Ketamine 'exciting' depression therapy | Hacker News Reader

Ketamine 'exciting' depression therapy

bbc.co.uk

125 pointspiokuc103 comments

While I was in university, I suffered (not knowingly at the time) from pretty bad depression. I basically was extremely self-destructive, and at 19 was experimenting with various drugs. My roommate's girlfriend stole a half used bottle of ketamine from a veterinary clinic she worked at. They dried the liquid into powder form in the microwave, and we all used it by snorting it. (as I said, I was hell bent on self destruction)

Obviously, whatever dose we obtained would be far, far beyond a clinical amount. I immediately sank into what is called a "k-hole" and had what is often described as an "out of body" sensation. I was 5 years old again, walking along the beach in winter, looking through my father's binoculars at the humpback whales. A feeling of peace and calm came to me, and some amount of time later (perhaps an hour) I awoke from the "k-hole."

The sense of peace I felt remained. I wasn't intoxicated, nor did I feel any other effects. I just felt like I had before my girlfriend had died two years before.

That was the last time I touched a drug other than alcohol or marijuana.

I have heard similar experiences for MDMA treating PTSD. (There are also a number of studies suggesting its effectiveness when used in conjunction with talk therapy to treat PTSD).

If you're interested in learning more, MAPS[0] has a ton of info.

[0] http://www.maps.org/

To my knowledge I never suffered from depression. When I was a teenager I also experimented with various drugs. At age around 17 me and some friends took a lot of ketamine at a friend's house one night. We went out for a walk at at some point I started k-holing. We were walking along a train line at the time. I collapsed on the line and watched myself lying there. My friends hadn't noticed me fall, they'd carried on. Then I calmly watched myself get hit by a train. I watched my bloody corpse lying there for quite a while.

I came back to my senses lying by the rails in a puddle of my own vomit. I hadn't really been hit by the train, although I had watched it, seen my body crumble and split.

I spent the next several hours vomiting and feeling atrocious. Ever since then, I occasionally see the image of my own dead body again. That was the last time I touched ketamine, though I carried on experimenting with everything else until my early 20s.

Not to detract from your experience, but ketamine can be a disgusting, dangerous drug, and taking it at home is not a sensible approach to depression, drug addiction, or anything.

Not to detract from your experience, but ketamine can be a disgusting, dangerous drug, and taking it at home is not a sensible approach to depression, drug addiction, or anything.

This is a very black and white statement. Most people probably shouldn't treat serious illnesses by self-medicating with powerful drugs, especially those obtained illegally where the purity of the drug might be questionable.

On the other hand, someone with crippling depression who has sought treatment from medical professionals to no avail and is on the verge of suicide has few options and not much to lose. Trying ketamine might well be a reasonable option for such a person - more reasonable than suicide, anyway.

I don't dispute that ketamine may perhaps have some clinical relevance for humans, but unfortunately it wreaks too much havoc on the kidneys for me to consider it as a viable option for treatment of depression.

Those points seemed already covered in the article, but somehow it must have been unclear.

First of all, it's unlikely to ever have ketamine as a first-line treatment for a depression. Probably more somewhere near electroconvulsive therapy. ECT also has adverse effects which can't be considered as minor (e.g. severe memory loss). However, at the same time it's recognized as a life-saver for certain population of patients.

As I have understood from this research and previous ones, it's hoped that the effect of ketamine would be long-lasting: at least up to months. Not so-called daily anti-depressant pill. The adverse effects of ECT would also be more severe if it would be administered on a daily basis. As it was mentioned, some patients relapsed within days, some were free from depression for up to three months.

According to animal research[1], it's prolonged not acute ketamine use that has shown signs of renal and bladder damage. In a review of ketamine-induced vesicopathy[2] it's also noted that 'Very little is known regarding the pathogenesis of its effects on the urinary tract.' I'm not claiming that it doesn't cause any damage, but that it needs more research and currently there's no indication of "renal havoc" after few doses.

In light of this, I can't even imagine how someone could call possibility of using ketamine for treatment of depression not viable. However, it may be because I know how disabling severe or even moderate depression is and how much damage it causes to person's life.

Each person reacts very differently to anti-depressants and there's large amount of people with treatment resistant depression. It's not like there's silver bullet and because of that we need as many as possible different treatment methods. Depression is life-threatening condition and thus all of those methods can't (and don't need to) be 100% safe. A lot of approved drugs have serious side-effects. Basically it's all about assessing the benefit:risk ratio of a drug. It's not rational to cross any treatment out, just because it may have side-effects. Especially if there's not reasonable amount research done - like with ketamine.

When we have more data, then it may show that certain population would need additional doses of ketamine after 1-3 months and the damage to organs is minor or non-existent in such case. Or it may show something else. It's just unthinkable to call it as "not viable" option, yet.

[1] Yeung, LY, Rudd JA, Lam WP, Mak YT, Yew DT. (2009) Mice are prone to kidney pathology after prolonged ketamine addiction. Toxicol Lett. 2009 Dec 15;191(2-3):275-8. doi: 10.1016/j.toxlet.2009.09.006. Epub 2009 Sep 17.

[2] Middela, S., Pearce, I. (2010) Ketamine-induced vesicopathy: a literature review. Int J Clin Pract. 2011 Jan;65(1):27-30. doi: 10.1111/j.1742-1241.2010.02502.x.

Sounds like a good experience, coming face to face with your own mortality and learning not to overdose on... anything, really.

Actually, the drug is always the same. The variable is the person taking it.

If you aren't obtaining medical-grade ketamine or if you aren't synthesizing it yourself, the drug is highly variable. For example, you could be getting a different isomer or different ratio of isomers every time (pure R, pure S, racemic, etc).

As beautiful as this story is, I would also like to mention the numerous friends that I have that have unfortunately become extremely addicted to the drug due to this serenity. For many this feeling does not stay and must be chased with more and more K.

Additionally, when in full possession of the knowledge of how terrible depression is, and knowing that for some people, using ketamine every day or few days is the only thing that works against their treatment-resistant depression, "the only known treatment for a life-endingly debilitating disease" and "functional addiction" are completely indistinguishable.

This happened to the closest person to me in my life, and it destroyed everything we'd worked to build together.

Fuck depression.

There are drugs like GLYX-13 which is somewhat related to ketamine which works very similarly, but without the psychedelic effects (but presumably _with_ the antidepressant effects). I have high hopes that we'll knock out depression within our generation.

> I have high hopes that we'll knock out depression within our generation.

Maybe, but depression is like cancer--a general classification with many many underlying causes. The fact that SSRIs, MAOIs and other medications reliable treat many people, and provide zero benefit to other chronic sufferers, suggest many root causes, and no single answer. I'm sure in the years ahead progress will be made, but I'm pessimistic having tried just about everything for the last 30 years with never a positive effect. I'm 45 and have never _not_ suffered from depression.

Some time ago, I was suffering from several months of severe depression.

Out of desperation, I obtained some Ketamine. I carefully measured a dose that was somewhere between theraputic and recreational.

I had the experience of seeing myself in the third person, as a narrator: "look at him," I said about my body, "just lying there on the couch."

Time passed and I returned to my normal awareness.

There was no noticible effect on my depression. Many months later, it gradually abated.

sorry for your loss, that's a lot to take in at that age.

I was a ketamine user for over a decade. It really did work wonders for clinical depression, even brought me right out of suicidal hysteria and despair within moments, but it comes with severe drawbacks. It can ruin your bladder. It will sap the b vitamins out of your system, and could cause nerve damage. More importantly, it is VERY addictive psychologically. I'm not saying to stay away, but to be careful and disciplined.

Thoughts on the research: to the extent that the mind is already chemical in nature, yes depression can be a chemical issue. However, I think they are looking at it all wrong. I believe the reason ketamine (and nitrous oxide, they may soon find out) are so effective at attacking depression is because they are disassociative in nature. Looking at it as simply a chemical problem erroneously reduces what is likely a complex issue in a complex organ. What ketamine and other disassociatives do is they "loosen" one's attachment and identification with various parts of their cognitive minds, allowing thoughts and feelings to exist in their own space without having such a strong hold on a person's conscious self, or seat of awareness, or whatever. Its basically like induced meditation, and from my experience with both disassociatives and years of meditation, I will tell you that they are VERY similar and the ancient traditions of buddhism and yoga got the nature of the mind and depression more right than any of the shit I learned in university or this kind of research. Meditation WORKS, it just takes practice and discipline. Like brushing teeth, but for the mind. If you dont do it, you will get plaque and your mind will rot. A drug may help pull a person out of the depression temporarily, which is definitely useful in times when a person can't break out of the loop and is immobilized with despair, but to reduce the whole thing down to this chemical or that chemical will only continue to find chemical solutions, which are never ideal.

very insightful post, thanks for sharing your thoughts. I think I'll give meditation a go

The best piece of advice I can give you is to do whatever you can to make, and keep, it as a daily habit. It is far better to do 5-10 minutes every morning than half an hour once a week. If you want any good resources, I've got a great list of books to choose from, but whatever method you just make sure you stick to it regularly. Think of it like brushing your teeth, brushing 3 times as long every 3 days doesn't work as well as brushing a shorter amount of time every day.

thanks for the advice. I'd appreciate a couple links to recommended books, as would other people here reading this. My techniques are very basic and uninspired currently, so I'd like to change that. Take care!

Good post. I agree.

I also have attained altered states of awareness thru both drugs and mediation. The mediation was hard work, but it seems the results I earned were longer lasting.

For future, I won't hesitate to use drugs to (maybe) snap me out of a funk if need be.

Two quotes from the article:

1. "Eight showed improvements in reported levels of depression, with four of them improving so much they were no longer classed as depressed. Some responded within six hours of the first infusion of ketamine."

2. "Lead researcher Dr Rupert McShane said: 'It really is dramatic for some people, it's the sort of thing really that makes it worth doing psychiatry, it's a really wonderful thing to see.'" [emphasis added]

Wait ... what? Saying, "Take this pill and you'll feel better" isn't how psychiatry is (or was) defined. That isn't psychiatry, it's pharmacology.

Also, none of the treatments, the old ones like talk therapy, or the new ones including drugs and/or deep-brain stimulation, suggest or identify a cause for depression. So far we've only been treating the symptoms of a disease whose cause we don't know.

I long for the good old days, the days of science, when we identified the cause of a disease, then designed a cure based on our understanding of its cause.

This isn't a cure, it's a symptomatic treatment, and to remain effective it would have to continue forever, reliant on a drug whose mechanism is as unknown as the thing being treated, just as with ADHD and PTSD. I'm sure Big Pharma is very upset that another perpetual market for drugs is opening up.

The "good old days" of psychiatry were a far cry from "the days of science."

Yes -- as true now as it was then. But moving away from talk therapy toward symptomatic drug treatment moves neither toward nor away from science.

Also, by "the good old days" I was referring to the medical practice of first identifying a disease's cause, then designing a cure. Most mental illnesses don't have this property, which open them up to exploitation by Big Pharma.

Agree that things haven't progressed much toward an ideal of rigorous science, but the process you're lauding of first identifying a cause and then designing a cure doesn't mean much when you're just making up stories for both things, which is essentially what those good old days were.

Of course scientists are trying to identify the underlying causes of mental illnesses. They're even making a lot of progress, but the brain is just unbelievably complex.

In the meantime, treatments are found by trial and error. Testing whether a drug treats a disease's symptoms can be scientific even if you don't know how the drug actually works.

Many people at bluelight.ru have blogged extensively about their experiences using ketamine to treat bipolar depression and major depression. The general consensus seems to be that using doses low enough to not feel any effect with very frequent dosing (every hour or so over the course of a few days) seems to have the strongest effects. I have tried both this route and the more traditional k-hole route to self-treat treatment resistant depression but haven't noticed much of an effect with either route in the long term. In the short term, I rather enjoy the psychedelic experience of ketamine trips. It is a rather "more-ish" drug though, because it is both short-lasting and hits dopamine so I urge people to experiment responsibility (ie; lay out the ketamine you are going to do, put the rest away, and don't touch it no matter how much you think one more line will be useful/fun)

The test was only done on 28 people and only 8 showed some improvements. The Improvements where self reported. What I wonder is the statistical error on such a small study. From this small study they are generalising to say that it is "exciting" and "dramatic"!

Usually a small study like this is done as a test of safety and potential benefit as a precursor to a larger more comprehensive study. I think its exciting and dramatic that there were enough initial positive results to move on to a better study.

Also interesting is the fact that the results are in the range that would be expected by the placebo effect.

"It shows that depression is something chemical, that it can be reversed with chemicals, it dispenses for once and for all that you can just pull your socks up."

This is entirely an assumption, and shows nothing conclusively. Just as an experience can trigger a depression (see @JPKab) an experience can cause it to end. There's no reason to look at a human being as a walking slab of meat for the sake of analysis.

This says nothing about "chemicals", and I'll bet you can find many of the same benefits are attained by people who are able to achieve similar experiences using meditation or other techniques.

Per the linked article, the particular test subjects had longterm depression and had undergone numerous, unsuccessful, treatments in the past. And, while that quote seems a bit too absolute in stating that "depression is something chemical". They probably should have said something like: depression can be caused by something chemical. And you are correct that for many, maybe even most, people it's probably not chemical in origin, that doesn't mean that it's never chemical.

Mhmm.. funny the article mentions it's an illegal party drug but not that is widely used in veterinary anesthesia.

You mean, apart from the bit at the end which says:

  The Home Office is reclassifying ketamine in the UK to be a class B drug, although it is already used in medicine for the treatment of back pain and as an anaesthetic.

I think it's also used on infants as well as it is does not effect the respiratory system.

Too true. Unfortunately, in the eyes of almost all world governments, any drug that's enjoyable seems to automatically lose any medically useful properties it may possess. It's a sad situation that could be fixed with real drug education and not the one-sided propaganda programs (D.A.R.E. and friends) that substitute for it.

And in humans, too! If you've had a colonoscopy, you may have been administered ketamine before the procedure.

I've had friends experiment with this, and they've reported good effects from taking small doses to help with depression. In small amounts, it isn't as scary of a drug as most people make it sound like. In small doses, its kinda like being tipsy (acts on similar receptors to alcohol), and if you know what you're doing there isn't much of a chance of 'accidentally' going into a K-hole, as its roughly a magnitude of difference between what you need to take for basic effects and a K-hole.

Several years ago and for a period of around 5 months I took Ketamine recreationally.

I was taking it nearly everyday and besides the effect of the drug itself, the resulting lifting of depression was very strong. It got to a point where I had feelings of intense love for people and my interactions became very emotionally charged in a positive way.

I also noticed that I had higher levels of clarity and my writing and thinking became clearer. The only explanation I've found is that ketamine reduces the level of kynurenic acid in the brain, something that I've found to have higher levels of.

As I started taking it less depression would start to kick back in 5-7 days. A relatively small dosage (not enough to get back in to a k-hole) would get rid of the depression almost instantly.

But there was a critical downside. After a while I noticed that my ability to do technical work diminished greatly. It made me stupider in many ways. I felt like I did not have access to the portion of my brain in which I could code. On the flipside it seemed to make me smarter socially, or at least give the impression as the increased verbal clarity and feelings of connection to people.

From looking around at other users at the time, I would say the effects of increased clarity were not commonly reported, and the anti-depression effect wasn't really talked about much, yet people got quite addicted to it.

At the end of around 5 months, I stopped taking it completely. I couldn't do it and hold down a technical job.

I'm curious: what kind of test did you undergo that let you see how much kynurenic acid you have in your brain?

A few points:

This is not just getting high. The antidepressant effects far outlast the brief trippy effects, which is an important reason why science is interested.

Although this is a small sample, this is not the first study of this antidepressant effect, which had been studied since at least 2000 (citation at end). I'd guess this study is probably getting extra attention from the BBC because of it's from a British group of researchers.

This area of research is important both because it's a new mechanism of antidepressant (opening doors to other drugs and a better understanding of depression) and it is faster acting than other antidepressants, which improve mood slowly over weeks. For the suicidal, this wait can be a lifetime.

There's currently a super interesting (to some of us) question about how important the acute trippy effects are to the sustained antidepressant effects. Is this something where we can engineer out the psychedelic components or are these somehow part of the antidepressant mechanism? See for example this paywalled paper from Zatare's group, which correlates what they call 'dissociative' effects with the antidepressant effect http://www.sciencedirect.com/science/article/pii/S0165032714...

(An early paper on the phenomenon is Berman RM, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000;47(4):351–354. Paywalled http://www.biologicalpsychiatryjournal.com/article/S0006-322... )

Lately, I seem to be hearing a lot about drugs of the "psychedelic" variety being used to treat thugs like depression. psilocybin, DMT, MDMA, Ketamine. The thing that jumps out at me is that they sound like / claim to be treatments in the way that antibiotics are rather than in the way painkillers are. IE, you go through treatment and get "cured."

Please correct me if I am wrong but as I understand it most medical treatments for mental illness is of the painkiller variety. It relieves symptoms while taken consistently and patients either stay medicated indefinitely or the illness runs its course while the effects are mitigated by the drug.

Are there any established treatments that we understand well of the antibiotics variety? Mental illnesses that are cured by a course of treatment rather than and indefinitely ongoing one.

Psychedelics are certainly not drugs in the antibiotic sense; they don't seek out depression-causing neurons and cure them or anything remotely like that.

Rather, psychedelic drugs offer a means for the user to "get out of their head" for a bit. In the right set and setting, the experience offers an opportunity for intense introspection. “Psychedelics probably work in addiction by making the brain function more chaotically for a period — a bit like shaking up a snow globe — weakening reinforced brain connections and dynamics.” It is the experience, not the drug, which causes a fundamental shift in attitude/mindset/worldview, and that is what "cures" the illness.

Very interesting. There have also been recent studies on the effects of anesthesia (Isoflurane in particular) on depression. See:

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjourna...

I thought the ketamine therapy was especially interesting in that it had good effect with relatively low doses. In the Isoflurane study they would put patients completely under (asleep? What is the technical term for being unconscious under anesthesia?) for about 15 minutes. Makes me wonder about the relation between sleep problems and depression.

> Makes me wonder about the relation between sleep problems and depression.

There is fairly strong evidence that sleep deprivation can trigger or exasperate depression [1].

As someone who has had chronic cyclical insomnia since my teens (17 years) in my case it has a massive effect.

When I'm coming out of an insomnia phase the first couple of days where I get a proper nights sleep I feel like I'm on drugs, it's a feeling of well-being and euphoria that is hard to describe, I have limitless energy and I'm enthusiastic about all the things I love to do.

When I'm in the middle of the no-sleep cycle, I struggle to do even basic tasks and anything requiring complete focus is basically ruled out, the world is a grey dreary place, summoning the energy to do anything is a major challenge.

I manage my insomnia without drugs (the problem with sleeping pills in my experience is that while they do make you sleep it's not a high quality sleep and that combined with the lag from the pills means I don't feel any better with them than without) by impeccable sleep hygiene, diet and exercise and the knowledge that eventually the cycle will end.

[1] http://www.ncbi.nlm.nih.gov/books/NBK19961/

> There is fairly strong evidence that sleep deprivation can trigger or exasperate [sic] depression ...

This is one I'm seeing more and more often. The word you were after is "exacerbate". It's my hope that exasperate and exacerbate won't suffer the same fate as literally and figuratively, which now mean the same thing:

http://www.merriam-webster.com/dictionary/literally

Literally has been used to mean "in the strongest metaphorical sense" for close to 300 years, so I think you're beating a bit of a dead horse on that.

Source: OED

It's true that this is an old misuse. But IMHO it's still deplorable that a word and its antonym have merged into one.

At what point does 'old misuse' become correct usage?

It happens all the time. Take "decimate" as just one example of hundreds that come to mind. It once meant to reduce by one-tenth. But through common usage it has come to mean:

http://www.merriam-webster.com/dictionary/decimate

"to destroy a large number of (plants, animals, people, etc.)"

But for exasperate as a replacement for exacerbate, that's more of a stretch. Not to say it won't happen.

What are some of the other "hundreds" of examples that come to mind?

What's my incentive to do this? I post an interesting and relevant fact, and get downvoted. The more interesting and relevant to the topic of discussion, the more downvotes in proportion. I prefer the company of adults.

I don't think it's unreasonable to interpret "literally" as still meaning literally but the "strongest metaphoric sense" use an example of hyperbole. "Literally" is never used to mean "further from literal than you were thinking".

Here on Hacker News there are a lot of people who use English as a second language. And there are a lot of hackers here who speak English as a native language who neglected their writing courses in high school or college in favor of more programming courses. So I am not surprised by spelling mistakes here, and only point them out when they are especially jarring and likely to lead to further misunderstanding.

> ... and only point them out when they are especially jarring and likely to lead to further misunderstanding.

Yes, which is why I posted my correction -- it met that criterion.

Those criteria... :P

Your pointing out a trivial error that didn't significantly impact the intelligibility of my comment adds absolutely nothing to the conversation except demonstrating that you have superior English skills to mine (which I suspect was entirely the point).

In addition if we are going to be rigourously accurate I will point out that merriam-webster also has exasperate down as "to make more grievous" as an obsolete meaning and since you seem to be concerned about changing the meaning of words over time we should perhaps allow the obsolete usage here.

> Your pointing out a trivial error that didn't significantly impact the intelligibility of my comment adds absolutely nothing to the conversation except demonstrating that you have superior English skills to mine (which I suspect was entirely the point).

If you had posted a flawed math equation, or a defective computer program snippet, would you make the same objection to a correction? Would a mathematical correction offered in good faith merit this criticism, or would it be welcomed as a useful contribution?

The answer is obvious -- spoken and written language is to a human what computer programming language is to a computer. Both should be open to correction. And for some reason I cannot fathom, one of them is welcomed and the other criticized, as though biological processors should be treated differently than silicon processors.

> In addition if we are going to be rigourously accurate I will point out that merriam-webster ...

Dictionaries don't prescribe, they describe. No matter how bizarre a word usage, if it appears in publications, it finds its way into the dictionary. So it's not a substantive argument to point out that a word meaning appears in a dictionary -- all of them end up there.

Aw. And to think, you could have just thanked him!

As a rule I don't thank pedants I just avoid them.

Interestingly, and although all my anecdotal evidence disagrees with this, on the short term sleep deprivation supposedly does the opposite [0].

I have trouble with insomnia as well, and my experience is basically the same as yours. If I don't get at least eight hours, the brain fog is so thick I just can't function. It doesn't make sense to me however, because many people I know can function perfectly with little to no sleep.

I've been looking into supplements to improve the quality of sleep. The most promising so far is glycine, which has at least some science demonstrating its efficacy (in both sleep quality and consequent daytime performance) [1]. Some anecdotal experience from reddit also makes it seem promising [2]. Also on my list to try are ZMA and low-dose melatonin.

[0] http://www.nature.com/scitable/blog/mind-read/an_unconventio...

[1] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328957/

[2] http://www.reddit.com/r/Supplements/comments/1a899m/what_do_...

I've tried different supplements before though not glycine and melatonin is not something that is easy to get in the UK.

It's hard to say in the singular case whether they work as I can't rule out the placebo effect what I've found for me though is that a good diet (lots of fish and fresh vegetables mostly) has as much or more of an impact.

I'll certainly look into glycine though, thanks.

EDIT: I took a look at the studies (well the overviews anyway) on Glycine, fascinating reading, I've ordered some from Amazon and will see, again, many thanks :)

I've had insomnia my whole life (I don't say 'suffer', because sometimes I enjoy it, though pay the price the next day).

I don't recommend melatonin, unless you've messed up your body clock and are trying to 'reset' when you go to sleep.

ZMA is just Zing/Magnesium/B6 (I don't know why it isn't called ZMB, maybe that's too similar to zombie?). I haven't taken ZMA specifically, but I have taken all of those supplements together at the same time bumping up the levels of a multi. I wouldn't say I noticed a huge difference in sleep performance.

Isoflurane doesn't replace REM sleep, though. http://www.ncbi.nlm.nih.gov/pubmed/20418293

I wonder what the effects of other arylcyclohexylamine compounds have on depression. There is plenty of anecdotal evidence on Bluelight.ru and Erowid.org suggesting that other chemicals of this class can have a positive impact on depression. Of course, there are plenty reports of addiction and negative behavior (mostly with PCP). I know that many people report the legal analogue Methoxetamine (legal in the US; Ketamine is schedule III and the federal analogue act only applies to schedules I and II) has potent antidepressant effects.

This is very interesting for the use of ketamine. My wife is currently undergoing a ketamine infusion for RSD/CRPS. RSD/CRPS is a crippling pain disorder, and ketamine infusions are so far the only thing that has given her any relief. Hopefully things like this will help to get ketamine treatments covered by insurance, because it is insane that they are not covered for those suffering RSD/CRPS.

Treatment of depression has improved enormously over the last four decades. It's a tough treatment and research problem because depression isn't just one disease at the biological level.

Quoting the full study abstract will probably be helpful to the discussion here.

"Background: Ketamine has a rapid antidepressant effect in treatment-resistant depression (TRD). The effects on cognitive function of multiple ketamine infusions and of concurrent antidepressant medication on response rate and duration are not known. Method: Twenty-eight patients with uni- or bipolar TRD were treated over three weeks with either three or six ketamine infusions (0.5 mg/kg over 40 minutes) in the recovery room of a routine ECT clinic. Post-treatment memory assessments were conducted on day 21 (4–7 days after the final infusion). Patients were followed up for six months where possible, with severity of depression and side effects monitored throughout. Results: Eight (29%) patients responded of whom four remitted. Only three (11%) patients had responded within six hours after a single infusion, but in all responders, the response had developed before the third infusion. The duration of response from the final infusion was variable (median 70, range 25–168 days). Discontinuations included two (7%) because of acute adverse reactions during the infusion and five (18%) because of failure to benefit and increasing anxiety. Ketamine was not associated with memory impairment. The ECT clinic was rated suitable by patients and offered appropriate levels of monitoring. Conclusion: This small, open label naturalistic study shows that up to six low dose ketamine infusions can safely be given within an existing NHS clinical structure to patients who continue their antidepressants. The response rate was comparable to that found in RCTs of single doses of ketamine in antidepressant-free patients but took slightly longer to develop."

The free full text of the article reporting this preliminary finding can be found online.[1] (Hat tip to the participant here who first found the abstract link, which leads to the full-text link.)

Depression is maddeningly difficult to treat because it is quite clear on multiple grounds that not everyone with signs of depression (extremely persistent low mood contrary to the patient's life circumstances) has the same underlying physical or psychological cause of depression. The human mood regulatory system is a SYSTEM, and as such it can be perturbed by a number of biochemical stressors internal to the patient, and also by a number of outside-the-patient environmental stressors (including sleep disturbance, already mentioned in this thread, and the use or abuse of various druggs). Not all patients have the same biological substrate to their depression, so not all patients will respond to the same treatment. To date, the most effective treatment for depression is a both-and of prescribed medication and professionally supervised talk therapy, and there is an active research program on identifying which patients respond to which medicines and to which kinds of talk therapy.[2]

In any research program on treatment of human subjects, the studies have to start with small numbers of subjects to verify safety of the treatment, and then gradually increase the number of subjects and add in double-blind protocols to verify both safety and effectiveness. (The study reported here is "open label," not double-blind.) New treatments are usually tested first on patients who don't respond to current treatments, as in the research reported here. It will be a long time before we know how helpful ketamine is compared to other treatments for depression, but that will be an ongoing program of research, and so far it looks somewhat promising.

[1] http://jop.sagepub.com/content/early/2014/03/17/026988111452...

[2] http://www.annualreviews.org/doi/abs/10.1146/annurev.psych.1...

I am not sure why they linked to sagepub but not the actual article. The full text journal article is available: http://jop.sagepub.com/content/early/2014/03/17/026988111452...

It was a lot of work to get BBC to link even that much. I would suggest a polite note thanking them for the link, and suggesting how to make it even more helpful :-)

THE WHITE ROOM, Trancentral, Thursday (NTNME) — The illegal party drug ketamine is an “exciting” and “dramatic” new treatment for depression, say doctors who waited about two decades too long before conducting the first trials in the UK.

The single small study has attracted due caution from evidence-based medicine experts, since 80% of single studies turn out to be in error. However, middle-aged doctors and researchers who feel they didn’t get out enough in their youth are clamouring to do multiple large-scale replications of the study, probably this weekend.

The findings open up whole new avenues of research. “It’s the sort of thing really that makes it worth doing psychiatry,” said lead researcher Dr Rupert McShane, or, as he now calls himself, DJ Rupe McK-Hole. “Can we get back into trials on LSD yet? I understand there’s also considerable clinical possibilities for the therapeutic qualities of sequences of repetitive beats, MDMA and the possibility of shagging cute raver chicks like the ones I remember.”

The duration of the effect is still a problem. “We’ll have to make sure we repeat the trials next weekend and the weekend after as well. For science and verifiability.”

I remember reading about this in a New scientist issue over 8 years ago. It's a shame that it's taken this long for newsworthy studies to be done on it.

ketamine

> Some patients who have faced incurable depression for decades have had symptoms disappear within hours of taking low doses of the drug.

So in other words they are getting high.

Yes, they are getting "high". I'm not sure what your point is however.

I've never understood the stigma associated with all mind-altering drugs, regardless the relative 'safety' of certain drugs in comparison to legal, and far more dangerous alternatives (nicotine and alcohol).

> I've never understood the stigma associated with all mind-altering drugs ...

One objection that comes immediately to mind is that it may divert from a search for the actual cause of depression. Remember that this treatment, like all depression treatments, is symptomatic. It doesn't either identify or treat the underlying condition, only its symptoms.

Drug-induced euphoria and depression are not mutually exclusive feelings. Ask any depressed person who's taken psychoactive drugs.

If ketamine functions as an antidepressant, that's a distinct and unusual effect.

Very true. Some hallucinogenic can significantly intensify depression.

> One objection that comes immediately to mind is that it may divert from a search for the actual cause of depression.

That's an insane objection, because understanding of how different depressions (depression isn't one thing, its just a set of symptoms) respond to different treatments is one method of determining the causes.

Linking observed symptoms to environmental factors (both those that precede the symptoms, those that occur with the symptoms, and those that cause changes to the symptoms) is a fairly essential part of the normal scientific method of determining the mechanism behind the symptoms.

That it also helps people in the here and now is a not insignificant side benefit, of course.

>> One objection that comes immediately to mind is that it may divert from a search for the actual cause of depression.

> That's an insane objection ...

Actually, it's called "science". Science isn't about descriptions, it's about explanations. If we knew why ketamine worked, we would have finally crossed the threshold of science.

Without science, we will continue to see one "breakthrough" after another, each lasting a few months, to eventually be discarded as its questionable statistical basis comes to light.

> Linking observed symptoms to environmental factors (both those that precede the symptoms, those that occur with the symptoms, and those that cause changes to the symptoms) is a fairly essential part of the normal scientific method of determining the mechanism behind the symptoms.

That can only be a preliminary to science. Science is not about "links", it is about testable, falsifiable explanations for those links. Without an effort to explain "links", any correlation becomes science. But that's not how science works.

> That it also helps people in the here and now is a not insignificant side benefit, of course.

But that has no value at all, in fact it's an obstacle to understanding. And it explains the many drugs presently available that are either known to be ineffective or that have adverse effects -- all of them gained a foothold by a study like this one, a questionable study, over-reliant on self-reporting.

>>> One objection that comes immediately to mind is that it may divert from a search for the actual cause of depression.

>> That's an insane objection ...

> Actually, it's called "science".

No, actually, its an objection to a necessary step of science, on the supposed basis that it prevents science. Which is what makes it insane.

So... Uhhh... Why does gravity work? I know we can describe it, but is it considered science yet?

> So... Uhhh... Why does gravity work? I know we can describe it, but is it considered science yet?

Bad example. General relativity describes gravity in great depth, and made a number of testable predictions, all of which have been proven in experiments many years after the original predictions. So yes, modern physics is not only a science, but it's the science to which other sciences are unfavorably compared.

Also, an explanation, a scientific theory, as useful as it is, doesn't say "why" something is so -- that's for philosophers.

> Actually, it's called "science". Science isn't about descriptions, it's about explanations. If we knew why ketamine worked, we would have finally crossed the threshold of science.

But you said that if we knew why it worked, it would have become science. You also said that it's about explanations, not about descriptions.

General relativity may describe gravity, but it doesn't explain it. According to your previous post, this excludes gravity from science. I was just pointing out the flaw in your reasoning.

Consider this a final response - I see you will keep any argument going for the sake of arguing throughout this post. It's clear you have some sort of agenda or preconceived notion to defend, and I'll leave you to that.

> But you said that if we knew why it worked, it would have become science.

No, I said if we explained it, that would be science. For God's sake, read the words. Explaining something like gravity doesn't try to justify why it is that way, it only shows that we understand it in depth.

> General relativity may describe gravity, but it doesn't explain it.

FALSE! GENERAL RELATIVITY IS THE PRESENT EXPLANATION FOR GRAVITY.

http://www.highexistence.com/einsteins-theory-of-relativity/

Title: "Einstein’s Theory of Relativity: Explained"

Circle the word you don't understand, and raise your hand.

> Consider this a final response ...

Unfortunately, you are among the science-illiterate.

>Explaining something like gravity doesn't try to justify why it is that way, it only shows that we understand it in depth.

So clearly there's some disagreement here about what "explain" means, so I'll avoid that semantic argument and skip to the point:

Understanding something "in depth" is not necessary for science. As long as a shallow understanding makes accurate predictions, it is scientific. Trying to make more detailed rules would just be violating Occam's Razor.

To get back to the original point: If we make the hypothesis "Ketamine cures depression" and find no evidence to the contrary, then it is a theory which is sufficient to describe the world, and speculation about the mechanism is a pointless exercise, just as it would be pointless to look for a more complicated theory of gravity to describe things adequately explained by GR.

However, if we were to find (as is more likely) that in some cases Ketamine doesn't cure depression, only then is there a reason to delve deeper to work out why.

> Actually, it's called "science". Science isn't about descriptions, it's about explanations. If we knew why ketamine worked, we would have finally crossed the threshold of science.

Actually, science is mostly observation and description. Sometimes the descriptions can lead to theories, but only after peer-majority agrees the theory adequately describes enough observed cases to be trusted for prediction. Most of the seemingly immutable parts of science are in fact maths.

And maths is mostly description of observation...

> Actually, science is mostly observation and description.

That's not science, that is a preliminary to science. If this were not so, astrologers -- who do lots of observing and describing -- would be scientists.

If you think observation is "preliminary" to science, then you fundamentally misunderstand the scientific method.

The reason Astrologers are not scientists is not that they don't try to work out why the positions of planets might affect the future.

The reason they are not scientists is that they don't observe the world to see if they actually do.

Yeah, but that's true of Prozac, as well. It turns out that depressed people are definitionally ineffective at finding the root causes of their problems, and if you cam artificially suspend the feedback loop, then they might have a chance to diagnose and fix the underlying problem. And then of course for some people, the underlying causes are already gone and the depression is just a standing wave of feedback, and temporarily inhibiting the cycle is enough to cause it to stop.

I don't know why they reference it as an "Illegal Party Drug". It has been used in veterinary and human medicine forever.

Not...necessarily. As I understand, there can be a big difference -- even when the drug is the same -- between the effects of drugs at therapeutic doses for people with conditions that they are effective for treating and typical recreational uses.

While its not always an accurate description of the mechanism, the difference can be thought of (and sometimes literally is) the difference between restoring a normal chemical balance where there had been a deficit, on the one hand, and creating an excess, on the other.

So, calling it "getting high" can be very badly misleading.

> So, calling it "getting high" can be very badly misleading.

If we understood what depression is, understood its cause, then a dismissive expression like "getting high" might be unjust. But as long as we're only treating symptoms, that's an appropriate description.

No, even in terms of treating symptoms, its still unjust. Even from an external, symptomatic view, there's a difference between a recreational "high" from a drug and someone successfully treated for depression with the same drug.

The fact that the observation of that difference precedes understanding of the underlying mechanism responsible for it doesn't make the difference any less real.

> Even from an external, symptomatic view, there's a difference between a recreational "high" from a drug and someone successfully treated for depression with the same drug.

To take this position you cannot have spent much time listening to drug addicts, who explain their behavior in just this way.

> The fact that the observation of that difference precedes understanding of the underlying mechanism responsible for it doesn't make the difference any less real.

On the contrary -- knowledge of the underlying mechanism is what separates science from quackery. Remember that all quack cures appear to work, for unknown reasons, mostly having to do with the Placebo effect. Remember also that the study under discussion relied on self-reporting for its conclusions.

But sometimes treating symptoms is the only usable treatment. There is a big difference between someone "self medicating" with a drug with high abuse potential, and falling into addiction and a controlled dose in a therapeutic setting where (as the article stated) the benefits far outlasted the high.

> But sometimes treating symptoms is the only usable treatment.

This is the argument of the mental health establishment as they continue to offer drugs that haven't been proven to have a connection with the actual condition, only its symptoms. The result is that an absurdly high percentage of people are on drugs of high cost, serious side effects, and questionable effectiveness.

An example, not about depression, but ADHD:

http://www.nbcnews.com/health/health-news/number-young-adult...

Quote: "The number of young adults taking drugs for ADHD has soared in five years, particularly among young women, whose use of the drugs is up 85 percent, according to a new report."

An 85% increase in five years, for a drug that only treats symptoms, and not very effectively at that. I guess the program is working.

Well, on a drug where you've forgotten the difference between up and down and are now convinced you're able to walk through solid objects, I'm pretty sure you'd forget about being depressed...

This is your brain on ONDCP propaganda.

Yeah, that seems a bit uninformed, though lots of people I know who like other drugs don't like ketamine. Cocaine, ecstasy and cannabis, when you're used to it, modify rather than replace what you're feeling. Ketamine can put you on the floor quite easily, with no/a crazy understanding of the world followed by twenty minutes of learning to understand it again. A lot of people don't like that. It can be taken in more moderate doses too, but it's hard to judge how much to take (how long is a line -- the same as a piece of string; tolerance develops quickly) and one can inadvertently take too much.

I think it's under-appreciated and find the experience exhilarating.

I think the key takeaway here was that the anti-depressive effects lasted for days to months afterwards, well past the peak effects/activity of the drug.

I don't know why you are being downvoted. My understanding is that yes, that's more or less how it works. Speaking from experience, whatever it is you are obsessing about, a ketamine trip makes you forget about it for about an hour. I think the main feeling you get when coming down from the trip is that you were just shown a world where your obsession doesn't make any sense, and it's a very good time to question your obsessions.

> I don't know why you are being downvoted.

He's being downvoted for making a moronic criticism: what the person feels under the influence of ketamine is obviously irrelevant, of no value for treating depression, this would be just as obvious to the researchers as to him, and so they couldn't possibly have meant that, and indeed, the second sentence of the article says benefits last well beyond the immediate influence.

You're an idiot, I wasn't making a moronic criticism, I happen to be 100% anti-drug prohibition, but yet again on Hacker News, I've been massively down-voted and insulted for making a joke.

I'm glad you think so! I was making a light-hearted observation and I'm actually 100% in favour of legalising and exploring the potentials of some of these substances for people with severe mental health problems. Mental health problems affect my family deeply and don't think any stone should be left unturned. It's just a shame everyone seemed to jump at me assuming I was criticising it somehow!

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