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randomized, controlled trial hailing ketamine as a promising treatment for depression
08-16-2010, 07:04 PM,
#1
randomized, controlled trial hailing ketamine as a promising treatment for depression
Monday, Aug. 02, 2010
Is Ketamine a Quick Fix for Hard-to-Treat Depression?
By John Cloud

During the 1990s, the brief popularity of all-night (and in some cases multiday) raves led to a national panic over club drugs. The federal government staged elaborate crackdowns on ecstasy (known colloquially as E and in the lab as MDMA, short for 3,4-methylenedioxymethamphetamine) and an anesthetic called ketamine (or K). While ecstasy had been outlawed in 1985, trafficking ketamine was no more illegal in the '90s than selling unused penicillin. But by 1999, the government had classified ketamine under the Controlled Substances Act, and today, dealing the drug can earn you the same sentence that you would get for selling heroin or meth.

Now it turns out that both ecstasy and ketamine may have healing qualities. On Aug. 2, the esteemed Archives of General Psychiatry published the results of a randomized, controlled trial hailing ketamine as a promising treatment for depression among patients with bipolar disorder. Just two weeks ago, another study showed that MDMA is a potentially valuable therapy for posttraumatic stress disorder. (See video of a mouth guard that may help reduce stress.)

I approached the new studies with skepticism, having written in the 1990s slightly panicky articles about both ecstasy and ketamine. (A more balanced cover story about ecstasy would follow.) But stranger substances than club drugs have been used for therapeutic benefit. The new study on ketamine makes the point that many severely depressed patients need unusual treatments; standard medications simply don't work for them, particularly when they are in a depressive crisis. Antidepressants can take weeks to have any effect. "This delayed onset of antidepressant effects can result in considerable morbidity, including increased suicide risk," the study authors write. (See a brief history of antidepressants.)

Typical treatments for bipolar depression include lithium and antidepressants like Zyprexa and Prozac. Does the unconventional drug ketamine work better? The best answer is that it works differently. Many antidepressants relieve depression by altering levels of the neurotransmitter serotonin in the brain. Ketamine dissociates patients from negative thoughts and feelings by preventing another neurotransmitter, glutamate, from interacting with a receptor in the brain that usually processes it. Brain autopsies have suggested that glutamate activity is associated with bipolar disorder, and past studies have shown that severing the glutamate-receptor link can rapidly lift symptoms in people with major depression within two hours. So the thinking is that in bipolar patients, a fast-acting injection of ketamine can break down emotional responses and counteract depression's most immediate effects.

The new study was conducted at the government-sponsored Mood Disorders Research Unit under the supervision of Dr. Carlos Zarate Jr., of the National Institute of Mental Health. Zarate and his team focused their study on patients with severe bipolar disorder who did not improved with prior orthodox treatments. (See the top 10 medical breakthroughs of 2009.)

Zarate and his team recruited only 18 patients to participate in their proof-of-concept trial, which — as in the ecstasy study two weeks ago — is the biggest drawback: it's a tiny sample. But the results were remarkable. All patients were randomly and blindly given one 0.5 mg/kg dose of ketamine and one equal dose of placebo saline through an IV drip two weeks apart. Patients taking ketamine were significantly more likely than those on the placebo to show short-term improvement in their depression symptoms. This is crucial for bipolar patients who are in depressive crisis and at high risk of suicide: if you can give them something to block short-term suicidal impulses, you may be able to settle them — and then treat them for long-term problems.

The new paper says that in most cases, ketamine "resulted in a robust and rapid (within minutes) antidepressant response." However, the authors note that the antidepressant effects did not last: two weeks after receiving ketamine, patients were no better off than before.

Physically speaking, ketamine is a safe drug. It is the rare anesthetic that has no direct effect on the heart or lungs, meaning that it could not, on its own, cause cardiac arrest. In fact, ketamine was used as a battlefield anesthetic during World War I because it's so forgiving to the central nervous system. The drug is still used in babies, very old people and others who might not be able to tolerate other anesthetics that slow breathing and heart rate. It is also widely used in veterinary medicine, which is the source of the dance-floor rumor that the drug is a horse or cat tranquilizer.

Many human patients dislike ketamine for the very reason some clubgoers seek it: at high doses, it can cause hallucinations. A prominent experimenter with ketamine was John Lilly, a neuroscientist who pioneered communication with dolphins and who was played by William Hurt in the 1980 film Altered States. In 1997, Lilly (who died in 2001) told me that a doctor had first given him ketamine in the '70s to treat his migraines. Lilly then began injecting himself and at one point was taking 50 mg of ketamine an hour, 20 hours a day, for three weeks. Fifty mg is a relatively small dose (clubgoers will typically snort that amount in a single bump) but considered over such a long period, Lilly took enough to anesthetize a whale. He became convinced that he was "a visitor from the year 3001" and that he was talking to aliens.

Will ketamine or ecstasy ever become mainstream treatments? Hard to say, but it's important to note that both drugs would be inexpensive for any psychiatric facility: neither was ever patented, and their chemical formulations are available to anyone. At least for the time being — Zarate and his colleague Dr. Husseini Manji of Johnson & Johnson have submitted a patent application on behalf of the government for the use of ketamine in treating depression. Still, that means potential therapies for depression and bipolar disorder may lie not in pricey new pharmaceutical research but in substances that we used to think of as party drugs.

Read about how ecstasy is showing promise in treating PTSD.
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08-16-2010, 07:33 PM, (This post was last modified: 08-16-2010, 07:34 PM by joeblow.)
#2
RE: randomized, controlled trial hailing ketamine as a promising treatment for depression
The original study:

A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression.

http://www.ncbi.nlm.nih.gov/pubmed/20679587

CONCLUSION: In patients with treatment-resistant bipolar depression, robust and rapid antidepressant effects resulted from a single intravenous dose of an N-methyl-D-aspartate antagonist.

There is a reason why a person whose specialty is only anesthesia is at hand for operations, all anesthetics are dangerous (I have never worked as a Medical Professional, despite having a couple of BCs in Biochem and Pharm):

Randomized clinical trial of propofol versus ketamine for procedural sedation in the emergency department.

http://www.ncbi.nlm.nih.gov/pubmed/20624140

CONCLUSIONS: This study detected a higher rate of subclinical respiratory depression in patients in the ketamine group than the propofol group. There was no difference in the rate of clinical interventions related to respiratory depression, pain, or recall of the procedure between the groups. Recovery agitation was seen more frequently in patients receiving ketamine than in those receiving propofol. The time to regain baseline mental status was longer in the ketamine group than the propofol group. This study suggests that the use of either ketamine or propofol is safe and effective for procedural sedation in the ED.
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08-16-2010, 07:43 PM, (This post was last modified: 08-16-2010, 07:43 PM by h3rm35.)
#3
RE: randomized, controlled trial hailing ketamine as a promising treatment for depression
Quote:There is a reason why a person whose specialty is only anesthesia is at hand for operations, all anesthetics are dangerous (I have never worked as a Medical Professional, despite having a couple of BCs in Biochem and Pharm):

Randomized clinical trial of propofol versus ketamine for procedural sedation in the emergency department.

http://www.ncbi.nlm.nih.gov/pubmed/20624140

CONCLUSIONS: This study detected a higher rate of subclinical respiratory depression in patients in the ketamine group than the propofol group. There was no difference in the rate of clinical interventions related to respiratory depression, pain, or recall of the procedure between the groups. Recovery agitation was seen more frequently in patients receiving ketamine than in those receiving propofol. The time to regain baseline mental status was longer in the ketamine group than the propofol group. This study suggests that the use of either ketamine or propofol is safe and effective for procedural sedation in the ED.

what's your point? do you have access to any studies that show propofol as effective in the treatment of major depression in bi-polar patients? or is this just a feeble attempt to tie two studies together that have absolutely nothing to do with one another to show how "dangerous" ketamine therapies can be?
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08-16-2010, 07:53 PM,
#4
RE: randomized, controlled trial hailing ketamine as a promising treatment for depression
I no longer live in an University town, so I can not get the actual studies and only can read the abstracts. Yes, I am against patients self-medicating without being under the supervision of a medical professional.

To prove your point for you, here is a better study:

Safety and efficacy of repeated-dose intravenous ketamine for treatment-resistant depression.

http://www.ncbi.nlm.nih.gov/pubmed/19897179

BACKGROUND: A single subanesthetic (intravenous) IV dose of ketamine might have rapid but transient antidepressant effects in patients with treatment-resistant depression (TRD). Here we tested the tolerability, safety, and efficacy of repeated-dose open-label IV ketamine (six infusions over 12 days) in 10 medication-free symptomatic patients with TRD who had previously shown a meaningful antidepressant response to a single dose.

RESULTS: Ketamine elicited minimal positive psychotic symptoms. Three patients experienced significant but transient dissociative symptoms. Side effects during and after each ketamine infusion were generally mild.

CONCLUSIONS: These pilot findings suggest feasibility of repeated-dose IV ketamine for the acute treatment of TRD.
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08-17-2010, 01:47 AM, (This post was last modified: 08-19-2010, 04:12 AM by nik.)
#5
RE: randomized, controlled trial hailing ketamine as a promising treatment for depression
is ketamine an interesting experience?
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08-17-2010, 04:58 PM,
#6
RE: randomized, controlled trial hailing ketamine as a promising treatment for depression
Personally have not done k or e don't believe in pills, but i have had several friends experiment with them and they do tell of it's benefits to there mental state afterwords, one friend was always mad, and quick to violence with strangers and new friends, but after partying it in Europe for 6 mths came back cool a a cuke, when i asked hm what changed his mental state he claimed E, said i should try it that it made one's emotional thresh holds stronger and brought a sense of "peace and love" to him. Him not being the tree hugging hippy type i was shocked at the answer, need less to say i'm not going to try it i got LSD and WEED but now that doctors r learning these effect of the drugs it's only a matter of time before there available to those with depressions and anxieties, see brave new world.
Remember Knowledge is the only thing THEY can't take from you, and Knowledge is Know how, and Know how is Power!!!

Live long and Prosper!!!! Have a plan beyond words, and worry not of why the storm is coming as to how you're going to survive in it!!!!

Deathanyl @gmail!!!!!!
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08-17-2010, 10:08 PM, (This post was last modified: 08-19-2010, 04:12 AM by nik.)
#7
RE: randomized, controlled trial hailing ketamine as a promising treatment for depression
nice story
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08-18-2010, 10:02 PM, (This post was last modified: 08-18-2010, 10:04 PM by kevlar.)
#8
RE: randomized, controlled trial hailing ketamine as a promising treatment for depression
I hate ketamine. I call it the zombie drug, out of all the drugs i have done, i would say ketamine is one of the most mentally destructive. After crystal meth. Excluding heroin and crack as i have never done them. Don't get me wrong, the drug is very enjoyable to do, but it is very destructive. I once took too much ketamine and i almost died. If i had not have gone home when i did and if it was not for the bottle of water next to my bed, i might not be here right now.
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08-18-2010, 10:16 PM, (This post was last modified: 08-19-2010, 04:11 AM by nik.)
#9
RE: randomized, controlled trial hailing ketamine as a promising treatment for depression
sounds scary!

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08-18-2010, 10:52 PM,
#10
RE: randomized, controlled trial hailing ketamine as a promising treatment for depression
Ketamine: horse tranqualiser isnt it? Yes Ive seen the zombies and looks awlful. How is that going to cheer anyone up?
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08-18-2010, 10:56 PM, (This post was last modified: 08-19-2010, 04:10 AM by nik.)
#11
RE: randomized, controlled trial hailing ketamine as a promising treatment for depression
is it smoked?
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08-18-2010, 11:36 PM,
#12
RE: randomized, controlled trial hailing ketamine as a promising treatment for depression
(08-18-2010, 10:52 PM)crystal Wrote: Yes Ive seen the zombies and looks awlful. How is that going to cheer anyone up?

Psychedelics absolutely cannot be judged by the outward appearance of the person that has taken them. The only way to understand those substances is to experience them.

[Image: 4v0dax.jpg]

[Image: ket4.jpg]
“Today’s scientists have substituted mathematics for experiments, and they wander off through equation after
equation, and eventually build a structure which has no relation to reality. ” -Nikola Tesla

"When the power of love overcomes the love of power the world will know peace." -Jimi Hendrix
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08-18-2010, 11:55 PM, (This post was last modified: 08-19-2010, 12:09 AM by h3rm35.)
#13
RE: randomized, controlled trial hailing ketamine as a promising treatment for depression
you shure youre not speaking of klonopin?
(08-18-2010, 10:52 PM)crystal Wrote: Ketamine: horse tranqualiser isnt it? Yes Ive seen the zombies and looks awlful. How is that going to cheer anyone up?
No - it's not a horse tranquilizer, but has been used in SMALL animals with chronic pain, but also in humans with opiate tolerance and allergy.
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08-19-2010, 12:00 AM, (This post was last modified: 08-19-2010, 04:13 AM by nik.)
#14
RE: randomized, controlled trial hailing ketamine as a promising treatment for depression
drugs just mess people up though, surely
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08-19-2010, 12:13 AM, (This post was last modified: 08-19-2010, 12:15 AM by h3rm35.)
#15
RE: randomized, controlled trial hailing ketamine as a promising treatment for depression
If anyone's seen someone as a "Zombie" after the fact, it must have been at most 2 hours after the administration of the drug. I can't speak for chronic users, but I've known many users, and the closest to chronic users may very well have taken in too much CBD rather than too much ketamine, and probably ran on too little sleep...

btw...
ketamine may transport you to a different reality, but it's not a "classic" psychedelic.
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