Research into ketamine as a treatment for severe depression | Hacker News Reader

Research into ketamine as a treatment for severe depression

washingtonpost.com

92 pointsmoosov51 comments

While this is undeniably impressive and hopeful, it should be noted that these are short-term affects. The article mentions this: "So far, there is no evidence of addiction at the low dose in which infusions are delivered. Ketamine does, however, have one major limitation: Its relief is temporary. Clinical trials at NIMH have found that relapse usually occurs about a week after a single infusion."

It then goes on to talk about possibly alleviating this with booster treatments.

For me, even the possibility of there being temporary relief makes it something I would seriously consider pursuing, for two reasons. First, when my depression gets really acute it basically means that I simply am unable to leave the house. If I were free of that chain I strongly suspect/hope it would be easier to seek out -- and be consistently dedicated to -- treatments that were more long term: meditation, therapy, etc.

Second, just the thought of being happy for a few moments. Well, the allure of that is likely obvious. Were the almost omnipresent internal dialog of "you suck, you stupid fuck, dumb faggot, stupid fucking nigger," etc. able to be minimized or eliminated, even if temporarily, it would make such a great difference in my life that I almost can't quite imagine it.

Right now I escape it by playing video games. This is not exactly the most positive way to live, however.

I have only been moderately depressed, and I have no experience with this particular treatment... but I have had experiences that for a few hours swept away my anxiety, poor self-image, and so on. Metaphorically, it's been like opening a window for someone who's been stuck in a basement. Even without extreme euphoria—just a simple sense of contentment, like nothing is very wrong—that's such a revelation.

A big part of depression seems to be this incapacity to even imagine any kind of robust, non-fake happiness. In bad moments one can even get paranoid: like, why is everyone going around pretending like they're happy, when they obviously cannot be? I think it's like this with any persistent mood; your whole world view is altered.

So however you find it, just a couple of hours of, say, having a conversation where you don't feel like the worst loser in the universe and the nadir of civilization, that just shows you something about life.

"Oh... I... I am just a person like these other people... I don't have to radiate horror and disgust... I can just stretch my arms right now and feel my body as an animal with the right to live and enjoy... Huh... Hah! Hahaha!"

And then the next morning maybe you feel like crap again, sure. But the understanding that these are just different mind states is so valuable. Like, for someone who really doesn't believe in anything except depression anymore, I totally understand suicide. So giving people the chance to feel something else, even just for an hour—if psychiatry can start to really do that, that's so wonderful.

> So however you find it, just a couple of hours of, say, having a conversation where you don't feel like the worst loser in the universe and the nadir of civilization, that just shows you something about life.

It really would have been nice for me while i was a child. yes. i should have been given ketamine as a child. my depression was so bad for most of my life that i could count the days where i didn't feel depressed, didn't feel like a leper or a zombie going through the motions of life, and it protected itself: at some point i just stopped acting out my terrible feelings because it seemed like it only caused trouble with the adults and alienated me from my peers. that became a feedback loop that prevented me from expressing depressive sentiments for over a decade. if i could have been functional enough even for one week to clearly explain what was wrong to someone, maybe the structural defects in my life that caused my depression could have been ameliorated.

but that's all hindsight. i want to live in a world where no child is left to wallow in their depression. i don't know what you've been through and (maybe still?) go through, but it sounds awfully similar to what i deal with. i wish you didn't have to.

You write as if it's all past tense for you. How did you end up getting better?

the past tense was because i was talking about being a child. i'm still depressive although today is possibly the best i've felt in months. today is good because i've been working on improving my mental hygiene and it's starting to pay off. it's been a long project. i'd say that the very first step i took towards taking care of my mental health was 2.5 years ago. it's difficult to summarize what's happened since then, and introspection is nowhere near as accurate as it feels. i won't try. the first step for me was admitting to my parents and my doctor that i was depressed. but was that the first step? how long did i prepare myself for that? who knows.

getting into a romantic relationship was difficult for me. even after a year together, i found myself paranoid about my partner. did they actually like me? i felt like they were humoring me every time we did anything together, that it was a burden to be around me. finally trusting them, finally trusting that they liked me was a gradual process. first i had to understand the idea intellectually, and only then could i try to internalize it. i'm still working on it, but there are days where i feel very happy to be me, because someone out there loves to spend time with me. learning to trust my romantic relationship is a microcosm of learning to trust all of my social relationships and my place in the world.

my latest improvement to my mental hygiene is to keep a journal. i have a habit of letting my head crowd up with thoughts which leaves me anxious, confused, and agitated. writing things down helps me clear thoughts out. i've realized that suppressing thoughts does not work. inhibitory patterns like that are the root of my depression (i'm sure everyone has a different root. some might have a fundamentally unassailable root and need drug therapy). having a truly clear head once in a while is a wonderful, wonderful experience.

my favorite books to read to keep my mind healthy are the Dao De Jing and the Zhuangzi. I prefer Ursula K. Le Guin's rendition of the former and the translation of the latter by Burton Watson. there are passages in these beautiful works that can pull me right out of a depressive episode, or at least comfort me intellectually while i weather it. there's something deeply and mysteriously comforting in their lines. these books have a way of putting thoughts in my head that push out the invasive, repetitive, agitating, stressful thoughts and let me breathe.

i'm not depressed right now, but maybe tonight, or tomorrow. i don't mind. i like myself, even my depressed self who hates themself. they know they like themself; they used to feel guilty about hating themself and guilty about being depressed, but they don't feel guilty anymore. it makes it easier to cope. they and i know how to keep ourself healthy better than we did before. it's a lifetime endeavor, learning your own nature, loving your own nature, letting yourself be the way you are. i feel like this post is very disorganized, scatterbrained, incoherent. i cannot begin to touch upon all of my experiences that have improved me. even if i could, what good is it if i can't transfer that deeply personal wisdom to others? the words don't carry any of the power of the signified.

'mental hygiene'. i think this is the key concept to understand. it's different for everyone. keeping physically clean keeps away physical disease. keeping mentally clean keeps away mental disease. you can still get sick, but you'll get sick less, and you'll get better faster. you may even get better for the first time in your life.

P.S. i also did a lot of acid but that's reckless. it's a good way to scar yourself. it's also a good way to shove your brain outside of its normal operational range. both have happened to me. i believe that one day there will be a drug gentler than lsd or psilocybin that will be used in controlled therapeutic settings. if you need to escape the inescapable, these drugs will do it.

It's not incoherent at all to me, but it may have been a year ago. I think it's like the blub paradox in a psychological context. Wish we could get a beer and chat.

> Its relief is temporary. Clinical trials at NIMH have found that relapse usually occurs about a week after a single infusion." It then goes on to talk about possibly alleviating this with booster treatments.

I know some people will naturally object to this, but to be honest - assuming people don't build up a tolerance to the effects[0], what's wrong with that?

People are accustomed to taking all sorts of drugs on a daily basis, from antidepressants to sleeping aids to coffee (caffeine!). If someone invented from scratch an antidepressant that could only be taken once a week, we'd be heralding it as a miracle drug.

The main opposition to Ketamine is likely to be its history of recreational use ("Special K"). But that narrative - opposing medicine because of its potential psychoactive effects - is nothing new.

[0] I don't mean a tolerance to Ketamine in general, but a tolerance to this anti-depressive effect

The basic problem is that it requires IV infusion, not oral or nasal administration (trials of the latter have issues with consistent dosage, AIUI), and that requires trips to a doctor to do, weekly.

if anything, for people who are trying to be functional, you'd want to gain tolerance to the recreational effects, but not the anti-depressant effects. tolerance to both seems more likely, but hopefully tolerance to the former outpaces the latter.

I got Ketamine at a psychiatric clinic. It really did make me feel strangely relieved, and basically immediately. Reminded me somehow of vacation days when I was a child. The feeling starts fading away once they stop the drip, and it's back to normal after a couple of hours.

Since they don't give out pills (not sure if war-on-drugs bullshit or actually dangerous), it's pointless. You're monitored for half an hour by a physician, and the drip gets done by an anesthetist, and if I remember correctly they insisted I be carted back to my room instead of walking. It's also only done on in-patients. So it was completely impractical as a treatment and had no long-lasting effect at all.

> Clinical trials at NIMH have found that relapse usually occurs about a week after a single infusion."

But if you read till the end, they say that Hartman has to get booster shots every 6 months or so:

> These days, he says that his periods of remission between infusions often stretch to six months.

i was depressed for a very long time. wasn't enjoying life and picked up some bad habits along the way. But now am a lot better. I think what finally helped me out of depression was to hangout with friends a lot and living with friends which distracted me away from my negative thoughts and with I actively trying to control my thought flow, cut negative thoughts out n doing something like following upon on something interesting, researching the way world works etc. It was a huge improvement. It was hard to get rid of bad habits i picked up while depressed, including laziness. Improved a lot in last 8 months. Am not depressed anymore. Negative internal dialogues too are gone. It was like a thought virus, which i finally got rid off. I hope my experience will be of some help for you.

I didn't try therapy or any medication.

> First, when my depression gets really acute it basically means that I simply am unable to leave the house.

You also would not really want to leave the house on Ketamine.

This isn't while high on ketamine, this is about the week following, when your brain is still feeling the after effects in a positive way. Proper depression fucking sucks -- it's not just about feeling sad, you get to a place where your body aches, and even getting the motivation to go across the room to get meds seems almost more trouble than it works. Depression is not just feeling sad, there are a lot more symptoms involved, and if it means needing a day out of seven to not go outside, that's still a lot better than only being able to go outside one to two days in seven.

They aren't prescribing recreational doses, he would be perfectly functional and experience no dissociation whatsoever, it's something the drug community has been talking about for a long time.

Lookup "microdosing" if you're interested, a lot of people do it with dissociatives or psychedelics and the point of it is to a below threshold dosage and avoid the typical drug high.

You're still in an "altered state" for an hour or so after an IV infusion, according to several practices I've seen offering the service - not necessarily dissociative or hallucinating, but definitely "out of it".

Ah, didn't realize they were doing IV infusion, if they made capsules or something with a time release mechanism they could probably avoid the "altered state".

A good resource on Ketamine is Erowid's Ketamine vault: https://www.erowid.org/chemicals/ketamine/

The list of Ketamine related publications at https://www.erowid.org/references/refs.php?S=ketamine lists the first study on effects on depression as from 2000 (just a quick Ctrl-F search, their might be earlier studies).

Here is anecdotal evidence for another interesting "drug":

http://www.ncbi.nlm.nih.gov/pubmed/16542786

In this study, N=small, but nevertheless, I think it is a very interesting article. Because the effects are so rapid, and magnesium supplementation is in general harmless, it is imho definitely a good idea to see if a magnesium deficiency is the cause of the disorder. Please take note that not all magnesium supplements are equal.

Technically, it's not a study. They present a few case histories, which is basically, "we found a few patients whose depression went away after taking magnesium, maybe we should look into it".

That being said, it would be pretty easy to investigate.

Anecdotal again, but if it helps anyone else - my SO used to suffer with regular migraines, but since taking daily magnesium they have completely gone away

Absolutely extraordinary success rate here. 75% success in treating depression and suicidal ideation? That's a revolution.

FTA: "While a single dose of ketamine is cheaper than a $2 bottle of water, the cost to the consumer varies wildly, running anywhere between $500 and $1,500 per treatment."

Sigh.... why? Why must we turn any opportunity into a money grab?

That seems like a silly statement. Treating a patient with a dose of ketamine includes a lot more costs than just the drug.

If a patient comes in and gets an infusion of ketamine, even if the procedure only takes 1 hr (infuse and observe), you need to pay for the building, the nurse, the physician, all the backroom staff, etc.

Hell, I go into my primary care doctor for an annual physician and it costs ~$200. I see the doctor for maybe 5 minutes and a nurse for maybe another 5 min.

It's like saying "the cost of a bottle of coke is only $0.20, and it's such a shame that it costs me $1.50 at a gas station".

A bottle of Coke would be even more than $1.50 if you were legally required to pay a team of upper middle class salaried attendants to sit you in a very expensive chair in a very expensive building and hand-feed it to you. Don't get me wrong, that is how I would like to enjoy a Coke now and then, but it's good to have less luxurious options available at a lower price.

I agree with you. There needs to be something like insulin autoinjector pens, but for ketamine.

This increases the chances of abuse, but ensuring a prescription only lasts 6 doses or whatever would reduce that.

Hopefully once drug laws become a bit more relaxed, this will be seen as acceptable.

It also includes the costs for people that don't pay (less of a thing at a clinic than a hospital) and probably some costs associated with Medicare and Medicaid (of course only if they reimburse below the actual cost).

It'd be cool if the bill explicitly listed the actual costs separately from the implicit taxes (hospitals must provide stabilizing treatment, they don't get direct reimbursements for it, this is effectively a tax).

We need not. We can fix this in a stroke of the pen with single-payer. Unlikely, but not impossible.

I'm sure that some of the treatment cost involved the doctor's time as well. And unless single-payer means that patient's sign away their ability to make liability claims, that is also a huge part of any anesthetic-like procedure cost.

The results from ketamine are very impressive, however there is still the possibility that it is due to the placebo effect:

"Consistent with all of the published randomized, placebo-controlled studies with ketamine, we also found short-lived perceptual disturbances26,49,50; such symptoms could have affected study blind. Hence, limitations in preserving study blind may have biased patient reporting by diminishing placebo effects, thereby potentially confounding results. One potential study design in future studies with ketamine might be to include an active comparator such as intravenous amphetamine (a dopamine agonist), which also produces psychotogenic effects."

http://archpsyc.jamanetwork.com/article.aspx?articleid=66819...

From my point of view - and I've gone through almost each available antidepressants in 10 years battle with depression - every new solution, that will relieve patients from their struggles (even for short part of time) - is a bless. Sure ketamine won't solve problem permanently, but todays 2nd and 3rd generation medicaments dont do it either. There is a moment, when you simply want to feel a relief - from sorrow, stagnation, fear, guilt and hopelessness. If it's true, that ketamine gives you this relief, then sign me up! :) And it don't have to do anything else. Because, there are people who simply cannot remember how it feels to live without depression - if you can somehow remind them how it is not to feel anything depressing, this may be powerfull boost for keep fighting.

So, the ~75% efficacy rate is seemingly great news for those suffering from depression. However, what stuck out to me was the reported synaptogenic effect that ketamine is thought to have.

An interesting study would posit that ketamine could potentially be used as a nootropic. If the synaptogenic effect is strong enough, could it not be used to restore brain function after head trauma, stroke, to treat cognitive decline with age, ect?

and no mention of John Lilly? I expected more of HN! Lilly of course is the exemplar of cautionary tales and why highly analytic people ought to treat K with much respect.

https://en.wikipedia.org/wiki/John_C._Lilly

Do you have to take it via an IV? Can taking it orally have similar benefits? I'm just curious why you need an IV.

Oral works as well - no pain in the nose, etc - but it does take more ketamine. As for the IV... these are doctors administrating it. An IV allows for more precision, and a point of the treatment, it seems, is to avoid the K-hole effect - which would seriously disturb a lot of patients.

If I was using opiates for a medical purpose, I would want to be precise - heroin vs making poppy tea.

When you administer it to horses, it's also done IV but using a syringe. It may not necessarily be done using a bag and a drip.

You'd probably have to insufflate (snort) it. That's the recreational method for most users, at least.

Can't you just take a pill?

Many drugs undergo first-pass metabolism by the liver and their metabolites are much less active or much more non-specific. I don't know if that is the case for ketamine, but I suspect that it must be.

Ugh Ketamine. "Only Fools and Horses" as we say on this side of the Atlantic.

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