
Esketamine Drug For Depression Treatment Nears FDA Approval - pseudolus
https://www.bloomberg.com/news/articles/2019-02-12/first-big-depression-advance-since-prozac-nears-fda-approval
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copper_think
So, it's just enantiomerically pure S-ketamine - not really a new drug
discovery. The drug is already around as an anesthetic but it is almost
finished with the FDA's approval process for treatment-resistant depression.
When used as an anesthetic it is administered intravenously, but the anti-
depressant formulation is a nasal spray. Cool! That definitely makes it more
accessible.

I wonder if J&J got a patent on S-ketamine? The patent system is often abused
this way. First you sell the racemic mixture, then when that patent is about
to expire, you start selling a new product that is just the active enantiomer.
And you can tell customers that it's new and improved: that you only need to
take half as much! See Prilosec/Nexium, Celexa/Lexapro, etc.

Although, maybe it's difficult to manufacture just the one enantiomer, at
scale?

~~~
WalterSear
It's even more confusing: R-ketamine is the more effective enantiomer, with
less dissociative effects.

~~~
civilian
Sweet, I like that J&J is using S-ketamine then. I think the dissociative
effects of ketamine are fantastic and beneficial, even though they can be
surprising. At a low dose it likely won't be an issue.

~~~
WalterSear
Personally, I have no issues with the dissociative effects per se. However,
studies have determined that they aren't related to the antidepressant effect.
Fwiw, a full clinical dose feels like ~1/4 of a 'rail'. There's no
introspective trip here, just slight drunkenness.

(Incidentally, we have some evidence that the metabolite that causes the
effect can be blocked via concurrent CBD administration - without reducing the
dissociative effect)

The standing appointment to get slightly high for a couple of hours every
three days does get inconvenient (though it's not as problematic as the
resultant insomnia). I expect esketamine will be more so, for less
antidepressant effect. And, being a controlled substance, I'm concerned I'll
be unable to increase my dosage to make up the difference.

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rdiddly
_" But Meisel said he was convinced by a patient survey Johnson & Johnson
conducted. 'We don’t take the patient voice into account enough,' he said."_

I suppose it didn't occur to him that the company trying to get their drug
approved might not have taken the patient voice into account enough either? Or
maybe under-reported certain patient voices? (The adverse ones. Hey, it's not
like it has never happened. At least take a closer look!)

~~~
torrance
This.

Evidence and studies like this should not be done by the company itself. The
OxyContin claims about low addictiveness should be a timely reminder for
independent clinical studies. Reading that set off alarm bells for me.

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pizza
It might be a realy big milestone if it comes to market. Especially if it
could come out as soon as within this year.

Sometimes I hear people mention that ketamine’s special effectiveness (in
those whom it is effective, which isn’t 100% of people afaik) wears off over
the length of a treatment protocol. It’d be nice to hear more about that,
especially in comparison to the long-term effectiveness of traditional
antidepressants and SSRIs in particular.

~~~
indalo
This. I've read some horror stories about patients that received infusions
which for a time, gave them their life back, and suddenly for all intents and
purposes it became ineffective. Some people described going back to feeling
depressed after seeing the alternative to be even less bearable.

I'm eager to see it come to market, and for it to work, but I'm scared to work
with my doctor to try it based on those stories.

~~~
rincebrain
Can confirm that this happens.

To put it mildly, not the most pleasant experience of my life, but still
looking forward to seeing where the next iterations on rapid-acting
antidepressants go, and whether they turn out to be any more durable.

(Also quite curious to see what research crops up about why the effects are
sometimes not durable, but that's gonna be a decent wait.)

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mark-r
So rather than approve the existing drug that's off patent, they approved a
knock-off that will undoubtedly cost 100x as much. How typical.

~~~
philwelch
Is there anything stopping doctors from prescribing or administering ordinary
ketamine off-label? I don't think the controlled substance issues would differ
between the two.

If the answer is "no, but the marginal differences between ordinary ketamine
and the new drug are enough that you'd want to prescribe the new drug
instead"\--well, that's new value added, isn't it?

~~~
dundercoder
Ketamine HCl can and is dispensed off label, both for in office IM/IV
treatment and at home nasal spray, or sublingual troche.

~~~
epmaybe
that requires the pharmacy to somehow obtain nasal spray. Unfortunately, no
manufacturer actually sells a nasal spray variety (yet) as there was no FDA-
approved use for intranasal ketamine. That being said, compounders have been
able to make intranasal ketamine formulations for a while now, since this
treatment for acute depression has been well recognized in the literature for
at least a decade.

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ipunchghosts
Who we the 14 people who approved?

~~~
all_blue_chucks
I'm curious as to who voted against this. I mean, sure, abuse of this could be
bad. But suicide caused by depression is far, far worse.

People who want recreational drugs will find them anyway. Letting innocent
people die from treatment-resistant depression is a perverse priority.

~~~
martinald
It's slightly worrying the language from pharma is very similar to the early
opiod days.

"The voice of the pain patient is underrepresented! We should approve opioids"

Now is

"The voice of the depressed patient is underrepresented! We should approve
nasal ketamine".

I'm all for new therapies but ketamine can be highly addictive and causes
really nasty side effects in high quantities (bladder problems being horrific
from what I've heard). I hope we don't see a huge spike in ketamine abuse in
10 years time like what happened after overprescription of opioids.

I also think this will be extremely popular. Current antidepressants are not
very effective and take a long time to work. This seems to work very quickly.
Who would want to wait 8 weeks Vs hours to get better? It would not surprise
me if J&J have massively downplayed the potential addiction risk of this.

~~~
sjjshvuiajhz
Ketamine is plentiful on the street and you can legally buy ketamine analogs
online. I don’t see this new route of getting it from a psychiatrist as a huge
abuse risk.

Subjectively, it’s not as good a “take the pill and forget your problems” drug
as opioids, benzos, and alcohol are. It can be used in that way if you take a
huge “k-hole” dose and dissociate completely, and some people do get addicted.
But at common doses, certainly whatever they are going to prescribe, it’s more
of a “think about your problems and figure out how to solve or accept them”
drug like mushrooms and LSD.

~~~
martinald
You could use the same argument for Oxycontin surely. Heroin was always out
there on the street, but it's only when opioids were prescribed to the masses
via doctors that it reached ecedemic proportions.

I'm not saying it is addictive as heroin etc but it's definitely addictive.
And will people start increasing their doses as they become tolerant to the
antidepressant effects, etc?

~~~
sjjshvuiajhz
I think responding to this requires giving a summary of the effects of
different drugs, to build a simple mental model of how they could cause
addiction.

Group A: Drugs like benzos, alcohol, and opioids provide pleasant sensations
upfront, killing your pains and anxieties, but those problems return in even
worse form when the drug wears off. It’s as though your brain’s baseline for
what counts as suffering had been lowered by the experience of being coddled.
It’s very clear how this leads to compulsive redosing and addiction.

Group B: Psychedelic drugs like mushrooms and LSD induce unpleasant feelings
as they take effect, followed by a more positive (perhaps euphoric) experience
once the brain adjusts to the presence of the drug, and then less potent
pleasant after-effects when the drug wears off. It seems like the brain has
raised the bar for suffering - suddenly the fact that you can see things in
the correct color, gravity is pointing in the right direction, and you have
clarity of thought makes life feel easy. You might redose to extend the peak
effects, but you aren’t going to take any more for a while once it wears off.
It would be tough to get addicted to these. However, a depressed person might
have trouble with the come-up, and could experience a panic attack. You’d want
a very skilled therapist if you’re trying to treat depression this way.

IMO ketamine kind of straddles the line here. The onset of the dissociation
can be stressful, but it’s not that hard. You don’t forget your problems, but
they feel like the problems of somebody that you know closely and care a lot
about, so you can try to solve them from a different perspective. You can feel
that you are doing something great, which can lead to compulsive redosing, but
you keep the lessons you learn when it wears off. It’s not as though your
problems come back in even worse form like you get with group A. Although if
you really blast yourself, the dissociation can get so strong that you don’t
care about your problems at all, which gives you more of a group A experience
while you are peaking. I’m not a scientist and I may be wrong about this, but
I think the antidepressant effects are not caused directly by the drug or
metabolites that one could become tolerant of. I think that they are a result
of the brain’s recent experience of looking at life from a non-depressed
perspective.

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eikenberry
"... lower than the abuse rates for other hallucinogens like ecstasy and LSD."

Ecstasy is a stimulant, not a hallucinogen. I thought bloomberg was generally
considered to be better at fact checking than that.

~~~
marcrosoft
Agreed, also LSD doesn't have a measurable abuse rate. It is literally anti-
abuse.

~~~
toomanybeersies
I think that in the article, abuse is used to mean illegal unintended use,
rather than abuse in the conventional sense.

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ChildOfChaos
Hmm but Prozac was never that great anyway.

There is very little evidence that depression is caused by chemical imbalance
in the brain, it's something that big pharma have sold you so they can sell
their drugs.

Great book on the topic, check out lost connections.

~~~
aaaaaaaaaaab
There’s very little evidence for a broken leg being caused by the lack of
plaster around it, yet nobody questions its efficacy...

~~~
wu-ikkyu
How is that comparable? Seems like a non sequitur

~~~
aaaaaaaaaaab
The treatment of a condition need not be the “inverse” of its cause.

A broken bone can be fixed by immobilizing it via a plaster cast. Did the bone
break due to the lack of plaster?

Eczema can be fixed by applying topical steroids. Did eczema develop due to
the lack of topical steroids?

Depression can be fixed by inducing changes in neurochemistry. Did depression
arise due to an imbalance in neurochemistry?

