Yale scientists explain how ketamine vanquishes depression within hours
news.yale.edu
news.yale.edu
This news doesn't surprise me at all.
My lesson was that drugs should be experimented with in the company of a friend or partner.
Thus, since you were in an already stressful situation, I'm not surprised that K wasn't relaxing or pleasant.
I'm not trying to stop them, but there are reports of Ketamine abuse being damaging to the bladder. Some people have had their bladders removed.
(http://www.bbc.co.uk/news/health-17411492)
(http://www.bbc.co.uk/news/uk-17344089)
I have no idea on the dosing needed for harmful effects - is several large doses enough? Would very many small doses be harmful?
Some people taking anti-depressants do so for a long time. Most are recommended to take them for at least two years to prevent relapse, but some medications (especially venlafaxine) can be hard to come off. (I've been told that I'll probably be taking venlafaxine for the rest of my life.)
So, this news is exciting because better understanding of mental health problems is really important, and better treatments would be fantastic. But please be careful when self-experimenting with possible nootropics.
I would also add "please be careful when following the advice of a physician."
In fact, I think it may be best to just say "Please be careful."
_________________
Abstract
Basic and clinical studies demonstrate that depression is associated with reduced size of brain regions that regulate mood and cognition, including the prefrontal cortex and the hippocampus, and decreased neuronal synapses in these areas. Antidepressants can block or reverse these neuronal deficits, although typical antidepressants have limited efficacy and delayed response times of weeks to months. A notable recent discovery shows that ketamine, a N-methyl-d-aspartate receptor antagonist, produces rapid (within hours) antidepressant responses in patients who are resistant to typical antidepressants. Basic studies show that ketamine rapidly induces synaptogenesis and reverses the synaptic deficits caused by chronic stress. These findings highlight the central importance of homeostatic control of mood circuit connections and form the basis of a synaptogenic hypothesis of depression and treatment response.
I heard a National Public Radio story with interviews of researchers on the same issue as the press release submitted here while on a drive this afternoon. What most excites researchers about the ketamine studies is not a prospect of using ketamine itself as a frequent first-line drug for treating depression, but rather as a model for understanding brain function better and eventually developing new drugs that are even longer-lasting for treating depression and even less likely to trigger mania. Human mood disorders are very diverse--there are probably hundreds of rare genetic variants that increase the risk of mood system disruption under varying kinds of environmental stress--so there surely will not be just one drug that will successfully treat all patients, but rather a gradually growing toolkit of better and better drugs to treat more and more patients with less risk and fewer side-effects.
AFTER EDIT: User shrivats just kindly pointed, in a subcomment, to the overall summary of the Science special issue on depression, in which the ketamine research and related research is discussed. A paragraph describing another article in that issue is especially helpful for HN participants: "However, not all is bleak. There are individuals who overcome difficult situations and show astonishing resilience in the face of adverse circumstances and other forms of acute or chronic traumatic stress. Studying them might provide us with clues about what can go right. Southwick and Charney (p. 79) provide an overview of current ideas about why some people are more protected against stress and depression than others and how this knowledge may help us develop better treatments and successful prevention strategies." Several HN participants regularly write about strategies of building resilience to face the stress that many hackers face. Further research on that issue will also be part of the package in future improved treatments for mood disorders.
There's burgeoning evidence that depression is tied to a lack of neurogenesis (creation of new brain cells), which may also be tied to serotonin levels. Some believe that the reason SSRIs take weeks to have antidepressive effects, even though serotonin levels are restored almost immediately, is that it takes a while for that to stimulate new brain cells. It's far from certain though that serotonin has anything to do with depression or neurogenesis. The atypical antidepressant tianeptine (currently unapproved in the US, but widely used in western europe) apparently reduces serotonin levels while boosting neurogenesis, the study of which is summarized well by Stanford neuroscientist Robert Sapolsky [1]:
> … tianeptine prevented many of these stress-induced changes. These included the spectroscopic alterations, the inhibition of cell proliferation, and a significant increase in hippocampal volume (as compared with stress + vehicle animals). Of significance (see below), tianeptine did not prevent the stress-induced rise in cortisol levels.
The restoration of hippocampal volume is important because it's been shown that low hippocampal volumes correlate with emotional abuse in adolescents [2] (also by Yale researchers). This was breathtaking for me - bad parenting literally causes brain damage.
Special K and tianeptine aren't the only efforts at curing depression through neurogenesis. Neuralstem [3] is testing a drug in humans to treat major depressive disorder by restoring hippocampal volume, with a controlled study to complete early next year. That is the only new drug I'm aware of. Regardless, the serotonin model of depression, the one which produced Prozac etc. isn't the last word, and it's looking more likely that a dearth of new synapses may be the culprit in clinical depression.
[1] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC60045/
[2] http://www.medpagetoday.com/Pediatrics/DomesticViolence/3002...
[3] http://www.neuralstem.com/pharmaceuticals-for-depression
For those of you who would like a reference supporting this claim, check out the following: http://www.ncbi.nlm.nih.gov/pubmed/10051225.
I often share stuff I read on HN with friends and it's useful to have evidence beyond "some dude on HN said so."
The review explains why the rapid action of ketamine excites so many researchers:
The discovery that ketamine rapidly increases the number and function of synaptic connections has focused attention on synaptogenesis as a fundamental process for the treatment of depressive symptoms and also suggests that disruption of synaptogenesis and loss of connections underlies the pathophysiology of depression.
This excites researchers not because ketamine itself would be used to combat depression, but because depression is still extremely symptomatically defined, making it difficult to design treatments for. That's roughly how it's diagnosed in the diagnostic manual used by most psychiatrists: check off a list of symptoms, if you have enough, you're depressed. It's like going to the doctor and explaining that your stomach hurts and they say "well, looks like you have abdominal pain, here's some Advil." Treating the symptoms would be great if only there were a happiness dial in the brain. Indeed, the effect of most anti-depressants is often demonstrated prior to a mechanistic understanding of why they make many patients feel better.
Recently there has been substantial evidence of "synaptogenesis" - the formation of new potential connections between neurons - from multiple treatments, including ketamine. So now we have this new picture emerging: depressed patients tend to have atrophied and "less-connected" neurons in some brain areas, and some drugs can reverse it, in particular ketamine can reverse it quite rapidly, and it works in rodents as well as humans.
That makes it very amenable to study. The way this often works in the lab is the following. Take some rodents, subject them to unpredictable stress to get them depressed, then give some ketamine. It makes them better. Euthanize the rodents, slice the brains, and note that the non-ketamine ones have less dendritic spines in certain areas ("potential input points to a neuron"), but remarkably, the ketamine ones have more in those areas.
The most important step comes next, where you try to find out what ketamine is actually doing, since, again, there's no happiness dial in the brain. Create strains of "knock-out" rodents, where you block the production of certain chemicals or proteins you think ketamine might affect by altering their genetic composition. This step is crucial, because it allows you to find out which effect of ketamine is providing the benefit, because there are many. You can do this both by observing both behavior (does the ketamine not improve mood in the genetically altered rodents?) and in physiology (does the ketamine still increase synaptogenesis in the altered rodents?).
In the end you can kind of work out a map of sorts: ketamine does X things to the brain and Y in X are the ones that are important, sometimes in certain combinations. Then you can start creating intelligent drugs that pinpoint those important processes, to avoid the unfortunate side effects of drugs like ketamine. Moreover, you now have a better physiological understanding of depression, instead of just a symptomatic one.
To put it in machine-learning language, it's like going from ideal observer analysis like mutual information, to an actual parametric model where you understand the distributions themselves.
This blew me away, but I only now realized why. It was because I knew depression was symptomatically defined, and she had probably found a way to define it physically. I thought that the "lesser" cases she couldn't detect weren't actually physically depressed, and that her discovery was amazing. Other students didn't share my enthusiasm, but maybe that was because it wasn't very interesting from a machine learning perspective.
I wonder what happened with that. I can't remember her name now.
EDIT: I found the paper: http://discovery.ucl.ac.uk/1316862/
The key finding seemed to be predicting whether or not treatment would be successful. This is quite powerful as it would help guide clinicians in figuring out whether or not a specific treatment regimen would be advisable or just a waste of time (and time is critical in treating depression).
Very interesting.
You manage to infer, as well as the author of the OP, that depression decreases the number of synapses or eventually induce a sort fatigue in synapses because of stress. That depression is not only correlated but also induced by synapse depletion, that increasing the number of synapse is what makes depressed people feel better, that depression (the symptom) has one cause, here stress inducing synapse fatigue or depletion, etc.
It takes just common sense thinking to understand that most of this reasoning is just crap. Suggesting to put that in a machine learning language is is even more depressing.
Could you be so kind as to elaborate on some of this common sense thinking? I must lack the same common sense you possess, because it seems to me that the parent comment makes a compelling case in favor of further study of the synaptogenesis hypothesis. I did not get the impression that kevinalexbrown was claiming that depression is caused by depletion of synapses, but rather summarizing for the record that this is the model suggested by the observed effectiveness of ketamine.
I'm confused. As I read the post, it contains the bits "The most important step comes next, where you try to find out what ketamine is actually doing, since, again, there's no happiness dial in the brain. ... This step is crucial, because it allows you to find out which effect of ketamine is providing the benefit, because there are many."
While the possibility you take as 'assumed' is the jumping off point for the hypothesis, it is explicitly a testable hypothesis for which the necessary test to (in)validate the original assumption is explicitly defined.
So what exactly is the problem?
In religion and politics, people are judged based on their origins and their "authority". Not in science.
The OP should have posted sources or links, but apart from that, his remark needs to be evaluated on its merits, not his merits.
"Science is the organized skepticism in the reliability of expert opinion." — Richard Feynman
I for one am not about to go chase down every potential citation about a subject I don't know anything about just in order to fully evaluate his remark on its merits just because the subject is somewhat interesting to read about.
In that situation, authority and expertise is important - you are perfectly justified that on average you will do better if you take medical advice from a doctor than a random person, for example.
DO you really think science only takes place between the covers of a journal?
> Authority or expertise is not evidence of the truth of what someone writes, but for most of us, in the absence of the time or expertise to evaluate the evidence, it often serves as a useful shortcut to determine what amount of trust to assign to a statement.
Yes, understood. But not for a scientist.
> I for one am not about to go chase down every potential citation about a subject I don't know anything about just in order to fully evaluate his remark on its merits just because the subject is somewhat interesting to read about.
So, because you won't do research, someone has to prove themselves to you? You're going about this all wrong -- when you decide to be intellectually lazy, the worst thing to do as an encore is to demand that someone prove themselves to you, and then accept claims of authority. Jim Jones' followers died because they were unwilling to think for themselves, do their own research. David Koresh. The list goes on.
> In that situation, authority and expertise is important ...
The bottom line in science, and in any scientific discussion, is that authority and expertise are never important. The greatest amount of scientific eminence is trumped by the smallest amount of scientific evidence.
> you are perfectly justified that on average you will do better if you take medical advice from a doctor than a random person, for example.
That's not a scientific example, because doctors aren't scientists. I'm beginning to realize you can't distinguish between science and anecdote. As they say, the plural of anecdote is not evidence.
DO you really think we are doing science in this discussion? Seriously?
If you genuinely think so, then we can end the discussion right here, as if that is the case, we are arguing on an entirely different basis.
Just to be clear, my argument is based on my expectation of engaging in a discussion that is not particularly scientific, but is a casual debate about a scientific result where most of the participants are not scientists, nor have sufficient knowledge or interest in the field in question to have read much actual research in the field. That fits _my_ observation of this debate. I see little to no evidence that there's much "science" going on in this debate.
> Yes, understood. But not for a scientist.
This is blatantly false. Scientists frequently engage in discussions about fields they only have a superficial interest in too, and where they don't have the time nor the interest to probe deeper, and I have personally seen plenty of examples of scientists deferring to authority on subjects they do not personally know for all kinds of purposes. Yes, that is not "science". But we're not all engaging in science every moment of our waking lives.
> So, because you won't do research, someone has to prove themselves to you?
No. Because I am here reading about something I don't have sufficient interest in to research, I appreciate an indicator of authority as a a contributing factor to judge what degree of trust to assign certain claims.
We all do that pretty much constantly, and largely automatically. Your username, for example, means I assign you a certain amount of trust in matters I have reason to believe you know something about. E.g. if you were to make statements about AppleWrite in conversation on HN, I'd likely take it on trust. Does that mean I'd be unwilling to do research about it in certain cases?
Of course not. If I was writing a scholarly article about the history of word processing, for example, of course I would obtain multiple sources and track down other evidence.
But I am not here conducting science, neither I'd gather are the vast majority of other people here. And then trust and authority does matter as shortcuts. I have plenty of other things to spend my time on. Things I _care_ about, which is not something I can say about neuroscience.
> Jim Jones' followers died because they were unwilling to think for themselves, do their own research.
Did you seriously compare someone asking for indicators of authority from someone who made statements that appeared to be a bit controversial to not being willing to think for oneself before joining a religious cult and participating in mass suicide? Are you for real?
Deferring to authority and assigning trust are not inherently bad just because there are nasty examples of the consequences of taking it too far.
For someone who harp about science, you've made some quite astounding leaps of logic.
> That's not a scientific example, because doctors aren't scientists.
Irrelevant. The issue here is not science, but whether trust and authority have value in determining whether or not it is necessary to do your own basic research of everything.
> The bottom line in science, and in any scientific discussion, is that authority and expertise are never important. The greatest amount of scientific eminence is trumped by the smallest amount of scientific evidence.
If this was a "scientific discussion" perhaps you'd have a point.
The reality is that in a casual discussion, - which is what this is to me, and clearly to a substantial number of the other participants, given the widespread lack of citations and evidence in this discussion - where a large number of the participants are either not scientists and/or not deeply familiar with the subject in question, nor invested enough to find it worthwhile to chase down source material, often it is not clear what the evidence - if presented - actually is and what it actually means to a lay person.
As such, authority and expertise is an important shortcut to get an overview for the purpose of the discussion without bogging the discussion down to the point where the participants lose interest.
> I'm beginning to realize you can't distinguish between science and anecdote. As they say, the plural of anecdote is not evidence.
I'm beginning to realize that you don't understand that in a social conversation, rather than, say, a scientific conference, evidence is not paramount, and often isn't even that important. That's not to say that some relevant evidence and citations are not appreciated, but most of us will not read them. That's not why people participate in these discussions. If we wanted in depth neuro-science, for example, we'd be busy reading the research not discussing a press-release on HN.
Good luck proving that your breakfast isn't poisonous before you eat it tomorrow. I hope you don't starve to death first.
Here is a quick rewrite of the snarkiest bit of the post that I think is not only drastically more civil but just as effective:
"I fear the reasoning here is incorrect as it conflates correlation with causation. Being too hasty in using this conclusion with machine learning would be a mistake."
I know there is a segment here that doesn't believe tone/communication style should matter, that it is, or should be, entirely about the underlying verisimilitude of their statements; unfortunately, that is not how 99% of human beings actually operate. So while you are free to rail against reality it will make you drastically less effective than you might otherwise be.
To my defense, I could say that English is not my mother language and that the conflation of correlation with causation error, as you say, is a source of strong irritation to me. ;)
Thank you for your clarifying and kind comment.
Okay, but first, locate and circle the words you have just assigned to me in my original post. What? Can't find those words? Know the expression "straw man"?
I ... never ... said .. any ... such ... thing.
Circle the words on the screen in front of you, where I ever uttered these words, anywhere, on God's green Earth.
You need to start reading what people say, not what your overactive imagination believes they said.
> ... seems to also imply you view this as a debate instead of a discussion ...
When someone invents a position to conveniently argue against, of course it's a debate -- a debate between fantasy and reality.
Notice how I have in each and every case replied directly to your words, which I quote in full. Notice how you don't have time to check in with reality before ascending your soapbox.
Can you then perhaps elaborate how else we should take this quote from you:
> I suggest that you resist posting this kind of inquiry in a scientific discussion. In science, only evidence counts, not authority or expertise. In science, the quality of evidence is all that matters, not its source.
As well as this in your reply to me:
> The bottom line in science, and in any scientific discussion, is that authority and expertise are never important. The greatest amount of scientific eminence is trumped by the smallest amount of scientific evidence.
Of course you might argue that this is not a "scientific discussion", but that would make both of these messages meaningless or intentionally obtuse in the context they were posted.
Getting back to the facts, there is nothing allowing us to think that depressed people feel better when taking ketamine BECAUSE the number of synapses increases when taking ketamin.
A possible correlation is presented as a cause relation. Was it verified on the same people ? If not we can't even consider this to be a true correlation.
The OP goes even beyond that, but this should be enough to justify my critic.
(pseudo) scientific PR are leveraging this common logical error for their promotion to such point that people get totally blind to it. This is debilitating and should be classified as crap information.
This seems to be a strange use of the word "allowing". I would say that the evidence presents an interesting and testable hypothesis about the role of synaptic connections in depression. The obvious next step would be to find other methods of inducing similar effects on synapses by means other than ketamine and see if they have similar effects on depression.
Out of interest, what do you think might be some of the biological mechanisms associated with chronic depression and how would you seek to investigate them?
Not really something you should want to self medicate with at this point until more research is done.
The levels of ketamine required to form Olney's Lesions are 40mg/kg (given olney.txt), whereas the typical dose to reach a k-hole (the highest recreational level) is 1mg/kg. http://www.erowid.org/chemicals/ketamine/ketamine_dose.shtml Also: http://en.wikipedia.org/wiki/Olneys_lesions#Controversy
In addition, the dosage levels of recreational ketamine are lower than the anesthetic dosages of ketamine. Repeated use of ketamine would probably still cause problems though, though the problems would be more along the lines of general drug dependency and not being able to think straight.
> Not really something you should want to self medicate with at this point until more research is done.
I dunno. Depression can be really dangerous & costly too-- both from suicide and just generally not being happy in life.
It's fascinating to see these demonised recreational drugs being researched finally for their beneficial side-effects, sometimes in very small doses. Another one that comes to mind is the reported use of sub-psychoactive doses of LSD to combat the horror of cluster headaches.
He's been cluster-headache free since January, and he's really happy that he doesn't have to rely on the black market for medication.
http://en.wikipedia.org/wiki/Olney's_lesions
MSG is monosodium glutamate, and there is research to show MSG is toxic -- it's the glutamate that's bad for you, not the sodium. Flooding your body with excess glutamate throws off the brain's delicate balance of this neurotransmitter and leads to excitotoxicity (http://en.wikipedia.org/wiki/Excitotoxicity).
The blood-brain barrier protects you from some of it, but the blood-brain barrier is not fully formed in babies, and this is why MSG not allowed in baby food. However, the blood brain barrier can be weakened by any number of reasons in adults, such as when you have a fever.
Why would ketamine's release of glutamate be different and good for you in this case?
Also see: http://en.wikipedia.org/wiki/NMDA_receptor_antagonist#Potent...
I've read too many Onion headlines to ever read headlines like this again.
"Drug Reverses Abnormal Brain Function in Rett Syndrome Mice"
http://www.sciencedaily.com/releases/2012/10/121003132418.ht...
"ScienceDaily (Oct. 3, 2012) — A promising study out October 3 in the Journal of Neuroscience showed that in a mouse model of Rett syndrome, researchers were able to reverse abnormalities in brain activity and improve neurological function by treating the animals with an FDA-approved anesthesia drug, ketamine. Rett syndrome is among the most severe autism-related disorders, affecting about one in 10,000 female births per year, with no effective treatments available."
Translation: "Yale scientists speculate about how ketamine vanquishes depression within hours" And until there's a strictly designed study with a control group, we'll be no closer to a definitive answer. But considering the drug and its role and target, a control group would be unethical.
Ben Goldacre talks about it here (http://www.badscience.net/2011/03/when-ethics-committees-kil...)
We have a variety of treatments that work for some people, but not for others. Combining these sometimes-effective evidence based treatments with the ethics panel weirdness above makes it hard.
People with depression are at increased risk of suicide. They are also at increased risk of suicide during recovery. (Perhaps they are so depressed that they lack motivation to complete suicide, and recovery gives them enough motivation to complete suicide but not enough mood recovery to stop).
That was the propaganda explanation that pharma companies created so they could still sell their drugs even though they cause suicidal ideation and increased suicide rate. It doesn't actually make any scientific sense though, because if you give healthy control volunteers SSRIs then they still have increased levels of suicidal ideation.
Do you have a citation for this? I've only ever heard the "too depressed to commit suicide" theory, so if there's evidence for the alternative, I'd be really interested in seeing it.
I would advice against drawing any strong conclusions from this.
And in any event, it's the best research we have. The idea that SSRIs make people suicidal by eliminating their depression doesn't even make sense, because placebos are just as effective as SSRIs for treating depression but they don't cause an increase in suicidal ideation or actual suicides.
Very interesting! Source?
edit: hivemind
Antidepression drugs, indeed all psychoactive drugs, are always a potential ethics issue. Consider the brouhaha that erupted when it was discovered that some antidepression drugs caused people to commit suicide or have suicidal thoughts:
http://www.medicinenet.com/script/main/art.asp?articlekey=31...
A quote: "The FDA has warned that children and adults taking antidepressants can become suicidal in the first weeks of therapy and that physicians should watch patients closely when first giving the drugs or changing dosages. The FDA is asking drug manufacturers to place explicit warnings about the drugs' side effects, including the risk of suicide, on their labels."
Any human-administered drug is a potential ethical issue, from vitamins upward. Imagine a study in which an experimental group is given a daily vitamin, and a control group is given a placebo but told they're receiving a vitamin. Several years go by and the relative health of the study participants is closely monitored.
Can you not see the ethical issue here? Can you not imagine the lawsuits that would result from the parents of those in the control group who perhaps didn't thrive as expected, or for some completely imaginary consequence having nothing to do with the vitamin study, but sufficient to sue for civil damages?
And finally, depression drugs are hardly "non lethal, not particularly damaging". They are a source of great controversy and have been the focus of a number of conflicts over the years.
After all, what you're generally trying to find out is whether the new treatment is better than what you already have - just being better than a placebo isn't very informative.
If you're interested in this sort of thing, I strongly recommend reading Ben Goldacre's work[1].
[1] Start at badscience.net.
That's one of the reasons such studies are so unreliable -- they depend on a comparison of two or more drugs that may operate in different ways, rather than comparing a drug to the absence of a drug.
The result is predictable -- unbiased meta-analyses show that antidepressants don't work:
http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fj...
This is not to say that wouldn't have been the outcome anyway, regardless of the methods used, only that testing two drugs at once introduces confounding factors.
Not necessarily. Imagine testing a drug that's supposed to reduce the suicide rate among teenagers, and yes -- it's been done.
Compare suicide rates, write up the result, then spend the next five years in court listening to outraged parents.
The outcome is that these kinds of drugs are no longer tested on humans. Antidepressants are at the top of the list of drugs that are difficult to realistically test, which explains why they were falsely believed to work for so long. On that topic, a recent meta-analysis reveals that they don't work:
http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fj...
A quote: "Meta-analyses of antidepressant medications have reported only modest benefits over placebo treatment, and when unpublished trial data are included, the benefit falls below accepted criteria for clinical significance."
Translation: "we located all those studies the drug companies suppressed, and when they are included in a balanced analysis, it wipes out the scientific justification for prescribing these drugs."
As far as the issue with some anti-depressives and suicide, the main issue was that drug trials showing this had in some cases been systematically downplayed and in some cases suppressed outright by the companies seeking to profit from these drugs. So the problem there was not with the procedure of medical trials, but rather with the corruption of the procedure of medical trials, for profit.
1. Never said it.
2. It's unethical unless one acquires informed consent from adults. Many of the adults in these studies don't understand enough to give informed consent, and many of the studies involve children.
> So the problem there was not with the procedure of medical trials, but rather with the corruption of the procedure of medical trials, for profit.
And that's the contextual background for any clinical study of antidepressants. Most adults think antidepressants work, but studies show that they don't work:
"Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration":
http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fj...
A quote: "Meta-analyses of antidepressant medications have reported only modest benefits over placebo treatment, and when unpublished trial data are included, the benefit falls below accepted criteria for clinical significance."
A situation ripe for exploitation.
It's essential in a discussion like this to quote the other person directly, word for word, as I have just done.
> And to claim that any clinical study of antidepressants is corrupted for profit ...
Circle where I ever said this anywhere. Want to have an imaginary debate? Make stuff up.
> would seem to ignore the fact that the evidence you are using about anti-depressants not working comes from clinical studies.
You're confused. Comparing industry-funded studies, in particular when only those with positive outcomes were even published, to a meta-analysis by non-industry sources that gather and analyze all studies, published and unpublished, is to compare apples and oranges.
For the second, you said it was the contextual background of any clinical study, before then going on to compare clinical studies which you are now saying shouldn't be compared.
Also depression is in and of itself dangerous. Even avoiding the entire topic of suicide, depression can lead to a variety of self destructive behaviors and poor decisions. Additionally plenty of people suffering from depression will naturally 'self medicate' with drugs that don't actually address the underlying neurological issues that ketamine might, and certainly can cause physical harm.
I think it's somewhat odd that in the 21st century we still aren't comfortable seeing physical and mental illness on the same level. People committing suicide die of an illness in no different a way than people dying of cancer. Yet there is very little in the way of public support of combating suicide the way there is for cancer. There is little debate that opiates (dramatically more risk for abuse) should be used to treat physical pain, and yet people get very nervous about the potential for misuse in a much less risky drug which could provide similar relief to mental anguish.
Yes, some of those that are illegal are certainly physically addictive but at the other end of the spectrum are the likes of LSD and Ketamine, so far off the map that if you could even find someone engaging in addict-like behavior they very likely already have a much larger mental problem.
People often suggests therapy and/or pills that changes you. But they rare suggests exploring external causes, and external solutions.
For example, it may be better to drug bullies rather than victims...
It also fits well with neo-liberal thought:"little concern for externalities", "rational consumer" and this kind of bullshit.
http://www.reddit.com/r/Drugs/comments/h3lbk/ketamine_as_a_p...
And the recreational dose is only a small fraction of the anesthetic dose. And furthermore, you only need to take it once or twice a year for it to be effective. Worrying about brain damage from the antidepressant dose of ketamine is a little like worrying about liver damage from a thimble full of beer.
However, the specific condition I was thinking of is 'Olney's lesions' (overview: http://www.camtriplehelix.com/journal/issue/3/breathing-in-t...). It should be noted that some critical research has been withdrawn in this area, which I had missed, so that raises questions about the accuracy of my original remarks: http://www.erowid.org/chemicals/dxm/dxm_health1.shtml
some guide to doses far below recreational use - looks like 0.15mg per Kg or less might do. I have history of depression in my family - so this is great news.
"Efforts to develop drugs that replicate the effects of ketamine have produced some promising results, but they do not act as quickly as ketamine. Researchers are investigating alternatives they hope can duplicate the efficacy and rapid response of ketamine."
So my question is, why not just administer K?
The hyper-rational type of people here are more likely to believe in the absoluteness of their own perception of reality and therefore are less likely to seek treatment. If you're a hold-out and apparently in need, truly you'd be surprised how much medically-manipulated brain chemistry can improve your quality of life. A person's emotional world is highly plastic but successfully changing it requires the precise knowledge and quality control that is provided by a doctor and medicine.
Except in severe depression, antidepressants have no clinical advantage over placebos:
http://www.thedailybeast.com/newsweek/2010/01/28/the-depress...
According to Kirsch, antidepressant trials were also compromised by side-effect leakage: the drugs had side effects while the placebos did not, so patients knew when they were not taking a placebo. That's the equivalent of putting your finger on the scale. As far as I know, there has been no attempt to measure that distorting effect (Kirsch only mentions it), nor any clinical trials of antidepressants conducted on a level playing field, where the placebo had similar side effects to the drug. But I haven't searched, and if such studies exist, I'd welcome correction.
ECT can have a much better effect in these cases.
http://www.mayoclinic.com/health/electroconvulsive-therapy/M...
http://www.cbsnews.com/8301-504763_162-57400793-10391704/ele...
And, it turns out, antidepressants can help ECT:
http://www.sciencedaily.com/releases/2009/07/090706161300.ht...
But keep in mind that ECT is only for crisis-level severe depression:
> ECT uses an electrical stimulus to the brain to induce seizures. It is prescribed for patients with crisis-level severe depression – who are catatonic (people who are so slowed down that they stop moving, talking and eating) or suicidal – or for patients with major depression who have not responded to medication.
A psychologist will help you identify the root cause of your depression in a calm, non-judgemental atmosphere. He or she will explain to you how the various defense mechanisms in your mind work and how they can result in the types of thoughts and thought patterns that led to your depression. A good psychologist will help you see for yourself what is wrong and how to fix it.
There are lots of off-patent medications that don't cost a fortune and can make a huge difference in quality of life for people who need them.
Either way a statement like "I'd rather be a zombie than continue on as I do today," made in earnest, sounds like someone in need of help.
(Is there an emoticon for a terribly stern expression? Imagine it here.)
This is a terrible stereotype that damages perceptions of people who happen to have mental illness.
Either way I disagree with him, anyway.