Experimental medication kicks depression in hours instea...( proved within one day in 71 percent of ...),Health

proved within one day in 71 percent of all those who received ketamine, and 29 percent of these patients became nearly symptom-free within one day. Thirty-five percent of patients who received ketamine still showed benefits seven days later. Participants receiving a placebo infusion showed no improvement. One week later, participants were given the opposite treatment, unless the beneficial effects of the first treatment were still evident. This "crossover" study design strengthens the validity of the results.

"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," said NIMH Director Thomas R. Insel, M.D.

Ketamine blocks a brain protein called the N-methyl-D-aspartic acid (NMDA) receptor. Previous studies have shown that agents that block the NMDA receptor reduce depression-like behaviors in animals.

NMDA receptors are critical for receiving the signals of glutamate, a brain chemical that enhances the electrical flow among brain cells that is required for normal function. Studies indicate that dysregulation in glutamate could be among the culprits in depression. Using ketamine to block glutamate's actions on the NMDA receptor appears to improve function of another brain receptor the AMPA receptor that also helps regulate brain cells' electrical flow.

Scientists think the reason current antidepressant medications take weeks to work is that they act on targets close to the beginning of a series of biochemical reactions that regulate mood. The medications' effects then have to trickle down through the rest of the reactions, which takes time. Scientists theorize that ketamine skips much of this route because its target, the NMDA receptor, is closer to the end of the series of reactions in question.

"This may be a key to developing medications that eliminate the weeks or months patients ha
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Contact: Susan Cahill
NIMHpress@nih.gov
301-443-4536
NIH/National Institute of Mental Health
7-Aug-2006

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