Placebo alters brain function of people with depression

Research presented in the January 2002 issue of the American Journal of Psychiatry is the first to show that placebo medication can induce changes in brain functioning for individuals with major depression--and that those alterations are different from the brain changes caused by antidepressants.

In the double-blind study, "Changes in brain function of depressed subjects during treatment with placebo," psychiatrist Andrew F. Leuchter, MD, research psychologist Elise A. Witte, PhD, and colleagues used quantitative electroencephalograhy to measure differences in brain function between a group of 25 participants with depression who received antidepressants and another group of 26 who received a placebo.

Over nine weeks, the researchers found that 52 percent of the antidepressant group and 38 percent of the placebo group responded to treatment, defined as a Hamilton depression scale score of 10 or less. However, the two groups' brain responses were very different. Patients who responded to placebo showed increased activity in the brain's prefrontal cortex, while those who responded to medication showed suppressed activity in the area. Medication responders showed brain function changes within 48 hours of starting treatment, while the placebo responders' changes began to occur after one to two weeks.

"People have known for years that if you give placebos to patients with depression or other illnesses, many of them will get better," says Leuchter, director of adult psychiatry and a professor at the UCLA Neuropsychiatric Institute and Hospital. Participants' decision to seek treatment, hopefulness for the treatment's effectiveness and positive interactions with health-service providers could all contribute to the "placebo effect," says Leuchter.

And while the findings do not explain why people respond to placebo treatment, "it does change the way we think about the placebo effect," says Leuchter. "What this study shows, for the first time, is that people who get better on placebo have a change in brain function, just as surely as people who get better on medication."

The researchers say that the findings raise doubts about two commonly held beliefs: First, administration of an inert pill appears to be an active treatment rather than a no-treatment comparison as previously thought. Second, the placebo response is not equivalent to an active drug response, since the two groups' brain physiology was altered differently.

Leuchter and his co-authors note, however, that the data do not provide a causal link between brain changes and the effect of placebo or medication; further studies are needed, they say, to conduct long-term follow-up of participants and examine other conditions.

"These findings show us that there are different pathways to improvement for people suffering from depression," Leuchter adds. "Medications are effective, but there may be other ways to help people get better."

--D. SMITH