
Has esketamine been overhyped? - behoove
https://www.gq-magazine.co.uk/lifestyle/article/esketamine-antidepressant
======
jakobegger
Holy shit:

> there are concerns about the drug’s withdrawal effects after three of the
> study’s participants committed suicide within 20 days of its end

It doesn't say how many people committed suicide from the control group, but
regardless, 3 suicides sounds pretty bad for an anti-depressant. Who would
approve a drug like this?

The cynic in me says an addictive drug with severe withdrawal effects is
exactly what pharma companies want...

~~~
Broken_Hippo
I cannot imagine being severely depressed, entering a study for it since I'm
resistant to most of the drugs, finding one that works....

and then having to stop the thing that works and return to a crappy mind
state. Only it is worse because I now have withdrawal symptoms on top of my
severe depression, which already put me at risk for suicide.

In my opinion, the issue isn't that there is dependency nor that there is
withdrawal effects. After all, these are things that happen and despite the
risks, might still be the best available choice for relief. The bigger issue
is that we didn't do enough to help folks during this time. We should have
provided adequate medical care to keep folks safe. Perhaps we should wean
folks off in a better manner and/or provided better psychiatric care to this
vulnerable group of folks after trials ended.

~~~
tempguy9999
I understand that. I was on prozac for years. I chose to come off it because
it was messing me up, otherwise I'd have been happy to take it for the rest of
my life (why not?)

I was aware that if the blackness returned and going back onto prozac failed
to work (which can happen) then my lifespan would be a few months at the most.

People without really bad depression can't understand how bad it can be. Death
really is better.

------
narag
About the safety:

[https://www.vice.com/en_us/article/nzdnak/why-ketamine-is-
th...](https://www.vice.com/en_us/article/nzdnak/why-ketamine-is-the-best-
drug-on-earth)

So the half S, half R compound (I assume "esketamine" is S ketamine and
"arketamine" R ketamine) is a commonly used drug in every emergency unit,
probably in much higher doses than the ones used for depression.

Using the S half only seems a way to get it patented.

The concern seems to be that a nasal spray could lead to addiction beacuse
fast assimilation. People that have used it illegally tell me that tolerance
builds up very quickly, but they're talking about high (K-hole) doses. They
don't use it often, just once in a month and mostly the racemate.

They say esketamine only is weird and a little scary. The R half is what gives
the happines feeling and mild hallucinogen effect, while the S half is the
cause for depersonalization.

A curious detail: the gq article says it's administered IV, while in vice
article it's said that IV is dangerous because laryngospasm.

------
LeanderK
I don't really get it. Why not just go with ketamine? Is it that the approval
takes too much money which other companies could then reuse (the investement
does not lead to benefits)?

~~~
wickoff
Yes, that's exactly the reason. They are filtering racemic Ketamine just so
that they can patent and upsell it at exorbitant rates.

~~~
rocqua
Can the results be used ti justify off-label use of normal ketamine?

~~~
wickoff
There are hundreds of Ketamine clinics using it off-label already, the problem
is that the insurance won't cover the off-label use and a course of about 10
infusions might cost around $5k at the current rates.

~~~
navigatesol
> _the problem is that the insurance won 't cover the off-label use and a
> course of about 10 infusions might cost around $5k at the current rates._

But I thought the goal of the pharmaceutical companies, according to your
earlier comment, is to synthesize K to charge exorbitant prices. Aren't prices
already exorbitant?

~~~
wickoff
The ketamine their are using costs a few bucks. Most of the money goes to the
clinics for facilitating the treatments. Depending on the kind of session it
can take about 2 hours and there are a few medical professionals involved.
This cost stays, the cost of esketamine will be added on top.

------
HeavenBanned
There's nothing wrong with bolstering the Psychiatrist's armamentarium with a
novel drug that could help with clinical edge-cases of depression. This
article was unfairly biased.

~~~
logiclogic
And why not just regular old ketamine instead of a dangerous, untested new
derivative? The whole system is broken beyond repair.

~~~
La1n
It is being tested and it's not a "dangerous, untested new derivative", it's a
enantiomer of ketamine, it's literally 50% of the molecules in ketamine. And
why don't we just use normal ketamine, why test any new drug, to see if it
works better than what we had before.

~~~
SomeOldThrow
> it's a enantiomer of ketamine, it's literally 50% of the molecules in
> ketamine

I’m not a biologist or a chemist. Why does this imply the chemical is as safe?
What is the benefit? It seems like a blatant patent grab to bypass the low
profit margins of ketamine. Is there evidence otherwise?

~~~
badamp
The short answer is it can be both (ie safe, beneficial and effectively a
patent grab). It is also unlikely that an enantiopure chemical is less safe
then it’s racemic counterpart and not unlikely that it is beneficial (this is
not without precedent... this is also chemistry 101 and I don’t feel this is
the forum for it)...

The doubt is not so much the safety but is the benefit of the enantiopure
version worth the cost.

~~~
tempguy9999
Per my comment above, thalidomide is a clear exception. This stands even if
the chirality changes within the body.

~~~
rocqua
That was an example on the other direction. A pure chirality was safe, but a
racemic mixture was dangerous. Here we know the racemic mixture is safe, which
strongly suggests that either chirality in isolation is also safe.

~~~
Nasrudith
And to make in the previous worse it would apparently "autobalance" and flip
to chirality which meant that even if they 100% isolated it at great expense
is why we never saw "rebranded Thalimoide but isolated to be all morning
sickness drug no birth defects". I don't know enough details to tell how long
it took and if it could even be used safely under ludicrously impractical
assumptions like "if you it freshly isolated in bulk and take it within five
seconds it would be safe but expire in an hour".

~~~
tempguy9999
I think it flipped when in the body, so however long the shelf life was, it
still wouldn't matter.

Incidentally, and AIUI, the body has a tagging system for unwanted proteins.
Once tagged, the proteins are removed. Thalidomide tagged the proteins the
were specific to embryonic limb formation, and the body duly cleared them,
leading to the infamous result. Again AIUI.

------
vincent-toups
Capitalism overhype a potential product? No way!

