Hacker News Board Hacker News, browsed like a classic message board
Live data from Hacker News

Has esketamine been overhyped?

gq-magazine.co.uk

Post reply on HN
Print view View original

41–50 of 51 posts

Re: Has esketamine been overhyped?

#41

Post by wickoff »

navigatesol wrote: post #39
wickoff wrote: post #35

Earlier quoted context omitted.

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.

> 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?

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.

Re: Has esketamine been overhyped?

#43

Post by Nasrudith »

rocqua wrote: post #29
tempguy9999 wrote: post #27

Earlier quoted context omitted.

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

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.

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".

Re: Has esketamine been overhyped?

#44

Post by Nasrudith »

LeanderK wrote: post #21

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)?

Vector of action is another reason - a nasal spray is far friendlier than injection. Although I don't know why that can't or shouldn't be done for ketamine.

Re: Has esketamine been overhyped?

#45

Post by logiclogic »

DanBC wrote: post #19
HeavenBanned wrote: post #2

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.

I think people with severe treatment-resistant depression deserve treatment that is safe and effective. The problem is that we have a drug that has a similar mechanism of action, and that we know is more effective than eskatamine. That's ketamine infusions. We don't use that because it doesn't have a licence for this use, and because infusions are expensive and time consuming. But also, it's off-patent and so it's ha…

So now patients will be offered to receive ketamine to treat their depressions, the drug they read so much about on the internet. But this time they'll get the RC Special K. Do you think the doctor will tell them all about the difference or just call it K?

Re: Has esketamine been overhyped?

#46

Post by tempguy9999 »

Nasrudith wrote: post #43
rocqua wrote: post #29

Earlier quoted context omitted.

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.

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 isola…

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.

Re: Has esketamine been overhyped?

#47

Post by soulofmischief »

jazoom wrote: post #34
XMPPwocky wrote: post #20

Earlier quoted context omitted.

Do you know of any examples where a racemic mixture has an effect dramatically different from what you'd expect from a combination of the enantiomers' effects?

Commenters so far haven't actually answered your question. They just gave examples where the 2 enantiomers have different effects. There are countless examples of these since our bodies' molecules naturally have "handedness". What you were essentially asking was would 100% of the "bad" enantiomer be significantly worse than a 50/50 mixture. This is the real question here. For there to be a significant difference in t…

> What you were essentially asking was would 100% of the "bad" enantiomer be significantly worse than a 50/50 mixture.

I literally said:

> The effects profile of racemic amphetamine is markedly different and much easier to handle physiologically than just dextroamphetamine by itself

I did answer the question... exactly as OP asked.

> For there to be a significant difference in this case one of the ketamine enantiomers would need to counteract the other's ill effects.

This is precisely the case with amphetamine, where levoamphetamine is more relaxing and subtle and dextroamphetamine is much more physiologically demanding. A racemic mixture provides the perfect combination of effects whereas just dextroamphetamine by itself can be pretty rough on you.

The difference in effect can be quite profound and drastically change your mood and behavior. I would know because I was force fed large amounts of amphetamines for my entire childhood. Name it and I've been prescribed to it.

Re: Has esketamine been overhyped?

#48

Post by jazoom »

soulofmischief wrote: post #47
jazoom wrote: post #34

Earlier quoted context omitted.

Commenters so far haven't actually answered your question. They just gave examples where the 2 enantiomers have different effects. There are countless examples of these since our bodies' molecules naturally have "handedness". What you were essentially asking was would 100% of the "bad" enantiomer be significantly worse than a 50/50 mixture. This is the real question here. For there to be a significant difference in t…

> What you were essentially asking was would 100% of the "bad" enantiomer be significantly worse than a 50/50 mixture. I literally said: > The effects profile of racemic amphetamine is markedly different and much easier to handle physiologically than just dextroamphetamine by itself I did answer the question... exactly as OP asked. > For there to be a significant difference in this case one of the ketamine enantiomer…

So a double strength dose of the racemic mixture has a much milder effect than a single strength dose of the strong enantiomer?

Re: Has esketamine been overhyped?

#49

Post by soulofmischief »

jazoom wrote: post #48
soulofmischief wrote: post #47

Earlier quoted context omitted.

> What you were essentially asking was would 100% of the "bad" enantiomer be significantly worse than a 50/50 mixture. I literally said: > The effects profile of racemic amphetamine is markedly different and much easier to handle physiologically than just dextroamphetamine by itself I did answer the question... exactly as OP asked. > For there to be a significant difference in this case one of the ketamine enantiomer…

So a double strength dose of the racemic mixture has a much milder effect than a single strength dose of the strong enantiomer?

> So a double strength dose of the racemic mixture has a much milder effect than a single strength dose of the strong enantiomer?

Is that the angle here? I thought we were comparing the total mass of each substance. OP asked about noticeable differences, not paradoxical effects. 25mg of dextro is obviously going to have a weaker overall effect than 50mg of racemic amp.

But that's not what OP asked and it's not the context. The context is whether esketamine and racemic ketamine could provide a noticeably different experience. And the answer is yes. Just like amphetamine, the ketamine isomers have similar pharmacokinetic properties but not necessarily similarly pharmacodynamic properties.

Re: Has esketamine been overhyped?

#50

Post by jazoom »

soulofmischief wrote: post #49
jazoom wrote: post #48

Earlier quoted context omitted.

So a double strength dose of the racemic mixture has a much milder effect than a single strength dose of the strong enantiomer?

> So a double strength dose of the racemic mixture has a much milder effect than a single strength dose of the strong enantiomer? Is that the angle here? I thought we were comparing the total mass of each substance. OP asked about noticeable differences, not paradoxical effects. 25mg of dextro is obviously going to have a weaker overall effect than 50mg of racemic amp. But that's not what OP asked and it's not the co…

You do realise we can prescribe whatever dose we like, right? Some drugs I prescribe in grams, some in milligrams and some in micrograms. The strength of a drug is somewhat irrelevant. I'm not going to prescribe a new and expensive drug just because the dose is 150mg when it's well-established, cheap cousin is available that happens to need a dose of 300mg.

It certainly is the context, and I believe it's what OP asked. If it wasn't, it should be, because it's the only question that really matters to me as the prescriber.

If what you're saying about the different pharmacodynamics is true (and this is actually what I'm talking about. I only mentioned milder effect because that seemed to be the difference in pharmacodynamics you were getting at), then this is an important difference. It would still have to somehow be quite different to the effect of the racemic version at any arbitrary dose to be preferentially prescribed.

Post reply on HN