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Study finds similar brain changes for those taking placebo and antidepressant

The depressed brain seems able to heal itself in the short run, although antidepressants may be key to long-term recovery from depression.The depressed brain seems able to heal itself in the short run, although antidepressants may still be the key to long-term recovery from depression.

That's the claim of a new study in which researchers took brain scans of 17 depressed men who received either a placebo or the popular antidepressant Prozac for six weeks.

Those who responded to the placebo and those who responded to the antidepressant had similar, but not identical, changes in the areas of their brains that control thinking and emotion, says lead author Dr. Helen Mayberg, who is currently a neuroscientist at the Rotman Research Institute at the Baycrest Centre for Geriatric Care in Toronto. The research was conducted at the University of Texas Health Science Center in San Antonio.

While the people taking placebo and those taking Prozac did show similarities in those two brain areas, the people taking Prozac had additional changes in other brain areas -- the brainstem, striatum and hippocampus, Mayberg says.

That difference might be critical.

The drug-triggered changes in these other brain regions may promote long-term recovery from depression and prevent a recurrence of depression, says Mayberg, who has done previous research on how different parts of the brain can work in concert to make the depressed brain better.

"So, the drug provides what may be in fact a filter, cushion or barrier that helps prevent depression relapse. Getting well is just one step. Staying well is a second step," Mayberg says.

She stresses this study in no way suggests a placebo is all that's needed to treat depression.

"That would be a terrible, terrible message. It would be the wrong message," Mayberg says.

This is the first time that positron emission tomography (PET) has been used to pinpoint and compare specific brain regions that respond to a placebo and an antidepressant. PET can detect changes in the metabolism of different parts of the brain.

"What we've looked at in the experiment is the process of getting better, and what are the brain correlates of that change," Mayberg says. "Our experiment actually identifies what needs to happen to get well."

The study included 17 depressed, hospitalized men who were given either Prozac or placebo over six weeks. Neither the patients nor the doctors knew who was getting a placebo and who was getting Prozac. Of the 15 people who completed the study, eight got better. Of those, four received the placebo and four were given Prozac.

The research was funded by the National Institutes of Mental Health and Eli Lilly and Co., the maker of Prozac -- a selective serotonin reuptake inhibitor (SSRI). Such drugs act in the brain on a chemical messenger called serotonin.

It's no surprise that some people on placebo got better, Mayberg says. The expectation of treatment and being in a hospital setting can contribute to a hopeful feeling and positive outcome in patients.

The fact that some of the placebo recipients improved indicates the brain may have some ability to heal itself of depression, Mayberg adds. Previous studies have indicated that effect is likely short-lived, she says.

There was no long-term follow-up of the people in this study. Because all the patients were put on medication after the six weeks ended, researchers don't know whether those on the placebo would have remained well following their discharge from the hospital.

The research appears in the May 2002 issue of the American Journal of Psychiatry.

"The most recent study in the American Journal of Psychiatry is not news, but rather supports a growing body of research that is finding evidence for a physical response in the brain from placebo compared to SSRIs," says a statement from Eli Lilly.

The Indianapolis-based company says it has funded more than 400 Prozac studies to increase understanding of the drug.

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