Health - Antidepressant effects of ketamine in depressed patients

[Euphoric]

http://www.newscientist.com/channel/...-alcohol_rss20

Ketamine relieves depression within hours

• 12:57 08 August 2006

A drug used as a general anaesthetic may also work as a remarkably rapid antidepressant, according to a preliminary study.
The drug’s hallucinogenic side effects mean it is unlikely to be prescribed to patients, but it could pave the way to new faster-acting antidepressants, the researchers suggest.
Ketamine is used as an animal tranquiliser, but is perhaps better known as an illicit street drug, sometimes called “special K”. Now researchers have found the drug can relieve depression in some patients within just 2 hours – and continue to do so for a week.
One problem with current antidepressants is that they typically take weeks to kick in. Some studies have found that patients may face a high risk of suicide in the first week after starting an antidepressant treatment because of this lag time. So researchers have been searching for alternative drugs.

[top]Fast acting

In 2000, a small study of eight people with major depression suggested that ketamine mitigated depression to a certain degree (Biological Psychiatry, vol 47, p 351).
Carlos Zarate, chief of the Mood and Anxiety Disorders Research Unit at the National Institute of Mental Health in Bethesda, Maryland, US and colleagues, set out to conduct a larger, more detailed trial of the drug’s antidepressant effects.
They analysed data from 17 participants, all whom suffered from moderate to severe depression and had failed to respond to at least two types of conventional drug treatments.
In the first part of the experiment, the volunteers were given a single intravenous dose of either ketamine or a placebo. A week later, the participants were given the opposite treatment, unless the beneficial effects of the first intravenous dose were still evident. Depression improved within one day for 12 of the 17 who received ketamine. These patients showed a 50% reduction in their symptoms, according to the Hamilton Depression Rating Scale.
In previous trials for established, long-acting antidepressants, only 63% of participants saw this same reduction in symptoms after eight weeks of medication.

[top]Lasting effect

Overall, while nine of the 17 patients had a 50% reduction in their depression within the first 2 hours of ketamine treatment, only one person receiving the placebo experienced the same effect in this period of time.
The antidepressant effects of ketamine lasted for a week in four people and at least two weeks in another two subjects. "We didn't believe it would last that long," says Zarate.
Most anti-depressants work by boosting levels of the brain chemical serotonin. But ketamine acts in a different way, by reducing the effects of another neurotransmitter, called glutamate. This may explain the drug’s faster action, and suggest an alternative pathway for other antidepressant drugs, the researchers say.

[top]Trails of light

However, one of the reasons that clubbers abuse ketamine is for its hallucinogenic properties, such as seeing trails of light, and this was one of the most significant side effects occurring in the "vast majority" of participants, Zarate says.
The hallucinations will also have revealed to patients in the trial when they had received ketamine, rather than an inert placebo. This knowledge could have made them more likely to report a positive response than to the placebo.
Zarate is currently exploring compounds derived from ketamine to see if they can find one that has antidepressant effects without causing hallucinations.
Journal reference: Archives of General Psychiatry (v 63, p 856)

[Jatelka]

and here are some papers in the archive...

http://www.drugs-forum.com/forum/loc...=1323&catid=29
http://www.drugs-forum.com/forum/loc...=1510&catid=29

[Chacer]

SWIM dosed his depressed gf with approx 50mg ketamine insufficated...
Her symptoms went away within 2 two hours and she was not depressed for 3 days after that. SWIM always keeps a little near by, in case she needs it again.

[rxbandit]

Researchers explore the antidepressant effects of ketamine

Drug treatments for depression can take many weeks for the beneficial effects to emerge. The excruciating and disabling nature of depression highlights the urgency of developing treatments that act more rapidly. Ketamine, a drug used in general medicine as an anesthetic, has recently been shown to produce improvements in depressed patients within hours of administration. A new study being published in the February 15th issue of Biological Psychiatry provides some new insight into the mechanisms by which ketamine exerts its effects.

Ketamine is classified as an N-methyl d-aspartate (NMDA) glutamate receptor antagonist. Maeng and colleagues now provide new evidence that these antidepressant effects of NMDA receptor antagonists are mediated by their ability to increase the stimulation of á-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) glutamate receptors. In other words, their findings indicate that the antidepressant-like effects of drugs like ketamine are dependent on AMPA receptor stimulation. This suggests that drugs that enhance AMPA receptor function might have rapid antidepressant properties.

Dr. Husseini Manji, corresponding author on this paper and a Deputy Editor of Biological Psychiatry, explains that “by aiming new medications at more direct molecular targets, such as NMDA or AMPA, we may be able to bypass some of the steps through which current antidepressants indirectly exert their effects — a roundabout route that accounts for the long time it takes for patients to begin feeling better with the conventional medications.” He adds, “Today’s antidepressant medications eventually end up doing the same thing, but they go about it the long way around, with a lot of biochemical steps that take time. Now we’ve shown what the key targets are and that we can get at them rapidly.”

This study is especially important because even though this important antidepressant effect has been found in ketamine, its use also has significant drawbacks. According to John H. Krystal, M.D., Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System, “the only NMDA receptor antagonist found to be effective so far, ketamine, produces transient changes in perception and impairments in cognition.” It is also in the same class of drugs as PCP (phencyclidine) and can cause hallucinations, among other side effects. Dr. Krystal notes that “it is possible that drugs that directly enhance the activity of AMPA glutamate receptors, the AMPAkines, would have antidepressant effects similar to ketamine, without the unwanted side effects.” Exploring the antidepressant effects of the AMPAkines will now be an important target for researchers.

Source : Elsevier

http://www.biologynews.net/archives/..._ketamine.html

[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