For some people with depression, the many drugs and therapies currently available don’t work. Now they may have another method to try: repetitive transcranial magnetic stimulation (rTMS). In carefully controlled research reported in the May issue of the Archives of General Psychiatry, the therapy did offer relief to some people with intractable mood disorder.
“I think there’s no longer a reasonable question as to whether TMS has antidepressant effects,” says Mark S. George, lead study investigator and director of the Center for Advanced Imaging Research and the Brain Stimulation Laboratory at the Medical University of South Carolina. “The question now shifts to how big those effects are, in which patients, and how do we make them bigger.”
In TMS, an electromagnet positioned over the head sends brief but powerful magnetic pulses through the skull, causing neurons to fire on the surface of the brain. The pulses are usually applied to the prefrontal cortex, which researchers believe affects areas associated with mood regulation. Unlike electroconvulsive therapy (ECT) and deep brain stimulation, TMS only indirectly induces electrical activity in the brain—it does not require surgery.
Although the first TMS device for treating depression was approved by the FDA in October 2008, many doctors are still skeptical about the treatment. One of the problems in assessing the effects of TMS in randomized trials has been how to compare it to an adequate sham control. In the new study, the researchers used a sham control that mimicked the sensations on the scalp caused by rTMS while blocking the magnetic field. They also established a strict protocol to ensure that the study remained “blind,” and the volunteer test subjects did not know if their “treatment” was the sham or full rTMS.
The multi-site study involved 190 patients who were randomized to receive rTMS or the sham treatment for 37.5 minutes every day for three weeks. All patients were medication free for at least two weeks at the time of the study treatment. In addition, to qualify for the study the patients needed to have previously tried and failed, or not tolerated, at least two antidepressant medications.
The researchers found that the overall remission rate for patients treated with rTMS was 15 percent compared with 5 percent in the group who had received the sham treatment. In addition, the six-month follow-up data, presented at the 2010 annual meeting of the American Psychiatric Association in New Orleans, showed only a 12 percent relapse rate in patients who had responded positively to rTMS and who were back on medication.
Lesley Fellows, a neuroscientist at the Montreal Neurological Institute, who was not involved with the study, says that the trial was well designed and has resolved some of the issues around TMS, although many questions remain. “We’re still not very clear on precise mechanisms that are triggered by TMS,” she says. “In addition, we don’t have a very good understanding of the differences in the brains of people with depression, so you’re putting two uncertainties together.”
Despite the unknowns, George is optimistic about TMS. “Right now it’s helping people who are not otherwise getting help. I think that’s good news,” says the study investigator. “And it implies a different approach to understanding depression. For so long people have been kind of stuck in the pharmacology model of increasing or decreasing serotonin or dopamine. I think that this really shifts the whole approach to modifying brain circuits and that this will continue to lead us to new treatments.”