Health - Antidepressant effects of ketamine in depressed patients

[Abrad]

news.bbc.co.uk
An anaesthetic can treat depression within hours, US research suggests.

The study involving 17 patients found ketamine - used as an anaesthetic but also taken as a recreational drug - relieved symptoms of depression.

Most existing treatments for depression take weeks or even months to relieve people's symptoms.

But the team, writing in Archives of General Psychiatry, said ketamine would need to be altered so it lost its existing hallucinatory side-effects.


This is the first report of any medication or other treatment that results in such a pronounced, rapid, prolonged response
Dr Thomas Insel, NIMH

Scientists from the National Institute of Mental Health (NIMH) injected 17 patients with either a very low dose of ketamine or a placebo of saline solution.

The participants were all depression sufferers who had tried an average of six treatments that had failed.

The researchers then measured their levels of depression minutes, hours and days after the dose was given.

Lead researcher Dr Carlos Zarate Junior, head of the mood and anxiety disorders programme at NIMH, said: "Within 110 minutes, half of the patients given ketamine showed a 50% decrease in symptoms."

By the end of day one, he added, 71% had responded to the drug. And at this point the team found 29% of these patients were nearly symptom free.

The researchers also discovered one dose lasted for at least a week in more than one-third of the participants.

Brain pathways

Dr Thomas Insel, director of NIMH, commented: "To my knowledge, this is the first report of any medication or other treatment that results in such a pronounced, rapid, prolonged response with a single dose.

"These were very treatment-resistant patients."

Many antidepressants target levels of brain chemicals, such as serotonin and dopamine, and, over time, the accumulation of these chemicals can affect a patient's mood. But this can take several weeks.

But the team believes ketamine is having a faster effect because it is targeting a different brain-protein, called the NMDA receptor, which is thought to play a critical role in learning and memory.

The team says ketamine, in its current form, would not be appropriate for medication because of side-effects at higher doses, which include hallucinations and euphoria.

Dr Zarate said: "This study is a tool to help us understand what part of ketamine is causing this effect so we can refine and develop better drugs.

"We are also looking at ways that we could use ketamine maybe in lower doses or with drugs that block its perceptual effects so we could perhaps use it clinically."

Professor John Henry, a clinical toxicologist at St Mary's Hospital in London, said: "This is a very interesting piece of work, very neatly done, with promising results.

"More studies need to be done to see if ketamine would work over a longer period given in repeated doses.

"The benefit of having a fast-working drug would mean people could return to work quickly, and it could reduce risk of self-harm or suicide that could happen during the time-lag that occurs with other drugs."

[rodent]

Very interesting!

I think I had heard other reports of salvia having similar effects on depression. SWIM did find his depression (which was partially caused by opiate withdrawal) almost dissapear for maybe a few days or more after only one very powerful visit with lady salvia.

I'm not sure but doesn't slavia also interact with NMDA receptors?
Sorry for taking this a bit off topic...

My SWIM has only a few ketamine experiences and depression was not an issue for him back then so he can't really comment on it's value there.

[matti_2003]

Swim could never see Ketamine as having antidepressant qualities to it. In his opinion it may help a user to forget all their problems whilst on it but afterwards Swim usually feels a bit down. However Swim has never tried using it in the very low doses discussed in the article.

[Nagognog2]

Very interesting. I'm glad they acknowledge the short-term aspect of using ketamine. I would be interested in knowing whether the depression returns in an even worse way after the ketamine use stops - a rebound effect per say. That could spell the end for such being suggested as a maninstream application, unless a sure-fire way to treat the depression during the interim period is discovered.

[bewilderment]

Originally Posted by Nagognog2

Very interesting. I'm glad they acknowledge the short-term aspect of using ketamine. I would be interested in knowing whether the depression returns in an even worse way after the ketamine use stops - a rebound effect per say. That could spell the end for such being suggested as a maninstream application, unless a sure-fire way to treat the depression during the interim period is discovered.

I would also expect a rebound of sorts as well. Swim, foolishly, used dxm for antidepressant reasons (among others, but she believes subconsciously this was the biggest reason). When she first began, the "hangover" was actually pleasant, more of an afterglow for the entire day afterwards. However, eventually the magic was gone and she was left much more emotionally fragile than she had been to begin with. This went away after a few months, but those few months were quite awful. But, DXM alters neurotransmitters in a different way so I wouldn't expect such a drastic reaction to ketamine use. But, swim tried a small dose of K for the first time last night and found it much less "magical" and euphoric than DXM had been during the early days. And, she felt lethargic and bored afterwards.

[Forthesevenlakes]

according to the new york times article about this study,

"Five participants recovered from depression in the first day and were still significantly improved a week later."

so if there's a rebound effect, it would seem to occur over a week later. this suggests to swim that there isnt an acute rebound, but maybe if the ketamine was administered week after week you'd see one.

[eltimmy]

One NMDA antagonist perhaps suitable for a mood lift with further research, and generally without hallucinogenic properties -- ethanol. Amazing! :P

[788.4]

Ketamine May Give 'Almost Instantaneous' Relief for Severe Depression
By Peggy Peck
Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of Pennsylvania School of Medicine., Psychiatric Times


BETHESDA, Md., Aug. 7 -- Symptoms of depression can be made to disappear in less than two hours with a common anesthetic, not the weeks or months required for onset of relief with traditional antidepressants, according to results of a pilot study.

"We have broken the sound barrier in depression treatment," said Carlos A. Zarate, Jr., M.D., chief of the mood disorders section the National Institute of Mental Health, who reported on the effects of ketamine, a common anesthetic, in the August 8 issue of the Archives of General Psychiatry.

Dr. Zarate and colleagues said a single injection of ketamine, which targets the N-methlyl-D-aspartate (NMDA) receptor, can eliminate depression symptoms within 110 minutes.

After a two-week drug-free run-in, patients were given IV ketamine hydrocholoride (0.5 mg/kg) or placebo on two test days a week apart. Twelve of the participants were women and the mean age of participants was 46.7 (range 16 to 60).

The endpoint of the trial was changes in score on the 21-item Hamilton Depression Rating Scale. The effect size for the drug difference was large (d=1.46 [95% CI 0.91-2.01]) after 24 hours and moderate to large (d=0.68 [95% CI 0.13-1.23]) after one week, they wrote.

At 110 minutes, patients given ketamine had an average Hamilton Depression Rating Scale score of 15, down from more than 25 at baseline which was significant (P<0.05) and at day one the average score was less than 15 which was highly significant (P<0.001). There were no significant chances from baseline among patients who received placebo injections.

"We are not replacing depression with a manic phase," Dr. Zarate said. "The effect is simply the elimination of depression. The patients, essentially, return to normal."

Of 17 patients who received ketamine injections 71% met response criteria and 29% met remission criteria the day following ketamine infusion, Dr. Zarate and colleagues wrote. Thirty-five percent of subject maintained that response for a week.

Interestingly, ketamine is a popular street drug, which is sold under a number of names including kit kat, jet and super C. Dr. Zarate, who acknowledged that common side effects included perceptual disturbances, confusion, increased blood pressure, euphoria, dizziness, and increased libido.

But the effects never lasted longer than 110 minutes, while the beneficial effect of a single dose was generally durable for seven days.

Ketamine is approved for human use, but is most commonly used as a veterinary anesthetic.

Despite his obvious enthusiasm for treatment, Dr. Zarate cautioned that the results are preliminary and are not yet ready for "the general clinician." Nonetheless, he said that the results of the 18-patient trial provide a proof-of-principle that rapid-almost instantaneous-treatment of clinical depression is possible.

And while the speed of the drug's effect was impressive, "how to maintain that effect and how to achieve it consistently is not so clear," he said.

Moreover, since the trial was limited to patients with treatment resistant major depression, it is not clear whether an N-methlyl-D-aspartate will work as well or as quickly in patients with less severe depression.

Additionally, the authors note that "limitations in preserving study blindness may have biased patient reporting by diminishing placebo effects, thereby potentially confounding results."
Dr. Zarate said his team plans additional studies with the aim of "developing strategies for maintaining the rapid response," which may mean adding one or more drugs that can "piggyback" the ketamine effect to maintain a durable response.

Reputation Comments on this post:

Nice find. interesting article.

[prescription]

interesting.... go special K!!

[matti_2003]

Also see Drug 'treats depression in hours'

[Euphoric]

SWIM knows someone who would not agree with this story. The individual suffers from manic depression and used K recreationally once in awhile. Never seemed to make a positive difference beyond the duration of the trip and the user stopped using after one trip in which she did too much and was stuck to the couch and tears were streaming down her face. Not to poo poo on K, just thought i'd relay this story.

[Riconoen {UGC}]

this is great hope to swim who suffers from depression and anything to get him to stop being a slave to effexor is good news to him.

[HandyMan81]

Safety Issues

There are some safety concerns, especially because it has been taken in high doses by substance abusers. "Ketamine should be studied in research settings and not used in a clinical setting at this time," Zarate says.
When used in high doses as a recreational drug, ketamine can cause delirium, amnesia, high blood pressure, depression, and severe breathing problems. But "at the dose used in the new study, there were no serious side effects. Some participants reported that their perception of time was off, or that they felt woozy or euphoric," he says, noting that these effects were short-lasting and independent of the antidepressant effects.

"The public health implications of being able to treat major depression this quickly would be enormous," says Elias A. Zerhouni, MD, the director of the National Institutes of Health in Bethesda, Md., in a written statement. "These new findings demonstrate the importance of developing new classes of antidepressants that are not simply variations of existing medications."
In the same news release, NIMH director Thomas R. Insel, MD, adds, "To my knowledge, this is the first report of any medication or other treatment that results in such a pronounced, rapid, prolonged response with a single dose. These were very treatment-resistant patients."

David Baron, DO, chairman of psychiatry and behavioral health sciences at Temple University School of Medicine and Temple University Hospital in Philadelphia, is a bit wary about the new findings. "It's like saying 'take this pill, drop 20 pounds overnight'," he tells WebMD. "I understand where there would be significant enthusiasm, but my own sense is that it needs to be more closely studied because sometimes a quick-fix solution ends up creating its own problems."

He tells WebMD that while the data is interesting, his "own personal optimism is fairly low. I don't want to throw a wet blanket over the whole thing, but we ought to be very cautious about jumping on the fact that this is a cure-all," he says. Still, he says, it may lead to a better understanding of depression and antidepressants. "My concern is that we don't take it out of context and have everybody in the street start popping ketamine to feel better," he says.



SOURCES: Zarate Jr., C. Archives of General Psychiatry, August 2006; vol 63: pp 856-864. Carlos Zarate Jr., MD, chief of the mood disorders research unit, National Institute of Mental Health, Bethesda, MD. David Baron, DO, chairman of psychiatry and behavioral health sciences, Temple University School of Medicine and Temple University Hospital, Philadelphia. News release, NIH/NIMH.


http://www.webmd.com/content/Article...m?pagenumber=2

[enquirewithin]

It's a very interesting idea that low doses of ketamine could fight depression, but there is another thread about this.

[bewilderment]

Originally Posted by Riconoen {UGC}

this is great hope to swim who suffers from depression and anything to get him to stop being a slave to effexor is good news to him.

Has swiy tried other antidepressants or just Effexor? It seems that many people don't react well to Effexor...

And, also, swim has changed her opinion of ketamine. She felt tired and sort of depressed after the first use, but she thinks she was just having a rough day anyway. Further experimentation didn't make her feel depressed either before or after ketamine use. She also suffers from depression...but, she still doubts that ketamine would help much with depression just based on her experience. But, I think that studying ketamine and finding what exactly it is about it that causes the relief could lead to the development of antidepressants which could be useful for those who are unresponsive to other approaches.

[arman]

Originally Posted by bewilderment

Has swiy tried other antidepressants or just Effexor? It seems that many people don't react well to Effexor...

And, also, swim has changed her opinion of ketamine. She felt tired and sort of depressed after the first use, but she thinks she was just having a rough day anyway. Further experimentation didn't make her feel depressed either before or after ketamine use. She also suffers from depression...but, she still doubts that ketamine would help much with depression just based on her experience. But, I think that studying ketamine and finding what exactly it is about it that causes the relief could lead to the development of antidepressants which could be useful for those who are unresponsive to other approaches.

the amount of ketamine administered could play a key role in depression treatment. as the research used a "very low dosage" (0.5 mg/kg). maybe the dosage of recreational use is just too much so does not relieve depression.

many drugs can have exactly opposite effects when taken in wrong doses. Anyone who knows a little bit about drugs knows that a single chemical can have significantly different effects when taken in different dosages.

[mfrieze]

Ketamine does help with my depression. When Swim is depressed he uses ketamine all the time, but only around 30 or 40mg. Its like meditating for about an hour. It really helps even after you come down off of it

[darawk]

While this research is really awesome and quite impressive...I think it's incredibly sad that they won't even consider a drug that can induce hallucinations or euphoria. So what if there are hallucinations at high doses? Why does this make the drug unusable?

This is really the fundamental problem with the drug war right here. It isn't about whether or not these drugs are harmful, it is the idea that getting "high" is immoral or in some way wrong. They aren't citing any adverse effect that ketamine might cause as a reason it can't be used medicinally, but rather the simple fact that the experience can be enjoyable and temporarily mind-altering makes it a treatment that isn't even legitimate to consider.

[Bajeda]

A new entry has been added to Drugs Archive

Description: A growing body of preclinical research suggests that brain glutamate systems may be involved in the pathophysiology of major depression and the mechanism of action of antidepressants. This is the first placebo-controlled, double-blinded trial to assess the treatment effects of a single dose of an N-methyl-D-asparate

Subjects with depression evidenced significant improvement in depressive symptoms within 72 hours after ketamine but not placebo infusion, suggesting a potential role for NMDA receptor-modulating drugs in the treatment of depression.

To check it out, rate it or add comments, visit Antidepressant effects of ketamine in depressed patients
The comments you make there will appear in the posts below.

[schwing]

I'm surprised that this experiment was conducted in the first place, given that (as noted in the paper itself) the potential for placebo effect is so high in this setup.

Maybe they could've used another anesthetic (or even something like a low-concentration ethanol just to give some discernable 'high') as the placebo instead of the totally benign saline solution.

[khrma]

SWIM, too feels that dissociatives help for depression. For pyschadelics SWIM feels that it is mainly placebo but for dissociatives it's different, subconsious-like. SWIM would love to find out if it could some how be researched more to be able to come up for medical treatment of depression.

[imyourlittlebare]

ive read this before and in my opinion it is very likely it does work. i believe it works the same way electroshock therapy works. it effects nmda and "rewires" the brain in a sense. great research! down with ssri's lol. they are a waste when there is other medicine out there that could help so much more

[Paracelsus]

i believe it works the same way electroshock therapy works.

Do you mean electroconvulsive therapy?

[kip]

ketamine makes SWIM feel really depressed the day after and sometimes even 2-3 days after

[schwing]

^^^

Wha...? A fictional character from a hypothetical book has heard rumors that he felt great after a nap post-K use as if it was the most refreshing sleep ever (in fact, even when he didn't sleep, after the comedown he felt as if he did take a nap! Anyone else heard of this effect?)

Does SWIK have a history of depression? The aforementioned character does.