An experimental treatment offers promise for some patients whose depression resists standard medications and shock therapy.
By Michael Craig Miller, M.D.
ast a year of disabling depression. Numerous psychiatric treatments failed to provide longed-for relief. Life was miserable until they began receiving an experimental treatment with a clumsy name: repetitive transcranial magnetic stimulation, or repetitive TMS.
This magnetism has nothing to do with magnets applied to the skin or with animal magnetism, the charlatanry invented by Franz Mesmer in the 19th century, although skeptics have worried that people cured by repetitive TMS have merely been mesmerized. Repetitive TMS uses real magnetic fields to induce changes in brain function, and there's some evidence it may make nerve-cell connections more efficient. It may modify how regions of the brain work together to regulate mood. It's a cousin of "shock therapy," or electroconvulsive therapy (ECT). Unlike ECT, however, it does not require anesthesia. It's localized, so side effects have been mild; some patients experience headache or scalp discomfort.
TMS was developed more than 20 years ago by neurologists studying brain function, rather than treatment. The technique exploits the relationship between electric currents and magnetic fields. When an electric current in a wire changes, it creates a magnetic field. That magnetic field can create an electrical current in another wire. In repetitive TMS, a coil that is shaped, for example, like a doughnut or figure-8 is held over the scalp. By rapidly changing the charge in the coil, the magnetic field induces an electric current in the brain that is strong enough to activate nerve cells below the scalp. The coil may look large, but the area affected can be as small as a pea. In contrast, ECT causes a generalized or whole-brain seizure, with electrical changes throughout the brain.
This modicum of intrusiveness appealed to Mark. One day when he was 15, he told his parents he was going to the library, but he went to a nearby bridge instead, planning to jump. Police rescued him. Two years of repeated hospitalization, medication and psychotherapy did not help; so he began ECT. It worked, but he required monthly maintenance treatments that were embarrassing and disruptive because he could not function well in the days around the periodic treatments.
Mark's mother found out about repetitive TMS from a news report almost 10 years ago when he was 17. She tracked down Dr. Alvaro Pascual-Leone of the Center for Noninvasive Brain Stimulation at Beth Israel Deaconess Medical Center in Boston. Within two weeks of treatment he received as part of a study, Mark developed a more positive outlook. He has needed maintenance treatment every four months or so, but it has not interfered with intellectual functioning the way ECT did. He finished high school, and earned two college degrees in education. Now he's a teaching assistant, optimistic that he will realize his goal of being a teacher.
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.
Anne had been expecting twins in a pregnancy that became complicated. One child, a son, died. Her daughter remained in a precarious state in the hospital for four months. Grief and worry led to postpartum depression and hallucinatory psychosis. Anne could barely function. She tried antidepressants, but felt no better until receiving repetitive TMS. In the last few years, she has had short courses of repetitive TMS about four times a year. She now works in a business with her husband, takes care of her children and describes herself as becoming what she was before she became depressed: a happy person.
The stories of Anne and Mark are stirring, but experts are still quite cautious. A relatively small number of patients have been treated so far, and the number of patients evaluated in controlled trials is also very limited. The maximum period of benefit averages around four months, at which point maintenance treatment can be offered and seems to work well. Though less intrusive than ECT, the treatment does require a complicated machine that has to be operated by a skilled technician in a controlled environment. It may have fewer side effects than medications, but it is more expensive and less convenient. There is also much to learn about how repetitive TMS interacts with standard drug treatments.
Repetitive TMS is already available for depression treatment in Canada, Australia, New Zealand, Israel and the European Union. The FDA may rule on repetitive TMS as a depression treatment in early 2007. Approval here would be good for Anne and Mark, because they now pay out of pocket for a treatment that costs about $300 per session. They don't feel they've been mesmerized. "If there was going to be a placebo effect," asked Anne, "couldn't it have happened sooner with one of the medications I tried?" Their interest in talking about their experience is propelled by vivid memories of the pain of depression and the subsequent relief. They know the hard work of living with the illness and the frustration of trial-and-error treatment. They encourage people to stay with it. Like many health-care professionals and patients, they hope depressed patients will have more options available. Because right now, there are still too few.
—Miller is editor in chief of the Harvard Mental Health Letter and a member of the faculty of Harvard Medical School. For more information go to health.harvard.edu/NEWSWEEK.