In Brief

Both cognitive-behavioral therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs) alleviate depression by lowering brain activity levels, but the drugs apparently depress limbic system activity while the therapy decreases frontal cortex activity, according to a new study in the Archives of General Psychiatry (Vol. 61, No. 1).

Previously, researchers thought comparable success rates suggested the treatments produced changes in the same area of the brain, says one of the study's authors, Helen Mayberg, MD, a scientist at the Rotman Research Institute in Toronto.

Mayberg and her collaborators recruited 17 clinically depressed middle-aged adults through a newspaper advertisement. The participants then attended 15 to 20 sessions of CBT, in which a practitioner trains people to re-evaluate information and monitor maladaptive thoughts.

Using positron emission tomography, the researchers recorded the metabolic activity of the participants' brains at the beginning of the treatment program and again at the end. They then compared changes in brain activity of CBT-treated participants with that of a similar group of patients recruited for a different study, which treated them for six weeks with the SSRI paroxetine, marketed as Paxil.

Of the two groups, only those participating in CBT showed decreased over-activity in the medial frontal cortex, an area of the brain implicated in self-monitoring and self-assessment. By comparison, the people who took paroxetine showed no change in this area, but they did experience decreased activity in the subgenual cingulate area, a limbic system region associated with mood regulation--an area apparently unaffected by CBT.

While the two treatments worked in different ways, they had a similar net effect--both the paroxetine and the CBT participants reported a decrease in their symptoms of depression, as measured by the Hamilton Depression Rating Scale. According to Mayberg, the clinical literature suggests that people who do not respond to CBT often do better when switched to antidepressants and vice versa. Experiments such as this one may eventually help explain why this is.

In the future, says Mayberg, clinicians may be able to use brain scans to determine abnormal brain activity and predict which treatment's particular effects will benefit a given patient.

"There is a whole circuit board that seems to go awry with people in depression," Mayberg explains. "How cognitive-behavioral therapy approaches the system is very different than how the drug targets it."