Friday, September 01, 2006

Medication that Lifts Depression in Hours Instead of Weeks

A single dose of an anesthesia drug produced relief from depression in as little as two hours in a small group of patients for whom several other treatments had failed, U.S. government researchers report.

The researchers said, however, that the drug, ketamine, is unlikely to be used in the treatment of depression because of possible side effects, including psychosis. But the new finding does signal an important direction for future research.

Currently available antidepressants can take weeks to work. "That was similar to the sound barrier. We felt we couldn't pass it," said Dr. Carlos A. Zarate Jr., lead author of the study and chief of the mood disorders research unit at the National Institute of Mental Health.

He added, "Now the sound barrier is broken. That doesn't mean you can get on the plane and take off right away, but it means it's possible that we can come up with a treatment that works very rapidly. That's down the road."

Ketamine is novel not only for the speed of its effect, but also because it targets a new system in the brain.

"It's novel because all antidepressants that are currently available work on neurotransmitters that are monoamines like dopamine and serotonin. That's the focus of the current antidepressant armamentarium," explained Dr. Richard A. Friedman, director of the psychopharmacology clinic at Cornell University's Medical Center in New York City. "Ketamine involves a particular system of the brain called glutamate. It's the main excitory neurotransmitter in the brain," he said.

Depression is a chronic, disabling condition affecting almost 15 million Americans -- almost 7 percent of the adult U.S. population -- in any given year. Some 4 percent of people with depression will end their own lives, resulting in 30,000 suicides each year.

Unfortunately, about half 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. Some people still don't get better even with this type of treatment, however.

This is one of the first studies in humans to look at the effect of ketamine on depression, although previous animal studies had shown promising results.

For the study, which is published in the August issue of the Archives of General Psychiatry, 18 treatment-resistant patients with depression were randomly assigned to receive either one intravenous dose of ketamine or a placebo. Participants had tried an average of six antidepressant medications without success in the past.

Depression improved within one day in 71 percent of participants who received ketamine; 29 percent of those became nearly symptom-free within one day. Thirty-five percent of those receiving ketamine still showed benefits after several weeks. Those in the placebo group showed no improvement.

One week later, participants were given the opposite treatment, unless they were still showing a benefit from the ketamine.

"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."

Short-term side effects, including perception disturbances, went away usually before the antidepressant effect kicked in. Participants were given a relatively low dose, so they did not experience the more severe side effects.

Ketamine works by blocking the N-methyl-D-aspartic acid (NMDA) receptor, which receives signals for glutamate. Using ketamine to block glutamate's action on the NMDA receptor also seemed to have a secondary effect on another brain receptor, the AMPA receptor.

Zarate and his team are now looking at several ways to use this information for depressed patients. "We're looking to see if we can refine ketamine for clinical use by taking care of side effects," he said. "We're also looking at other drugs."

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