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Has esketamine been overhyped?

gq-magazine.co.uk

11–20 of 51 posts

Re: Has esketamine been overhyped?

#11

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.

"Could" is nowhere close to good enough for a drug with potentially serious side-effects.

then you'd have to take literally every antidepressant off the market.

Re: Has esketamine been overhyped?

#12

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.

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

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.

Re: Has esketamine been overhyped?

#13

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 phar…

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.

Re: Has esketamine been overhyped?

#14
post #12

Earlier quoted context omitted.

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

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.

> 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?

Re: Has esketamine been overhyped?

#15
post #12

Earlier quoted context omitted.

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.

> 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?

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.

Re: Has esketamine been overhyped?

#16

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 phar…

There's definitely a readjustment period where your brain tries to reach homeostasis again, which can lead to depressive episodes. But it's important to remember these people were likely morbidly depressed to begin with, and taking ketamine trials was an act of desperation.

Re: Has esketamine been overhyped?

#17
post #12

Earlier quoted context omitted.

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

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.

A lot of chemicals are "50%" of each other but completely different. That's not how chemistry works.

Water is H₂0. Hydrogen peroxide is H₂0₂. I wouldn't substitute one for the other.

Re: Has esketamine been overhyped?

#18
post #12

Earlier quoted context omitted.

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.

> 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?

Not a biologist or chemist either, but I'll try to give my layperson understanding: basically, many molecules exist in two different versions which are mirror images of each other (enantiomers). Most drugs are actually an equal mixture of both enantiomers (called a racemic mixture), but often only one of the enantiomers has the desired drug effect, and the other doesn't actually do anything. It is possible to create a drug which has only the effective enantiomer; usually, a pure dose of the effective enantiomer will be effective at half the dose as the racemic mixture. Medically, there are some advantages – both forms need to be metabolised by the liver, so being able to use half the dose to get the same effect gives the liver less work to do, which can reduce the risk of drug-induced liver injury. If the racemic mixture is already being widely used, then the risk of the pure effective enantiomer is likely to be low, since it is basically just a more effective form of the already used drug, and the side effect profile should be similar to the existing drug. Chemically, the manufacturing process is more complex, which adds to manufacturing costs; however, the main driver of additional costs is that you can get a new patent for the active enantiomer even after the patent on the racemic mixture is expired. For example, the common SSRI anti-depressant citalopram is the racemic mixture, whereas escitalopram is the S-enantiomer. Similarly, esketamine would be the S-enantiomer of ketamine.

Re: Has esketamine been overhyped?

#19

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 hard to make money from it.

Eskatamine only exists to bring a patentable medication to market, and so far the testing we have show it doesn't work particularly well.

Re: Has esketamine been overhyped?

#20
post #12

Earlier quoted context omitted.

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.

A lot of chemicals are "50%" of each other but completely different. That's not how chemistry works. Water is H₂0. Hydrogen peroxide is H₂0₂. I wouldn't substitute one for the other.

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?
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