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

science.org

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

#121

Post by NickM »

insickness wrote: post #55
huuhee3 wrote: post #6

Then it's still no worse than widely used SSRI's, which also mostly don't differ from placebo

The effect of SSRIs on depression is moderate but statistically significant: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5667359/ I suspect the response varies greatly by individuals: some respond a lot and some don't respond at all. My experience with SSRIs was very positive. I took a low dose for depression for a few years and it helped significantly. I went off it a few years ago and my depression hasn't returned…

That study found a small effect size compared to placebo, and a large placebo response.

That seems consistent with OP's comment of "SSRIs...mostly don't differ from placebo" (emph added).

Also not addressed in the paper is the fact that SSRIs and SNRIs have well-known and pronounced side effects, with make it questionable whether double-blind studies are really fully blinded.

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

#122

Post by sfpotter »

FollowingTheDao wrote: post #77
sfpotter wrote: post #48

Earlier quoted context omitted.

Thanks for sharing your very interesting experiences with meditation. Makes me want to have another go at it. (FYI, you mean to use the word “propel” in place of “propulse” above… they aren’t synonymous, surprisingly.)

Do it! https://en.wikipedia.org/wiki/Zuowang

I've always been very interested in taoism, but never took it much further than reading the Tao Te Ching and a few other related things like The Tao of Pooh and The Te of Piglet. This form of meditation seems exactly right for me. Do you have any recommendations for how to pursue it? Thanks.

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

#123

Post by naasking »

PragmaticPulp wrote: post #104
reubenmorais wrote: post #8

Earlier quoted context omitted.

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…

> Drugs with overt recreational effects very frequently distract the patient from the therapeutic effect in unproductive ways.

How are you quantifying "frequently"? Does that necessarily mean that the recreational effects cannot themselves be therapeutic?

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

#124

Post by naasking »

mtlmtlmtlmtl wrote: post #12
tokai wrote: post #10

Earlier quoted context omitted.

Literally the last line of the article: "Future studies of novel antidepressants with acute psychoactive effects should make stronger efforts to mask treatment assignment to minimize the effects of subject-expectancy bias." Instead of pondering if their method is at fault for their negative result, the conclusion is to double down and working even harder at masking the effects.

Well, what they're trying to do is provide better blinding. Doing proper blind studies of ketamine is quite hard because its subjective effects are far too noticable. That line just says people should do better at this in future to get more accurate results. It's not a statement about the ultimate form the treatment should take.

> That line just says people should do better at this in future to get more accurate results

But it's also doubling down on the assumption that the subjective effects aren't the source of the benefit.

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

#125

Post by cubefox »

andybak wrote: post #110
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…

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…

The trip is very short, but the effect as a useful antidepressant has to last a lot longer. It's not clear why the trip itself would have anything but short term effects on depression.

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

#126

Post by pcthrowaway »

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.

Or general anesthesia prevents ketamine from having it's usual effect on the brain.

This is such a stupid study, I hope they didn't anesthetize people just to study this

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

#127

Post by jcranmer »

vasco wrote: post #115
PragmaticPulp wrote: post #104

Earlier quoted context omitted.

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…

I took LSD twice in my life only and it changed my outlook ever since. It's been almost 10 years. I wasn't depressed and had other benefits from it, but I can see how that experience could've fixed depression, and know of people who say it did for them even though I'm not in any hippy-like community or whatever. I think a possible reason why medical research prefers a pill that works forever for continued use is that…

> I think a possible reason why medical research prefers a pill that works forever for continued use is that if you buy something cheap twice in your life and it fixes whatever needs fixing the pharma industry can't make money off of you the same way they can put you on antidepressants for life.

Drug discovery is difficult enough that the pharma companies don't have the ability to make a meaningful choice between fix-once-and-you're-set-for-life versus manage-symptoms-forever.

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

#128

Post by belltaco »

pcthrowaway wrote: post #126
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.

Or general anesthesia prevents ketamine from having it's usual effect on the brain. This is such a stupid study, I hope they didn't anesthetize people just to study this

> I hope they didn't anesthetize people just to study this

Why not? Apart from potential side effects of anesthesia, this sounds like a great study to find the mechanism of ketamine helping depression.

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

#129

Post by jjk166 »

bheadmaster wrote: post #13
tokai wrote: post #7

Earlier quoted context omitted.

Don't post lies and FUD here please.

If you're gonna accuse someone of posting lies and FUD, at least have some sort of reference [0] to point to, please. Otherwise you're just participating in a "uh-huh!", "nuh-uh!" pissing contest. [0] https://www.nature.com/articles/s41380-022-01661-0

The burden of proof is on the person making the initial claim, ie that SSRIs are no better than placebo.

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

#130

Post by bheadmaster »

tsimionescu wrote: post #111
bheadmaster wrote: post #38

Earlier quoted context omitted.

If it's so obvious and well-established, it shouldn't be hard to find some reference to support it, no? How else would I know that the emperor is, indeed, wearing clothes?

Do you disagree that SSRIs are an FDA-approved treatment for depression, should I find references for that? Or do you not know what is the standard for FDA approval?

Does drug being approved by FDA prove its effectiveness? If you can demonstrate without reasonable doubt that it does, i.e. that it's virtually impossible for a drug to be both approved by the FDA and as effective as placebo, then that would make a good argument.

In any case, any argument is better than just a "Stop spreading FUD and misinformation, you antivaxxer"-style comment.

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