Minds and Magnets

Is Mark's success story unusual? No more unusual than any other success story among people with hard-to-treat depression. Such sufferers commonly cycle through many treatments before they find the one that helps. Trial-and-error is the state of the art, since no one can predict which treatment will work for a given patient. The question for researchers--and the U.S. Food and Drug Administration, which is reviewing its status--is whether repetitive TMS should join antidepressants and ECT as an approved treatment for depression.

In early experiments, data were inconsistent, partly because there were no guidelines. Repetitive TMS treatment varies depending on the part of the brain targeted, the precision of the targeting, the intensity of the signal and the number of cycles per second, among other factors.

Individuality should be celebrated, but it makes research more difficult: subjects in depression studies are never a uniform group. As we learn more about the brain, we hope to know which people have which kind of depression. One day, measurements of brain activity may also help guide how and precisely where to administer repetitive TMS. Until then, we will have limited ability to predict how many and which people might respond to repetitive TMS or any other therapy.

Despite the problems, recent results are encouraging. Most studies involve patients who haven't been helped by anything else and are therefore less likely than average to feel improvement. Yet as practitioners refine their methods, they seem to be getting better results. In one randomized controlled study of almost 70 patients based in the state of Washington, subjects were given either repetitive TMS or a sham (placebo) treatment. In the repetitive TMS group, about 30 percent had a significant response and 20 percent had a complete remission (compared with 6 percent and 3 percent in the sham group). In Australia, 50 patients were assigned either to repetitive TMS or sham treatment. A significant response was seen in 44 percent of patients receiving repetitive TMS (8 percent in the sham group). More than a third in the repetitive TMS group had a complete remission, compared with none in the sham group.

Success in these studies may be due to modifications in how the treatment was given. Patients are now receiving stimuli of higher intensity, a larger number of stimuli in each repetitive TMS session and more stimulation sessions. And in the Australian study, patients had both the left and the right sides of the brain treated. Researchers note, however, that it is harder to create a placebo condition for repetitive TMS. The researchers know which treatment they are giving, and often the patients can tell the difference, too.

In fact, Anne entered one of Dr. Pascual-Leone's trials almost 10 years ago and anticipated that she might receive the sham treatment. But she knew right away that she had been placed in the repetitive TMS group. She felt a characteristic head tapping and twitching in her face that she now knows so well that she can tell the technicians when they have focused on the wrong spot. Her mood improved after the first treatment. At the end of the two-week course, she was dramatically better.