When it comes to antidepressants, nobody really knows anything, anyway, so why not go with ketamine, a mild hallucinogen known to club freaks as Special K?

Researchers at the National Institute of Mental Health announced a study recently in which 18 chronically depressed patients infused with low dosages of ketamine improved within two hours. Seventy-one percent improved within a day, and nearly 30 percent were depression-free by that time. These were people who had been dealing with depression from three to 47 years. They had failed to respond to just about every drug. Most of them stayed depression-free for up to a week.

Doesn’t it make Prozac and friends look like punks? The subsequent news stories focused on the speed—antidepressants generally take two weeks or longer to work—but the true breakthrough, scientists say, is that ketamine seems to do something entirely new. It focuses on glutamate, a chemical neurotransmitter that is involved in electrical flow among brain cells, which previously had not been targeted.

Think of depression as a leaky water faucet in the kitchen of the mind. Prozac and friends start working on the problem back at the water plant and, in about half of the cases, eventually find the problem. In this trial, glutamate (and the “glutamatergic system’’) was shown to be a wrench-toting plumber who makes house calls. It got right to the problem. “It’s not quite the director of the orchestra, but it’s involved with many other systems in the brain than other antidepressants,’’ said Carlos Zarate, chief of the mood disorders research unit at NIMH, and lead author of the study.

“It’s early, but this is exciting because this gives us a new target, and it’s a heck of a first move on it,’’ said Raymond DePaulo, chief of the Department of Psychiatry at Johns Hopkins School of Medicine and one of the nation’s preeminent researchers on depression. He was not involved in the ketamine trials. “This is working on ... a different set of chemicals. It says the malfunction may be in several different parts of the brain. Ketamine has potential negative effects, but we could create 100 drugs to hit this target of glutamate.’’

Says Peter Kramer, author of Listening to Prozac and clinical professor of psychiatry and human behaviour at Brown University: “Prozac wasn’t effective at more major depressions, but only with more minor forms. I think the field is very much waiting for the next breakthrough.’’

No one thinks your family doc will be writing you a script for ketamine any time soon, but research continues. Zarate said the next step is developing counter-medications to mask ketamine’s side effects, then on to other medicines that target glutamate. We’re talking years here.

—Washington Post / Neely Tucker