Interesting article up at New Scientist on some of the recent studies about ketamine and depression. I had mentioned something about this on the side bar last year. The downside was (to me) the rather small sample size. (17 people?)
The drug, often used as a tranquilizer on animals and occasionally on humans, appears to "reset" parts of the brain that get caught up in unwanted "cycles." So it can help one not only jolt out of depression but also things like chronic pain. It's thought it might help with post-traumatic stress, and perhaps addiction. Of course it seems pretty early to make too broad of claims. The problem of this being a reasonably popular abused drug might give some people pause as well.
Since the article is subscriber only I'll quote a few of the interesting bits about theories regarding what causes depression. It's largely a mystery with there being many theories as to what's going on. Of course I suspect, as with many mental illnesses, what we call a single illness based upon symptom may actually be very different illnesses in terms of cause and structure but which simply manifest similar symptoms.
Enter the neurotrophic theory. Put simply, the idea is that extreme or prolonged stress can cause depression by damaging nerve cells in certain brain regions, particularly an area important for storing and consolidating memories called the hippocampus. Brain scans and autopsies find shrinkage in this area in depressed people.
There's even research suggesting exactly how stress could cause this damage. Under stress, the brain releases an excess of the excitatory neurotransmitter glutamate. Too much glutamate can damage or kill cells, a process known as excitotoxicity. The hippocampus is especially vulnerable.
So stress leads to nerve damage, which causes depression. Further evidence is that every drug known to help lift depression also seems to induce higher levels of peptides that encourage nerve growth, most notably BDNF, or brain-derived neurotrophic factor. This helps to repair injured cells and promotes the growth of new ones. Nerves take time to grow, though, hence the delay.
Ketamine, of course, isn't likely to be busy restoring or replacing damaged cells, so what is it doing? No one really knows, but there are some plausible ideas. Ketamine is known to work by blocking a glutamate receptor called the NMDA receptor, preventing glutamate from transmitting its message across the synapse. Faulty NMDA receptor function has recently been implicated in depression, and repeated doses of conventional antidepressants have been shown to slowly correct it in animal models. Perhaps ketamine does the job in one fell swoop. "One way of thinking about it is that the ketamine has reset the normal activity that was disturbed," says Monteggia. In other words, briefly blocking NMDA receptors with ketamine somehow reboots the system.
The reboot idea isn't the only possibility. Ketamine activates another glutamate receptor, known as AMPA, and this has been found to have antidepressant effects in animals; what is more, forthcoming research from NIMH appears to show that preventing AMPA activation blocks ketamine's antidepressant effect. Another possibility is that ketamine works by directly increasing levels of BDNF. That wouldn't account for ketamine's rapid action, of course, but it's possible that BDNF may act not just as a growth factor but as a neurotransmitter too. Some animal studies have found that infusing BDNF into the brain reverses depression-like symptoms in three days
Some of the treatments folks are studying seem a bit extreme. One mentioned by New Scientist includes a dose of ketamine high enough to nearly put people into coma. Obviously more than self-medicators would be willing (or should be willing) to try. It's a dangerous drug and anesthesia is always a dangerous, difficult process. There's some suggestion that despite the amazing effects on some, that perhaps it isn't a cure on its own. It might reboot the brain enough that more traditional drugs like Prozac can then be used to control depression in those who have it.
As exciting for some as the treatments are, the interesting bit to me is what this may tell us about the brain one day.
Isn't this what Dr. House used once?
I think he talked about it, but if its the episode I'm thinking of he used LSD for one of its secondary effects.
No, I think it was the last season finale, the one where he was hallucinating the whole time, and at the very end he tells the doctors "Tell (somebody) I want ketamine" and then the ending credits rolled.
The next season (the current one) he was fine, and his leg didn't hurt - at least for a couple of episodes.
yep - here it is on the source of all knowledge, Wikipedia:
http://en.wikipedia.org/wiki/No_Reason_%28House_episode%29
"Before the episode ends, House asks for Ketamine, that he supposedly received during the imagined events of the episode."
and
http://en.wikipedia.org/wiki/Gregory_House
"Additionally, at the beginning of season 3, House was under treatment with ketamine and he underwent a seemingly complete recovery with regard to pain in his leg. The pain began to recur, so (characteristically) instead of asking for help from any of his colleagues, he obtained more Vicodin by forging Wilson's signature on at least one prescription."
Ah, you're right. I wonder if they based that off of this. I know that many of the cases, while they seem fantastic, are heavily based upon actual cases the doctors among the writers encountered or had heard of.
I think they did - there was mention in the episode that the idea was fairly new and cutting edge (and dangerous).
There may be another reason our good doctor was requesting katemine:
"Ketamine puts the user in a dissociated state, meaning that they are not connected to a sense of self, or to reality around them. If a large enough amount is taken, they go through a "k-hole", and experience other worlds or dimensions that are impossible to describe in our language, while being completely unaware of their identity or the outside world. They feel as though their perception is located so deep inside their mind that the real world seems distant (hence the use of a "hole" to describe the experience). Often the user does not remember this part of the experience after they regain consciousness. The "re-integration" process is slow, and the user gradually becomes aware of things around them. At first they may not remember their name, or even know that they are a human, or what that means. Movement is extremely difficult, and they may not be aware that they have a body at all. It may be possible to use this state therapeutically, taking advantage of the dissociation and removing associations from one's brain. After the experience is over, some of these changes may remain."
Rich
Well I don't doubt ketamine is useful in times of need but my concern is that this drug can create addiction and dependence, and that's why I think it's use should be strictly supervised by the doctor.
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