A drug you're as likely to find at a rave as at a veterinarian's office may be the next big antidepressant. A single dose of ketamine, a veterinary anesthetic that's also renowned as the recreational drug "Special K," improved the mood of patients with major depression in as little as 2 hours, with effects lasting up to a week, according to a new study.
For half a century, depression treatments have largely targeted a class of neurotransmitters called monoamines. Recent drugs such as Prozac and Paxil, for example, work by blocking serotonin uptake, making more of the neurotransmitter available to stimulate neurons typically understimulated in depressed people. The monoamines are limited to particular tasks within the brain, however. A more general communication system relies on an amino acid called glutamate. The glutamate system is associated with learning and memory, but it has been increasingly implicated in mood regulation (ScienceNOW, 24 April 1998).
A team led by Carlos Zarate, a psychopharmacologist at the National Institute of Mental Health in Bethesda, Maryland, and colleagues targeted a key player in the glutamate system, a receptor known as N-methyl d-aspartate (NMDA). Seventeen patients, who had major depression and had not responded to traditional antidepressants, were injected with either a placebo or ketamine, a known NMDA receptor blocker. Based on their reported moods and the observations of the team, 12 responded to the treatment, with 5 of them meeting the criteria for remission of depression, the team reports in this month's issue of Archives of General Psychiatry. In addition, 5 patients experienced relief for at least a week from the single injection. The patients on placebo reported no improvement.
The truly exciting part, says Zarate, is the speed with which the treatment works: Just one day after getting a shot of ketamine, patients reported improvements equivalent to those reported after 2 months of standard antidepressants. That's a big deal, he says, because the time lag associated with standard antidepressants can prove fatal in cases of major depression; suicidal behavior has been noted particularly in the first 9 days of therapy.
This study adds significantly to the mounting body of evidence that the glutamate system is a more specific target for depression therapies, says John Krystal, a psychopharmacologist at Yale University, who conducted a study in 2000 hinting at ketamine's antidepressant effects. "We have needed to develop approaches that don't simply repeat treatment strategies already in place, ... and the glutamate story as it has emerged is very promising."
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