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> 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 dismissing those that say the opposite.

Ketamine is a temporary boost for some people, but it has also been overhyped in recent years. The single biggest downside is that it’s not a long-term solution. The duration of the antidepressant effect is relatively short (days to weeks) and the antidepressant effect appears to diminish with repeated dosing.

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.

Ketamine prescribing also got out of control fast. I traveled to a city where Ketamine clinics were advertising on the radio and billboards and competing with coupons and discounts and exaggerated promises of efficacy. Reddit and other forums are also filling up with stories of people who think their ketamine “stopped working” because they weren’t properly informed that it was a temporary effect for most people that needed to be combined with traditional therapy. Way too many clinics and influencers looking to ride the hype train without honestly assessing the situation.

> 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?

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.

> 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.

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.

I couldnt disagree more with your second paragraph.

I have a partner who has been prescribed Ketamine for the last 3 years. I firmly believe that the drugs ability to rebuild neural pathways and thus work around / resolve damage to be the only reason why partner is still alive today, and is now ready to return to work after so many years and such a brutal road.

In Australia, being prescribed Ketamine is very difficult, and thus very uncommon. While I do not believe it should be opened up to everyone, my experience over the last few years makes me a massive fan of the drug for specific situations.

The study actually shows ketamine works as well with anesthetia (45%) as without (40%), if you read the non-anesthetia study linked in https://news.ycombinator.com/item?id=36030251.

(Of course you can argue they are not using enough K at the 0.5 mg/kg mark, because disccociation starts at 1 to 3 mg/kg per StatPearls.)

> Of course you can argue they are not using enough K at the 0.5 mg/kg mark, because disccociation starts at 1 to 3 mg/kg

Dissociation isn’t necessary for the antidepressant effect, according to studies. In fact, many of the more responsible clinics target longer duration, lower peak dose infusions for this reason.

Well, yeah. But the parent comment is insisting that the spiritual bits is doing something, and I was just way too lazy to look for a dose response study.

>I'm not terribly surprised that ketamine may not produce strong antidepressant effects if the patient is not conscious.

That's incorrect, it actually produced larger antidepressant effects (50% response rate and 40% remission [1]) than when the patient is conscious (40% response rate and 30% remission according to a large meta-analysis [2]).

[1] https://www.medrxiv.org/content/10.1101/2023.04.28.23289210v... [2] https://pubmed.ncbi.nlm.nih.gov/35688035/

But that large response had nothing to do with ketamine, as the non-ketamine group had the same or higher response.

They only measured response for the next three days. Is it possible k has an effect for longer than three days while placebo only lasts three days or so?

Unlikely. I see another comment says "The duration of the antidepressant effect is relatively short (days to weeks) and the antidepressant effect appears to diminish with repeated dosing."

Did you read the article? It explains the study is attempting to narrow down the mechanism for ketamine's effects, not disprove them.

The title is misleading though, unfortunately. What the study found is that Ketamine-while-unconscious is no better.

> It is not magic and does not work in every case,

That is exactly what they are saying in the study. No better than placebo means Ketamine does not cure depression. If ketamine cured depression it would work in every case.

Increasing serotonin receptor density trough Ketamine use may relieve depression, but so can being cared for.

Your beliefs do not matter, biology matters. And it may in fact be that your "strong beliefs" in ketamine are why it helps you.

The FDA does not approve medicine based on beliefs.

I am sharing my personal perspective, alongside the fact that controlled studies have proven it is one of the most effective treatments known to exist.

Nobody thinks ketamine cures depression, it is one treatment.

> The FDA does not approve medicine based on beliefs.

Yes, sometimes they do.

https://www.pbs.org/newshour/health/fda-increasingly-approve...

Downvoted! For a fact!

The internet is filled with crooked bots, captured bots, bots that want capitalism and governmental collusion to seem "silly".

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 might say: the sars covid-19 virus doesn't cause illness because some exposed people showed no symptoms. The families of the dead people would disagree.

> 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/researching the cause of each individuals depression. Why is there such limited nutritional and genetic testing on people with severe depression?

> With your logic, one might say: the sars covid-19 virus doesn't cause illness because some exposed people showed no symptoms. The families of the dead people would disagree.

If SARS2 does not cause illness in me that is all I care about. And if it does not cause illness in me you should all be interested in me.

> 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?

No, in fact it does not "work well for a lot of people" as the study found. I am not making it controversial, you are, by denying what they found in the paper.

What you are really hearing is the massive marketing that is flooding the airwaves so some corporations can make a profit off of sick people and when it does not work they can say "Oh well" and walk away with the money and all you get is rebound depression.

Erm... you realize this isn't the first study on ketamine, right?

This is one study, that has not yet been peer-reviewed, that explicitly acknowledged the study design could be subject to significant subject-expectancy bias, using one particular treatment regimen, with a treatment group of ~20 people. At most, this study tells us that we have more to learn about what's going on and why we see significant effects. Both groups did see significant effects relative to base rates that are unlikely to be random even at that small sample size! Funny how you've come to radically different conclusions on the findings than the scientists themselves.

I am actually only vaguely aware of the marketing around this -- I've been following this space for about a decade and have read quite a few studies around it. Even if this study is generalizable and ketamine is no more effective at treating depression than the idea that ketamine will have an effect in treating the depression (placebo), we know from the evidence that it's having a significant effect relative to simple regression to the mean (depressed people simply getting less depressed without treatment). If it's a placebo, it's a powerful placebo, and placebo effects that are effective aren't a bad thing.

Something can be effective, especially more effective than a placebo, without being a cure. We have many "treatments" for all sorts of illnesses where the treatment isn't a cure. SSRIs for depression are a treatment, not a cure, just as one example. Hell, even Nyquil is a treatment for symptoms without being a cure.

When it comes to mental health we also have these big umbrella categories (depression, schizophrenia) that are made up of groups of illnesses. Schizophrenia has so many different causes, and thus different treatments, that viewing it as a single illness can actually be problematic.

Anyways, my point is that what you're saying makes no sense at all.

>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.