Ketamine no better than placebo at alleviating depression, unusual trial finds • Hacker News Board

Re: Ketamine no better than placebo at alleviating depression, unusual trial finds

#91

Post by 35997279 » Mon, May 22, 2023, 1:35 PM UTC

PragmaticPulp wrote: post #82

cypherpunks01 wrote: post #59

This is rubbish. Ketamine is a life-saver and has been proven to relieve depression, regardless of the administration setting. It is not magic and does not work in every case, but the effects are proven across countless studies. S-ketamine has even gone fully through FDA approval. Personally I have used it at home, and at a treatment center. There is no difference in the antidepressant properties, whether someone was…

> Ketamine is a life-saver and has been proven to relieve depression, regardless of the administration setting. It’s really not uncommon for some trials to fail to differentiate from placebo when it comes to depression studies. That doesn’t make this study “rubbish”, it just shows that you need to examine the body of evidence rather than cherry-picking studies that appear to match the outcome you want while dismissin…

> It can be a great help for suicidal patients or for getting traditional treatment started, but it’s not a singular solution to depression for most people.

Is there any singular solution to depression for most people?

Re: Ketamine no better than placebo at alleviating depression, unusual trial finds

#92

Post by rsynnott » Mon, May 22, 2023, 1:36 PM UTC

SiempreViernes wrote: post #18

cameronh90 wrote: post #3

> They gave volunteers ketamine while they were under general anesthesia, theoretically preventing the participants from going on a trip. Maybe it's the trip that helps.

And you object to them trying to find out if it does?

It's a perfectly reasonable experiment, but it's reasonable to have some concerns about how much the result actually _means_ one way or another.

Re: Ketamine no better than placebo at alleviating depression, unusual trial finds

#93

Post by PragmaticPulp » Mon, May 22, 2023, 1:36 PM UTC

cameronh90 wrote: post #3

> They gave volunteers ketamine while they were under general anesthesia, theoretically preventing the participants from going on a trip. Maybe it's the trip that helps.

Ketamine depression treatment doesn’t have to induce a “trip” to elicit the effect, according to studies and the protocol.

It can produce some sensory distortions, but anyone who is going into a full “k hole” is almost certainly taking too much. It’s not a case of more is better.

Re: Ketamine no better than placebo at alleviating depression, unusual trial finds

#94

Post by mtlmtlmtlmtl » Mon, May 22, 2023, 1:36 PM UTC

namlem wrote: post #58

SiempreViernes wrote: post #27

Earlier quoted context omitted.

Actually, what it shows is both that getting ketamine while under general anaesthesia is roughly as effective as when taken without anaesthesia (40% here vs 45% in [1]), and as effective as just taking anaesthesia (their placebo treatment). [1]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3992936/

I believe propofol (common general anesthetic) is also known to have some antidepressant effect.

Anything that puts you under and also inhibits REM sleep, can have effects against depression. REM sleep is important for memory consolidation, and consolidation of memory is linked to depression in that the reliving and reconsolidation of painful memories is thought to be involved in at least some types of depression.

This is why sleep deprivation can have an acute antidepressive effect, and also why cannabis can have a similar shorter effect in some cases. Usually when there's no tolerance.

I think it's quite possible indeed that something similar happened during this study.

Re: Ketamine no better than placebo at alleviating depression, unusual trial finds

#95

Post by mtlmtlmtlmtl » Mon, May 22, 2023, 1:40 PM UTC

oaktrout wrote: post #81

mtlmtlmtlmtl wrote: post #24

Earlier quoted context omitted.

I agree in principle, though having tried most of the various types of trippy substances, I've yet to encounter one that hasn't showed potential for a short term antidepressant effect. I guess I haven't tried those weird delta opioid ligands(salvia divonorum). I guess deliriants(like diphenhydramine) would have about zero antidepressant effect too, but that would have possible negative effects, even being liable to c…

Small correction, the active ingredient in Salvia is a kappa opioid agonist.

You're right, thanks for the correction! Really should check more of these things and not just do it from memory.

Re: Ketamine no better than placebo at alleviating depression, unusual trial finds

#96

Post by BobbyJo » Mon, May 22, 2023, 1:41 PM UTC

cubefox wrote: post #83

> But it’s a problem for researchers running double-blinded clinical trials, as participants can usually tell whether they have received ketamine or a placebo. [...] The scientists gave the volunteers ketamine or saline as placebo right after they were put under anesthesia, but before their surgery, essentially blinding them to any psychedelic or dissociative effects. That's a genius way to avoid unblinding. All psyc…

If I did drug trials for pain killers this way, would it give any useful data?

Depression and pain are subjective. Personally, I think removing the subjectivity from the trial voids the trial. It is a clever design, but it really just proves the benefit is in the experience and not the physical mechanism.

Re: Ketamine no better than placebo at alleviating depression, unusual trial finds

#97

Post by aftoprokrustes » Mon, May 22, 2023, 1:41 PM UTC

LocalH wrote: post #63

amelius wrote: post #37

Earlier quoted context omitted.

Can we create a trip without drugs but e.g. using VR goggles only?

Only if it's so immersive that it feels more real than reality . If you can at all tell that it's not "real", then it all falls apart.

This might be true if what you want is to emulate the experience under actual psychedelic drugs; I do not think that this is necessary if your only aim is to create _transformative_ or _healing_ experiences.

One of the core concepts of Rob Burbea I mentionned above is the idea of "imaginal middle way", which, in short, consists in seeing mental images as "neither real nor not real", "simultanously discovered and created". Going deeper into that topic would require way too much text and time for a simple comment here, but I can tell from experience that this way to engage with imaginative faculties can have deep and long lasting effects. And the important aspect here is that, while engaging with the image, one is constantly balancing between reification (considereing the image, for instance of a divinity, as having independent reality) and disdain (considering the image as "just made up").

Re: Ketamine no better than placebo at alleviating depression, unusual trial finds

#98

Post by mjburgess » Mon, May 22, 2023, 1:42 PM UTC

throwawaaarrgh wrote: post #36

Amazingly, talk therapy also is no better at reducing depression than placebo while under general anesthesia.

In other news, in a double-blind study, participants who were drunk during their surgery reported no development of their social lives.

Re: Ketamine no better than placebo at alleviating depression, unusual trial finds

#99

Post by cypherpunks01 » Mon, May 22, 2023, 1:44 PM UTC

PragmaticPulp wrote: post #82

cypherpunks01 wrote: post #59

This is rubbish. Ketamine is a life-saver and has been proven to relieve depression, regardless of the administration setting. It is not magic and does not work in every case, but the effects are proven across countless studies. S-ketamine has even gone fully through FDA approval. Personally I have used it at home, and at a treatment center. There is no difference in the antidepressant properties, whether someone was…

> Ketamine is a life-saver and has been proven to relieve depression, regardless of the administration setting. It’s really not uncommon for some trials to fail to differentiate from placebo when it comes to depression studies. That doesn’t make this study “rubbish”, it just shows that you need to examine the body of evidence rather than cherry-picking studies that appear to match the outcome you want while dismissin…

Agreed on all points.

Doing studies isn't bad in itself, of course they will produce conflicting outcomes and need to be studied as a large body of evidence.

Yes, it cannot be used as a long-term solution. It's more of a fast-acting effect and has been over-hyped beyond its capabilities.

My immediate reaction was just that their conclusion ("has no short-term effect on the severity of depression symptoms" and what the co-author said in the linked article) is not reasonable to draw based on the study they designed, because they failed to consider whether the therapy needed a conscious patient or not.

Re: Ketamine no better than placebo at alleviating depression, unusual trial finds

#100

Post by rtkwe » Mon, May 22, 2023, 1:45 PM UTC

insane_dreamer wrote: post #89

Interesting study. However, I would argue that the study introduces an additional confound (anesthesia) rather than removing a confound (in order to isolate the effectiveness of ketamine).

I think it's also very probable that the trip is indeed part of the therapeutic effects of ketamine therapies.

On top of just the anesthesia confounding variable there's also the fact they were all getting surgery so improvements might have come from getting over the stress of whatever procedures they were having done.

My main worry is this will be waved around by people as an argument against the therapy without understanding what they were actually testing which is if you need to experience the trip for ketamine to have an antidepressant effect or if the effect is more principally neurochemical. The article has hints of this and at the bottom the authors also say that's mainly what they were looking to test here.