Injection May Treat Depression Much Faster

By Shankar Vedantam
Washington Post Staff Writer
Tuesday, August 8, 2006

Government researchers announced yesterday that they have had striking success in treating depression in a matter of hours, using an experimental injectable drug that acts much more quickly than conventional antidepressants.

The study, based on a small sample, is part of a push by researchers to develop treatments that can bring quick relief to patients with mental disorders. Patients and their doctors report that it often takes weeks or months for most available medications to improve symptoms.

Much more work needs to be done before patients can see benefits from the breakthrough, the researchers said. Among the unanswered questions are whether patients will be able to tolerate the drug for long periods, and whether it will continue to be effective. Researchers said they hope the finding will prompt the pharmaceutical industry to develop similar compounds with fewer side effects that can then be tested on a large scale.

"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 published a paper about their findings in yesterday's issue of the Archives of General Psychiatry.

In the study, 18 patients were injected with a drug called ketamine, which has been used for a long time as an anesthetic. Patients briefly experienced a well-known side effect of the drug -- a mild feeling of dissociation, where they felt disconnected or found it difficult to put thoughts into words.

Ketamine is a controlled substance and can produce mild euphoria.

But the dissociative symptoms disappeared within a couple of hours, and shortly afterward patients and physicians reported a dramatic improvement in mood. Half the patients had a 50 percent decline in depression symptoms after two hours, and by the end of the first day, 71 percent reported a similar improvement. More than a third continued to report such a benefit after seven days, and nearly a third reported a complete end of symptoms. Conventional antidepressants approach those kinds of numbers only after eight to 10 weeks of treatment.

"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."

Rather than go after the conventional targets of serotonin and norepinephrine, the new drug targets an entirely different neurotransmitter in the brain called glutamate.

"This is not a subtle change," Insel added. "It is almost like rebooting a computer. It is a chemical reboot, and the striking thing is the effect lasts for about a week."

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