11 ms·

Ketamine blocks bursting in the lateral habenula to rapidly relieve depression

148 points by beefman 9y ago

Karunamon 9y ago
Obligatory working scihub link: http://sci-hub.tw/https://www.nature.com/articles/nature25509 http://sci-hub.tw/https://www.nature.com/articles/nature2550...
softbuilder 9y ago
From Wikipedia[1]: >The habenula receives input from the brain via the stria medullaris thalami and outputs to many midbrain areas involved in releasing neurotransmitters, such as dopamine, norepinephrine, and serotonin. [1 ]https://en.wikipedia.org/wiki/Habenula https://en.wikipedia.org/wiki/Habenula
rhombocombus 9y ago
It's so exciting that there is now a putative mechanism for this! Ketamine is such a curious drug, and this effect of it is one of the most interesting of all. Knowing the target will allow more focused therapies and possibly a greater understanding of depression in general.
starpilot 9y ago
I have been looking into Ketamine as there is a clinic which administers Ketamine therapy in my area. The disappointing thing is that it looks like the effects are short lived, and one may need "booster" treatments every 4 weeks, at $400 a shot, for years and possibly forever. I hope with this understanding, we come up with something more permanent.
- foobaw 9y ago
  curious: are you based in the US? Would it not be covered by insurance? $400/shot is a lot for Ketamine.
  - nylonstrung 9y ago
    Insurance absolutely does not cover ketamine therapy in the US
  - blobwalker 9y ago
    $400 is a fairly typical price. The ketamine itself is cheap, but operating a clinic doing off-label infusions that take an hour or two each is expensive. And nope... no insurance in the US that I know of covers it.
  - refurb 9y ago
    Ketamine is a generic drug and dirt cheap. I just checked and it's under $10 for a vial with enough to use in surgery, not even this setting. The $400 must be the clinic charge. I'm not sure what administration looks like, but a regular doctor's visit is $100-$150 and if the patient needs to stay for a longer period of time until it's safe to release them, $400 doesn't seem that far off of what you'd expect.
    - Praitor 9y ago
      That's on the low end. I've looked into it and seen prices on the order of $1000-1500 per treatment. If you filter those out, many metro areas simply have no provider that charges what would seem to be a justifiable price. Abusive pricing is a big problem for this product it seems. Several advocacy sites that I saw that maintain provider lists make note of this.
      - nefitty 9y ago
        Is it abusive pricing or are they covering for potential legal issues, etc? It would be great to hear from a clinician with first-hand experience.
        jessaustin 9y ago
        Is it abusive pricing... Medical clinic in USA? Signs point to "yes".
- contingencies 9y ago
  It's not that expensive on darknet markets.
  - cpncrunch 9y ago
    If I was going to use ketamine, I'd prefer to get it from a reputable source.
    - contingencies 9y ago
      Reputation is the key service of darknet markets. If you would prefer to pay $380 extra every four weeks, that's your call.
      - starpilot 9y ago
        Are darknet markets still easy to get into? I used SR when it was around, with events in the interim I'm a bit more hesitant.
        LaikaF 9y ago
        No, they're in a state of flux right now.
        goatsi 9y ago
        Things aren't as stable as there were in the past but the guides and supporting infrastructure has matured. Read around a bit at reddit.com/r/darknetmarketsnoobs (check out the noob bible especially) if you want to learn more.
      - cpncrunch 9y ago
        By reputable I mean manufactured in an approved facility to Health Canada standards (or equivalent). It seems unlikely that some dude on darknet would meet these standards. It's like saying that your local drug dealer has a good reputation because he hasn't killed too many people with fentanyl.
- cpncrunch 9y ago
  $400/month seems a very cheap price for getting your life back.
  - benevol 9y ago
    I agree that $10/session does sound better. That's what you pay (at most) for LSD, the traditional longer-term anti-depressive and anti-anxiety effect being there as well (3-6 months). But: You have to buy a test kit (an additional $25/kit) and be extremely well informed about what do to and what not to do. And plan everything in detail and very carefully. Don't expect miracles if you're not serious about it.
    - atomical 9y ago
      Who are you agreeing with? This is really dangerous advice.
    - sterlind 9y ago
      as much as I love LSD, it's by no means a safe drug for severe clinical depression. bad trips can easily push someone over the edge, especially if they have suicidal ideation. ketamine, on the other hand, has a MoA that doesn't depend on how well the trip went. it's also a known quantity to doctors and far safer and more predictable. please do not encourage severely depressed people to try acid.
- atomical 9y ago
  $325-$350 - Albuquerque $500-600 - Chicago Area $900 - Seattle $1000 - LA It's actually cheaper to fly in to the cheapest center. Ketamine as a drug is safe and cheap. Probably somewhere around $5 a vial. But the doctors are taking a risk with their license and you they have to put an IV in you.
lazerpants 9y ago
This is actually one of two papers published by the lab in Nature. The papers together go much further than just describing the mechanism of action of ketamine and propose a potential mechanism for a cause of depression. Kir4.1 paper: https://www.nature.com/articles/nature25752 https://www.nature.com/articles/nature25752
- jtmcmc 9y ago
  This is really great. I'm excited to read these fully unpaywalled later. I'm interested to see how they'll test this in humans PET or fMRI scanning perhaps possibly before/after depressed patients taking antidepressants/therapy/ketamine/etc...
Ophelias_Rue 9y ago
I know it's anecdotal, but I've been receiving ketamine at a local clinic for a few years for chronic depression and a spinal injury. It has proven too be the most effective treatment I've had for treating depression. As another poster said, it is short lived (around two months) But the release from depression, and back pain is life changing for me. To go with the article, it is incredibly fast acting. Like same day results, I don't know if it's placebo or the ketamine but I'm happy with it as it gave me life back.
- mabbo 9y ago
  You get this done at a clinic- what's the effects like? I've heard terms like "K-hole" for heavy off-prescription users getting zonked by the stuff. I'm assuming you're taking a light dose? Can you drive yourself home?
  - blobwalker 9y ago
    I generally leave my clinic about half an hour after my infusion ends, but I'm taking the subway. If I were going to drive I'd probably hang out for 60-90 minutes. The dissociative and psychotomimetic effects wear off pretty quickly. But this depends on dose... my doc used to use higher doses before there was as much research around what works, and back then it would sometimes take a few hours before I felt back to normal in terms of cognitive and motor skills.
    - Ophelias_Rue 9y ago
      I'm in the opposite boat, the dose I receive is fairly high and I'm unable to even stand for around 20 minutes after it ends. There's no way I can drive the day of. As for the events, the feeling of dissociation takes around a day to fade for me. I also have a high deal of cognitive impairment from it, or detachment in my thoughts?
      - unixhero 9y ago
        Is enjoyable?
oceanghost 9y ago
This really, really works. I experimented for years with it after reading about trials. I'd be happy to answer questions.
- starpilot 9y ago
  Where did you get it, and how did you administer it?
  - oceanghost 9y ago
    Ketamine is available both as a veterinary medicine and is used as an emergency anesthetic (usually for setting broken bones) because it doesn't require an anesthesiologist. Where I obtained it-- Darknet. I used veterinary needles to do an IM injection. There are also analogues that can be snorted.
    - deleted 9y ago
      [deleted]
    - starpilot 9y ago
      How is the darknet these days? I used SR when it was around. Is it still that easy?
      - oceanghost 9y ago
        I wouldn't recommend it at this moment. The powers that be did a pretty good job of knocking a lot of vendors offline-- then the runup in bitcoin made exit scams attractive while simultaneously making it cost a fortune to tumble/transfer.
- atomical 9y ago
  Did you administer it with IV or intramuscular? If not, it's completely different from how the studies are conducted.
  - 9y ago
newnewpdro 9y ago
Isn't regular Ketamine use especially bad for the bladder? I recall reading multiple anecdotes from the Erowid ketamine vaults where people lost their bladders due to recreational Ketamine use.
- jtmcmc 9y ago
  yes https://www.ncbi.nlm.nih.gov/pubmed/27001627 https://www.ncbi.nlm.nih.gov/pubmed/27001627
  - newnewpdro 9y ago
    Why is this being downvoted?
- IntronExon 9y ago
  As the other poster said, yes. China is dealing with a fairly grim pattern of ketamine abuse cystitis. https://www.sciencedirect.com/science/article/pii/S1879522615004121 https://www.sciencedirect.com/science/article/pii/S187952261... http://www.bbc.com/news/av/world-asia-china-33472971/inside-a-chinese-ketamine-village http://www.bbc.com/news/av/world-asia-china-33472971/inside-...
- blobwalker 9y ago
  It's a huge problem for recreational use. Some individuals have trouble with it even with prescription ketamine, but it's not nearly as common. Last time I asked him, my doctor hasn't had any patients who were forced to discontinue treatment because of it. n=1, but I've been receiving ketamine therapy for about 6 years and have not developed ketamine cystitis.
  - collyw 9y ago
    Are recreational doses significantly higher than prescription doses? Why the difference?
    - deleted 9y ago
      [deleted]
aaavl2821 9y ago
i did some work around ketamine a few years ago and many physicians i spoke with said it was incredibly helpful for their patients. however there are many others who have said it doesnt work for many of their patients. there are many studies that suggest it works and a lot of other unpublished data suggesting maybe it isnt as great the mechanism of action is also poorly understood, and while this article may certainly be an important mechanism, ketamine is a "dirty" drug with many potentially active components that act in ways we dont understand ketamine is also a drug that has been fda approved for anesthesia for years. to properly study its effects in depression would require large clinical studies. however, the drug is off patent, and no company will fund this work other companies have developed "new" drugs that are structurally similar to ketamine, but different enough to patent. in 2015 allergan bought a company called naurex that had a few phase 2 drugs that acted on the NMDA receptor (the main receptor that ketamine is thought to act on, though there are others -- hence it being a "dirty" drug) but with some chemical modifications aimed at getting the antidepressant effects of ketamine without the "bad" dissociative effects. however, several docs i spoke with said that there isnt sufficient evidence that their chemical only gets the "good" effects, and it may actually be less effective than ketamine because they removed some of the chemical structure that moderated depression. the real reason they used a new chemical was so they could patent it J&J has another similar product, called esketamine, is an enantiomer of ketamine (imagine ketamine occurred in two forms, a left hand and a right hand one. esketamine is just the left hand version without the right hand). they also deliver it intranasally (while the approved ketamine formulation is IV). both of these tactics help extend patent life or exclusivity. they published phase 2 data last december that looked pretty good these companies will probably aggressively market their drugs as "better" than ketamine because they have "improved" the chemistry, although there are no data to definitively state this. many anesthesiologists currently offer ketamine treatment for depression, though it is not widely reimbursed or offered. i believe some groups reimburse for it though. it can be expensive because you need to be supervised when you take it, so you have to pay for the time of a medical professional to monitor you. as others have noted though, the effects wear off basically right after you stop taking the drug. some people are studying a protocol where you "jolt" someone into a non-depressed state with ketamine, and then stop ketamine treatment and start treating them with CBT or another form of therapy. jury is still out on whether this works though seems promising
pdfernhout 9y ago
Some alternatives for improving depression: https://news.ycombinator.com/item?id=15455259 https://news.ycombinator.com/item?id=15455259
rincebrain 9y ago
Ketamine was both the best and most depressing depression treatment option I've ever tried. Within a couple of weeks after having had the initial round of six treatments in two weeks, I was the most functional and productive human being I've _ever_ been - things that used to be impossible or utterly agonizing to complete were as trivial as they "should" be, I was enjoying life, it was great. After a couple of months of periodic booster treatments, over the course of a week, I felt it completely drain out of me, and no variance or repetition of ketamine treatments has been able to reproduce it since. (We spent months varying dosage levels, frequency, and trying a few OTC things that the doctor had seen synergize ketamine response in people before, to no avail.) It was...possibly the single worst experience of my life, feeling that slip away, and now having recent crystal-clear memories of how much that fog had been complicating my life.
no_identd 9y ago
Reminder that the FDA seems to fast track the wrong drug: They gave "breakthrough designation" ( https://en.wikipedia.org/wiki/Breakthrough_therapy https://en.wikipedia.org/wiki/Breakthrough_therapy ) to Esketamine under pressure from Johnson & Johnson: https://en.wikipedia.org/wiki/Esketamine#Depression https://en.wikipedia.org/wiki/Esketamine#Depression Although Arketamine seems like it has a lot more responsibility for the antidepressant effect of racemic ketamine: https://en.wikipedia.org/wiki/Arketamine#Novel_antidepressant https://en.wikipedia.org/wiki/Arketamine#Novel_antidepressan... https://en.wikipedia.org/wiki/Hydroxynorketamine https://en.wikipedia.org/wiki/Hydroxynorketamine https://www.ncbi.nlm.nih.gov/pubmed/24316345 https://www.ncbi.nlm.nih.gov/pubmed/24316345 (2013) http://www.cpn.or.kr/journal/view.html?doi=10.9758/cpn.2014.12.1.72 http://www.cpn.or.kr/journal/view.html?doi=10.9758/cpn.2014.... (2014) https://www.ncbi.nlm.nih.gov/pubmed/26327690 https://www.ncbi.nlm.nih.gov/pubmed/26327690 (2015) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4910398/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4910398/ (2016) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487269/#__sec4title https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487269/#__sec4... (2017) That isn't to say Esketamine doesn't have an antidepressant effect. In light of the fact that Esketamine makes you Trip Balls(tm) while Arketamine doesn't, I like to think of it this way: You can likely get an antidepressant effect out of Esketamine in the same way that you can get an antidepressant effect out of psychdelics like LSD-25 & Psilocin. However, like those, it could possibly also make depression worse, and unlike Arketamine doesn't seem to represent anything awfully novel. It however also makes me suspect that like with other racemic drugs like Amphetamine, a shifted ratio preparation might make for a better drug overall than isolating the stereoisomers. For example, Adderall contains 75% dexamphetamine, 25% levoamphetamine, in the form of various amphetamine salts (wheras racemic amphetamine contains 50% of each, typically as a single salt.). [Semi-related: I still don't comprehend why pharmaceutical companies have yet to create a combination preparation of Lisdexamfetamine with something like Lislevoamfetamine, - which I haven't seen synthesized but I don't see anything speaking against it -, in a ratio akin to the one seen in Adderall. The rational behind that ratio seems sound, albeit I'd perhaps go for an 80/20 split instead of a 75/25 split...]

148 points by beefman 9y ago

Obligatory working scihub link: http://sci-hub.tw/https://www.nature.com/articles/nature25509 http://sci-hub.tw/https://www.nature.com/articles/nature2550...

softbuilder 9y ago

From Wikipedia[1]: >The habenula receives input from the brain via the stria medullaris thalami and outputs to many midbrain areas involved in releasing neurotransmitters, such as dopamine, norepinephrine, and serotonin. [1 ]https://en.wikipedia.org/wiki/Habenula https://en.wikipedia.org/wiki/Habenula

rhombocombus 9y ago

It's so exciting that there is now a putative mechanism for this! Ketamine is such a curious drug, and this effect of it is one of the most interesting of all. Knowing the target will allow more focused therapies and possibly a greater understanding of depression in general.

starpilot 9y ago

I have been looking into Ketamine as there is a clinic which administers Ketamine therapy in my area. The disappointing thing is that it looks like the effects are short lived, and one may need "booster" treatments every 4 weeks, at $400 a shot, for years and possibly forever. I hope with this understanding, we come up with something more permanent.

foobaw 9y ago
curious: are you based in the US? Would it not be covered by insurance? $400/shot is a lot for Ketamine.
- nylonstrung 9y ago
  Insurance absolutely does not cover ketamine therapy in the US
- blobwalker 9y ago
  $400 is a fairly typical price. The ketamine itself is cheap, but operating a clinic doing off-label infusions that take an hour or two each is expensive. And nope... no insurance in the US that I know of covers it.
- refurb 9y ago
  Ketamine is a generic drug and dirt cheap. I just checked and it's under $10 for a vial with enough to use in surgery, not even this setting. The $400 must be the clinic charge. I'm not sure what administration looks like, but a regular doctor's visit is $100-$150 and if the patient needs to stay for a longer period of time until it's safe to release them, $400 doesn't seem that far off of what you'd expect.
  - Praitor 9y ago
    That's on the low end. I've looked into it and seen prices on the order of $1000-1500 per treatment. If you filter those out, many metro areas simply have no provider that charges what would seem to be a justifiable price. Abusive pricing is a big problem for this product it seems. Several advocacy sites that I saw that maintain provider lists make note of this.
    - nefitty 9y ago
      Is it abusive pricing or are they covering for potential legal issues, etc? It would be great to hear from a clinician with first-hand experience.
      - jessaustin 9y ago
        Is it abusive pricing... Medical clinic in USA? Signs point to "yes".
contingencies 9y ago
It's not that expensive on darknet markets.
- cpncrunch 9y ago
  If I was going to use ketamine, I'd prefer to get it from a reputable source.
  - contingencies 9y ago
    Reputation is the key service of darknet markets. If you would prefer to pay $380 extra every four weeks, that's your call.
    - starpilot 9y ago
      Are darknet markets still easy to get into? I used SR when it was around, with events in the interim I'm a bit more hesitant.
      - LaikaF 9y ago
        No, they're in a state of flux right now.
      - goatsi 9y ago
        Things aren't as stable as there were in the past but the guides and supporting infrastructure has matured. Read around a bit at reddit.com/r/darknetmarketsnoobs (check out the noob bible especially) if you want to learn more.
    - cpncrunch 9y ago
      By reputable I mean manufactured in an approved facility to Health Canada standards (or equivalent). It seems unlikely that some dude on darknet would meet these standards. It's like saying that your local drug dealer has a good reputation because he hasn't killed too many people with fentanyl.
cpncrunch 9y ago
$400/month seems a very cheap price for getting your life back.
- benevol 9y ago
  I agree that $10/session does sound better. That's what you pay (at most) for LSD, the traditional longer-term anti-depressive and anti-anxiety effect being there as well (3-6 months). But: You have to buy a test kit (an additional $25/kit) and be extremely well informed about what do to and what not to do. And plan everything in detail and very carefully. Don't expect miracles if you're not serious about it.
  - atomical 9y ago
    Who are you agreeing with? This is really dangerous advice.
  - sterlind 9y ago
    as much as I love LSD, it's by no means a safe drug for severe clinical depression. bad trips can easily push someone over the edge, especially if they have suicidal ideation. ketamine, on the other hand, has a MoA that doesn't depend on how well the trip went. it's also a known quantity to doctors and far safer and more predictable. please do not encourage severely depressed people to try acid.
atomical 9y ago
$325-$350 - Albuquerque $500-600 - Chicago Area $900 - Seattle $1000 - LA It's actually cheaper to fly in to the cheapest center. Ketamine as a drug is safe and cheap. Probably somewhere around $5 a vial. But the doctors are taking a risk with their license and you they have to put an IV in you.

lazerpants 9y ago

This is actually one of two papers published by the lab in Nature. The papers together go much further than just describing the mechanism of action of ketamine and propose a potential mechanism for a cause of depression. Kir4.1 paper: https://www.nature.com/articles/nature25752 https://www.nature.com/articles/nature25752

jtmcmc 9y ago
This is really great. I'm excited to read these fully unpaywalled later. I'm interested to see how they'll test this in humans PET or fMRI scanning perhaps possibly before/after depressed patients taking antidepressants/therapy/ketamine/etc...

Ophelias_Rue 9y ago

I know it's anecdotal, but I've been receiving ketamine at a local clinic for a few years for chronic depression and a spinal injury. It has proven too be the most effective treatment I've had for treating depression. As another poster said, it is short lived (around two months) But the release from depression, and back pain is life changing for me. To go with the article, it is incredibly fast acting. Like same day results, I don't know if it's placebo or the ketamine but I'm happy with it as it gave me life back.

mabbo 9y ago
You get this done at a clinic- what's the effects like? I've heard terms like "K-hole" for heavy off-prescription users getting zonked by the stuff. I'm assuming you're taking a light dose? Can you drive yourself home?
- blobwalker 9y ago
  I generally leave my clinic about half an hour after my infusion ends, but I'm taking the subway. If I were going to drive I'd probably hang out for 60-90 minutes. The dissociative and psychotomimetic effects wear off pretty quickly. But this depends on dose... my doc used to use higher doses before there was as much research around what works, and back then it would sometimes take a few hours before I felt back to normal in terms of cognitive and motor skills.
  - Ophelias_Rue 9y ago
    I'm in the opposite boat, the dose I receive is fairly high and I'm unable to even stand for around 20 minutes after it ends. There's no way I can drive the day of. As for the events, the feeling of dissociation takes around a day to fade for me. I also have a high deal of cognitive impairment from it, or detachment in my thoughts?
    - unixhero 9y ago
      Is enjoyable?

oceanghost 9y ago

This really, really works. I experimented for years with it after reading about trials. I'd be happy to answer questions.

starpilot 9y ago
Where did you get it, and how did you administer it?
- oceanghost 9y ago
  Ketamine is available both as a veterinary medicine and is used as an emergency anesthetic (usually for setting broken bones) because it doesn't require an anesthesiologist. Where I obtained it-- Darknet. I used veterinary needles to do an IM injection. There are also analogues that can be snorted.
  - deleted 9y ago
    [deleted]
  - starpilot 9y ago
    How is the darknet these days? I used SR when it was around. Is it still that easy?
    - oceanghost 9y ago
      I wouldn't recommend it at this moment. The powers that be did a pretty good job of knocking a lot of vendors offline-- then the runup in bitcoin made exit scams attractive while simultaneously making it cost a fortune to tumble/transfer.
atomical 9y ago
Did you administer it with IV or intramuscular? If not, it's completely different from how the studies are conducted.
- 9y ago

newnewpdro 9y ago

Isn't regular Ketamine use especially bad for the bladder? I recall reading multiple anecdotes from the Erowid ketamine vaults where people lost their bladders due to recreational Ketamine use.

jtmcmc 9y ago
yes https://www.ncbi.nlm.nih.gov/pubmed/27001627 https://www.ncbi.nlm.nih.gov/pubmed/27001627
- newnewpdro 9y ago
  Why is this being downvoted?
IntronExon 9y ago
As the other poster said, yes. China is dealing with a fairly grim pattern of ketamine abuse cystitis. https://www.sciencedirect.com/science/article/pii/S1879522615004121 https://www.sciencedirect.com/science/article/pii/S187952261... http://www.bbc.com/news/av/world-asia-china-33472971/inside-a-chinese-ketamine-village http://www.bbc.com/news/av/world-asia-china-33472971/inside-...
blobwalker 9y ago
It's a huge problem for recreational use. Some individuals have trouble with it even with prescription ketamine, but it's not nearly as common. Last time I asked him, my doctor hasn't had any patients who were forced to discontinue treatment because of it. n=1, but I've been receiving ketamine therapy for about 6 years and have not developed ketamine cystitis.
- collyw 9y ago
  Are recreational doses significantly higher than prescription doses? Why the difference?
  - deleted 9y ago
    [deleted]

aaavl2821 9y ago

i did some work around ketamine a few years ago and many physicians i spoke with said it was incredibly helpful for their patients. however there are many others who have said it doesnt work for many of their patients. there are many studies that suggest it works and a lot of other unpublished data suggesting maybe it isnt as great the mechanism of action is also poorly understood, and while this article may certainly be an important mechanism, ketamine is a "dirty" drug with many potentially active components that act in ways we dont understand ketamine is also a drug that has been fda approved for anesthesia for years. to properly study its effects in depression would require large clinical studies. however, the drug is off patent, and no company will fund this work other companies have developed "new" drugs that are structurally similar to ketamine, but different enough to patent. in 2015 allergan bought a company called naurex that had a few phase 2 drugs that acted on the NMDA receptor (the main receptor that ketamine is thought to act on, though there are others -- hence it being a "dirty" drug) but with some chemical modifications aimed at getting the antidepressant effects of ketamine without the "bad" dissociative effects. however, several docs i spoke with said that there isnt sufficient evidence that their chemical only gets the "good" effects, and it may actually be less effective than ketamine because they removed some of the chemical structure that moderated depression. the real reason they used a new chemical was so they could patent it J&J has another similar product, called esketamine, is an enantiomer of ketamine (imagine ketamine occurred in two forms, a left hand and a right hand one. esketamine is just the left hand version without the right hand). they also deliver it intranasally (while the approved ketamine formulation is IV). both of these tactics help extend patent life or exclusivity. they published phase 2 data last december that looked pretty good these companies will probably aggressively market their drugs as "better" than ketamine because they have "improved" the chemistry, although there are no data to definitively state this. many anesthesiologists currently offer ketamine treatment for depression, though it is not widely reimbursed or offered. i believe some groups reimburse for it though. it can be expensive because you need to be supervised when you take it, so you have to pay for the time of a medical professional to monitor you. as others have noted though, the effects wear off basically right after you stop taking the drug. some people are studying a protocol where you "jolt" someone into a non-depressed state with ketamine, and then stop ketamine treatment and start treating them with CBT or another form of therapy. jury is still out on whether this works though seems promising

pdfernhout 9y ago

Some alternatives for improving depression: https://news.ycombinator.com/item?id=15455259 https://news.ycombinator.com/item?id=15455259

rincebrain 9y ago

Ketamine was both the best and most depressing depression treatment option I've ever tried. Within a couple of weeks after having had the initial round of six treatments in two weeks, I was the most functional and productive human being I've _ever_ been - things that used to be impossible or utterly agonizing to complete were as trivial as they "should" be, I was enjoying life, it was great. After a couple of months of periodic booster treatments, over the course of a week, I felt it completely drain out of me, and no variance or repetition of ketamine treatments has been able to reproduce it since. (We spent months varying dosage levels, frequency, and trying a few OTC things that the doctor had seen synergize ketamine response in people before, to no avail.) It was...possibly the single worst experience of my life, feeling that slip away, and now having recent crystal-clear memories of how much that fog had been complicating my life.

no_identd 9y ago

Reminder that the FDA seems to fast track the wrong drug: They gave "breakthrough designation" ( https://en.wikipedia.org/wiki/Breakthrough_therapy https://en.wikipedia.org/wiki/Breakthrough_therapy ) to Esketamine under pressure from Johnson & Johnson: https://en.wikipedia.org/wiki/Esketamine#Depression https://en.wikipedia.org/wiki/Esketamine#Depression Although Arketamine seems like it has a lot more responsibility for the antidepressant effect of racemic ketamine: https://en.wikipedia.org/wiki/Arketamine#Novel_antidepressant https://en.wikipedia.org/wiki/Arketamine#Novel_antidepressan... https://en.wikipedia.org/wiki/Hydroxynorketamine https://en.wikipedia.org/wiki/Hydroxynorketamine https://www.ncbi.nlm.nih.gov/pubmed/24316345 https://www.ncbi.nlm.nih.gov/pubmed/24316345 (2013) http://www.cpn.or.kr/journal/view.html?doi=10.9758/cpn.2014.12.1.72 http://www.cpn.or.kr/journal/view.html?doi=10.9758/cpn.2014.... (2014) https://www.ncbi.nlm.nih.gov/pubmed/26327690 https://www.ncbi.nlm.nih.gov/pubmed/26327690 (2015) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4910398/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4910398/ (2016) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487269/#__sec4title https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487269/#__sec4... (2017) That isn't to say Esketamine doesn't have an antidepressant effect. In light of the fact that Esketamine makes you Trip Balls(tm) while Arketamine doesn't, I like to think of it this way: You can likely get an antidepressant effect out of Esketamine in the same way that you can get an antidepressant effect out of psychdelics like LSD-25 & Psilocin. However, like those, it could possibly also make depression worse, and unlike Arketamine doesn't seem to represent anything awfully novel. It however also makes me suspect that like with other racemic drugs like Amphetamine, a shifted ratio preparation might make for a better drug overall than isolating the stereoisomers. For example, Adderall contains 75% dexamphetamine, 25% levoamphetamine, in the form of various amphetamine salts (wheras racemic amphetamine contains 50% of each, typically as a single salt.). [Semi-related: I still don't comprehend why pharmaceutical companies have yet to create a combination preparation of Lisdexamfetamine with something like Lislevoamfetamine, - which I haven't seen synthesized but I don't see anything speaking against it -, in a ratio akin to the one seen in Adderall. The rational behind that ratio seems sound, albeit I'd perhaps go for an 80/20 split instead of a 75/25 split...]