Nearly 25 years after the Prozac revolution, scientists are seeking faster, more effective ways to loosen the grip of depression.
Imagine your doctor has just diagnosed you with depression. She sits down to write you a prescription for an antidepressant, but not before she performs a simple blood test that tells her exactly which medication will work best for you. You take a pill in her office, and within two hours your mood is already lighter.

Or suppose you decide to go into therapy—except in addition to seeing a shrink, you also check in with a computer program that leads you through a series of depression-relieving exercises. Or let's say drugs and therapy have failed to relieve your symptoms, so your psychiatrist suggests an alternative treatment. He positions a device on your scalp that's designed to stimulate activity in certain areas of your brain, and after several weeks of sessions, your depression lifts.

Such scenarios may sound far-fetched, but in fact they may not be long out of reach. And they represent a new generation of research that, according to Andrew Leuchter, MD, professor of psychiatry and biobehavioral sciences at UCLA, may offer "treatments that are a marked improvement over what's available now."

Today many people with depression are prescribed drugs (like Prozac and Zoloft) that belong to a family of medications known as selective serotonin reuptake inhibitors (SSRIs). But these drugs have drawbacks. One is that only about 30 percent of patients see improvement from the first SSRI they take; others must try another medication, or two or three, before they find one that does the trick. Leuchter is working to eliminate the trial and error by using biomarkers—signals from our bodies that can indicate whether a treatment will be successful. Right now one of the most promising biomarkers is changes in brain activity. By comparing a brain scan taken immediately before a patient starts an antidepressant to a scan conducted just one week later, Leuchter says he can predict with 74 percent accuracy whether the medication will ultimately make the person well. The future may bring an even speedier shortcut: a blood test that would match a patient with the right drug based on her genetic makeup, before she ever takes a pill.

The other drawback to SSRIs is that they can take up to 12 weeks to make people feel better. That's because the drugs work in part by setting off a chain of neurochemical events that eventually regulates brain levels of glutamate, a neurotransmitter that improves communication between neurons. A drug that targets glutamate levels directly could improve mood much faster. One drug that has been shown to do so is ketamine, which is currently used as an anesthetic.

In one experiment, researchers at the National Institute of Mental Health (NIMH) administered an intravenous dose of ketamine to a group of people with depression. "Less than two hours later, the participants reported feeling better. Within 24 hours, they had achieved the same level of depression relief that people on SSRIs get in approximately six weeks," says Carlos Zarate, MD, a scientist in the Mood and Anxiety Disorders Program at the NIMH and lead researcher on the study. "When it comes to the speed of depression treatment, that's like breaking the sound barrier." However, ketamine can also temporarily distort sensory perception, so Zarate and his colleagues are hoping to create newer versions that would be just as effective but safer.

Computer-assisted therapy (CAT) and a new, painless version of electro-shock therapy


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