Plumbing the Depths Of Depression

Got that?

Of course, no one knows why that works, save for a general analogy that when any machine doesn't work well, it starts to fall apart.

Genetics plays a part in depression, too, as it clearly runs in families -- but there is no single gene responsible, geneticists say. Exercise alleviates some measures of depression. Light therapy in winter. Reducing stress. Manic depressives -- a different category of illness -- respond more to lithium. Psychotics, the most severe form of mental illness, respond to still other drugs.

"Everyone is aware that we don't treat depression that well," says Peter D. Kramer, author of "Listening to Prozac" and clinical professor of psychiatry and human behavior at Brown University. "Prozac wasn't effective at more major depressions, but only with more minor forms of mood disorder. I think the field is very much waiting for the next breakthrough. We'd like to have a few more arrows in the quiver."

No kidding, says Cheryl Murphy, a Las Vegas woman who, at 60, has tried to commit suicide five times. She has a daughter and granddaughter who are bipolar. She says she'll be lucky if those two live another 10 years before they succeed in killing themselves. She describes depression, in a telephone interview, as "having your kid's funeral planned in your mind."

Here's her trip through the back aisles of the pharmacy:

"I was on Zoloft first, for years. I was doing fine. Then I decided I was doing so well I didn't need it. When I tried to go back on it, it didn't work. I tried Prozac, and I wanted to kill everybody. It was like drinking tequila. I tried Wellbutrin, Effexor, numerous others. I'm on Neurontin now. It works more for anxiety than it does for the depression, but it keeps me from going off the deep end."

Now there's this target of glutamate, coming in the form of ketamine. It's a cousin of PCP, though, and is mainly used as an anesthetic for pets -- hence one of its nicknames, "cat Valium." People sometimes break into vet clinics to get it, for use as a club drug.

So no one thinks your family doc is going to be writing you a script for an orange bottle of ketamine anytime soon, but the research is continuing. Zarate, the NIMH director, said the next step will be to develop counter-medications to mask ketamine's side effects, and then on to other medicines that target glutamate. We're talking about years here.

Kay Redfield Jamison, a Washington-based psychologist and author (whose memoir of her own struggles with bipolar disorder was a national bestseller), thinks the research is exciting because it seems to throw much more light on how depression works in the brain.

"It's hard to put into words how painful severe depression is. It's just awful. It's life-threatening, it threatens work and relationships. When you knock out the ability to think clearly, or the energy to get up and do things, you haven't got much left as a human being. . . . The exciting thing here is the proof of principle. There is something that can work very quickly."

As the poets tell us, nothing is going to ever dull the pain of human life, or the depth of grief over the death of loved ones, or psychosis, or our sense of existential alienation in the universe.

"It is important to remember how deeply ingrained depression is in human consciousness," Kramer writes in "Against Depression." But, he notes, it seems perverse to describe as normal a condition that "eats away at the brain."

So perhaps it is the struggle against depression that uniquely human, too, in whatever form that might take -- prayer, art or a popped pill. Perhaps somewhere in the glutamatergic system or in some other wet corner of the brain there is a medication that can hack the vines away and let terribly ill people see the way to the warmth of love, the hope of redemption or even, as the priest in the Old Testament would have said, the tender mercies of the Deity. All those things are real, or can be felt as real, and all of those things are worth living for.

Even Freud knew that.