Low doses of ketamine, a medication used as an anesthetic in humans and animals, relieves depression in just two hours and the effect may last as long as a week, new research shows.
Ketamine is also sometimes abused as a "club drug." Known in slang as "special K," it can cause hallucinations and euphoria in higher doses.
According to a study in the August issue of the Archives of General Psychiatry, researchers tested 18 adult men and women diagnosed with depression who had failed at least two antidepressant regimens. None of the participants had a current substance abuse problem at the time of the study.
They were first tested with a one-time dose of intravenous ketamine or plain saline. Then a week later, the ketamine group got a dose of saline, and the saline group got a dose of ketamine.
Within an hour and a half after the injection, those who received the ketamine had improvement of their depression -- with effects lasting for a week.
By contrast, current antidepressants, including the popular selective serotonin reuptake inhibitors (SSRIs) -- such as Prozac and Paxil -- can take weeks or months to kick in.
One day after the ketamine injection, 71 percent of participants responded with 50 percent or greater improvement on a standard scale used to measure depression and 29 percent met the criteria for remission. For 35 percent, the improved effects lasted through the week, the study showed.
While the new results may not apply to all groups of depressed people, "there is no treatment for depression that works this rapidly and dramatically with a single administration," researcher Carlos Zarate Jr., MD, tells WebMD. Zarate is the chief of the mood disorders research unit at the National Institute of Mental Health (NIMH) in Bethesda, Md.
Exactly how the anesthetic relieves depression is not fully understood, but animal studies have suggested that blocking a brain chemical receptor called the N-methyl-D-aspartate (NMDA) receptor can reduce depression-like behaviors. Ketamine blocks the NMDA receptor.
In its simplest terms, ketamine hits the cascade of brain chemicals that causes depression closer to home than available antidepressants, he says. "If you had a leaky faucet, we start in the kitchen at the source of the leak, [the NMDA receptor], while other antidepressants may begin at the water processing plant, [the serotonin and other brain chemicals believed to play a role in depression]," he explains. "We can localize it to right where the leak is, so we don’t have to be satisfied anymore with not getting results for weeks to months," he says.
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.
By Denise Mann, reviewed by Louise Chang, MD
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.