Ketamine has 'fast-acting benefits' for depression
bbc.co.uk
bbc.co.uk
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.
similarly for ketamine.
Oh well, you learn something new every day.
A couple of antipsychotics or even more esoteric drug types are used (off-label and otherwise) for antidepressant effects, often at dosages lower than they'd usually be thought to be effective for whatever the primary usage would be. Why does it work? Ask again in 50 years, maybe.
- Seroquel (off-label)
- Adderall/Ritalin for people with drive problems
- Wellbutrin is a smoking addiction aid, antidepressant, and SAD-specific antidepressant (because why not, biochemistry)
- Strattera is nominally an ADHD med but has been using it as an antidepressant off-label for at least 15y (source: I was given it for that, then)
- Abilify is on-label used as an anti-psychotic, anti-depressant augment, and Tourette's med, because again, why not
- Also, one thing a lot of people don't realize is that you don't want to mix a unipolar antidepressant with untreated bipolar, because surprise, side effects may include P(manic episodes) approaching 1, so the options for each of those can sometimes overlap and sometimes not
Biochemistry is really weird, and neurochemistry is one of the densest places for it in the body.
What you said makes perfect sense to me. My reply was just me being surprised by someone who apparently got an antipsychotic for clinical depression alone (... which turned out to not be the case, but yeah...)
It doesn’t “cure” depression... it’s more like it gives you an audience with... something... that then tells you exactly what you need to know about life, the universe, and everything. It’s up to you to then make sense of it, integrate, and execute, which can in itself be difficult for people.
It’s not a cure, it’s a debugger for your brain.
With all psychedelics, it's very important to integrate the insights you gain during the experience back in to your ordinary life, or they are likely to fade.
It's also important to use psychedelics constructively: with a constructive intention, with an experienced sitter that you trust, in a safe setting. There are lots of other things one can do to prepare. I'd recommend reading "The Secret Chief Revealed" and "The Psychedelic Explorer's Guide".[1][2]
[1] - https://www.amazon.com/Secret-Chief-Revealed-Myron-Stolaroff...
[2] - https://www.amazon.com/Psychedelic-Explorers-Guide-Therapeut...
I think Ketamine itself isn't a real solution but hopefully some of the isolated metabolites will be
I know some people have been on it for an extended interval without any sort of tolerance problem, which is how I initially heard about it firsthand, so it's one more of those strange biochemistry things that's inconsistent, because of course it is.
The interesting thing, to me, would be figuring out what the method of action is for the effect, in order to replicate it in other drugs, but we'll see.
(I'm also curious whether repeating the dense dosages would be effective again for me now, over a year later, or whether the tolerance would be, indeed, permanent.)
We tried increasing the dosage, which made the dissociation more potent, but had no improved psychiatric benefits for me.
This was specifically and prominently addressed by the article:
>> However, at 25 days the effects had levelled out.
>> The study's authors suggest it could offer an effective rapid treatment for people severely depressed and at imminent risk of suicide and could help in the initial stages of treatment, as most anti-depressants take four to six weeks to become fully effective.
They see it as a bridge treatment which is temporarily useful until anti-depressants kick in. Because, as it said, after 25 days the benefits begin diminishing... which sounds perfectly reasonable and has the added benefit of reducing the risks of addiction.
As in, it's potentially only useful as a bridge treatment once. If you decide to lapse your long term anti-depressant after several months and suddenly need another bridge treatment as you ramp back up again, the durability of the tolerance from your initial ketamine treatment would prevent it from being useful the second time.
The idea that taking something that fixes a symptom, but then creates a permanent tolerance, makes me think that getting that chemical too directly in the past may have caused the tolerance that caused the initial symptom.
Ironically, perhaps when I find a sufficiently effective combination again, I'll give it a look. Thanks!
That is a huge asset, but long endured depressions leave many unhealthy neural circuits over the years. These have be unlearned one by one, which takes time.
Ketamine increases freedom of thought and emotion, but you still need a goal and long-term plan to precisely target and unwork all the patterns that circle back to depression.
Luckily the entrypoint away from happiness is discernable and it is bittersweet: giving up, thereby reducing stress. Which is sweet at first, but turns into hell fast.
In my case, while it was effective, I was a much more productive and healthy person than I'd ever been, cleaning up lots of mess and accumulated dross I'd never been able to convince myself to go through, more physical activity, more consistent eating...but then it all abruptly came crashing down, eventually, so either the learned behaviors have quite a thresholding behavior, or it's a more complex mechanism.
It is part of a series examining what happens to people that discover they have a minor super-power.
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.
http://web.archive.org/web/20061112225415/http://www.subreal...
The only downside is the cost (it’s not covered by insurance) and the potential that there are long term side effects that have yet to be discovered. We pay $375 for a 40-minute infusion. The recommended initial course is six infusions over two weeks. After that a booster or two is usually needed very two to six weeks. (It’s been about every three weeks for my girlfriend.)
Some other tidbits of information:
- only thing that seemed to work even after TMS and other treatments.
- New pathways (SF and San Mateo locations) is really good.
- more and more treatment places opening up in different cities etc.
- uber assist or drive the patient home (full lucidity afterwards but you don’t want to drive).
- long-term benefits aren’t apparent after the first two treatments. After the third it seemed to last for 2-3 days. After the fourth longer.
- it really seems like a ‘break out of depression’ breakthrough treatment. Though no cure all (talk therapy or a good support system is important too).
- ketamine is used for many purposes (anesthesia, etc.). When given for depression it’s given in much low dosages (presumably without harmful liver or kidney side effects).
- usually the patient listens to music with headphones while the infusion is in progress.
- a nurse monitors BP and heart rate etc., but so far there have been no compications other than a nurse who was bad at putting in an IV (once).
- feel very thankful for it.
- I could see it going mainstream in the near future.
And yeah I’m not sure about the dosage. I know it’s much less than ketamine for pain management or for anesthesia. I’ll try to ask next time.
A better "close to k-hole" dose would be 100mg. At least based on our experiences 100mg would get some people in the hole, while it took some others 50mg - 100mg more.
I can imagine there being a great short term benefit to ketamine, as people who are severely depressed can't exercise due to the depression. Has there been any mention switching from ketamine to daily exercise, or doing both?
More, I don't know what ketamine does in the long term to the brain beyond stimulating the parts of the brain that get strengthened during exercise. Maybe it's doing something else and that was the motive for the curiosity. What exactly is ketamine doing in the long run to the brain?
If the answer is zero (which I think it is) do those who have it a favor and shut up. Depression is hard enough without "you just have to exercise, huahua" comments.
I read the OPs intention as "use K to get the person back from the bottom of depression and then leverage that boost in mood to start a habit of excersize"
That seems reasonable and a good approach. You want to reinvest the motivation and better mood into relationships and behaviors that will continue to compound feeling good.
I'd also recommend Gratitude as a practice and ultimately some sort of somatic work where you are encouraged to go deeply into any uncomfortable feelings with your full body.
Nothing is more irksome than the trend in public discussions to tell others to "shut up" if they haven't specifically experienced something.
This is a public forum. We're discussing a publicly posted article. The OP brought to the table a valid point. Let them talk.
I get where you're coming from with this response - if you haven't been there, there is just no way you can understand how desperately bleak things can become.
But if someone is ignorant about mental health, why not try to educate that tell them to "shut up"?
We need to talk about these things, not humiliate and shut down anyone who doesn't understand.
I've posted this before. There's a newer study that has better results.
http://www.cochrane.org/CD004366/DEPRESSN_exercise-for-depre...
---begin
Exercise is moderately more effective than no therapy for reducing symptoms of depression. Exercise is no more effective than antidepressants for reducing symptoms of depression, although this conclusion is based on a small number of studies. Exercise is no more effective than psychological therapies for reducing symptoms of depression, although this conclusion is based on small number of studies. The reviewers also note that when only high-quality studies were included, the difference between exercise and no therapy is less conclusive. Attendance rates for exercise treatments ranged from 50% to 100%. The evidence about whether exercise for depression improves quality of life is inconclusive.
---end
http://www.cochrane.org/CD011612/DEPRESSN_ketamine-and-other...
Not for medical which is maybe what you are referring to. But long term (recreational) ketamine use (abuse) is well known. Perhaps down to the method of injection (nasal) or the impurities in illicit ketamine, but there is a lot of information on bladder problems, stomach cramps along with heavy addiction
Having no knowledge on the matter, what's the price comparison to just buying ketamine illegally and taking it without a doctor's help?
Depression is like (or possibly is) a form of chronic pain. People suffering from it severely might be willing to do anything for relief. Here's good information that a currently-illegal drug can help but if you want to do it legally you might need to take on a third job just to pay the costs.
It reminds me a bit of the South Park episode[0] where 'concentrated dose of about $180,000 shot directly into the bloodstream' is discovered as the cure to AIDS. Volunteers inform poverty-stricken Africa that all those suffering from AIDS have to do is inject themselves with piles of cash.
I think the most of that $375 goes towards staffing costs, rather than the drug itself. Ketamine though legitimate channels costs about $5-$10 per gram from what I've heard.
Typically they use 0.5mg/kg. I think you may be confusing milligrams (mg) with grams (g).
It's way cheaper on the black market. The actual cost of manufacture isn't very high, and I don't think it falls under any patents needing licensing. Probably you're mostly paying for the labor.
- Ketamine seems to have a much larger effect size (-~0.99 [1] vs -~0.35 for typical antidepressants [2]) [If anyone spots an error, please let me know]
For context, an SMD of 0.2 is small, >0.5 is medium, and >0.8 is large.[3]
To me this seems to be by far the most important/interesting thing: Ketamine seems to have a much stronger antidepressant effect than our current antidepressants.
- Benefits occur within hours rather than weeks
- Doesn't seem to interfere with sexual function, unlike many antidepressants
Main downsides of Ketamine for depression
- Much more expensive and normally not covered by insurance
- It's less well studied
- You have to go in for additional ketamine infusions to maintain the effects, it seems roughly ~1x a month long term
(The SMD for typical antidepressants seems to range from ~-0.13 to ~-0.35, with Tricyclic antidepressants slightly higher at around -~0.42.[4][5][6])
[1]: https://www.ncbi.nlm.nih.gov/pubmed/25038867
[2]: https://onlinelibrary.wiley.com/doi/pdf/10.1002/wps.20112
[3]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730804/
[4]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903535/
[5]: http://www.annfammed.org/content/3/5/449.full
[6]: http://www.cochrane.org/CD011735/MUSKEL_selective-serotonin-...
If it was just about bioavailability, I guess they'd just give large oral doses.
I recall reading of people self treating with ketamine off the darknet, and I imagine they are not giving themselves an infusion?
I've heard that 35% figure bandied about for awhile now. Does this take into account multiple SSRI's? If one took Welbutrin and it didn't work, for example, and then one decides to try Paxil, is there still a 35% chance that Paxil will work? (both Paxil and Welbutrin are SSRI's)
Or is the 35% figure meaning that if one tried all the SSRI's out there, there is only a 35% chance that any of them at all will help you?
I tried reading your reference, but it doesn't seem to mention this.
[0] http://www.bbc.co.uk/newsbeat/article/29811499/k-bladder-the...
The recreational doses are also relatively small (10-50%) compared to anesthetic doses, too. Being unconscious isn’t the recreational user’s aim.
You would have to be taking grams and grams of the stuff on the regular; infrequent or one-off dosages won't cause bladder damage.
Edit: even in the article you can see that the guy developed "K bladder" after taking 15g per day. 15g is a truly scary amount of powder to be ingesting.
However, for use as an antidepressant, 100-200mg (0.1-0.2g) twice a month is sufficient, so it shouldn’t be an issue.
I will second that. A friend would use around that much and it would last almost 2 full weeks without feeling the need to take another 100mg. Once the 2 weeks hit though, he could feel his depression / anxiety coming back slowly.
Most of the studies of using ketamine to treat depression are using under 1 gram per month.
Infrequent use of ketamine (less than once a week, less than 1 g), whether medical or recreational has no negative side effects.
It's also unknown whether it's actually caused by ketamine, or by whatever is being used to cut street ket.
It's a problem, but seems to be limited to those exhibiting problem usage (even within the context of recreational use)
Ketamine is sourced pretty much exclusively from pharmaceutical manufacturers and is medical grade.
A lot of people that I used to hang out with back then are on a private email list now, where we talk about more boring stuff like our families and jobs and so on, since everyone basically aged out of the scene in our early 30s.
I recently made a post about how my mom had been abusive towards me as a kid.
Almost every single person on the email list responded with a similar story of abuse, sometimes of a horrific nature. And almost everyone talked about dealing with trauma and depression their whole lives — and how the rave scene and the drugs they took probably saved them. Several talked about suicide attempts before getting into raves.
I had known these people for almost 15 years and I had never really talked about this except for the random conversation on ecstasy with one or two of them where they or I as sort of worked out our issues with them at an after party or whatever.
I was pretty surprised at how consistent the story was. I know that’s how I felt about the drugs— that the combination of those two (and lsd to a lesser extent) and the community around the music probably saved my life — even though I took a lot of dumb chances and went well beyond the therapeutic info the hedonistic from time to time.
I went from being a lonely, closed up victim of abuse at home and a decade of bullying at school to being outgoing and popular in that scene - even to the point where I learned to DJ and played gigs in front of crowds of 1000+ people.
It helped me not just in the scene but in my personal life and my career. I learned to recognize some of my learned toxic behaviors that pushed people away from me and how to recognize them in other people. I distanced myself from my family and home town friends who had been treating me terribly, and my career took off — even with no degree — and largely because of connections I made in the scene.
I don’t know where I’m going with this, but it seemed transparently obvious at the time that MDMA, LSD and ketamine were near-miraculous substances and deserving of serious scientific study, and it always seemed perverse that the government was doing everything in its power to prevent people from taking them, while at the same time pushing people to take anti depressants and stimulants that were so much less helpful and enlightening.
I haven’t used drugs in nearly a decade and don’t intend to, but I’m glad that researchers are starting to take them seriously.
The reason this treatment isn't mainstream isn't because "the research is still out" (though that may still be). It's because there are no financial interests to get it over the hoops into the highly convoluted state that enables affordable medical care.
And this interest isn't completely fruitless just because the pharma industry will never support it. Individuals (admittedly, only those who can afford it) can still try to benefit from e.g. off-license prescriptions.
The very article you're commenting on directly contradicts what you're saying. Big pharma is actively running studies and trying to get this fast tracked for treatment in the US and Europe.
Granted the article is somewhat poor reporting because the title should read "esketamine" not ketamine.
[1] http://slatestarcodex.com/2014/06/15/fish-now-by-prescriptio...
If said cost applies to only some of the employees, the employer won't have much in the way of even indirect incentives.
Why not? Probably need about $25M - $50M
Also Ketamine seems to be pallative vs. a cure, if I'm not mistaken.
Get 50 of those to each chip in $1 mill - it's pocket-change to them.
Just because a thing exists (the FDA or taxes for instance), doesn't make it a good thing.
I'm still anarchist in 2018, but I haven't been anywhere near the an-cap territory of it since around 2006. Sticking to a political dogma out in the libertarian hinterlands is really only good for pointlessly arguing with other libertarians on the Internet.
That can be fun sometimes, but it's not as entertaining as it used to be, what with everyone pointing at Twitler and saying "You see? This is exactly as (insert libertarian variant) predicted!"
The public interest is for medical treatments to have the following qualities: safe, effective, affordable. The business interest for healthcare providers is for medical treatments to have the following property: profitable. Those interests only partially overlap.
It is possible to imagine many different institutional architectures that cater to the public's interests, and a large number of them are theoretically better than the actual results yielded from the FDA and the rest of the modern American health care system.
Thus, one of the consequences of maintaining the status quo is the foregone advantage of moving to a different and wholly incompatible system. That's the kind of argument only an economist could love, because it ties your brain up in knots trying to figure it out, and you can plausibly justify any prejudicial opinion you might care to support.
Yes, but the burden of proof lies with those who prefer an alternative. If you want to demonstrate an alternative is better, you need an honest and in depth comparison with the current. Just saying "the current sucks" isn't an argument.
I do agree it is difficult for drugs like ketamine, psilocybin, and MDMA(/MDA/MDE/etc) to get research funding, but that doesn't mean the current options are useless; we know they are useful, just not in every case. Nor does it mean that those mentioned drugs are better; we do not know.
That burden of proof lay originally with those that introduced, e.g., the FDA. We could go back to investigate whether we find that proof sufficient, if any was even provided, but your interpretation of the proof would perhaps be different than mine.
But decisions like creating an FDA are not based on proof, I would argue. It is based on other factors, especially on what can give government more power and what people will vote for. The average voter does not investigate any proof on the matter, but instead rely solely on gut feeling, for instance the feeling that drug companies are greedy enough to deliberately release drugs they know will harm people.
You can't set up an alternative to the FDA in order to test it, because the FDA is the supreme dictator over the regulatory domain, and you can't get around Mom saying "no" by asking Dad behind her back.
You can, however, look at the European pharmaceuticals regime, and note that an identical drug costs three times in the US the amount it costs in France.
Clearly, the FDA is not optimal. Equally clearly, we do not demand meta-studies proving that the FDA itself is safe and effective for its stated purpose.
Well, it would be interesting to look at impartial cost/efficiency research regarding "health inspections". I routinely travel to countries where those inspections are just a pure formality, or completely non-existent - and, I must say, in most cases there's no trouble finding a good, safe place to eat.
How do you imagine abolishing the FDA would improve outcomes instead of increasing supplies (and marketing) of snake oil?
Can you prove that FDA improves the outcome? Is FDA somehow free from lobbying, or are the people working there consistently uninfluenced by certain counterproductive incentives? How could we go about ever proving that the absence or existence of a government agency has improved conditions overall? Sorry if this comes off as lecturing, but these are questions that I think should be asked and is not intended for you specifically.
In any case, you cannot take away that FDA approval likely costs millions of dollars and makes it more costly to introduce a drug. It is self-evident that making something more expensive to do reduces the incentive to do it (weighed against the potential profit).
No argument - but you didn't answer my questions at all other than to say "FDA is fallible!"
I can't prove the FDA is non-evil/non-fallible. I don't have numbers to share, so I'm going off of very fallible impressions. However, those impressions are that the FDA has done a better job of keeping crappy products off the market than a free-market world.
You complain about the opposite - good products being prevented because of lack of incentives. It's impossible to measure what hasn't happened, but do we have evidence that lack of incentive cause more harm than preventing crap/toxic/poisonous products that we have a recorded history of?
We have a solution today, a solution with problems, but a solution that I'm confident is better than the original problem. What is your basis to claim that removing the solution will in fact be better than the problem?
This is incorrect.
There are ongoing phase 3 clinical trials for nasally applied esketamine that will lead to FDA approval if succesfully reviewed. These trials are conducted worldwide and are very encouraging. The specific application seems to be patentable. First results should be available around 2019ish or 2020.
You can find the trials here:
https://clinicaltrials.gov/ct2/results?term=esketamine+depre...
And one of the patent applications here:
Specifically esketamine, not ketamine, because focusing on this specific isomer was the only way to get a new patent.
What if racemic ketamine performs better than esketamine? We'll never know because they won't test that.
It's quite likely some public institutions (e.g., universities, public research labs, etc.) or other countries (e.g., in India, China) will test exactly that. It's also in their interest to pubblish the results. So we'll get to know the differences between racemic ketamine, esketamine and arketamine.
The question is if different variants will also be approved, which is much more expensive.
But Vitamin D is not patent protected and it's dirt cheap, so not only does Big Pharma have no interest in promoting it, but it would rather you take much more dangerous drugs and much more expensive drugs to cure the same things Vitamin D does.
This is what a private healthcare system gets you, where profit is always a bigger priority than the well-being of the patient.
This is a very odd comment thread. Lots of people criticizing our health system for not studying things it actually does study a lot.
http://www.maps.org/news/media/7082-press-release-maps-compl...
I get the feeling this is not a Gates kind of philanthropist, lol.
I would think given compelling enough research that there would be plenty of private foundation dollars to complete trials.
It never really worked for me as that, at least not more than lsd or so would. And some friends claim that it has way less effect on them today even thought it seemed have to worked before.
It may is the abuse (probably higher amount on some occasions) it may are long term effects.
But it surely is not the magic cure some make it out to be.
That's different to a small dose once a month in a medically supervised environment.
One big problem with recreational drugs (from personal experience) is that you get conditioned to them if you overuse them, then life seems sort of shit without them.
With MDMA, you can even permanently lose the magic if you take too much too often.
I am not sure what the medical amount for ketamin would be, but i would think the average is more around 100mg a month (and using about every 3) within my circle. Which is not exactly that much.
As far as I know are long term studies still lacking of a proper sample size as well.
However, over use can certainly habituate a user to it such that it "loses its magic" as in the psychoactive effect is far far far less than what it originally was.
This could be a breakthrough for individuals in the midst of major depressions, which are often very hard to treat, considering how long it can take for other anti-depressants to start to work.
Contrary to the posts in this thread there isn't a body of evidence that suggests Ketamine's anti-depressant effect lasts longer than a week.
The real question is, how long do the effects last and what are the side effects.
"""NMDA receptor antagonists can mimic these problems; they sometimes induce "psychotomimetic" side effects, symptoms resembling psychosis. Such side effects caused by NMDA receptor inhibitors include hallucinations, paranoid delusions, confusion, difficulty concentrating, agitation, alterations in mood, nightmares, catatonia,;ataxia, anesthesia, and learning and memory deficits.""" (From Wikipedia)
Ibuprofen hits the COX enzymes, for which no psychological effects are noted.
Edit: of course I'm not discounting your own observations, just regurgitating some textbook knowledge.
https://www.nhs.uk/news/medication/ibuprofen-linked-testoste...
Congrats on the self study and experimentation and on finding an over the counter solution.
Have you tried any non-ordinary states of concioisness work, like Holotropic Breathwork?
https://www.smithsonianmag.com/smart-news/painkillers-might-...
Ibuprofen actually does work, believe it or not.
Ketamine dissolves pretty well in water.
[0] https://www.thestar.com.my/lifestyle/health/2011/03/20/ketam...
[1] https://www.sciencedirect.com/science/article/pii/S016622361...
Can anyone comment on how long it might take for it to hit the market, from this stage?
[1] https://en.wikipedia.org/wiki/Phases_of_clinical_research#Ph...
It's possible that the J&J spray will be approved in 2018.
Perhaps your effects were down to the ROA?