Hmm so people report better symptoms when they know they’re being given recreational drugs but report no change when they’re not sure what they got.
No: they report milder symptoms in both cases, and the improvements are of almost the same size.
Ketamine no better than placebo at alleviating depression, unusual trial finds
101–110 of 196 posts
Re: Ketamine no better than placebo at alleviating depression, unusual trial finds
#102This 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’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 dismissing those that say the opposite.
But this study doesn't say the opposite. It fails to show an effect. That's different from proving the absence of an effect. Every Ph.D. student in an empirical field learns this in their first year. I'm surprised this study gets so much attention.
You can make a study verifying that a pound gold and a pound feathers accelerate downwards at the same speed in a vacuum, and perhaps you messed up the vacuum, so they actually fall with different speeds in your study. Doesn't prove gravity is messed up. You just failed to prove that it's not. Can have many reasons. Same with this study.
Re: Ketamine no better than placebo at alleviating depression, unusual trial finds
#103This 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 Anyone who talks in such terms shouldn't have their opinions on medicine listened to. There's a reason that medicine typically sticks to such terms as QALY (quality adjusted life year) and other such terms to produce the best outcomes in a resource constrained environment. By your reasoning, many things are "life savers", but not every intervention is equal, is it?
> >Ketamine is a life-saver
> Anyone who talks in such terms shouldn't have their opinions on medicine listened to.
Criticizing hyperbole by using hyperbole is a questionable strategy.
Re: Ketamine no better than placebo at alleviating depression, unusual trial finds
#104> 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.
I see so many studies trying to somehow distill trippy drugs into an isolated, side-effect free, take a pill and get back to work treatment. Maybe there's something to be found there, would be huge, but my hope is that we don't waste all the will and funding down this path without more fully exploring the path where we admit that yes, the trip helps, and we'll just need to deal with the lack of blinding.
The problem is real, though. Drugs with overt recreational effects very frequently distract the patient from the therapeutic effect in unproductive ways. The recreational effects generally disappear quickly as tolerance develops, which can give patients the false impression that the medication “stopped working”.
A common example would be ADHD stimulants, where the early stimulating and mood-boosting effects disappear over time while the concentration-enhancing effects mostly remain. This leads a lot of patients to assume the medication isn’t working because it doesn’t feel like those first few doses, which can lead to discontinuation or abuse.
Ketamine has a similar story arc. The antidepressant effect doesn’t require full blown dissociation, but so many headlines and fame-seeking authors have hyped it as “psychedelic medicine” that some patients assume it isn’t working until they disassociate/hallucinate. This can create a sort of nocebo effect where patients may actually be improving but they think they’re not because they didn’t have the wild hallucinations they read about in some exaggerated internet article.
Re: Ketamine no better than placebo at alleviating depression, unusual trial finds
#105> 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.
Having amnesia (forgetting whether they had a trip and whether they were in the treatment group) would probably be better than anesthesia induced unconsciousness. Though I don't know whether short term amnesia can be easily induced.
Re: Ketamine no better than placebo at alleviating depression, unusual trial finds
#106Earlier quoted context omitted.
I don't have a position on the paper (I haven't even read it), but this statement you just made seems unjustified: > If ketamine cured depression it would work in every case. Depression can have many different causes, and people have many different biological variables, so it should not be surprising that a given treatment isn't 100% effective. There are many example of this in the real world. With your logic, one mi…
> Depression can have many different causes, Then why this singular focus on ketamine and psychedelics all the sudden? If it has many different causes why focus on activating a single serotonin receptor? > and people have many different biological variables, so it should not be surprising that a given treatment isn't 100% effective. Yes, and that is why we need to stop recommending mediation to people without knowing…
> Then why this singular focus on ketamine and psychedelics all the sudden? If it has many different causes why focus on activating a single serotonin receptor?
Because it does work really well for a lot of people for whom other things don't work really well. Why would that be controversial?
Re: Ketamine no better than placebo at alleviating depression, unusual trial finds
#107Earlier quoted context omitted.
> 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’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 dismissing those that say the opposite. But this study doesn't say the opposite. It fails to show an effect. That's dif…
But this study doesn't say the opposite. It fails to show an effect. That's different from proving the absence of an effect.
This was my first thought, jaded as I am from bad scientific reporting (such as the linked article) which doesn’t distinguish between these two cases, so I had a look at the actual study.
In this case, it looks like the 95% confidence interval just barely overlaps the null hypothesis, however the mean effect favors placebo:
The mixed-effects model showed no evidence of effect of group assignment on post-infusion MADRS scores at 1 to 3 days post-infusion (-5.82, 95% CI -13.3 to 1.64, p=0.13).
(See also figure 2, which clarifies the direction of effect.)
So, potential methodological issues aside, I’d actually consider this evidence against a strong benefit relative to placebo, and possibly very weak evidence of harm.
Re: Ketamine no better than placebo at alleviating depression, unusual trial finds
#108> 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.
yes, but the phase 3 (efficacy) trial just barely crossed the threshold (if I remember correctly), mostly because the company wanted to use one stereoisomer because the other was not patentable (and this is the one that is less trippy)
https://slatestarcodex.com/2019/03/11/ketamine-now-by-prescr...
Re: Ketamine no better than placebo at alleviating depression, unusual trial finds
#109> 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.
Not to mention other possible effects of being in general anesthesia (aside from the lack of consciousness) that prevent the effectiveness.
But you're neglecting the fact that this study found the same or higher effectiveness than non-blinded trials.
In this trial, there was a 50% response rate and 40% remission [1], whereas in a meta-analysis of previous unblinded trials there was 40% response and 30% remission [2].
[1] https://www.medrxiv.org/content/10.1101/2023.04.28.23289210v... [2] https://pubmed.ncbi.nlm.nih.gov/35688035/
So it's not that this trial wasn't effective, just that the placebo effect is very effective, and it likely resulted in the improvements seen.
Re: Ketamine no better than placebo at alleviating depression, unusual trial finds
#110> 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…
Am I missing something blindingly obvious here? I would have assumed that the therapeutic effects of a strong mind-altering substance relies on being conscious to, you know, experience the effects.
Saying "It didn't work while the subject was asleep so therefore must be placebo" is just a bizarre position to take.
Imagine if a study stated "Cognitive Behavioural Therapy found to be ineffective on unconscious patients".