, I’m worried the stress will create a situation where the K no longer works.