A drug that works through the same brain mechanism as the fast-acting antidepressant ketamine briefly improved treatment-resistant patients' depression symptoms in minutes, with minimal untoward side effects, in a clinical trial conducted by the National Institutes of Health. The experimental agent, called AZD6765, acts through the brain's glutamate chemical messenger system.
Existing antidepressants available through prescription, which work through the brain's serotonin system, take a few weeks to work, imperiling severely depressed patients, who can be at high risk for suicide. Ketamine also works in hours, but its usefulness is limited by its potential for dissociative side-effects, including hallucinations. It is being studied mostly for clues to how it works.
"Our findings serve as a proof of concept that we can tap into an important component of the glutamate pathway to develop a new generation of safe, rapid-acting practical treatments for depression," said Carlos Zarate, M.D., of the NIH's National Institute of Mental Health, which conducted the research.
Zarate, and colleagues, reported on their results online Dec. 1, 2012 in the journal Biological Psychiatry.
AZD6765, like ketamine, works by blocking glutamate binding to a protein on the surface of neurons, called the NMDA receptor. It is a less powerful blocker of the NMDA receptor, which may be a reason why it is better tolerated than ketamine.