Drug lifts depression's dark veil almost instantaneously

By Melissa Healy, Los Angeles Times, June 16, 2011:

The long-used (and abused) sedative ketamine appears to lift depression's dark veil almost instantaneously by boosting the production of a protein that helps protect and maintain brain cells and regenerate them after injury, a new study says.

Ketamine makes children blithely unaware of pain during difficult medical procedures. But it has another remarkable quality: When given intravenously at a lower dose than is used for anesthesia, ketamine acts as a powerful and fast-acting antidepressant for adults.

This property, recognized in recent years by a growing number of researchers, offers an important addition to the current formulary of medications available for depression. Most of those can take weeks to attain their full effect, and even after trying several different antidepressants, as many as four in 10 patients don't see their depression lift.

But suicidal patients can't wait that long: for them, finding a speedy and effective treatment could make the difference between life and death.

Ketamine's not an ideal medication, even as a rescue drug for depression: It has to be given intravenously and sometimes causes short-term psychotic symptoms. But unlocking the mystery of how it works could help point the way to other drugs and alternative approaches to treating depression, stat.

In a letter published this week in the journal Nature, a trio of researchers at the University of Texas Southwestern Medical Center report on experiments with mice that suggest ketamine works by causing a surge in the production of brain-derived neurotrophic factor.

If production of brain-derived neurotrophic factor could be dialed up by ketamine or other drugs that work like it, the result might not only provide fast relief from depressive symptoms: such drugs might help the brain protect and regenerate itself when under attack from a host of degenerative brain diseases, including Parkinson's disease, multiple sclerosis, Lou Gehrig's disease and Huntington's disease.