7 ms·
Has esketamine been overhyped?
- HeavenBanned 7y agoThere'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.
- jacobush 7y ago“the FDA set a worrisome new precedent by allowing Janssen to use a “withdrawal” study as its second “positive” study. These studies tend to be slanted in favour of the test drug because they only consist of patients who responded well to the drug in the short-term trials. For this reason, they have never previously been deemed adequate in satisfying FDA requirements.” Sounds pretty damning
- logiclogic 7y agoAnd why not just regular old ketamine instead of a dangerous, untested new derivative? The whole system is broken beyond repair.
- La1n 7y agoIt 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 7y ago> 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 7y agoThe 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 7y agoPer my comment above, thalidomide is a clear exception. This stands even if the chirality changes within the body.
- rocqua 7y agoThat 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 7y agoAnd 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 7y agoI 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.
- soulofmischief 7y agoA 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.
- XMPPwocky 7y agoDo 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?
- kellerbw 7y agoThalidomide. One enantiomer is a great morning sickness drug, the other causes catastrophic birth defects.
- refurb 7y agoThalidomide interconverts in the body. There is no difference between the enantiomers in the human body (there is in a petri dish).
- tempguy9999 7y agoI'm not sure I understand the question[0] fully but thalidomide? https://en.wikipedia.org/wiki/Thalidomide https://en.wikipedia.org/wiki/Thalidomide "Thalidomide is provided as a racemic mixture of two enantiomers; while there are reports that only one of the enantiomers may cause birth defects, the body converts each enantiomer into the other through mechanisms that are not well understood." [0] because a racemic mixture (https://en.wikipedia.org/wiki/Racemates https://en.wikipedia.org/wiki/Racemates) is a 50/50 mix of enantiomers: "In chemistry, a racemic mixture, or racemate [...] has equal amounts of left- and right-handed enantiomers of a chiral molecule" so if you took a racemic mixture surely you'd be getting a combination of the enantiomers' effects?
- soulofmischief 7y agoAmphetamine, for one. Levoamphetamine or dextroamphetamine provide two different physiological experiences (think coffee vs meth). The effects profile of racemic amphetamine is markedly different and much easier to handle physiologically than just dextroamphetamine by itself (the most common isomer found in amphetamine prescription products). From a perspective of safety, I don't have any reason to suspect esketamine to be any worse. However from a psychological perspective, we could be talking pretty big differences in some individuals where subtle changes in behavior or thought can have cascading effects on mood. But... that's why we're testing its efficacy, right? It's stupid not to try, and these test subjects are willing. One of the two isomers will be better in some categories. Could be that both together are the way to go. Having only encountered racemic ketamine I can definitely understand its uses in treating depression.
- deleted 7y ago[deleted]
- gyuserbti 7y agoIt amazes me how the problems with our drug and medical regulation system never come up even when it's staring us in the face. This article is typical, framing it as a problem with pharm companies rather than with the regulatory system. Between stuff like this, the opioid crisis, and cannabis deregulation, it should be obvious how broken and monopolistic the system is (referring to the FDA, DEA, and medical licensure system).
- TheOtherHobbes 7y ago"Could" is nowhere close to good enough for a drug with potentially serious side-effects.
- cvshepherd 7y agothen you'd have to take literally every antidepressant off the market.
- tempguy9999 7y agoOh I dunno. A potentially serious side effect of clinical depression is death. See my other comment https://news.ycombinator.com/item?id=20572927 https://news.ycombinator.com/item?id=20572927 The side effects of prozac and gamanil for me weren't at all nice but they were far better than the blackness. In those circumstances, 'could' could be quite good enough for me.
- hannob 7y agoThe article has a pretty balanced view and several of the people asked say that esketamine could have some benefit for some patients. But other than that your statement doesn't make a lot of sense. Of course there can be everything wrong with a novel drug that "could" help with edge-cases. Because if you don't know if it helps and if it may harm people - it could very well do more harm than good. That's why we want robust science for new drugs: To decide whether they'll help more than harm.
- DanBC 7y agoI 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.
- logiclogic 7y agoSo 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?
- jakobegger 7y agoHoly 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...
- ggm 7y agoThe question about the control group is pretty important because the test subjects had to severely depressed to qualify (I believe)
- DanBC 7y agoThe drug is licensed for people with treatment resistant depression. This group has significantly higher risk of death by suicide. I dislike speculating on causes of suicides, but if they've been told "here's this thing that appears to give relief from depression for people like you", and they try it, and it doesn't, I can see how that would further increase their risk.
- Broken_Hippo 7y agoI 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 7y agoI 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.
- deleted 7y ago[deleted]
- LeanderK 7y agoI 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 7y agoYes, that's exactly the reason. They are filtering racemic Ketamine just so that they can patent and upsell it at exorbitant rates.
- rocqua 7y agoCan the results be used ti justify off-label use of normal ketamine?
- wickoff 7y agoThere 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 7y ago>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 7y agoThe 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.
- narag 7y agoAbout the safety: https://www.vice.com/en_us/article/nzdnak/why-ketamine-is-the-best-drug-on-earth https://www.vice.com/en_us/article/nzdnak/why-ketamine-is-th... 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.
- vincent-toups 7y agoCapitalism overhype a potential product? No way!