Plumbing the Depths Of Depression

By Neely Tucker
Washington Post Staff Writer
Tuesday, September 26, 2006

Ketamine, sweet ketamine, answer to our glutamatergic dreams. In the long November night of the soul, in the ever-dark downpour of depression, it turns out that there might be a better umbrella than Prozac and Zoloft and Paxil and their serotonin-loving ilk.

Of course, 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?

Yes, yes, break out the male Wistar rats and the injection needles -- 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. In 24 hours! These were people who had been dealing with depression from three to 47 years. They had failed to respond to just about every drug on the market.

Most of them stayed depression-free for up to a week.

Chronic depression, one of the most common, debilitating diseases known to mankind, blown away like a flower petal on a passing breeze.

Is it not the modern nirvana, the utopia of a neurotic generation, the idea that the demons lurking in the nether regions of the cerebral cortex could just . . . evaporate? Reigning there in the wet muck of the Freudian dark, the gargoyles of the mind took ketamine like a hit of kryptonite.

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. It has not been targeted by any other antidepressant medication.

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 A. Zarate Jr., 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 J. Raymond DePaulo Jr., 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 problems with potential negative effects, but we could create 100 drugs to hit this target of glutamate."

If, you know, that is where the demon actually resides.

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