UF researchers aim to show whether magnetic brain stimulation eases depression

Magnetic brain stimulation may help control severe depression, but University of Florida researchers are exploring whether the experimental therapy's apparent success is related to the treatment itself or is simply a function of mind over matter.

UF scientists, suspecting patient expectations may play a role in positive outcomes, are comparing the treatment with a bit of high-tech trickery designed to mimic it.

"Repetitive transcranial magnetic stimulation, known as rTMS, involves the use of a powerful magnetic field to generate small electrical currents inside the brain," said William Triggs, M.D., an associate professor of neurology at UF's College of Medicine.

Researchers don't yet know how rTMS works, but it appears to increase or decrease the activity level of brain cells, depending on the amount of current used. Previous clinical studies - including one conducted at Shands at the University of Florida medical center in 1999 - suggest it eases medication-resistant severe depression for up to three months in some patients.

"Severe depression strikes more than 6 million adult Americans each year, according to a two-year study on depression led by experts from Harvard University and the National Institute of Mental Health and described in the June 18 issue of the Journal of the American Medical Association. Up to 50 percent of patients suffering severe depression do not respond well to medication," Triggs said.

The current treatment strategy for medication-resistant severe depression combines psychotherapy and electroconvulsive therapy, also known as shock therapy.

Although rTMS has not been approved by the federal Food and Drug Administration for use in patient care, researchers have investigated it since the mid-1990s as a potential therapy for stroke, Alzheimer's disease, depression and other neurological conditions. Its possible placebo effects on depressed patients are debated widely.

"What's going on in the patient's mind around the time of the treatment is important," said Triggs, co-director of the new study. "We think that's why so many uncontrolled studies, where every patient gets the actual treatment, had such positive results. All the patients knew they were getting the treatment."

"Placebo effects typically influence the outcome of depression-treatment studies anywhere from 5 percent to 30 percent, depending on factors such as the degree of a patient's depression, the type of treatment and how much the treatment changes a patient's usual routine," said Ziad Nahas, M.D., medical director of the Brain Stimulation Laboratory at the Medical University of South Carolina in Charleston.

"In the current UF study, some patients receive rTMS, while others receive an elaborate imitation," Triggs said.

The five-year study began in October 2001 and is funded by a five-year, $655,000 grant from the U.S. Department of Veterans Affairs.

"There have been other controlled studies where investigators tried to give fake stimulation," Triggs said, "but we think we've come up with a better technique."

In total, about 100 volunteers - men and women who suffer medication-resistant severe depression - will attend 10 consecutive weekday sessions at the Shands rTMS facility, he said. Researchers randomly assign two-thirds of them to receive the actual treatment. The rest experience a seemingly identical procedure with one key difference - no magnetic force is used.

During the actual treatment, patients are seated with their heads stabilized by an array of adjustable pads. They remain still for 30 minutes while a bank of electronic equipment generates high-voltage electricity.

Every 30 seconds, a physician directs rapid pulses of electricity through a cable to a small wand tipped with a pair of insulated wire loops, producing a magnetic field comparable to that generated by an MRI scanner, though much more focused. The wand, placed on an adjustable frame and aimed at a patient's left or right frontal lobe, generates brief, painless magnetic pulses that cause a distinctive tapping sound and sensation and make the scalp tingle.

For the volunteers receiving the sham treatment, the wand is a specially manufactured replica that generates no magnetism but looks, sounds and feels like the real thing.

Psychiatrists and nurses attending the volunteers are not told who receives the sham treatment. Outcomes are evaluated using self-assessment and psychiatrists' observations during a three-month follow-up period.

"We really think we'll be able to fool the patients," Triggs said. "That's the best way to find out whether it's rTMS or patients' expectations that determines whether they get better."

"Both factors might play a role," said Stephen Nadeau, M.D., a UF professor of neurology and co-director of the study. "Research indicates that brain cells briefly form connections during the treatment, and this might facilitate changes in brain connectivity leading to improvement of depression. So if patients feel optimistic during rTMS sessions, the stimulation might increase the establishment of neural connections associated with a more positive outlook and mood," he said.

If the UF study reveals that both rTMS and expectations contribute to patient improvement, more research would be needed to determine how the treatment setting contributes, Nadeau said.

"We're optimistic that even if our study isn't successful that, by delving below the surface, we'll uncover other issues that need to be addressed scientifically," he said.

"Although rTMS isn't yet available to the general public, researchers should continue to explore ways to maximize its benefits to patients," Nahas said.

"There's clearly an antidepressant effect," he said. "I don't think (rTMS) will replace any other therapies, but it's another option."