May have application in treating alcoholism and pain, as well.

Ketamine successful in rapid treatment of depression
By Kathy Jones
Aug 8, 2006, 09:03

8 Aug, ( - People with clinical depression that did not respond to various treatments experienced rapid relief when injected with low doses of Ketamine, an anesthesia drug, according to government researchers.

The finding could signal a paradigm shift in the way mental health professionals handle treatment-resistant depression. But researchers did admit that ketamine would not find wider use in treating depression because of presence of serious side effects including psychosis.
"Psychiatrists have gotten used to the idea we have to wait weeks or months, but we can break the sound barrier and get an antidepressant effect within hours," said Carlos Zarate Jr., chief of the mood disorders research unit at the National Institute of Mental Health.

Zarate and his colleagues conducted a small study involving 18 patients. All patients had treatment-resistant depression, who had tried an average of six anti-depressant medications without any success. Researchers assigned the participants to receive either one intravenous dose of ketamine or a placebo.

The drug had almost a miraculous effect in lifting depression:
* 71 percent of participants who received ketamine reported relief in one day
* 29 percent of those became nearly symptom-free in just 24 hours.
* 35 percent of patients in the ketamine group had considerable effect even after weeks.

Those in the placebo group showed no improvement in their depression symptoms.

Conventional antidepressants can achieve such results only after eight to 10 weeks of treatment, but with ketamine the effect was visible within hours.

"People had tried six to seven antidepressants on average and had been ill for 30 years. The current episode was three years in duration," Zarate said. "All people who went through this reported a tremendous relief of suffering."

There were some short-term side effects like perception disturbances, but these went away before the anti-depressant effect was noticed. To make sure that ketamine indeed handles depression rapidly, the researchers switched the groups to unless the effects of ketamine were still present after one week.

"It's almost like there's a sound barrier for those us who do depression research, and we have not been able to break it," said Zarate of the study published in the August issue of the Archives of General Psychiatry.

Scientists are currently testing used and abused drugs including ecstasy and psilocybin as potential therapeutics. Ketamine was initially invented for anesthesia in 1962. The drug is well known for causing hallucinations and out-of-body experiences. But these effects are mild; hence ketamine is legally used as an anesthetic as well as horse tranquillizer.

Researchers are currently looking at whether it can be used to treat alcoholism and chronic pain, as well as depression. Ketamine produces its effects by acting on a brain protein called the N-methyl-D-aspartate (NMDA) receptor. Currently available antidepressants target brain chemicals such as serotonin. However there is growing evidence that these drugs eventually affect NMDA receptors.

Researchers speculate that ketamine lifts depression rapidly since it directly acts on these receptors, in effect taking a short cut to this part of the brain.

Zarate's team found that the euphoric effects of ketamine wore off once the anti-depressant action began, suggesting that the drug's psychotic and antidepressant effects are separate.

"We can truly raise the bar on what we can expect of antidepressant treatments," said Thomas Insel, director of the National Institute of Mental Health. "A modest response after six weeks is what we used to define as success. What I love about this project is it redefines success not in terms of weeks, but in terms of hours."

Dr. Richard A. Friedman, director of the psychopharmacology clinic at Cornell University's Medical Center in New York City said that the new treatment regimen was "novel" since all antidepressants that are currently available work on neurotransmitters that are monoamines like dopamine and serotonin.

"Ketamine involves a particular system of the brain called glutamate. It's the main excitory neurotransmitter in the brain," he said.
Depression is a serious medical illness, that is chronic and disabling. It affects an estimated 15 million Americans or 7 percent of the adult U.S. population in any given year. Around 4 percent of those affected will end their lives accounting for 30,000 suicides each year.

Research has shown that nearly 50 percent of people with depression don't receive treatment and, of those who do get treatment, only about 40 percent get the best, "evidence-based" treatment. For some people though, even these treatments do not relive symptoms of depression.

That is why ketamine looks so promising. "We're looking to see if we can refine ketamine for clinical use by taking care of side effects," Zarate said. "We're also looking at other drugs."

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