Placebos' Brain Power

Placebos, or fake treatments, are widely known to improve some people's well-being. Now, a study in depressed patients shows that this benefit is linked to a change in brain activity--although in a completely unexpected way.

Placebo treatments--usually in the form of a sugar pill or saline injection--are often used as a control when new drugs or other therapies are tested. About 33% of people treated with a placebo report that their symptoms improve. But how this is possible, and why placebos affect only some people, remains a puzzle. One problem is that placebos don't produce objectively measurable changes in the patients' physiology; to gauge their effects, doctors must rely on highly subjective patient interviews.

Clinical psychiatrist Andrew Leuchter and his team at the University of California, Los Angeles, enlisted the help of 51 people suffering from major depression to find a better way to distinguish between medication and the placebo effect. Patients were treated with either a placebo pill or one of two depression medications. The team then used EEGs to monitor electrical activity in their brains during a 9-week period. Of the patients treated with a real drug, 58% reported they felt increasingly better, compared to 38% in the placebo group, the team reports in the January issue of the American Journal of Psychiatry--a result that's fairly typical for antidepressant trials.

The surprise was in the EEGs. Patients who responded to medication had shown less activity than before in the prefrontal cortex--a result seen in previous trials. But in those who got better on a placebo, brain activity in the same area increased. (People who did not get better on either treatment showed no significant change.) It's unclear how opposite effects can both make people feel better; apparently there's more than one path to recovery from depression, Leuchter says.

The discovery that the placebo effect can be quantitatively measured opens up a range of new possibilities for research, he adds. Fred Quitkin, a psychiatrist at Columbia University, agrees. But he cautions that this was only a small study that needs to be replicated with larger numbers of patients. "There may still be less here than meets the eye," Quitkin says.

Related sites

Andrew Leuchter's page about placebos
Science story about placebos and depression (Science, 9 April 1999, p. 238)